Screening for Cardiac Amyloidosis With Nuclear Cardiology for Minority Populations
Conditions: Amyloid Cardiomyopathy, Transthyretin-Related
Sponsor: Mathew S. Maurer, MD

CLINICAL STUDY PROTOCOL 
 
Screening for Cardiac Amyloidosis with Nuclear 
imaging in Minority Populations study (SCAN-MP) 
 
 
Protocol Version: 
 
4.2 
Protocol Date: 
 
June 24, 2022 
ClinicalTrials.gov: 
 
NCT03812172 
Sponsor: 
 
 
Columbia University Medical Center 
Clinical Cardiovascular Research Laboratory for the 
Elderly (CCRLE) 
21 Audubon Ave. SB-0180 
New York, NY 10032, USA 
 
Sponsor-Investigator:  
Mathew Maurer, MD 
Co-Principal Investigator 
212-932-4537 
 
Frederick Ruberg, MD 
Co-Principal Investigator 
617-638-8733 
 
Site Investigator: 
 
Ed Miller 
 
 
 
 
Site Investigator 
 
 
 
 
203-785-4127 
 
 
 
 
 
 
Collaborating Investigators: Gillian Murtagh, MD 
Abbott Diagnostics 
 
Agim Beshiri, MD 
Abbott Diagnostics 
 

SCAN-MP – Study Protocol v4.0 
 
Page | 2  
STUDY SYNOPSIS 
Protocol Title 
Screening for Cardiac Amyloidosis with Nuclear imaging in Minority 
Populations study (SCAN-MP) 
Protocol Number 
4.2 
Design 
This is a multicenter, diagnostic screening study to evaluate the 
prevalence of wild-type and Val122Ile ATTR cardiac amyloidosis 
(ATTR-CA) in a population of Black and Hispanic subjects with heart 
failure at participating sites. ATTR-CA is an age-related infiltrative 
cardiomyopathy that causes heart failure and death that is frequently 
unrecognized and underdiagnosed. 
Consented eligible patients will be evaluated for the presence and clinical 
manifestations of ATTR Cardiac Amyloidosis. 
Patients will undergo a Screening/Baseline visit, using nuclear medicine 
screening and TTR genetic test.  Those who have myocardial retention of 
the imaging radiotracer with a Periguini score >=2 (uptake equal to bone) 
and/or H/CL ratio > 1.3 will be diagnosed with ATTR amyloidosis and 
followed up in 6 months and again at 12 months. 
Study Sites 
This study is to be conducted at five study sites: Recruitment and 
Screening at Harlem Hospital.  All study procedures at NYP Allen 
Hospital, NYP Milstein Hospital, Boston University Medical Center and 
Yale New Haven Hospital.   
Time on Study 
The duration of patient participation in this study is approximately 12 
months. 
Primary Objective To improve identification of minority patients with ATTR-CA and 
enhance the understanding of genotype-phenotype associations in 
Blacks/Hispanics with ATTR-CA due to the Val122Ile mutation or 
ATTR wild-type. 
Sample Size 
Up to 800 patients will be screened in this study.  
Inclusion 
and 
Exclusion Criteria 
Every participant must meet all of the following inclusion criteria to be 
eligible for enrollment in this study: 
1. Black or Hispanic of Caribbean origin. 
2. Age ≥60 years. 
3. Diagnosis of heart failure, confirmed by one of two methods: 
a. Modified criteria utilized by Rich et al. which include a 
history of acute pulmonary edema or the occurrence of at least 
two of the following that improved with diuretic therapy 
without another identifiable cause: dyspnea on exertion, 
paroxysmal nocturnal dyspnea, orthopnea, bilateral lower 
extremity edema or exertional fatigue, and 

SCAN-MP – Study Protocol v4.0 
 
Page | 3  
b. NHANES CHF criteria with a score ≥3 (see Appendix 1). 
4. Left ventricular septal OR inferolateral wall thickness ≥12 mm. 
5. Ejection fraction >30%. 
6. Able to understand and sign the informed consent document after 
the nature of the study has been fully explained. 
The presence of any of the following excludes eligibility for enrollment 
in this study: 
1. Primary amyloidosis (AL) or secondary amyloidosis (AA). 
2. Prior liver or heart transplantation. 
3. Active malignancy or non-amyloid disease with expected survival 
of less than 1 year. 
4. Heart failure, in the opinion of the investigator, primarily caused 
by severe left-sided valve disease. Note: if valve was repaired, 
subject may be considered as no longer with severe valve disease. 
5. Heart failure, in the opinion of the investigator, primarily caused 
by ischemic heart disease. 
6. Ventricular assist device or anticipated within the next 6 months. 
7. Impairment from stroke, injury or other medical disorder that 
precludes participation in the study. 
8. Disabling dementia or other mental or behavioral disease. 
9. Enrollment in a clinical trial not approved for co-enrollment. 
10. Expected use of continuous intravenous inotropic therapy in the 
next 6 months. 
11. High risk for non-adherence as determined by screening 
evaluation. 
12. Inability or unwillingness to comply with the study requirements. 
13. Chronic kidney disease with eGFR <15 mL/min/1.73 m2 or 
ESRD. 
14. Weight >350 lb. 
15. Nursing home resident. 
16. Other reason that would make the subject inappropriate for entry 
into this study. 
Aims 
The specific aims of this epidemiologic investigation include: 
1. To determine the prevalence of ATTR Val122Ile CA in Caribbean 
Hispanics and Blacks with HF. 
2. To demonstrate that circulating RBP4 concentration is integral to 
TTR tetramer stability which in turn determines the clinical 

SCAN-MP – Study Protocol v4.0 
 
Page | 4  
characteristics of ATTR CA. 
We will explore the following: 
1. The prevalence of the Val122Ile genotype and ATTRm CA 
phenotype among Hispanics of Caribbean origin compared to 
Blacks. 
2. Gender differences in ATTR-CA identified by myocardial uptake 
of Tc99-PYP or Tc99-HMDP. 
3. The development of a risk based calculator based on clinical, 
electrocardiographic, echo and biochemical variables to identify 
ATTR-CA. 
4. Disease progression and prognosis between Val122Ile vs. 
ATTRwt in this population so as to inform whether the genetic 
form of this condition results in a more malignant phenotype. 
5. Differences in ATTR stability between ATTRm Val122Ile vs 
ATTRwt and non-amyloid controls which will associate with 
clinical features and outcomes. 
6. Differences in RBP4 concentrations in plasma and urine in 
ATTRm Val122Ile vs ATTRwt and non-amyloid controls and 
their association with genetic penetrance in ATTRm V122I and 
prognosis. 
Safety 
Assessments 
 
The safety of study participants will be evaluated by: 
1. Assessment of adverse events (AEs), including serious adverse 
events (SAEs). 
2. Clinical laboratory safety tests (serum chemistry). 
3. Vital sign measurements (blood pressure, pulse rate, and 
respiratory rate). 
4. 12-Lead electrocardiogram (ECG). 
5. Physical examinations 

SCAN-MP – Study Protocol v4.0 
 
Page | 5  
SCHEDULE OF ACTIVITIESThe following table summarizes the activities to be performed at 
each of the designated study visits. Details of the different procedures can be found in subsequent 
sections of this manual. 
Procedure 
Screening 
Baseline 
6 Months* 
(±2 Weeks) 
12 Months* 
(±4 Weeks) 
Informed Consent 
X 
 
 
 
Inclusion and Exclusion Criteria 
X 
 
 
 
Baseline History 
 
X 
 
 
Height and Weight† 
 
X 
X 
X 
Vitals Signs 
 
X 
X 
X 
Medications 
 
X 
X 
X 
Clinical Examination 
 
X 
X 
X 
Adverse Events Review 
 
X 
X 
X 
Electrocardiogram 
 
X 
X 
X 
Laboratory Analysis 
 
 
 
 
   Basic Metabolic Panel 
 
X 
X 
X 
   Hepatic Function Panel 
 
X 
X 
X 
   Cardiac Biomarkers‡ 
 
X 
X 
X 
   Vitamin A/RBP4 in plasma/urine§ 
 
X 
X 
X 
   Prealbumin 
 
X 
X 
X 
   TTR Kinetic Stability 
 
X 
 
X 
   TTR Gene Sequencing 
 
X 
 
 
   Ancestry Analysis 
 
X 
 
 
Six-Minute Walk Test 
 
X 
X 
X 
Short Physical Performance Battery 
 
X 
X 
X  
QoL Questionnaires 
 
X 
X 
X 
Health Literacy Questionnaire 
 
X 
 
 
Echocardiogram 
 
X 
 
X 
99mTc-PYP Scintigraphy** 
 
X 
 
 
Phone Call Follow-Up¶ 
 
 
X 
X 
* Follow-up visits are to be conducted on subjects who test positive to the Cardiac Amyloid Scintigraphy scan and/or are 
carrier of the V122I mutation. Window for the 6-month visit is ±2 weeks and for the 12-month visit is ±4 weeks. 
† Height measured only at baseline visit. Subjects with weight >350 lb will not participate in the study. 
‡ Includes BNP, NT-proBNP, galectin-3, troponin I and T. 
§ Includes Vitamin A and RBP4 in on site spot urine. 
¶ For participants with no TTR CA, a phone call follow-up will be conducted instead. 
**In the event that PYP is unavailable due to supply shortage, the investigator has the option of using HDP until PYP becomes 
available again to ensure study continuation per FDA.  

SCAN-MP – Study Protocol v4.0 
 
Page | 6  
For every study visit, a checklist will be used to help ensure completion of all the study procedures. 
The checklist is also a guide that suggests the order in which the assessments should be performed (See 
Appendix 3). 
 

SCAN-MP – Study Protocol v4.0 
 
Page | 7  
TABLE OF CONTENTS 
STUDY SYNOPSIS ............................................................................................................... 2 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................ 9 
1. INTRODUCTION .......................................................................................................... 10 
1.1 
Background and Rationale ..................................................................................... 10 
1.1.1 
Transthyretin Biology ....................................................................................... 10 
1.1.2 
Transthyretin-mediated amyloidosis definition ................................................. 10 
1.1.3 
Pathogenesis and Outcome ............................................................................. 11 
1.1.4 
ATTR-CM and Heart Failure ............................................................................ 11 
1.2 
ATTR-CM Population Burden ................................................................................. 13 
1.2.1 
ATTR amyloid is an under-recognized cause of heart failure .......................... 13 
1.2.2 
Are Hispanics affected by TTR-CA? ................................................................ 14 
1.2.3 
TTR-CA from mutant protein has more severe phenotype than wild type ....... 14 
1.3 
Natural History of Transthyretin Cardiac Amyloidosis ............................................ 15 
1.3.1 
Clinical Characteristics and Outcome in ATTR-CA in TRACS ......................... 15 
1.3.2 
Predictors of Mortality ...................................................................................... 16 
1.4 
Therapeutic Options ............................................................................................... 17 
1.4.1 
Novel Therapies Require Early Identification of Affected Individuals ............... 17 
1.4.2 
Tc-PYP & Tc-HMDP can detect TTR-CA without the need for an amyloid biopsy
 
18 
1.4.3 
Myocardial retention of Tc99-PYP is prognostic in TTR-CA ............................ 18 
1.4.4 
Myocardial Contraction Fraction (MCF) to identification and prognosticate in 
TTR-CA19 
1.4.5 
A method to quantify TTR kinetic stability ........................................................ 20 
2. STUDY OBJECTIVES & STUDY DESIGN ................................................................... 21 
2.1 
Primary Objective ................................................................................................... 21 
2.1.1 
Research Goal ................................................................................................. 21 
2.1.2 
Overview of Study Design ................................................................................ 21 
2.1.3 
Patient Recruitment ......................................................................................... 22 
2.1.4 
Selection Criteria ............................................................................................. 23 
2.1.5 
Study Procedures ............................................................................................ 23 
2.1.6 
Hypotheses ...................................................................................................... 29 
2.1.7 
Statistical Considerations and Sample Size ..................................................... 30 

SCAN-MP – Study Protocol v4.0 
 
Page | 8  
2.1.8 
Data Analysis Plan ........................................................................................... 31 
2.2 
Limitations and Assumptions .................................................................................. 32 
2.3 
Patient Numbering .................................................................................................. 34 
3. ADVERSE AND SERIOUS ADVERSE EVENTS .......................................................... 35 
3.1 
Adverse Events Definition ...................................................................................... 35 
3.2 
Serious Adverse Event (SAE) Definition ................................................................ 35 
3.3 
Collecting and Reviewing Adverse Event and Outcome Information ...................... 35 
3.4 
Stopping Study Procedure Due to Adverse Event .................................................. 36 
3.5 
Adverse Event Reporting ....................................................................................... 36 
3.5.1 
Reporting to the Sponsor ................................................................................. 36 
3.5.2 
Reporting to the IRB ........................................................................................ 37 
3.5.3 
Reporting to the FDA ....................................................................................... 37 
3.5.4 
Reporting to Participating Sites ........................................................................ 38 
4. REGULATORY GUIDELINES ...................................................................................... 39 
4.1 
Institutional Review Board/Independent Ethics Committee .................................... 39 
4.2 
Regulatory Authorities ............................................................................................ 39 
4.3 
Modification of the Protocol .................................................................................... 39 
4.4 
Informed Consent Form ......................................................................................... 39 
4.5 
Study Data Recording and Retention ..................................................................... 40 
4.6 
Confidentiality ......................................................................................................... 40 
4.7 
Lead Site monitoring of sub-site research activity .................................................. 40 
5. REFERENCES ............................................................................................................. 41 
6. APPENDICES ............................................................................................................... 48 
APPENDIX 1 HEART FAILURE CLINICAL SCORE ...................................................... 49 
APPENDIX 2 THE BORG SCALE ................................................................................. 50 
APPENDIX 3 NUTRITION FACTS OF A CONTAINER OF A PINT OF ICE CREAM .... 51 
APPENDIX 4 CASE REPORT FORMS ......................................................................... 52 
 
 
 

SCAN-MP – Study Protocol v4.0 
 
Page | 9  
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Abbreviation or Specialist Term 
Explanation 
6-MWD 
Six-minute walk distance 
6-MWT 
Six-minute Walk Test 
SPPB 
Short Physical Performance Battery 
99mTc-PYP 
99mTechnetium pyrophosphate 
99m Tc-HMDP 
99m Hydroxymethylene Diphosphonate 
AE 
Adverse event 
TTR 
Transthyretin  
ATTRm 
Mutant Transthyretin amyloidosis 
ATTRwt 
Wild-type Transthyretin amyloidosis 
ATTR-CA 
Transthyretin cardiac amyloidosis 
RBP4 
Retinol-Binding Protein 4 
 
 

SCAN-MP – Study Protocol v4.0 
 
Page | 10  
1. 
INTRODUCTION 
1.1 
Background and Rationale 
1.1.1 Transthyretin Biology 
Transthyretin (TTR), also known as prealbumin, is a tetrameric protein produced predominantly by 
hepatocytes (>95% of TTR is liver-derived), with small fractions produced in the choroid plexus and 
retina.1 The primary physiological role of TTR is to serve as a carrier of retinol (also known as vitamin 
A) through its interaction with retinol binding protein (RBP); it also plays a minor role as a carrier for 
thyroxine (T4). In humans, approximately 15% of T4 circulating in the plasma is bound to TTR; the 
remainder is predominantly bound to thyroxine-binding globulin. 
Mutations in the TTR protein as well as idiopathic mechanisms lead to destabilization of the tetrameric 
form and dissociation into dimers and monomers. The misfolding of mutated monomers results in 
tissue deposition of oligomers and amyloid fibrils. Amyloid deposits typically contain both mutant (mt) 
and wild-type (wt) TTR in addition to serum amyloid P protein and glycosaminoglycans, and over time 
these deposits lead to significant tissue injury. The clinical manifestation of this process is called ATTR 
amyloidosis. 
1.1.2 Transthyretin-mediated amyloidosis definition 
Transthyretin-mediated amyloidosis (ATTR) is caused by deposition of TTR amyloid fibrils in various 
tissues. The hereditary form of ATTR is caused by an autosomal dominant mutation in the TTR gene 
that leads to destabilization of the TTR tetramer and aggregation of misfolded monomers; this, in turn, 
results in cardiac and neuronal extracellular deposition of TTR amyloid fibrils culminating in life-
threatening cardiomyopathy and/or debilitating neuropathy, called ATTR mutant form or ATTRm. 
There are over 120 reported TTR genetic mutations2 that phenotypically result in at least 2 distinct 
clinical syndromes of ATTRm:  familial amyloidotic cardiomyopathy (FAC) and familial amyloidotic 
polyneuropathy (FAP), both of which are characterized by amyloid deposits of mutant and wild-type 
TTR.3 ATTR wild-type (ATTRwt) is another form of ATTR, occurring more predominately in elderly 
males and characterized by deposition of wild-type TTR in the heart tissue.4  
The Val122Ile mutation is the most common and estimated to be present in up to 4% of African 
Americans and in over 5% of West African populations.5 Disease develops predominantly in males 
with the mean age at diagnosis of approximately 70 years, and symptom onset typically occurring after 
the age of 60. In the US there are estimated to be approximately 100,000- 150,000 African American 
males over age 65 who are heterozygous carriers of the V122I allele.6 However, the extent of disease 
penetrance is currently unknown. 
Also unknown is the prevalence of ATTRwt within the African-American population.  While some 
cases have been documented it is unclear whether African-Americans develop wild-type disease with 
the same prevalence as non-African Americans. There are no data on the prevalence of ATTRwt or 
ATTRm amyloidosis in the Hispanic population in the US. 

SCAN-MP – Study Protocol v4.0 
 
Page | 11  
1.1.3 Pathogenesis and Outcome 
Cardiomyopathy in ATTR (ATTR-CA) occurs when insoluble TTR amyloid fibrils deposit in cardiac 
tissue causing heart wall thickening with diastolic and systolic dysfunction, conduction defects, and 
arrhythmias, leading to congestive heart failure and death. 
While there is a paucity of longitudinal clinical data on ATTR-CA, a few published reports have shown 
that ATTR patients have a significantly worse prognosis compared to other causes of heart failure, with 
rapid deterioration of functional capacity, including their ability to walk as measured by the 6-MWD, 
and quality of life (QOL) resulting in early mortality. 
The median survival of Val122Ile patients from time of diagnosis in two retrospective studies was 277 
to 41 months7, 8 and in the prospective Transthyretin Amyloidosis Cardiac Study (TRACS) study 
median survival was 26 months.9 
There is currently only one approved disease-modifying treatment option specifically for patients with 
ATTR-CA, Tafamidis Meglumine. Another therapy that has shown efficacy in TTR amyloid 
polyneuropathy is diflunisal (a non-steroidal anti-inflammatory agent) which when administered at a 
dose of 250 mg PO twice a day delayed progression of neuropathy when compared to placebo.10 As 
ATTR-CA is progressive and many patients are anxious to receive a potentially disease modifying 
agent, there has been an increasing use of diflunisal in such patients, with a single report of safety over 
an intermediate time period in an uncontrolled study.11 
1.1.4 ATTR-CM and Heart Failure 
1.1.4.1 Heart failure (HF) is a growing epidemic among urban, multi-ethnic populations 
The epidemic of HF disproportionately affects older and multi-ethnic populations.  Blacks (incidence 
rate: 4.6 per 1000 person-years) have the highest incidence rate of HF, followed by Hispanic (3.5), 
white (2.4) and Chinese-American (1.0).  The higher risk among Blacks has been related to differences 
in the prevalence of hypertension and diabetes mellitus, as well as socioeconomic status12. 
Additionally, Blacks are at high risk for the development of HF with preserved ejection fraction 
(HFpEF)13.  Data from Medicare records revealed that hospitalization and readmission for HF was 
higher among Blacks and Hispanic patients than among non-Hispanic white patients14.  Despite recent 
advances, HF remains a major public health problem with rising incidence/ prevalence and associated 
annual health care costs in excess of $32 billion12, 13. The incidence/prevalence of HF are strikingly 
age-dependent, with prevalence in adults > 80 years of age approaching 10% and mortality rates 
increasing exponentially with advancing age. Epidemiologic studies demonstrate that >50% of patients 
with HF have HFpEF. The hospitalization rate has continued to rise among subjects with HFpEF as 
compared to a flattening in those with systolic HF13. Large-scale clinical trials for the population with 
HFpEF have unfortunately not identified any specific therapies15-17. Thus, identifying and treating 
patients with personalized and precise medical approaches from underserved minority communities at 
risk of HF are urgently needed. 

SCAN-MP – Study Protocol v4.0 
 
Page | 12  
1.1.4.2 Amyloid infiltration is an under-recognized mechanism underlying HFpEF 
With an increasing burden of disease and lack of efficacy in recently conducted clinical trials, a greater 
understanding of pathobiologic mechanism(s) that contribute to diastolic dysfunction and the genesis 
of HFpEF are warranted.  Numerous biologic mechanisms that have been implicated in the genesis of 
myocardial stiffness18-20 including intrinsic cardiomyocyte stiffness19, 21 related to abnormal calcium 
homeostasis22, the cytoskeleton (e.g. microtubules and intermediate filaments23, 24 or titin25, 26) as well 
as, abnormalities in the extracellular matrix related to collagen and elastin26-29. Amyloid infiltration of 
the extracellular matrix can markedly alter myocardial stiffness resulting is upward and leftward shifts 
in the end diastolic pressure volume relation30, and has been associated with most severe forms of 
diastolic dysfunction as assessed by Doppler imaging31.  In-vitro length-tension experiments 
demonstrate increased diastolic force among subjects with amyloid in comparison to controls.32 More 
recent data has demonstrated that transthyretin or TTR cardiac amyloidosis (TTR-CA) accounts for up 
to 15% of cases of HFpEF33. Collectively, these data suggest that amyloid infiltration is not only a 
plausible pathobiologic mechanism in the genesis of HFPEF, but is under-appreciated and under-
recognized.  
1.1.4.3 Pathobiology of ATTR-CA 
TTR is a 127 amino acid protein, primarily synthesized in the liver, although other tissues including 
choroid plexus, the retinal pigment epithelium and kidney also synthesize TTR34-37. The known plasma 
functions of TTR are to carry thyroxine and retinol (vitamin A)-retinol binding protein complex. TTR 
binding to the smaller retinol-RBP complex prevents renal filtration of this retinoid-transport protein38.  
In its native state, TTR exists as a 55 kDa tetramer, i.e. four single chain TTR monomers form a 
tetrameric complex.  The crystal structure and physical properties of TTR are well characterized34-37.  
Human TTR is encoded by a single copy gene on chromosome 1839.  The TTR gene spans about 7 kB 
and contains 4 exons and 3 introns39.  Although each monomer of TTR consists of only 127 amino 
acids, about 120 human TTR mutations have been identified40.  More than 90 of these TTR variants 
are associated with human amyloidoses40.  While the phenotypes are variable for the TTR-associated 
amyloidoses, polyneuropathy and cardiomyopathy represent the two most common clinical 
manifestations. These phenotypes result from extracellular deposition of amyloid fibrils composed of 
mutant and wild type (WT) TTR (the vast majority of the familial patients are heterozygotes), although 
the wild type protein alone in genetically normal aged individuals can form amyloid fibrils37, 41, 42. 
More than 20 TTR mutations have been specifically linked to cardiac involvement, but the Val122Ile 
mutation, accounts for the highest proportion of amyloid TTR cardiomyopathy cases, especially in 
Black Americans5, 43. The prevailing hypothesis (Figure 1) to explain amyloidogenic mutations is that 
the mutations destabilize the TTR tetramer, facilitating faster or more extensive dissociation, the rate-
limiting step that precedes the formation of abnormally folded monomers that aggregate into amyloid 

SCAN-MP – Study Protocol v4.0 
 
Page | 13  
fibrils37, 42, 44. These TTR amyloid fibrils are deposited extracellularly in tissues where they cause post-
mitotic tissue damage and ultimately cell death. Collectively, the literature makes a compelling case 
that TTR amyloid infiltration is an under-appreciated cause of HFpEF.  
1.2 
ATTR-CM Population Burden 
1.2.1 ATTR amyloid is an under-recognized cause of heart failure 
Cardiac involvement in ATTR, also known as familial amyloid cardiomyopathy (FAC) when 
associated with variant and WT TTR aggregation, previously senile systemic amyloidosis (SSA) when 
associated solely with WT TTR aggregation, is caused by amyloid fibril infiltration of the myocardium. 
This results in diastolic dysfunction progressing to restrictive cardiomyopathy and HF. ATTR 
cardiomyopathy is a late onset disease with symptoms typically occurring in patients over 60 years old. 
Although there are more than 20 mutations which have been associated with specific cardiac 
involvement, one mutation, Val122Ile, has been reported with high frequency in Blacks (prevalence of 
3.4% to 3.9%5, 45, 46).  The prevalence of ATTR dominated by a cardiomyopathy phenotype is unknown, 
but is certainly under-diagnosed43. Both Black Val122Ile carriers and Black patients with ATTRwt, 
who present typically after age 60, are often mistakenly thought to have hypertensive heart disease43. 
The prevalence of the Val122Ile allele in older adults with manifest cardiovascular disease, such as 
HF, is much higher.   Among 207 of 650 Blacks enrolled in the BEST Trial with NYHA Class III 
(92%) and IV (8%) HF, with a left ventricular ejection fraction <35%, the Val122Ile variant was found 
in 13 (6.3 %) of the subjects47.  Of note, four of the 116 individuals in the under 60 years of age cohort 
(3.5%) were positive, whereas 9 of the 91 over 60 years of age (10%) had the amyloidogenic Val122Ile 
allele. Studies indicate that the Val122Ile mutation is 5 times more prevalent in Blacks with HF than 
in a community cohort of comparable age47. Notably, a mutation in TTR is not a prerequisite for 
developing ATTR cardiomyopathy.  In the elderly, WT (normal) TTR may become structurally 
unstable for unknown reasons (this will be quantitatively explored herein), resulting in deposition of 
amyloid fibrils primarily in heart tissue and leading to HFpEF48-51. The frequency of TTR amyloid 
deposition in cardiac ventricles reported from autopsy studies, range from 1.8% to 25% 52, 53, with a 
rate of clinical cardiac disease pre-mortem of 34%52. More recent data demonstrates that among HFpEF 
subjects who were an average age of 74±14 at diagnosis, 21.2% had amyloid deposits on autopsy 
performed at an average age of 76±14 years.  Of HFpEF patients ≥ age 75 years at HF diagnosis (n = 
63), 20 (32%) had amyloid deposition vs. 4 of 50 (8%) patients < 75 years at HF diagnosis (p = 0.002).  
Of the 29 patients with amyloid deposition at autopsy, only 6 had a pre-morbid diagnosis of amyloid 
Figure 1. Native TTR is present in the circulation 
primarily as a tetramer but tetrameric TTR 
undergoes 
some 
dissociation 
into 
subunits.  
Mutations in TTR can result in an increased 
incidence in misfolded monomeric TTR, which is 
prone to aggregation, giving rise to spherical, 
amorphous and fibrillar TTR structures which are 
insoluble and result in amyloid deposition and 
ultimately amyloid-induced tissue damage. 

SCAN-MP – Study Protocol v4.0 
 
Page | 14  
at death54.  The prevalence of ATTRwt is unknown, but is certainly under-diagnosed. Intriguingly, the 
vast majority (>90%) of ATTRwt patients in the reported series9, 55-57 are White, while limited 
population based data suggests that the prevalence of ATTRwt does not differ among Whites and 
Blacks.58 Thus, TTR-CA is an under-recognized cause of HFpEF particularly among Blacks, among 
which ~4% of the population are allele carries of the Val122Ile TTR mutation that results in amyloid 
deposition in the heart. Additionally, despite similar prevalence of ATTRwt in Whites and Blacks,58 
reported series almost exclusively describes Whites as being affected9, 56, 59. Collectively, these data 
suggest racial disparities in the identification of Black subjects with TTR cardiac amyloid, which is a 
focus of our proposed studies. 
1.2.2 Are Hispanics affected by TTR-CA? 
More than 53 million Hispanics currently live in the US, which constitutes 17% of the total US 
population, which make them the largest racial/ethnic minority. They represent the fastest-growing 
racial or ethnic population in the US, an ethnic group that is expected to constitute 30% of the total US 
population by 2050. While 64% of the US Hispanic population is of Mexican origin, 9% are of Puerto 
Rican origin, 3% each of Cuban, Salvadoran and Dominican origins, the remainder being of other 
Central American or South American origin. New York and in particular Washington Heights and 
Harlem have the highest percentages of Hispanics identifying as Black (up to 25%), compared to 2.5% 
of Hispanics nationwide. Overall, the Northeast region has the largest concentration of Black 
Hispanics, this is partly because of the large Puerto Rican, Dominican, and other mostly or partly 
African descended Hispanic populations in the region. Genetic data suggests that among Hispanics of 
Caribbean origin (e.g. Haiti, Dominican Republic, Cuba and Puerto Rico) that African ancestry ranges 
from 30-95%60. The Val122Ile mutation has been described almost exclusively in Blacks of African or 
Afro-Caribbean descent.  Surprisingly, despite the common ancestry shared by many Hispanics in the 
Northeast of the US, published reports of TTR cardiac amyloid have not focused on this relevant 
population. Only one previous report in an urban mid-west city did not find that the Val122Ile mutation 
in any newborn of Hispanic descent61, though whether these subjects were of Mexican or Caribbean 
origin was not specified.  The proposed SCAN-MP (Screening for Cardiac Amyloidosis with Nuclear 
imaging in Minority Populations) study will provide critically important information on the impact of 
TTR-CA in the Hispanic population with significant African ancestry, which we hypothesize are 
affected, but currently unrecognized. 
1.2.3 TTR-CA from mutant protein has more severe phenotype than wild type 
We characterized the cardiac phenotype among subjects (n=88) diagnosed with biopsy proven TTR-
CA at our institution. Subjects underwent DNA sequencing to confirm the presence of Val122Ile or 
ATTRwt. ATTR cardiac amyloid subjects were almost exclusively elderly males. Racial differences 
between Val122Ile and ATTRwt were distinct. Despite a younger age, subjects with Val122Ile 
mutation had a more advanced phenotype as evidenced by a higher troponin and reduced ejection 
fraction, as compared to ATTRwt. Additionally, survival in subjects with Val122Ile mutations was less 
(median survival of 2.53 years [95% CI; 1.7 to 3.2] compared to WT subjects with a median survival 

SCAN-MP – Study Protocol v4.0 
 
Page | 15  
of 4.3 years (95% CI of 2.5 to 5.4), 
p=0.0024 by log rank. Similar 
findings were confirmed in a 
multicenter. 
Transthyretin 
Cardiac 
Amyloid 
Study 
(TRACS).30 
Thus, despite the ability to 
identify 
subjects 
with 
the 
Val122Ile mutation by DNA 
sequencing, these patients present 
at a more advanced stage of 
disease than ATTRwt subjects for 
whom serologic testing is not 
available. Additionally, only 1 
subject (1.7%) with ATTRwt was 
Black and only 1 subject with the 
Val122Ile mutation was Hispanic, 
despite 
our 
catchment 
area 
including Harlem, where 62% of 
the population is Black according 
to 
the 
2010 
census 
and 
Washington Heights, where 69% 
of the population is Dominican. 
Whether these differences are 
attributable to a different natural history or delayed diagnosis is unknown. With the advent of a non-
invasive  nuclear imaging approach to identify TTR-CA without the need for a biopsy, we have a 
unique ability to address the questions raised about the prevalence and outcomes of this condition in 
urban, minority populations. 
1.3 
Natural History of Transthyretin Cardiac Amyloidosis 
The Transthyretin Amyloidosis Cardiac Study (TRACS)9, 30 was a multi-center, prospective 
observational trial examining the natural history and disease progression in patients diagnosed with 
TTR-CA. 
1.3.1 Clinical Characteristics and Outcome in ATTR-CA in TRACS 
Mean patient age at TRACS enrollment was 74 years, with the majority male (92%).  Of the twenty-
nine patients (18 WT and 11 Val122Ile), twelve (41%) subjects died or underwent a cardiac transplant 
after a mean follow-up period of 478 days (range 31-807). 
Table 1 
 
 
 
 
Parameter 
 
ATTRwt 
(N=57) 
V122I 
(N=31) 
P value 
Demographics 
Age at Diagnosis (years) 
77.2±5.8 
69.5± 7.9 
<0.001 
Gender (% male) 
94.7% 
83.8% 
0.124 
Race (% Black) 
1.7% 
83.8.% 
<0.001 
Electrocardiography (%) 
Atrial Fibrillation/Flutter 
26.80% 
8.50% 
0.119 
Pacemaker 
11.00% 
1.20% 
0.075 
Laboratory 
BNP (pg/ml) 
614±532.4 
935±736.2 
0.014 
Troponin I (ng/ml) 
0.1±0.3 
0.2±0.5 
0.335 
eGFR (ml/min) 
50.3±26.2 
49.2±19.0 
0.639 
Echocardiogram 
LVIDd (mm) 
39±15 
41±13 
0.963 
IVS (mm) 
16±7 
16±6 
0.567 
EF (%) 
43.8±19 
27.5±16.1 
<0.001 
LV Mass (grams) 
304.6±153.9 
290.1±146.6 
0.86 
LV Mass Index (grams/m2) 
11.6±6.3 
12.1±5.0 
0.911 
LA size (mm) 
37±22 
35±21 
0.149 
Right Heart Catheterization 
RA Pressure (mmHg) 
7.7±7.6 
8.4±7.7 
0.630 
PA Pressure (mmHg) 
33.6±23.3 
32.7±22.5 
0.398 
PCWP (mmHg) 
13.9±9.9 
13.4± 10.4 
0.654 
PaSat (%) 
41.2±30.0 
40.2±27.0 
0.013 
Cardiac Output (L/min) 
2.6±1.9 
2.4±1.7 
0.027 
PVR (dynes) 
87.9±131.4 
135.5±235.7 
0.005 
PVR (woods) 
  
1.1±1.6 
1.9±2.9 
0.007 

SCAN-MP – Study Protocol v4.0 
 
Page | 16  
1.3.2 Predictors of Mortality 
Age and gender did not differ between survivor and non-survivors. Subjects with Val122Ile mutations 
had a significantly higher mortality (72%, 8 of 11) compared with wild type patients (22%, 4 of 18). 
Survival analysis showed that in univariate analysis disease duration, a heart rate >70 bpm, lower stroke 
volume, a LVEF <50% and the presence of the Val122Ile mutation were all associated with shorter 
survival.  However, in multivariate analysis only stroke volume and disease duration, but not the 
Val122Ile mutation, had independent associations with reduced survival. This suggests that subjects 
with a mutation may have a more malignant phenotype presenting at a later stage of the disease. To 
further explore the mechanisms underlying the reduction in stroke volume in subjects with TTR-CA, 
we employed non-invasive pressure volume analysis.  TTR-CA is a disease characterized by significant 
abnormalities in passive diastolic function, progressive upward shifts in the end diastolic pressure 
volume relation (EDPVR), as well as decrements in the chamber contractility manifested by declines 
in the end systolic pressure volume ratio (ESPVR) and altered ventricular vascular coupling. Each of 
these could contribute to the inability of the ventricle to perform work. Using 2D echocardiographic 
measures of left ventricular volumes and mass with full Doppler studies, we estimated non-invasive 
pressure volume relations. As shown in the Figure 2, in TTR-CA, abnormalities in passive ventricular 
filling, reductions in chamber contractility and altered ventricular vascular coupling were each 
associated with a reduced ability of the ventricle to perform work, and ultimately associated with 
reduced survival in these subjects.  By calculating the relationship between the isovolumetric pressure 
volume area and end diastolic pressure (PVAiso-EDP), we demonstrated that in TTR-CA, there are 
progressive declines in ventricular function over time (left panel), ventricular function at baseline was 
worse in subjects with the Val122Ile mutation than in ATTRwt subjects (middle panel) and that the 
decrement in PVAiso-EDP relation was independently associated with reduce survival (right panel). 

SCAN-MP – Study Protocol v4.0 
 
Page | 17  
These data show that subjects with Val122Ile had a more severe phenotype with a reduced ability of 
the ventricle to perform work. This could be due a more malignant course among subjects with the 
Val122Ile mutation compared to the ATTRwt genotype or are due to later presentation among the 
Blacks with Val122Ile than among ATTRwt subjects, as a result of racial disparities resulting in poor 
access to care.  Accordingly, using such measures in a larger and unselected cohort of Blacks/Hispanics 
with both forms of TTR-CA, identified by  cardiac amyloid scanning, we can evaluate the physiologic 
effect of the amyloid infiltration in those with and without a genetic cause. Thus, we can determine the 
true impact of the genotype on the phenotype and on outcomes in Blacks/Hispanics from the same 
geographic and socio-economic region. 
1.4 
Therapeutic Options 
1.4.1 Novel Therapies Require Early Identification of Affected Individuals 
A proven treatment based on lifespan extension for the familial TTR amyloidosis is liver 
transplantation; however, this strategy has numerous limitations, including a shortage of donors, a 
requirement for surgery, need for lifelong immunosuppression and the high cost. Furthermore, most 
patients, especially those with cardiac involvement, are not acceptable transplant candidates or require 
combined heart/liver transplantation, which is not feasible for the large population of affected older 
adults. Recent studies have provided insight into the pathogenesis of TTR amyloidosis and suggested 
new strategies for therapeutic intervention. The other approved therapeutic strategy is to kinetically 
stabilize the TTR tetramer (native state) through its binding to a small molecule62, 63. Approximately 
70% of patients identified early in their course of disease and treated with tafamidis (a TTR stabilizer) 
remain progression-arrested, whereas in a demographically identical group, on placebo for 18 months 
before receiving the stabilizer, only ≈ 50% remain progression arrested64. We have demonstrated 
stabilization in a small open label trial the safety of diflunisal in subjects with ATTR cardiomyopathy11. 
Other therapeutic approaches approved for familial amyloid polyneuropathy include small interfering 
RNAs or antisense oligonucleotides to degrade TTR mRNA65, 66.  These two strategies (antisense 
oligonucleotides and RNAi) have shown efficacy in recently reported trials of ATTR peripheral 
neuropathy67, 68 and are expected to be effective for amyloid cardiomyopathy, as lowering the TTR 
concentration should decrease the TTR aggregation efficiency, a process thought to cause 
cardiomyopathy. All of the proposed therapies require early detection of subjects, because emerging 
therapies aim to prevent progression of disease by inhibiting newly synthesized TTR from converting 
into amyloid. These strategies do not directly reverse previous amyloid infiltration. In summary, there 
are multiple emerging therapies for ATTR cardiomyopathy which have demonstrated therapeutic 
stabilization and silencing in clinical trials. However, it appears to be critical to recruit TTR-CA 
patients early in the course of their disease to maximize the efficacy of these therapies and if effective, 
to ameliorate the racial disparities in outcomes for this population. 

SCAN-MP – Study Protocol v4.0 
 
Page | 18  
1.4.2 Technetium-based radiotracers can detect TTR-CA without the need for an amyloid 
biopsy 
Guidelines have been established for formalizing the diagnosis of amyloidosis, requiring a biopsy of 
tissue delineating the presence of amyloid in either the heart or another organ.69 Unfortunately, for a 
significant percentage of patients with TTR-CA, more easily performed biopsies, such as fat pad 
biopsies have a low yield.56 The performance of endomyocardial biopsy has been restricted to large 
centers with significant expertise, not only in the performance of the biopsy, but also in the 
pathologically evaluation of the type of amyloid, which is critical to accurate diagnosis and appropriate 
treatment. Our own single center data has shown that 99mTc-PYP imaging has a sensitivity and 
specificity for detecting TTR cardiac amyloid from either ATTRwt or Val122Ile and differentiation 
form AL in of 97% and 100% of patients, respectively with an area under the curve of 0.997.70 More 
recent multicenter data with 99mTc-PYP imaging from Columbia University, Boston University and the 
Mayo Clinic evaluated the utility of this non-invasive approach to diagnose TTR-CA without the need 
for endomyocardial biopsy71. Cardiac retention of 99mTc-PYP was visually scored using the ratio of 
myocardial uptake to the contralateral chest (the H/CL: heart contralateral ratio), which when >1.5 had 
a very high sensitivity (90%) and specificity (92%) for identifying the subjects with TTR-CA. 
Additionally, an even larger international collaboration employing 99mTc-DPD, 99mTc-PYP or 99mTc-
HDP imaging; using the following grading system; Grade 0 – absent cardiac uptake; Grade 1 – mild 
uptake less than bone, Grade 2 - moderate uptake equal to bone; Grade 3 - uptake greater than bone, 
has demonstrated that the vast majority of subjects with biopsy proven WT TTR (89.5%) or Val122Ile 
TTR (97.6%) demonstrated grade 2/3 uptake indicative of TTR-CA.  Among subjects who had grade 
2/3 uptake using either of the three isotopes and no monoclonal protein (as evident by serum protein 
electrophoresis with immunofixation without a monoclonal band and free light chain ratio that was 
between 0.26 or 1.65), the specificity of nuclear scintigraphy for identifying TTR-CA (compared to 
AL, hypertrophic cardiomyopathy, HFpEF from hypertension or another infiltrative disease) was 
100%!72 These data demonstrate that TTR-CA can be reliably diagnosed in the absence of histology 
and these data serve as the basis for employing this non-invasive test to evaluate subjects at risk for 
TTR-CA in the SCAN-MP trial73. 
1.4.3 Myocardial retention of Tc99-PYP is prognostic in TTR-CA 
In a retrospective, cohort study71 of 196 subjects with heart failure at 3 academic medical centers 
(Columbia University Medical Center, Boston University Medical Center and the Mayo Clinic) we 
evaluate cardiac retention of 99mTc-PYP using a quantitative heart-to-contralateral (H/CL) ratio. H/CL 
was calculated as total counts in a region of interest (ROI) over the heart divided by background counts 
in an identical size ROI over the contralateral chest. The outcome measured was time to death after 
99mTc-PYP scan.  Among the 144 subjects with TTR cardiac amyloid (the majority of who had 
ATTRwt [n=72] or the Val122Ile mutation ([n=24]), univariate analysis shown in Table 2 
demonstrated that the H/CL >1.6 predicted worse survival (hazard ratio (HR) 4.273, 95% CI 1.27–
14.37, P=0.02). In multivariate analysis encompassing age, gender, race, TTR mutation, NYHA class, 
troponin, BNP and eGFR, the HR for the H/CL ratio of >1.6 was still significant 6.2, 95% CI 1.5-30.4, 

SCAN-MP – Study Protocol v4.0 
 
Page | 19  
p=0.0043). In Kaplan-Meier analysis over a 4-
year follow-up, survival was significantly 
worse if H/CL was >1.6 vs. <1.6 (P=0.0029 
log-rank test). As shown in Figure 3, only 4 of 
44 subjects (9.7%) with a H/CL < 1.6 died over 
the follow-up period while 32 deaths occurred 
in the cohort with a H/CL ratio of > 1.6 (35% 
mortality). Thus, not only can 99mTc-PYP 
imaging diagnose ATTR-CA without a biopsy 
(irrespective of genotype), but this approach 
has prognostic significance. These data 
collectively suggest that 99mTc-PYP scans can 
identify ATTR-CA early, enhance diagnostic accuracy 
and can provide prognostic information. Accordingly, 
the use of such radiotracer imaging is a major advance 
in the field of cardiac amyloid which is being 
incorporated into clinical algorithms73 and is being 
relied upon in the proposed SCAN-MP study. 
1.4.4 Myocardial Contraction Fraction (MCF) to identification and prognosticate in TTR-CA 
We previously described the MCF74, defined as the ratio of LV stroke volume to myocardial volume 
and demonstrated that the MCF could successfully distinguish patients with HFpEF from athletes with 
physiologic hypertrophy and normal controls. The MCF provided a measure of ventricular function 
independent of chamber size that represents a volumetric measure of abnormal myocardial shortening, 
which was able to distinguish physiologic from pathologic hypertrophy. Measures of LV chamber 
performance are based on the premise that the myocardium is nearly incompressible and does not 
change volume significantly from end-diastole to end-systole.75 Capitalizing on this fundamental 
principle of the incompressibility of the myocardium and by indexing the stroke volume to the 
myocardial volume, the MCF is an index of the volumetric shortening of the myocardium. During 
systole, the myocardium shortens and thickens, reducing its contained volume by the stroke volume. 
The MCF, though operationalized prior to the advent and widespread measurement of strain using 
echocardiography, is highly correlated with global longitudinal strain.76 MCF is analogous to ejection 
fraction (EF) in that is a ratiometric measure that is easily obtainable, unit less and therefore does not 
need to be indexed to body size, age or gender. We have shown in a small cohort with cardiac amyloid 
in whom the average EF was preserved (51.2% +/- 13.1) while the MCF was significantly decreased 
(29.9% +/- 15.8) and was an independent predictor of survival.77 Similar prognostic ability was 

SCAN-MP – Study Protocol v4.0 
 
Page | 20  
confirmed by colleagues at the Mayo Clinic in AL amyloid76 and by colleagues in London.78 More 
recently, the prognostic capacity of MCF was confirmed in TTR cardiac amyloidosis in the 
Transthyretin Amyloidosis Outcomes Survey (THAOS).79 Classically, the voltage to mass ratio (V/M) 
has been employed to identify the phenotype of CA, but its use is confounded by the fact that many 
elderly patients with amyloid have a paced rhythm, making calculation of the V/M ratio impractical. 
Preliminary data demonstrates that the MCF with an area under the curve of 0.773 (p<0.0002, 95% CI 
0.66–0.86) for identifying TTR-CA was similar to the V/M ratio with an AUC of 0.678 (p=0.07, 95% 
CI 0.54–0.79). Accordingly, the MCF has potential as a simple measure to raise suspicion of TTR-CA 
as well as informing prognosis. 
1.4.5 A method to quantify TTR kinetic stability 
In collaboration with Jeff Kelly and colleagues at Scripps, we have been studying the structure, 
energetics and dynamics of WT and mutant TTR in human plasma, towards development of 
mechanisms to identify individuals susceptible to TTR-CA and predict clinical benefit in treating TTR-
CA.  Using a published subunit exchange method for quantifying the kinetic stability of human TTR 
in plasma, we were able to demonstrate that tafamidis kinetically stabilizes TTR and that the extent of 
TTR kinetic stabilization correlated with the tafamidis plasma concentration.80 Additionally, using this 
simple assay carried under physiological conditions, we were able to optimize the dose of tafamidis in 
a patient's plasma to maximize TTR kinetic stability.81 We hypothesize that by studying the kinetic 
stability of WT TTR in plasma, that we can identify those at risk for developing TTR-CA (see below). 

SCAN-MP – Study Protocol v4.0 
 
Page | 21  
2. 
STUDY OBJECTIVES & STUDY DESIGN 
2.1 
Primary Objective 
To enhance the understanding of genotype-phenotype associations in Blacks/ Hispanics with ATTR-
CA due to the Val122Ile mutation or ATTRwt and to improve identification of minority patients with 
ATTR-CA. 
2.1.1 Research Goal 
The goal of our research is to change the approach to transthyretin cardiac amyloidosis, which is a 
devastating disease, by screening and early diagnosis, and by studying prospectively a cohort of older 
Blacks/Hispanics with heart failure  in order to address the following aims and hypotheses: 
Specific Aim 1: To determine the prevalence of ATTR CA in Caribbean Hispanics and Blacks with 
HF. The hypotheses to be tested include:  
(1) the prevalence of ATTR CA will be 10-15%  
(2) ATTRwt CA will be higher among Caribbean Hispanics compared to US Blacks, whereas 
the prevalence of ATTRm CA will be lower 
(3) the gender distribution of ATTR CA identified by this active ascertainment approach will 
be similar 
(4) disease progression will demonstrate that ATTRm is associated with a more rapid decline 
vs. ATTRwt 
(5) the accuracy of our clinic-based risk calculator will be confirmed in this large prospectively 
recruited cohort  
Specific Aim 2: To demonstrate that circulating RBP4 concentration is integral to TTR tetramer 
stability which in turn determines the clinical characteristics of ATTR CA. We will measure TTR 
tetramer stability and RBP4 concentration in serum and urine collected in Aim 1. The hypotheses to 
be tested include: 
(1) TTR tetramer stability will be lower in ATTR CA and directly relate to RBP concentration 
(2) TTR tetramer stability will associate with clinical features and 
(3) Increased renal clearance of RBP4 in ATTR CA will be determined by measurement of 
RBP4 in plasma and urine. 
2.1.2 Overview of Study Design 
We will undertake a prospective cohort study among outpatient subjects with heart failure seen at one 
of five sites: (1) Columbia University Medical Center, (2) Allen Hospital of NY Presbyterian, (3) 
Harlem Hospital, (4) Boston University/Boston Medical Center and (5) Yale New Haven Hospital. 

SCAN-MP – Study Protocol v4.0 
 
Page | 22  
Black/Hispanic subjects over the age of 60 years with heart failure will undergo comprehensive 
cardiovascular examinations including: (1) complete medical history documenting the presence of HF 
and any symptoms that could be associated with TTR amyloidosis, as well as any additional co-morbid 
conditions or symptoms, (2) targeted physical exams including orthostatic blood pressure 
measurements, assessment for gallops and volume status (e.g. JVP, rales, edema) and determination of 
functional class, (3) standard 12 lead electrocardiogram, (4) measurement of plasma N-terminal B-type 
natriuretic peptide, troponin T and I RBP, Vitamin A and TTR kinetic stability, (5) RBP in urine,  (6) 
six minute hall walks and (6) full two-dimensional and three-dimensional echocardiograms with 
Doppler flow assessment and tissue Doppler and speckle tracking (See procedures for details), (7) 
99mTc-PYP or 99mTc-HMDP scintigraphy and (8) genetic analysis for the Val122Ile mutation in all 
subjects in a CLIA lab.  
2.1.3 Patient Recruitment 
The SCAN- MP study is designed to identify a sufficient number of cases to support the following 
analytical objectives: 
1. Stratify prevalence of ATTR-CA in subjects with HF by relevant demographic characteristics 
(gender, race/ethnicity, genotype); and 
2. Evaluate relationships among ATTR-CA and baseline risk factors (presence of Vall122Ile 
mutation and others) with disease outcomes. 
To accomplish these objectives, a 
hybrid 
approach 
to 
cohort 
identification and selection is used 
that combines deliberate selection of 
subjects with heart failure who are at 
increased risk for ATTR-CA and 
selection of participants with relevant 
characteristics 
(age, 
gender, 
race/ethnicity, country of origin). Planned proportion of enrolled subjects by relevant characteristics is 
shown in the Table 3. Community involvement is essential for its success and recruitment will involve 
intensive community engagement through various means among the sites.  In aggregate, we will recruit 
an equal number of men and women from the racial/ethnic groups. The expected marginal distributions 
of race/ethnicity are shown in Table 3. We will have overlapping ethnic groups among centers to 
minimize confounding of ethnicity by site. As recruitment of elderly members of minority groups is 
challenging, toward end of the recruitment period, participants will be asked to refer elderly persons to 
the study.  
At CUMC we have seen 24,682 unique patients with HF over the last five years of which 2,969 (12%) 
self-identified as Black and 4,387 of 14,466 (29.9%) patients who declared their ethnicity were 
Hispanic and whose average age was 63 years. Harlem Hospital provides health care services to the 
primary service area of Harlem, Washington Heights/Inwood and the South Bronx with the vast 
Table 3. Planned Enrollment by Age, Race, and Gender 
Age 
(yr) 
Black 
Hispanic or 
Latino ethnicity 
Total 
 
M 
F 
M 
F 
M 
F 
≤75 
150 
150 
50 
50 
200 
200 
>75 
150 
150 
50 
50 
200 
200 

SCAN-MP – Study Protocol v4.0 
 
Page | 23  
majority of residents being African American (44.5%) and Hispanic (40.8%). Thus, there are ~1500 
potential subjects per year from which we aim to recruit at least 100 subjects per year at the CUMC 
site. For the Boston site, we propose to recruit an equal number of participants with similar 
demographic distribution. The overall patient population at Boston Medical Center is ethnically diverse 
with 39% Black and 15% Hispanic of all patients seen. A preliminary assessment of recruitment 
feasibility suggests that ~750 patients are seen annually with HF who are Black or Hispanic.   
2.1.4 Selection Criteria 
800 patients will be enrolled in this protocol. Inclusion Criteria will include: Black or Hispanic of 
Caribbean origin, Age > 60 years with heart failure and able to understand and sign the informed 
consent document after the nature of the study has been fully explained, prior to any study procedures. 
Exclusion Criteria will include confirmed primary amyloidosis (AL) or secondary amyloidosis (AA), 
prior liver or heart transplantation and active malignancy or non-amyloid disease with expected 
survival of less than 1 year, or heart failure attributable to ischemic or valvular heart disease. 
2.1.5 Study Procedures 
The timing of all procedures in this study is outlined in Table 4. Eligible patients will be identified. 
Patients who are interested in the study will have a screening visit to evaluate for eligibility and obtain 
informed consent.  If patients qualify for study and do consent they will have their study visit within 4 
weeks of screening. At that visit they will have all of the following testing done. 
Table 4. Study Procedures 
Procedure 
Screening 
Baseline 
6 Months* 
(±2 weeks) 
12 Months* 
(±4 weeks) 
Informed Consent 
X 
 
 
 
Inclusion and Exclusion Criteria 
X 
 
 
 
Baseline History 
 
X 
 
 
Height and weight† 
 
X 
X 
X 
Vitals Signs 
 
X 
X 
X 
Medications 
 
X 
X 
X 
Clinical Examination 
 
X 
X 
X 
Adverse Events Review 
 
X 
X 
X 
Electrocardiogram 
 
X 
X 
X 
Laboratory Analysis 
 
 
 
 
     Basic Metabolic Panel 
 
X 
X 
X 
     Hepatic Function Panel 
 
X 
X 
X 
     Cardiac Biomarkers‡ 
 
X 
X 
X 
   Vitamin A/RBP4 in plasma/urine§ 
 
X 
X 
X 

SCAN-MP – Study Protocol v4.0 
 
Page | 24  
     Prealbumin 
 
X 
X 
X 
     TTR Kinetic Stability 
 
X 
 
X 
     TTR Gene Sequencing 
 
X 
 
 
     Ancestry Analysis 
 
X 
 
 
Six-Minute Walk Test 
 
X 
X 
X 
Short Physical Performance Battery 
 
X 
X 
X 
QoL Questionnaires 
 
X 
X 
X 
Health Literacy Questionnaire 
 
X 
 
 
Echocardiogram 
 
X 
 
X 
99mTc-PYP Scintigraphy** 
 
X 
 
 
Phone call follow-up¶ 
 
 
X 
X 
* Follow-up visits are to be conducted on subjects who test positive to the cardiac amyloid nuclear scan and/or are carrier of 
the V122I mutation. Window for the 6-month visit is ±2 weeks and for the 12-month visit is ±4 weeks. 
† Height measured only at baseline visit. 
‡ Includes BNP, NT-proBNP, galectin-3, troponin I and T. 
§ Includes Vitamin A and RBP4 in on site spot urine. 
**In the event that PYP is unavailable due to supply shortage, the investigator has the option of using HDP until PYP 
becomes available again to ensure study continuation per FDA.  
¶ For participants with no TTR CA, a phone call follow-up will be conducted instead. 
2.1.5.1 Clinical Examination 
A detailed82 health investigation will be performed in all patients by a provider experienced in the care 
of patients with HF. This will include a medical history focused on the presence of HF as defined by 
standard clinical criteria (NHANES83 and European Society of Cardiology58 for HFpEF), etiology of 
HF, NYHA functional class assessed by standardized questionnaires82 and co-morbid conditions; 
physical examination including vital signs both supine and upright, volume status, cardiopulmonary 
examinations and neurologic examination with focus on neuropathic findings. Exams will take ~45 
minutes. 
2.1.5.2 99mTc-PYP Scintigraphy 
A nuclear medicine technologist will perform planar cardiac imaging of the chest using dual-headed 
gamma cameras equipped with low energy, high resolution collimators. 10-25 mCi of 99mTc-PYP or 
will be administered intravenously and imaging will be performed after approximately 3 hours. The 
anterior and lateral planar views centered on the heart will be obtained simultaneously for a total of at 
least 750K counts/view (approx. 3-8 min of imaging). Cardiac retention will be assessed by both a 
semi-quantitative visual score (range: 0 [no uptake] to 3 [uptake greater than rib]) and a quantitative 
heart-to-contralateral (H/CL) ratio of total counts in a region of interest (ROI) over the heart divided 
by background counts in an identical size ROI over the contralateral chest including soft tissue, ribs, 
and blood pool. A visual score 2 or greater and/or calculated H/CL ratio 1.3 or greater, with myocardial 
retention of 99mTc-PYP confirmed in all cases by SPECT imaging with or without CT attenuation, will 

SCAN-MP – Study Protocol v4.0 
 
Page | 25  
be required to indicate TTR-CA according to prior published data.70 The details of the imaging 
procedures for 99mTc-PYP or  99mTc-PYP imaging are shown in Tables 5a-5c below. 
Table 5a 
Acquisition Procedure 
- Planar Imaging 
 
System 
Standard Gamma Camera 
Participant Position 
Supine on the imaging table - raise arms above the head 
Collimator 
LEHR 
Matrix 
256 x 256 
Peak 
140 KeV 
Energy Window 
15% to 20% 
Zoom 
1.46 (or closest) 
Views 
Anterior and Left Lateral 
Acquisition Counts 
Minimum 750,000 counts 
 
 
Table  5b 
Acquisition Procedure 
– SPECT Imaging 
 
System 
Standard Gamma Camera 
Participant Position 
Supine on the imaging table - raise arms above the head 
Orientation 
Feet First 
Organ 
Cardiac 
Collimator 
LEHR 
Matrix 
64 x 64 
Number of Angles 
64 
Peak 
140 KeV 
Energy Window 
15% to 20% 
Zoom 
1.46 (or closest) 
Acquisition Bit Depth 
8 bit or 16 bit 
Detector Configuration 
90 degree (Cardiac) 
Orbit Type 
Non-circular or Circular 
Orbit Acq 
180 degrees 
Start Position 
0 degrees 
Orbit Direction 
Counter-Clockwise 
Acquisition Type 
Step and Shoot 
Rotations 
1 
Time per Stop 
30 sec 
Total Time 
~15 min 
 
 
Table 5c 
 
Imaging Protocol for CT Attenuation Correction (performed as available) 
Indication: CT attenuation correction 
Breathing Instructions: 
Free breathing 
Other Instructions:  
raised arms above head 

SCAN-MP – Study Protocol v4.0 
 
Page | 26  
Duration: 
3 mins 
This imaging protocol utilizes a patient's radiation exposure that is as low as reasonable 
achievable while maintaining diagnostic image quality. Dose modulation software, when 
utilized, sets an appropriate exposure and CTDI proportional to the patient's size. 
PATIENT POSITION 
Supine  
SERIES DESCRIPTION 
  
SCOUT / TOPOGRAM 
Standard 
AXIAL, HELICAL OR VOLUME 
Helical 
Tube Potential 
120 kV 
Tube current (If NO mA modulation) 
31 mA 
SFOV (mm) 
600/500 
DFOV (mm) 
600/500 
DETECTOR COVERAGE (mm) 
160x1.5 
PITCH-SPEED 
0.938 
ROTATION TIME (s) 
0.75 
DOSE MODULATION 
N/A 
NOISE INDEX 
N/A 
Scan Length (mm) 
216 
DLP (mGy.cm) 
46.299 
CTDI PHANTOM (cm) 
32 
CTDIvol (mGy) (If NO mA modulation) 
N/A 
DOSE NOTIFICATION VALUE (mGy) 
N/A 
SCAN ACQUISITION DIRECTION 
N/A 
NUMBER OF PASSES 
N/A 
RECON 1 
Filtered Back projection 
SLICE THICKNESS (mm) 
3 
INTERVALS (mm) 
3 
ALGORITHM / KERNEL 
B 
ITERATIVE RECONSTRUCTION 
N/A 
SEND TO PACS 
Yes 
Each Tc-PYP or Tc-HMDP scan will be read by 3 independent readers blinded to clinical information.  
Previous unpublished data shows a high degree of agreement among four independent readers using a 
semi-quantitative score (0 to 3) with kappa ranging from 0.882 to 1.00 with an average of 0.95 for 50 
scans read independently.   When scores were dichotomized by positive (semi-quantitative score of 2 
or 3) compared with negative (semi-quantitative score of 0 or 1), the degree of agreement among the 
readers was even higher (kappa of 0.891 to 1.00). (See Table 6 below) Using the quantitative score 
system of H/Cl ratio provided greater certainty in characterizing positive and negative scans. 
Table 6. Degree of Agreement – DPD Scans Qualitative 0-1 vs 2-3 
Group 
Kappa 
P value 
Reader 1 vs. Reader 2 
0.947 
<0.0001 
Reader 1 vs. Reader 3 
0.947 
<0.0001 
Reader 1 vs. Reader 4 
0.947 
<0.0001 

SCAN-MP – Study Protocol v4.0 
 
Page | 27  
Reader 2 vs. Reader 3 
0.891 
<0.0001 
Reader 2 vs. Reader 4 
1.000. 
<0.0001 
Reader 3 vs. Reader 4 
0.891 
<0.0001 
 
Based on an international multicenter collaboration, three 99m technetium-labeled radiotracers, 
99mTc-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), 99mTc-pyrophosphate (PYP), 
and 99mTc-hydroxymethylene diphosphonate (HDP), termed “bone avid” and traditionally used for 
bone scintigraphy, have been shown to have high diagnostic accuracy for the identification of patients 
with ATTR-CA when coupled with an assessment for monoclonal proteins to exclude the substrate for 
AL amyloidosis. In the event that PYP is unavailable due to supply shortage, the investigator has the 
option of using HDP until PYP becomes available again to ensure study continuation per FDA. 
2.1.5.3  Two- Dimensional Echocardiography with Complete Doppler Analysis 
A complete two-dimensional (2D) echo will be performed utilizing a commercially available GE 
Vivid-9 or Philips iU33 Echocardiography System. A standard imaging protocol will be performed.  
The following linear echocardiographic measurements will be obtained (by 2D or M-mode) in both 
end-diastole and end-systole: left ventricular (LV) internal dimension, septal wall thickness (SWT), 
and posterior wall thickness (PWT). Quantification of LV mass will be derived by the formula of 
Devereux RB et al84 and by three dimensional-guided modified biplane Simpson’s rule85, 86. LV and 
left atrial (LA) volumes (systolic and diastolic) will be measured by the biplane method of discs 
(modified Simpson’s rule).  LV ejection fraction and LA function will be calculated from these volume 
measurements. Doppler measures including peak early (E) and late (A) diastolic velocities from pulsed 
wave Doppler recordings of the mitral and the tricuspid flow velocities respectively, and E/A ratio will 
be calculated, along with deceleration time (DT) of early filling velocity and LV isovolumic relaxation 
time (IVRT). Pulsed-wave tissue Doppler imaging (TDI) will be obtained from the apical 4-chamber 
view for the lateral mitral annulus, medial mitral annulus and tricuspid annulus. Peak systolic (S), early 
(e’) and late (a’) diastolic velocities will be measured.  Mitral-to-apical flow propagation will be 
measured using color M-mode technique.87 Color-coded tissue Doppler will be obtained for derivation 
of global longitudinal strain88 and speckle-tissue imaging (STI) on short-axis views to derive radial and 
circumferential strain and strain rate89 according to ASE guidelines.90 The myocardial contraction 
fraction, ratio of stroke volume to myocardial volume, will be calculated as previously described.77 
Pressure volume based measures including ventricular elastance, arterial elastance, the EDPVR and 
PVAiso-EDP relations will be estimated as previously described.30 
2.1.5.3 Electrocardiogram 
A standard 12 lead electrocardiogram will be performed with standard instrument sensitivity of 10 mm 
= 1 mV. A sum of precordial voltage (sum of S wave in lead V1 plus R wave in lead V5 or V6 [SVl + 
RV5 or V6]) will be calculated for all electrocardiograms. This sum will be used to compare data from 
patients with myocardial retention of  radiotracer from controls. LVH will be defined when this sum is 
greater than 35 mm. When the sum was less than 15 mm, low voltage in the precordial leads is present. 

SCAN-MP – Study Protocol v4.0 
 
Page | 28  
Additional criteria to define low voltage only in the limb leads include no QRS deflection greater than 
5 mm in any limb lead and low voltage in all leads is present when the average voltage in the three 
limb leads is <5 mm, and the average voltage in the chest leads is <10 mm.91 Finally, the mass: voltage 
ratio will be calculated using the LV mass divided by the sum of S wave in lead VI plus R wave in lead 
V5 or V6 [SV1 + RV5 or V6]. The ECG tracings will be scanned and uploaded in RedCap. 
2.1.5.4 Laboratory Analysis 
Blood will be drawn and analyzed for standard chemistry (Chem-7), liver function, BNP, NT-proBNP, 
galectin-3, troponin I and T, vitamin A, retinol binding protein 4 (RBP4) and prealbumin. BNP, TnT, 
Gla-3, TnI and NT-proBNP will be measured through a research agreement with Abbott Laboratories, 
while the others are measured by local or affiliated research laboratories. Additionally, the kinetic 
stability of plasma TTR will be assessed at Scripps Laboratories using the published subunit exchange 
strategy, in which recombinant tagged TTR homotetramers are added to human TTR in plasma at equal 
concentrations to measure the rate at which the subunits exchange80. Tetramer dissociation is the rate-
limiting step for subunit exchange and for amyloidogenesis. We hypothesize that those individuals at 
risk for developing WT ATTR-CA produce WT TTR exhibiting inferior kinetic stability. 
Quantification of TTR kinetic stabilization could serve as a surrogate biomarker for the prediction of 
clinical outcomes and could become part of a risk calculation or an early diagnosis strategy, after 
validation. Additional aliquots will be used for genetic analysis (see below) and stored at -80° for 
analysis in the future. Ancestry analysis will also be performed on all participants. Urine specimen will 
be analyzed for Vitamin A and RBP4 measurements, to learn whether its levels differ among subjects 
with TTR amyloidosis, and to learn more about the specific physiology of the disorder. 
TTR Gene Sequencing: Genotyping will be performed on genomic DNA obtained from blood from 
participants for the Val122Ile mutation using a PCR-based assay in the CLIA certified laboratory at 
Boston University. 
Ancestry Analysis: Ancestry information will be obtained after buffy coat samples are extracted from 
participants’ blood. Analysis for ancestry will take place in a specialized laboratory at Columbia 
University. 
CCRLE and NIH Repository: Several specimens collected during the study will be stored 
indefinitely in a -80°C freezer located at the CCRLE lab and used for future analysis. Some of these 
samples will ultimately be transferred to a NIH repository. 
2.1.5.5 QOL Questionnaires 
Two quality of life scales will be employed including two disease specific measures: the Kansas City 
Cardiomyopathy Questionnaire (KCCQ) and a more general instrument, the 12-Item Short Form 
Survey (SF-12v2). 
2.1.5.6 Health Literacy Questionnaire 
The participants’ capacity to handle health -related information will be assessed with four instruments: 
Health Literacy, Trust, Perceived Discrimination, and English Proficiency. 

SCAN-MP – Study Protocol v4.0 
 
Page | 29  
2.1.5.7 Functional Capacity 
Functional capacity will be determined by a hall walk of six minute duration92 and a short physical 
performance battery.93 
2.1.5.8 Phone Call Follow-Up 
Participants who have no evidence of TTR CA and/or are not V122I mutation carriers will be followed-
up by phone at 6 and 12 months to gather information about vital status and document reasons and 
dates of hospitalizations (if any occurred). 
2.1.6 Hypotheses 
Aim 1: To determine the prevalence of ATTR CA in Caribbean Hispanics and Blacks with HF 
 
Hypothesis 1. Overall prevalence of ATTR CA:  The prevalence of ATTR CA will be defined 
by the number of cases with both ATTRwt and ATTRm CA as a percentage of total enrollment. 
The background prevalence of Val122Ile in the US Black population is 3.4%, and we 
hypothesize a prevalence rate of 8% of ATTRm Val122Ile in our outpatient HF population. 
Since there are no data in Hispanics regarding ATTR CA prevalence, we further hypothesize 
that we will observe a prevalence of ATTRwt CA of 2-8% of the Hispanic population. Thus, 
we have conservatively defined the predicted prevalence of ATTR CA as 10-15%. 
Hypothesis 2. Relative proportion of ATTR CA comprised by ATTRwt and ATTRm: As 
noted above, based upon the background allele frequency, we anticipate that Black patients will 
be much more likely to manifest ATTRm (Val122Ile) vs. ATTRwt CA, whereas Hispanic 
patients will be more likely to manifest ATTRwt CA. We will be able to explore the Val122Ile 
genotype frequency in the Hispanic population, and with the addition of cardiac amyloid 
scintigraphy scanning, the relative contribution of ATTRm in this population, which we 
postulate to be lower than Blacks. We will utilize genetic ancestry analysis data to further 
characterize race and ethnicity, and, as an exploratory analysis, evaluate the interaction of 
genetic variants identified with Val122Ile and ATTR CA as defined by radiotracer uptake. 
Hypothesis 3. Proportion of gender: Published reports of ATTR Val122Ile are 75% male and 
reports of ATTRwt are 95% male. We hypothesize that highly sensitive cardiac amyloid 
scintigraphy testing will reveal a gender distribution of ATTR that is closer to 50%, based upon 
allele distribution. We will explore comorbidities, TTR stability, and RBP4 differences among 
men and women with ATTR to determine interactions with phenotypic expression. 
Hypothesis 4. Progression of disease: Markers of disease progression are lacking in ATTR 
CA. We hypothesize that attainment of a hierarchical composite endpoint at 1-year of death, 
heart failure hospitalization, and 30% decline in 6-minute hall walk will be higher in ATTRm 
vs. ATTRwt CA. In addition, we will explore the capacity of specific markers to assess disease 
progression including: (1) established circulating biomarkers such as troponin I/T, NT-proBNP, 
BNP and Galectin-3, (2) novel biomarkers such as RBP4 and TTR concentration, (3) ECG, and 

SCAN-MP – Study Protocol v4.0 
 
Page | 30  
echocardiographic measures including longitudinal strain and MCF, (4) functional capacity by 
6-minute hall walk and SPPB, and (5) QOL. Our preliminary data and published work9 suggests 
reduced median survival for ATTRm Val122Ile CA (25 months) vs ATTRwt (43 months) in 
different race cohorts. We hypothesize that we will observe reduced survival and greater 
functional decline in ATTR Val122Ile vs ATTRwt within race cohorts. 
Hypothesis 5. Performance of risk calculator: Our point-of-care risk calculation utilizing 
RBP4 and TTR concentration with echocardiographic and ECG determined parameters will be 
tested in this cohort. We will re-derive the prediction model based upon clinical variables noted 
above. We anticipate showing a similar degree of accuracy (ROC AUC > 0.95) for 
identification of cases with ATTR vs. controls 
 
Specific Aim 2: To demonstrate that circulating RBP4 concentration is integral to TTR tetramer 
stability, which in turn determines the clinical characteristics of ATTR CA. We will measure TTR 
tetramer stability and RBP4 concentration in serum and urine collected in Aim 1. The overall 
hypotheses of this Aim are that measurements of TTR kinetic stability, RBP4 and TTR concentration 
will differentiate patients with ATTR CA vs. non-amyloid HF controls and associate with disease 
progression and outcomes. Specific hypotheses are as follows:  
Hypothesis 1: TTR kinetic stability and RBP4 concentration: We hypothesize that at 
baseline, TTR kinetic stability will be lower in ATTR CA vs. non-amyloid HFpEF, and that 
stability will be inversely proportional to plasma RBP4 concentration. We further hypothesize 
that TTR kinetic stability will be lower for ATTRm vs. ATTRwt. 
Hypothesis 2: TTR kinetic stability and disease progression: We hypothesize that TTR 
stability will associate with the specific outcomes of survival and disease progression detailed 
in Aim 1, sub-aim 4. We will explore further TTR stability among patients with indeterminate 
grade 1 cardiac amyloid scintigraphy scan results (early disease), and hypothesize that stability 
will be lower than non-amyloid HF controls. 
Hypothesis 3: Urinary RBP4 concentrations: We hypothesize that RBP4 will be lower in 
plasma and higher in urine indexed for renal function by urinary creatinine, and vitamin A 
concentration, among patients with ATTR CA vs. non-amyloid controls. Reduced RBP4 
binding, owing to TTR kinetic instability in blood, will result in increased clearance (and higher 
urine levels) of the protein. We will also explore RBP4 concentrations among patients with 
indeterminate grade 1 cardiac amyloid scintigraphy scan results, and hypothesize that serum 
RBP4 will be lower and urinary RBP4 higher than non-amyloid HF controls.  
2.1.7 Statistical Considerations and Sample Size 
Power and Sample Size: The total enrollment proposed for this study is of 800 subjects: 600 Blacks 
and 200 Hispanics. Amongst them, we expect approximately 80-160 ATTR CA subjects and 640-720 
non-amyloid controls. The sample size planned for each race/ethnicity group achieves 80% power to 

SCAN-MP – Study Protocol v4.0 
 
Page | 31  
detect, as in Aim 1: (1) a prevalence of ATTR-CA of 10-15%, (2) a two-fold difference in the 
prevalence of ATTRm between Blacks and Hispanics (i.e., 0.08 vs 0.04, respectively), as well as, a 
similar difference in the prevalence of ATTRwt between Blacks and Hispanics, (3) a difference as 
small as 0.03 (if one truly exits) in the prevalence of ATTRwt with respect to gender (male) distribution 
between the two race/ethnic groups, and (4) in the ATTR CA group alone, we plan to measure the 
hierarchical composite endpoint of death, heart failure hospitalization, and 30% decline in 6-minute 
hall walk after 1 year  A two-sided logrank test with an overall sample size of 80 subjects (40 in the 
ATTRwt and 40 in the ATTRm) achieves 82% power at a 0.05 significance level to detect a hazard 
ratio (HR) of 0.44 when the proportion of patients that did not progress in the mutant group is 0.60. 
This corresponds to a minimum difference of 15% in the probability of not having progressed past 12 
months between the two groups. 
Aim 2 focuses on comparing differences in TTR kinetic stability and RBP4 concentration between 
ATTR CA (N=80-120) and the non-amyloid group (N=680-720). These sample sizes generate >95% 
power to detect: Hypothesis 1) a minimum difference in RBP4 of 5, assuming SDs of 9 and 20 for 
ATTR CA and non-amyloid, respectively; Hypothesis 2) a mean change difference in TTR stability as 
small as 0.01, SD of 0.002. 
2.1.8 Data Analysis Plan 
Descriptive statistics will be used to summarize subjects’ demographics and study outcomes. Sample 
proportions with exact 95% confidence intervals will be used to estimate the overall 
prevalence of ATTRm CA in Blacks and Hispanics and by sex. All analyses will be performed in SAS 
v.9.4 (Cary,NC), at a significance level of 0.05. 
AIM 1: 
Hypotheses 1-3: The differences in proportions for prevalence (#1), genetic mutation 
status (#2), and sex (#3) will be assessed using Chi-squared/Fisher Exact tests. The genetic ancestry 
analysis will use 500K SNP data to perform principal components analysis (PCA) and determine the 
percentage of African admixture in all participants. To identify the associations of rare genetic variants 
in the TTR gene in ATTR CA cases vs controls, we will utilize burden testing.94 Hypothesis 4: The 
main analysis will use the Kaplan-Meier method to estimate the probabilities of the composite 
endpoint, with medians (95% CI) being reported for each group. Cox regression analysis will be 
performed to generate the hazard ratio (95% CI), and to allow adjustment for other covariates such as 
sex or race/ethnicity, or explore interaction with other variables including cardiac biomarkers, echo 
parameters, or QOL. Alternatively, we will apply and compare Finkelstein-Schoenfeld’s unmatched 
approach95 to the matched win ratio,96 both methods being used for reporting composite endpoints, 
with more appropriate priority given to the more clinically important event, e.g. mortality. Hypothesis 
5: We will test the clinic-based risk calculator that was previously developed and validated in a smaller 
matched cohort study.97 The proposed 4-variable model included: RBP4, LVEF, inter-ventricular 
septal thickness, mean limb lead QRS voltage, and generated an ROC AUC >90%. This model will be 
tested in our larger cohort and assessed with respect to prediction capability (AUC ROC) and goodness-
of fit (Hosmer-Lemeshow test). We also plan to fit additional multivariable logistic regressions using 
the variables collected employing variable selection/model-building strategies and comparing the 

SCAN-MP – Study Protocol v4.0 
 
Page | 32  
resulting model(s) to the one proposed above. The variables in the final clinical risk model will be 
based on weights from the multivariate model. 
AIM 2: 
Hypothesis 1 and 3: Means (95% CI) and/or medians (inter-quartile range) will be 
computed for all continuous measurements including RBP4/TTR concentrations. Pearson/Spearman 
correlation coefficients will be calculated to quantify the strength of the association between RBP4 
plasma and urine concentrations in the overall ATTR CA cohort and separately by ATTRm vs. 
ATTRwt groups. Linear regression models will be used to assess differences in TTR kinetic stability 
between the two groups, adjusting for RBP4 concentration and vitamin A. Hypothesis 2: In addition 
to descriptive statistics, linear regression models will be employed to test the associations between 
RBP4 concentration, TTR stability, and cardiac amyloid scintigraphy heart to contralateral chest ratio 
between the two groups, ATTR CA vs non-amyloid HF controls, adjusting for clinical characteristics 
and retinol concentration. 
2.2 
Limitations and Assumptions 
Limited subject recruitment: Our feasibility studies suggest completion of enrollment within the 5-year 
grant period, leveraging the resources available to us at the various sites. Furthermore, one of our sites 
(BMC) has already demonstrated recruitment of such a cohort in a currently funded NIH study. 
Identification of other types of cardiac amyloidosis: While unlikely, our target population may identify 
patients with light-chain (AL) amyloidosis. To account for other types of CA, the Co-PIs will scrutinize 
non-invasive testing data including echocardiography and electrocardiography for all recruited 
subjects. Any participant with normal TTR genotype but with testing or clinical features suggestive of 
CA will be referred for further characterization including serum immunofixation electrophoresis and 
free-light chain assay. Light-chain amyloidosis is unlikely to be identified in this small sample size 
given a reported incidence of 1:100,000. Subject drop out or unwillingness to complete clinical 
evaluation for CA: We do not anticipate dropout before the study blood sample is obtained (i.e. 
immediately after enrollment).  Thus, we will be able to perform the TTR genotype analysis and 
RBP4/TTR measurements as described above.  However, a subject might decline to proceed with all 
clinically recommended testing. Cardiac biopsy is needed to establish the diagnosis of ATTR which 
occurs in the setting of a monoclonal gammopathy and a diagnostic cardiac amyloid scintigraphy scan, 
hence some patients may require this as part of clinical care. We anticipate that the number of 
participants requiring cardiac biopsy will be quite small based upon clinical experience (< 10% of those 
with positive cardiac amyloid scintigraphy scan)72. False negative rate of  Cardiac Amyloid 
Scintigraphy Imaging: In the large multicenter international study72, with imaging performed with 
different isotopes (DPD, PYP and HDP) and at different times (1 and 3 hours) only 0.4% of biopsy 
proven ATTR CA patients had grade 0 scans, and 9% had grade 1 scans. Scan with Grades 0 and 1 
result are more common with 3 hour imaging which is among the reasons we have chosen to image at 
3 hours. We interpret grade 0 as being truly negative, thus the false negative rate is likely quite low. For 
those with grade 1 scans, while not adjudicated as positive and thus meeting diagnostic criteria for 
ATTR-CM, amyloid deposition may be present though quantitatively less, and below our diagnostic 
threshold. Our centers clinical experience with 1 hour imaging suggest that Grade 1 scans are not 

SCAN-MP – Study Protocol v4.0 
 
Page | 33  
common. Among the 110 patients with hypertensive, non-amyloid HFpEF, or HCM, 93% had a grade 
0 scan, and 6% had a grade 1 scan. In this application, while we anticipate subjects with grade 1 uptake 
of CARDIAC AMYLOID SCINTIGRAPHY will be low (<10%), we will explore the significance of 
a grade 1 scan result in the following ways. First, we will perform SPECT/CT imaging in some subjects 
with grade 1 myocardial retention of radiotracer to distinguish true myocardial uptake versus blood 
pool in the LV cavity.. Those with the latter (grade 1 scans without myocardial retention of radiotracer 
but with blood pool in the LV cavity) will represent the false negative population, from which we can 
calculate the false negative rate. We can also determine if patients with grade 1 radiotracer uptake have 
a distinct clinical profile by biomarkers, echo, or functional measures and adverse outcomes as we are 
following patients prospectively in this study. The potential to have false positive with cardiac amyloid 
nuclear scintigraphy will be addressed by evaluation for AL cardiac amyloid in anyone who has 
myocardial retention of radiotracer greater or equal to grade 2, as this is the most common cause of a 
false positive scan. Every such case will be scrutinized and any subjects with normal TTR genotype 
but with testing or clinical features suggestive of CA will be referred for further characterization as 
part of routine clinical care for serum immunofixation electrophoresis and free-light chain assay to 
exclude light chain amyloidosis.  While rare (incidence of 1:100,000), light-chain amyloidosis is the 
most common cause of a false positive scan. Other causes of a false positive nuclear scintigraphy that 
have been reported in the literature including hydroxychloroquine-mediated cardiotoxicity98 and 
apolipoprotein A-1 amyloid cardiomyopathy99 both of which are exceedingly rare and thus unlikely to 
be seen in our sample. LVEF criterion: ATTR CA is typically associated with HFpEF (LVEF>40%), 
but some patients with advanced disease can have moderate depressed systolic function. Notably, data 
is emerging that subjects with the Val122Ile variant more often present with a reduced EF. In order not 
to exclude this important cohort which is a focus of our efforts, we will enroll subjects with an EF 
>=30%. This may result in recruitment of controls with reduced EF, but we predict that exclusion of 
ischemic/valvular heart disease as the cause of HF will limit low EF control numbers. Why is African 
ancestry not an inclusion criterion? Given the association of the Val122Ile mutation with African 
ancestry, use as an inclusion criterion would enhance the identification of subjects. However, the 
strength of the association of Val122Ile with African ancestry is unknown. Additionally, requirement 
of African ancestry by genetic analysis would complicate enrollment. We will quantify ancestry100 to 
determine its contribution to the observed phenotypes. Will the Aim 2 on outcomes be confounded by 
participation in future clinical trials? We will censor data on subjects enrolled in investigational trials 
in the longitudinal portion of the SCAN-MP study. If approved by FDA, we will not restrict access of 
eligible patients to any therapy that could be of clinical benefit. Early vs. advanced disease: We needed 
to choose between selecting a cohort with sufficient chance of identifying enough subjects with ATTR 
CA (those with HF) versus identification of subjects with early disease. Our active ascertainment of 
cases and use of Tc99-PYP or Tc99-HMDP, which identifies ATTR CA prior to echocardiographic 
changes101, 102 coupled with inclusion of subjects with mild forms of HF, should ensure identification 
of subjects with earlier disease than current practice. Reduced RBP4 expression/Vitamin A 
confounding: We are not able, in this design, to specifically determine the expression of RBP4 as this 
would require liver biopsy and quantitative PCR. However, data suggest that RBP concentrations vary 
not by expression but rather by clearance38, as we have postulated. Furthermore, we are measuring 

SCAN-MP – Study Protocol v4.0 
 
Page | 34  
serum vitamin A, and urinary creatinine, as a means to correct for confounding factors.  Unequal 
percentage of subjects with insulin resistance between groups: As serum RBP4 concentration is 
increased in insulin resistance, to control for the potential confounder of unequal distribution of insulin 
resistance across our subject groups, we will adjust the analysis by history of diabetes and serum 
glucose. Our preliminary data has shown that glycated hemoglobin or lipids levels do not significantly 
interact with RBP4 concentrations in the target HFpEF population . 
2.3 
Patient Numbering 
Each patient will be uniquely identified in the study by a combination of the site number and screening 
number. The site number will be assigned by the coordinating site.  The screening number will be 
assigned sequentially. 
 
 

SCAN-MP – Study Protocol v4.0 
 
Page | 35  
3. 
ADVERSE AND SERIOUS ADVERSE EVENTS 
3.1 
Adverse Events Definition 
An AE is any untoward medical occurrence in a human subject, including any abnormal sign (for 
example, abnormal physical exam or laboratory finding), symptom, or disease temporally associated 
with the subject’s participation in the research. 
3.2 
Serious Adverse Event (SAE) Definition 
An SAE is any untoward medical occurrence related to study participation that: 
1. Results in death. 
2. Is life-threatening (an event which places the patient at immediate risk of death from the event 
as it occurred. It does not include an event that had it occurred in a more severe form might 
have caused death). 
3. Requires in-patient hospitalization or prolongation of existing hospitalization. 
4. Results in persistent or significant disability or incapacity. 
5. Is a congenital abnormality or birth defect. 
6. An important medical event that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the patient and may require intervention to prevent one of 
the other outcomes listed in the definition above (e.g. events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias, convulsions, 
or the development of drug dependency or abuse). 
3.3 
Collecting and Reviewing Adverse Event and Outcome Information 
During follow-up visits, whether in person or via telephone,  the subjects will be asked about medically 
relevant changes in their health since the previous visit including hospitalization, and whether those 
hospitalizations were related to cardiovascular health. 
In addition to patient observations, relevant events and outcomes will be documented from any 
clinically relevant laboratory findings, physical examination findings, ECG changes, or other findings 
found in the electronic medical record. The study team will record such information on Case Report 
Forms (CRFs) for each study visit and enter the information into the data collection system (RedCap) 
throughout the study. A checklist of potential adverse reactions to the imaging agent will be used to 
track all adverse events related to imaging agent for each subject.  According to the package insert for 
Technetium Pyrophosphate, common side effects include flushing, hypotension, fever chills, nausea, 
vomiting and dizziness, as well as hypersensitivity reactions such as itching and various skin rashes 
The study team will record AE information for start dates/times occurring any time after informed 
consent is obtained until 48 hours after  the time of imaging agent infusion.   
To assess relationship of an event to study procedure, the following guidelines are used: 

SCAN-MP – Study Protocol v4.0 
 
Page | 36  
• Unrelated 
• Unlikely to be related 
• Possibly related 
• Probably related 
• Definitely related 
All adverse events must have their relationship to study participation, expectedness and severity of the 
event assessed by a qualified investigator, upon reporting of the event.  These determinations will be 
made according to the professional opinion of the investigator using the package insert of the imaging 
agent and the investigators assessment will be entered into the Redcap data collection software by 
research staff. 
3.4 
Stopping Study Procedure Due to Adverse Event 
In the ordinary ongoing off-label use of this procedure there have been no reports of serious adverse 
reactions.  Nevertheless, the injection and scan procedure will be stopped and the results will be marked 
as incomplete if there are any adverse reactions during its administration as part of this study.  The 
adverse reactions that will lead the investigators to stop the cardiac amyloid scintigraphy scanning 
portion of the study procedures include but are not limited to the events listed in the package insert:  
hypotension, fever, chills, nausea, vomiting and dizziness, as well as hypersensitivity reactions such as 
itching and various skin rashes.   
The scan will also be stopped in cases of severe cardiac symptomology such as: chest pain, shortness 
of breath, palpitations, tachycardia. In such cases, other study procedures may be continued. 
In addition, subjects will be asked to contact the investigators if any additional adverse or allergic 
reactions are noted within the first 24 hours following the injection.  If any such events are reported, 
the principal investigator will determine if they are potentially related to the administration of the 
imaging agent.  Appropriate clinical care will be advised for any events determined by the investigator 
to be related to the scanning injection, and information about the reactions will be reported as described 
below. 
 
3.5 
Adverse Event Reporting 
3.5.1 Reporting to the Sponsor 
Each participating investigator must report every serious adverse event (SAE) to the IND sponsor at 
Columbia University Medical Center as soon as possible, but no later than 48 hours after becoming 
aware of the event via phone, email or facsimile, and must complete the new SAE field on the Redcap 
database as soon as possible but no later than 48 hours after becoming aware of the event. The site 
investigator must document the time of his or her awareness of the SAE in an email or facsimile to: 

SCAN-MP – Study Protocol v4.0 
 
Page | 37  
Name: Mathew S. Maurer, MD 
Tel: 
(212) 932-4537 
Fax: 
(212) 932-4538 
Email: msm10@cumc.columbia.edu 
 
The participating investigator must also provide follow-up information on the SAE once new or 
updated information is available. The follow-up information must be added to the Redcap SAE field, 
as a follow-up to the initial entry. 
Non-serious adverse events will be reported to the IND sponsor at Columbia University Medical Center 
on the Adverse Event Form through ordinary electronic data capture at RedCap.  All non-serious entries 
related to adverse events must be completed by the participating investigator within 5 business days. 
3.5.2 Reporting to the IRB 
Unanticipated Problem (UP): 
An unanticipated problem is any incident, experience or outcome involving risks to subjects or others 
in any human subjects research that meets all of the following criteria: 
• Unexpected (in terms of nature, severity or frequency) given (a) the research procedures that 
are described in the IRB-approval protocol and informed consent document, and (b) the 
characteristics of the subject population being studied; 
• Related or possibly related to participation in such research (e.g., there is a reasonable 
possibility that the incident, experience or outcome may have been caused by the procedures 
involved in such research); and  
• Suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic or social harm) than was previously known or recognized.  
Reports of all events (including follow-up information) that meet the definition of an unanticipated 
problem posing risk to subjects or others must be submitted to the IRB within one week (5 business 
days) following the occurrence of the unanticipated problem or the investigator’s acquiring knowledge 
of the unanticipated problem in accordance with IRB policy. Additionally, the investigator will submit 
a summary of all unanticipated problems that occurred since the beginning of the study at the time of 
continuing review. 
3.5.3 Reporting to the FDA 
Suspected Adverse Reaction: 
In accordance with 21 CFR 312.32(a), a suspected adverse reaction (SAR) means any adverse event 
for which there is a reasonable possibility that the drug caused the adverse event. 
The IND Sponsor will be responsible for all communication with the FDA and will report to the FDA, 
any adverse event that is serious, unexpected and for which there is reasonable possibility that the drug 
caused the adverse event. These must be reported to the FDA as soon as possible, but no later than 15 

SCAN-MP – Study Protocol v4.0 
 
Page | 38  
calendar days after the Sponsor determines that the information qualifies for reporting.  Any fatal or 
life-threatening SARs will be reported to the FDA as soon as possible, but no later than 7 calendar days 
after the Sponsor determines that the information qualifies for such reporting. 
All other serious adverse events will be included in the IND annual reports that are to be submitted to 
the FDA within 60 days of the anniversary date of the IND each year. 
3.5.4 Reporting to Participating Sites 
The IND Sponsor will notify all participating sites of any adverse event associated with the use of the 
drug that is both serious and unexpected, as well as any finding from tests in laboratory animals that 
suggest a significant risk for human subjects. In addition, the IND sponsor will review available reports 
concerning similar adverse events and analyze the significance of available information. 
 
 

SCAN-MP – Study Protocol v4.0 
 
Page | 39  
4. 
REGULATORY GUIDELINES 
This study will be performed in accordance with the protocol, all applicable government laws, 
regulations, and guidances in whatever city and state it in conducted within, including policies with the 
Health Insurance Portability and Accountability Act of 1996 ("HIPAA"), and all other applicable 
medical privacy laws and regulations. 
4.1 
Institutional Review Board/Independent Ethics Committee 
National regulations and ICH require that approval be obtained from an IRB or an IEC prior to 
participation of patients in research studies. Prior to the study onset, the protocol, any protocol 
amendments, ICFs, advertisements to be used for patient recruitment, and any other written information 
regarding this study to be provided to a patient or patient's legal guardian must be approved by the IRB 
or IEC. 
All IRB and IEC approvals must be dated and contain IRB/IEC Chairman or designee authorization 
and must identify the IRB/IEC (e.g., name and address), the clinical protocol by title and/or protocol 
number, and the date of approval or favorable opinion was granted for the clinical research. 
The Investigator is responsible for obtaining continuing review of the clinical research at least annually 
or more often if specified by the IRB or IEC. The Investigator must supply the Sponsor with written 
documentation of the approval of the continued clinical research. 
The Investigator will make all attempts to ensure that the IRB or IEC is constituted and operates in 
accordance with Federal and ICH GCP and any local regulations. 
4.2 
Regulatory Authorities 
Regulatory authorities will receive the protocol, amendments, reports on SAEs, and the Integrated 
Clinical Trial Report according to national and any local regulations. 
4.3 
Modification of the Protocol 
Major changes in this research activity, except those to remove an apparent immediate hazard to the 
patient, must be reviewed and approved by the IRB that approved the study.  Amendments to the 
protocol must be submitted in writing to the Investigator's IRB for approval prior to patients being 
enrolled under the amended protocol. 
4.4 
Informed Consent Form 
Written informed consent in compliance with 21 Code of Federal Regulations (CFR) § 50 and ICH will 
be obtained from each patient prior to undergoing any protocol-specific tests or procedures that are not 
part of routine care. 
 
 

SCAN-MP – Study Protocol v4.0 
 
Page | 40  
4.5 
Study Data Recording and Retention 
All study results will be recorded upon paper CRFs and such data will be recorded into a shared RedCap 
electronic database by sites no later than five days following study visit. 
Essential documents should be retained for the period of time required by applicable local law. The 
essential documents include the signed and dated final protocol, signed and dated amendments(s), if 
applicable, signed and dated curriculum vitae of the Investigators, copies of the completed CRFs, 
signed ICFs, IRB approval and all related correspondence, financial agreements, regulatory approval, 
drug accountability, study correspondence, and patient identification codes. 
4.6 
Confidentiality 
The Investigator must ensure that the patients’ anonymity will be maintained. On the CRFs patients 
should not be identified by their names, but by the assigned patient number and initials.   
Following the principles of the Good Clinical Practice, if local regulations specify a patient’s number 
and initials will be used to identify the patient on their study records. Laboratory samples may be 
labeled with an independent numbering code, and the label will not contain any other personal 
identification information. 
4.7 
Lead Site monitoring of sub-site research activity 
Columbia University Medical Center as lead site will conduct a pre-study visit, annual follow-up visits, 
weekly conference calls and a close-out visit, meeting with the sub-site investigators to review study 
goals and requirements, including but not limited to good clinical practice, regulatory documentation, 
informed consent process and documentation, eligibility criteria, study procedures, reportable events 
and source documentation. Qualifications of investigators and personnel, their training and delegation 
of authority will also be reviewed. 
Within two weeks of each annual visit, the lead site will prepare a report of the monitoring visit findings 
including a list of records reviewed, any failure to report AEs, SAEs or UPs and general adherence to 
the protocol. 
The lead site will report all SUSARs to the FDA as required by 21 CFR 312, document any non-
compliance and, if necessary, remove the sub-site PI for major protocol or regulatory violations. 

SCAN-MP – Study Protocol v4.0 
 
Page | 41  
5. 
REFERENCES 
1. 
Stangou AJ and Hawkins PN. Liver transplantation in transthyretin-related familial amyloid 
polyneuropathy. Current opinion in neurology. 2004;17:615-20. 
2. 
Connors LH, Lim A, Prokaeva T, Roskens VA and Costello CE. Tabulation of human 
transthyretin (TTR) variants, 2003. Amyloid : the international journal of experimental and clinical 
investigation : the official journal of the International Society of Amyloidosis. 2003;10:160-84. 
3. 
Yazaki M, Tokuda T, Nakamura A, Higashikata T, Koyama J, Higuchi K, Harihara Y, Baba S, 
Kametani F and Ikeda S. Cardiac amyloid in patients with familial amyloid polyneuropathy consists 
of abundant wild-type transthyretin. Biochemical and biophysical research communications. 
2000;274:702-6. 
4. 
Westermark P, Bergstrom J, Solomon A, Murphy C and Sletten K. Transthyretin-derived senile 
systemic amyloidosis: clinicopathologic and structural considerations. Amyloid : the international 
journal of experimental and clinical investigation : the official journal of the International Society of 
Amyloidosis. 2003;10 Suppl 1:48-54. 
5. 
Jacobson DR, Pastore RD, Yaghoubian R, Kane I, Gallo G, Buck FS and Buxbaum JN. Variant-
sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans. N Engl 
J Med. 1997;336:466-73. 
6. 
Dharmarajan K and Maurer MS. Transthyretin cardiac amyloidoses in older North Americans. 
Journal of the American Geriatrics Society. 2012;60:765-74. 
7. 
Connors LH, Prokaeva T, Lim A, Theberge R, Falk RH, Doros G, Berg A, Costello CE, O'Hara 
C, Seldin DC and Skinner M. Cardiac amyloidosis in African Americans: comparison of clinical and 
laboratory features of transthyretin V122I amyloidosis and immunoglobulin light chain amyloidosis. 
Am Heart J. 2009;158:607-14. 
8. 
Connors LH, Doros G, Sam F, Badiee A, Seldin DC and Skinner M. Clinical features and 
survival in senile systemic amyloidosis: comparison to familial transthyretin cardiomyopathy. Amyloid 
: the international journal of experimental and clinical investigation : the official journal of the 
International Society of Amyloidosis. 2011;18 Suppl 1:157-9. 
9. 
Ruberg FL, Maurer MS, Judge DP, Zeldenrust S, Skinner M, Kim AY, Falk RH, Cheung KN, 
Patel AR, Pano A, Packman J and Grogan DR. Prospective evaluation of the morbidity and mortality 
of wild-type and V122I mutant transthyretin amyloid cardiomyopathy: the Transthyretin Amyloidosis 
Cardiac Study (TRACS). Am Heart J. 2012;164:222-228 e1. 
10. 
Berk JL, Suhr OB, Obici L, Sekijima Y, Zeldenrust SR, Yamashita T, Heneghan MA, Gorevic 
PD, Litchy WJ, Wiesman JF, Nordh E, Corato M, Lozza A, Cortese A, Robinson-Papp J, Colton T, 
Rybin DV, Bisbee AB, Ando Y, Ikeda S, Seldin DC, Merlini G, Skinner M, Kelly JW and Dyck PJ. 
Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. Jama. 
2013;310:2658-67. 
11. 
Castaño A HS, Alvarez J and MS Maurer. Diflunisal for ATTR cardiac amyloidosis. Congestive 
Heart Failure. 2012. 
12. 
Bahrami H, Kronmal R, Bluemke DA, Olson J, Shea S, Liu K, Burke GL and Lima JA. 
Differences in the incidence of congestive heart failure by ethnicity: the multi-ethnic study of 
atherosclerosis. Arch Intern Med. 2008;168:2138-45. 
13. 
Bahrami H, Bluemke DA, Kronmal R, Bertoni AG, Lloyd-Jones DM, Shahar E, Szklo M and 
Lima JA. Novel metabolic risk factors for incident heart failure and their relationship with obesity: the 
MESA (Multi-Ethnic Study of Atherosclerosis) study. J Am Coll Cardiol. 2008;51:1775-83. 

SCAN-MP – Study Protocol v4.0 
 
Page | 42  
14. 
Mathew Maurer  ILP, and Anne L. Taylor. Chapter 49: Heart Failure in Special Populations: 
Racial and Ethnic Minorities, Elderly Persons, and Women: Elsevier; 2010. 
15. 
Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, Anderson S, 
Donovan M, Iverson E, Staiger C, Ptaszynska A and Investigators IP. Irbesartan in patients with heart 
failure and preserved ejection fraction. N Engl J Med. 2008;359:2456-67. 
16. 
Cleland JG, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J and Investigators P-C. 
The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J. 
2006;27:2338-45. 
17. 
Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, 
Olofsson B, Ostergren J, Investigators C and Committees. Effects of candesartan in patients with 
chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. 
Lancet. 2003;362:777-81. 
18. 
van Heerebeek L, Borbely A, Niessen HW, Bronzwaer JG, van der Velden J, Stienen GJ, Linke 
WA, Laarman GJ and Paulus WJ. Myocardial structure and function differ in systolic and diastolic 
heart failure. Circulation. 2006;113:1966-73. 
19. 
Borbely A, van der Velden J, Papp Z, Bronzwaer JG, Edes I, Stienen GJ and Paulus WJ. 
Cardiomyocyte stiffness in diastolic heart failure. Circulation. 2005;111:774-81. 
20. 
Bronzwaer JG and Paulus WJ. Matrix, cytoskeleton, or myofilaments: which one to blame for 
diastolic left ventricular dysfunction? Prog Cardiovasc Dis. 2005;47:276-84. 
21. 
van Heerebeek L, Hamdani N, Handoko ML, Falcao-Pires I, Musters RJ, Kupreishvili K, 
Ijsselmuiden AJ, Schalkwijk CG, Bronzwaer JG, Diamant M, Borbely A, van der Velden J, Stienen 
GJ, Laarman GJ, Niessen HW and Paulus WJ. Diastolic stiffness of the failing diabetic heart: 
importance of fibrosis, advanced glycation end products, and myocyte resting tension. Circulation. 
2008;117:43-51. 
22. 
Lebeche D, Davidoff AJ and Hajjar RJ. Interplay between impaired calcium regulation and 
insulin signaling abnormalities in diabetic cardiomyopathy. Nat Clin Pract Cardiovasc Med. 
2008;5:715-24. 
23. 
Zile MR, Richardson K, Cowles MK, Buckley JM, Koide M, Cowles BA, Gharpuray V and 
Cooper Gt. Constitutive properties of adult mammalian cardiac muscle cells. Circulation. 1998;98:567-
79. 
24. 
Granzier HL and Irving TC. Passive tension in cardiac muscle: contribution of collagen, titin, 
microtubules, and intermediate filaments. Biophys J. 1995;68:1027-44. 
25. 
LeWinter MM and Granzier H. Cardiac titin: a multifunctional giant. Circulation. 
2010;121:2137-45. 
26. 
Borbely A, Papp Z, Edes I and Paulus WJ. Molecular determinants of heart failure with normal 
left ventricular ejection fraction. Pharmacol Rep. 2009;61:139-45. 
27. 
Gonzalez A, Lopez B, Querejeta R, Zubillaga E, Echeverria T and Diez J. Filling pressures and 
collagen metabolism in hypertensive patients with heart failure and normal ejection fraction. 
Hypertension. 2010;55:1418-24. 
28. 
Bradshaw AD, Baicu CF, Rentz TJ, Van Laer AO, Boggs J, Lacy JM and Zile MR. Pressure 
overload-induced alterations in fibrillar collagen content and myocardial diastolic function: role of 
secreted protein acidic and rich in cysteine (SPARC) in post-synthetic procollagen processing. 
Circulation. 2009;119:269-80. 
29. 
Ahmed SH, Clark LL, Pennington WR, Webb CS, Bonnema DD, Leonardi AH, McClure CD, 
Spinale FG and Zile MR. Matrix metalloproteinases/tissue inhibitors of metalloproteinases: 
relationship between changes in proteolytic determinants of matrix composition and structural, 
functional, and clinical manifestations of hypertensive heart disease. Circulation. 2006;113:2089-96. 

SCAN-MP – Study Protocol v4.0 
 
Page | 43  
30. 
Bhuiyan T, Helmke S, Patel AR, Ruberg FL, Packman J, Cheung K, Grogan D and Maurer M. 
Pressure-Volume Relationships in Patients with Transthyretin (ATTR) Cardiac Amyloidosis 
Secondary to V122I Mutations and Wild Type TTR: TRACS (Transthyretin Cardiac Amyloid Study). 
Circ Heart Fail. 2010. 
31. 
Lavine SJ. Genesis of the restrictive filling pattern: pericardial constraint or myocardial 
restraint. J Am Soc Echocardiogr. 2004;17:152-60. 
32. 
Petre RE, Quaile MP, Wendt K, Houser SR, Wald J, Goldman BI and Margulies KB. 
Regionally heterogeneous tissue mechanics in cardiac amyloidosis. Amyloid : the international journal 
of experimental and clinical investigation : the official journal of the International Society of 
Amyloidosis. 2005;12:246-50. 
33. 
Gonzalez-Lopez E, Gallego-Delgado M, Guzzo-Merello G, de Haro-Del Moral FJ, Cobo-
Marcos M, Robles C, Bornstein B, Salas C, Lara-Pezzi E, Alonso-Pulpon L and Garcia-Pavia P. Wild-
type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 
2015;36:2585-94. 
34. 
Goodman DS. Plasma retinol-binding protein. Orlando, FL.: Academic Press; 1984. 
35. 
Hamilton JA and Benson MD. Transthyretin: a review from a structural perspective. Cell Mol 
Life Sci. 2001;58:1491-521. 
36. 
Zanotti G and Berni R. Plasma retinol-binding protein: structure and interactions with retinol, 
retinoids, and transthyretin. Vitam Horm. 2004;69:271-95. 
37. 
Buxbaum JN and Reixach N. Transthyretin: the servant of many masters. Cell Mol Life Sci. 
2009;66:3095-101. 
38. 
van Bennekum AM, Wei S, Gamble MV, Vogel S, Piantedosi R, Gottesman M, Episkopou V 
and Blaner WS. Biochemical basis for depressed serum retinol levels in transthyretin-deficient mice. J 
Biol Chem. 2001;276:1107-13. 
39. 
Ingenbleek Y and Young V. Transthyretin (prealbumin) in health and disease: nutritional 
implications. Annu Rev Nutr. 1994;14:495-533. 
40. 
Inoue S, Ohta M, Li Z, Zhao G, Takaoka Y, Sakashita N, Miyakawa K, Takada K, Tei H, 
Suzuki M, Masuoka M, Sakaki Y, Takahashi K and Yamamura K. Specific pathogen free conditions 
prevent transthyretin amyloidosis in mouse models. Transgenic Res. 2008;17:817-26. 
41. 
Klabunde T, Petrassi HM, Oza VB, Raman P, Kelly JW and Sacchettini JC. Rational design of 
potent human transthyretin amyloid disease inhibitors. Nat Struct Biol. 2000;7:312-21. 
42. 
Sekijima Y, Wiseman RL, Matteson J, Hammarstrom P, Miller SR, Sawkar AR, Balch WE and 
Kelly JW. The biological and chemical basis for tissue-selective amyloid disease. Cell. 2005;121:73-
85. 
43. 
Shah KB, Mankad AK, Castano A, Akinboboye OO, Duncan PB, Fergus IV and Maurer MS. 
Transthyretin Cardiac Amyloidosis in Black Americans. Circ Heart Fail. 2016;9:e002558. 
44. 
Kelly JW. Mechanisms of amyloidogenesis. Nat Struct Biol. 2000;7:824-6. 
45. 
Jacobson DR, Gorevic PD and Buxbaum JN. A homozygous transthyretin variant associated 
with senile systemic amyloidosis: evidence for a late-onset disease of genetic etiology. Am J Hum 
Genet. 1990;47:127-36. 
46. 
Jacobson DR, Alexander AA, Tagoe C and Buxbaum JN. Prevalence of the amyloidogenic 
transthyretin (TTR) V122I allele in 14 333 African-Americans. Amyloid : the international journal of 
experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 
2015;22:171-4. 
47. 
Buxbaum J, Jacobson DR, Tagoe C, Alexander A, Kitzman DW, Greenberg B, Thaneemit-
Chen S and Lavori P. Transthyretin V122I in African Americans with congestive heart failure. J Am 
Coll Cardiol. 2006;47:1724-5. 

SCAN-MP – Study Protocol v4.0 
 
Page | 44  
48. 
Pages RA, Robbins J and Edelhoch H. Binding of thyroxine and thyroxine analogs to human 
serum prealbumin. Biochemistry. 1973;12:2773-9. 
49. 
Saraiva MJ. Transthyretin mutations in hyperthyroxinemia and amyloid diseases. Hum Mutat. 
2001;17:493-503. 
50. 
Quintas A, Vaz DC, Cardoso I, Saraiva MJ and Brito RM. Tetramer dissociation and monomer 
partial unfolding precedes protofibril formation in amyloidogenic transthyretin variants. J Biol Chem. 
2001;276:27207-13. 
51. 
Hammarstrom P, Jiang X, Hurshman AR, Powers ET and Kelly JW. Sequence-dependent 
denaturation energetics: A major determinant in amyloid disease diversity. Proc Natl Acad Sci U S A. 
2002;99 Suppl 4:16427-32. 
52. 
Costa PP, Figueira AS and Bravo FR. Amyloid fibril protein related to prealbumin in familial 
amyloidotic polyneuropathy. Proc Natl Acad Sci U S A. 1978;75:4499-503. 
53. 
Tanskanen M, Peuralinna T, Polvikoski T, Notkola IL, Sulkava R, Hardy J, Singleton A, Kiuru-
Enari S, Paetau A, Tienari PJ and Myllykangas L. Senile systemic amyloidosis affects 25% of the very 
aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based 
autopsy study. Ann Med. 2008;40:232-9. 
54. 
Mirzoyev SA EW, Mohammed SF, Donovan SL, Roger VL, Grogan D, Redfield MM. Cardiac 
Amyloid Deposition is Common in Elderly Patients with Heart Failure and Preserved Ejection 
Fraction. Circulation. 2010;122. 
55. 
Sikora JL, Logue MW, Chan GG, Spencer BH, Prokaeva TB, Baldwin CT, Seldin DC and 
Connors LH. Genetic variation of the transthyretin gene in wild-type transthyretin amyloidosis 
(ATTRwt). Hum Genet. 2015;134:111-21. 
56. 
Ng B, Connors LH, Davidoff R, Skinner M and Falk RH. Senile systemic amyloidosis 
presenting with heart failure: a comparison with light chain-associated amyloidosis. Arch Intern Med. 
2005;165:1425-9. 
57. 
Givens RC, Russo C, Green P and Maurer MS. Comparison of cardiac amyloidosis due to wild-
type and V122I transthyretin in older adults referred to an academic medical center. Aging health. 
2013;9:229-235. 
58. 
Gillmore JD and Hawkins PN. V122I transthyretin variant in elderly black Americans. N Engl 
J Med. 2015;372:1769. 
59. 
Connors LH, Sam F, Skinner M, Salinaro F, Sun F, Ruberg FL, Berk JL and Seldin DC. Heart 
Failure Due to Age-Related Cardiac Amyloid Disease Associated With Wild-Type Transthyretin: A 
Prospective, Observational Cohort Study. Circulation. 2015. 
60. 
Conomos MP, Laurie CA, Stilp AM, Gogarten SM, McHugh CP, Nelson SC, Sofer T, 
Fernandez-Rhodes L, Justice AE, Graff M, Young KL, Seyerle AA, Avery CL, Taylor KD, Rotter JI, 
Talavera GA, Daviglus ML, Wassertheil-Smoller S, Schneiderman N, Heiss G, Kaplan RC, 
Franceschini N, Reiner AP, Shaffer JR, Barr RG, Kerr KF, Browning SR, Browning BL, Weir BS, 
Aviles-Santa ML, Papanicolaou GJ, Lumley T, Szpiro AA, North KE, Rice K, Thornton TA and Laurie 
CC. Genetic Diversity and Association Studies in US Hispanic/Latino Populations: Applications in the 
Hispanic Community Health Study/Study of Latinos. Am J Hum Genet. 2016;98:165-84. 
61. 
Yamashita T, Hamidi Asl K, Yazaki M and Benson MD. A prospective evaluation of the 
transthyretin Ile122 allele frequency in an African-American population. Amyloid : the international 
journal of experimental and clinical investigation : the official journal of the International Society of 
Amyloidosis. 2005;12:127-30. 
62. 
Johnson SM, Connelly S, Fearns C, Powers ET and Kelly JW. The Transthyretin Amyloidoses: 
From Delineating the Molecular Mechanism of Aggregation Linked to Pathology to a Regulatory-
Agency-Approved Drug. J Mol Biol. 2012. 

SCAN-MP – Study Protocol v4.0 
 
Page | 45  
63. 
Coelho T, Merlini G, Bulawa CE, Fleming JA, Judge DP, Kelly JW, Maurer MS, Plante-
Bordeneuve V, Labaudiniere R, Mundayat R, Riley S, Lombardo I and Huertas P. Mechanism of 
Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis. Neurol Ther. 
2016. 
64. 
Coelho T, Maia LF, Martins da Silva A, Waddington Cruz M, Plante-Bordeneuve V, Lozeron 
P, Suhr OB, Campistol JM, Conceicao IM, Schmidt HH, Trigo P, Kelly JW, Labaudiniere R, Chan J, 
Packman J, Wilson A and Grogan DR. Tafamidis for transthyretin familial amyloid polyneuropathy: a 
randomized, controlled trial. Neurology. 2012;79:785-92. 
65. 
Benson MD, Kluve-Beckerman B, Zeldenrust SR, Siesky AM, Bodenmiller DM, Showalter 
AD and Sloop KW. Targeted suppression of an amyloidogenic transthyretin with antisense 
oligonucleotides. Muscle Nerve. 2006;33:609-18. 
66. 
Kurosawa T, Igarashi S, Nishizawa M and Onodera O. Selective silencing of a mutant 
transthyretin allele by small interfering RNAs. Biochemical and biophysical research communications. 
2005;337:1012-8. 
67. 
Suhr OB, Coelho T, Buades J, Pouget J, Conceicao I, Berk J, Schmidt H, Waddington-Cruz M, 
Campistol JM, Bettencourt BR, Vaishnaw A, Gollob J and Adams D. Efficacy and safety of patisiran 
for familial amyloidotic polyneuropathy: a phase II multi-dose study. Orphanet journal of rare 
diseases. 2015;10:109. 
68. 
Wang AK, Coehlo T, Waddington-Cruz M, Polydefkis MJ, Dyck PJ, Scheinberg M, Plante-
Bordeneuve V, Berk J, Barroso F, Adams D, Brannagan T, Whelan C, Merlini G, Drachman B, Heitner 
S, Conceicao I, Schmidt H, Vita G, Campistol JM, Gamez J, Gane E, Gorevic P, Oliveria ASB, Monia 
B, Hughes SG, Kwoh J, McEvoy BW, Baker BF, Shenker A, Millns H, Bergemann R, Ackermann EJ, 
Gertz M and Benson MD. Safety and Efficacy of Inotersen in Patients with Hereditary Transthyretin 
Amyloidosis with Polyneuropathy (NEURO-TTR). Ann Neurol. 2017;82:S108-S109. 
69. 
Gertz MA, Comenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN, Merlini G, Moreau 
P, Ronco P, Sanchorawala V, Sezer O, Solomon A and Grateau G. Definition of organ involvement 
and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 
10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004. Am J 
Hematol. 2005;79:319-28. 
70. 
Bokhari S, Castano A, Pozniakoff T, Deslisle S, Latif F and Maurer MS. (99m)Tc-
pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-
related familial and senile cardiac amyloidoses. Circ Cardiovasc Imaging. 2013;6:195-201. 
71. 
Castano A, Haq M, Narotsky DL, Goldsmith J, Weinberg RL, Morgenstern R, Pozniakoff T, 
Ruberg FL, Miller EJ, Berk JL, Dispenzieri A, Grogan M, Johnson G, Bokhari S and Maurer MS. 
Multicenter Study of Planar Technetium 99m Pyrophosphate Cardiac Imaging: Predicting Survival for 
Patients With ATTR Cardiac Amyloidosis. JAMA Cardiol. 2016;1:880-889. 
72. 
Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, Wechalekar AD, Berk 
JL, Quarta CC, Grogan M, Lachmann HJ, Bokhari S, Castano A, Dorbala S, Johnson GB, Glaudemans 
AW, Rezk T, Fontana M, Palladini G, Milani P, Guidalotti PL, Flatman K, Lane T, Vonberg FW, 
Whelan CJ, Moon JC, Ruberg FL, Miller EJ, Hutt DF, Hazenberg BP, Rapezzi C and Hawkins PN. 
Non-Biopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. 2016. 
73. 
Maurer MS. Noninvasive Identification of ATTRwt Cardiac Amyloid: The Re-emergence of 
Nuclear Cardiology. Am J Med. 2015. 
74. 
King DL, El-Khoury Coffin L and Maurer MS. Myocardial contraction fraction: a volumetric 
index of myocardial shortening by freehand three-dimensional echocardiography. J Am Coll Cardiol. 
2002;40:325-9. 

SCAN-MP – Study Protocol v4.0 
 
Page | 46  
75. 
King DL, Coffin Lel K and Maurer MS. Noncompressibility of myocardium during systole 
with freehand three-dimensional echocardiography. J Am Soc Echocardiogr. 2002;15:1503-6. 
76. 
Milani P DA, Gertz MA, Lacy MQ, Baudi FK. Kumar SK, Maurer MS, Klarich K, Hayman 
SR, Leung N, Dingli D, Lust LA, Lin Y, Kapoor P, Go RS, Hwa YL, Zeldenrust SR, Kyle RA, 
Rajkumar SV and M Grogan. In Patients with Light-Chain (AL) Amyloidosis Myocardial Contraction 
Fraction (MCF) Is a Simple, but Powerful Prognostic Measure That Can be Calculated from a Standard 
Echocardiogram (ECHO). Blood. 
77. 
Tendler A, Helmke S, Teruya S, Alvarez J and Maurer MS. The myocardial contraction fraction 
is superior to ejection fraction in predicting survival in patients with AL cardiac amyloidosis. Amyloid 
: the international journal of experimental and clinical investigation : the official journal of the 
International Society of Amyloidosis. 2015;22:61-6. 
78. 
Fontana M, Pica S, Reant P, Abdel-Gadir A, Treibel TA, Banypersad SM, Maestrini V, Barcella 
W, Rosmini S, Bulluck H, Sayed RH, Patel K, Mamhood S, Bucciarelli-Ducci C, Whelan CJ, Herrey 
AS, Lachmann HJ, Wechalekar AD, Manisty CH, Schelbert EB, Kellman P, Gillmore JD, Hawkins 
PN and Moon JC. Response to Letters Regarding Article, "Prognostic Value of Late Gadolinium 
Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis". Circulation. 
2016;133:e450-1. 
79. 
Steidley DE, Schumacher J, Carlsson M, Ong ML and Maurer M. Myocardial Contraction 
Fraction: A Volumetric Index for Predicting Mortality in Transthyretin Cardiomyopathy. Journal of 
Cardiac Failure. 22:S48. 
80. 
Rappley I, Monteiro C, Novais M, Baranczak A, Solis G, Wiseman RL, Helmke S, Maurer MS, 
Coelho T, Powers ET and Kelly JW. Quantification of transthyretin kinetic stability in human plasma 
using subunit exchange. Biochemistry. 2014;53:1993-2006. 
81. 
Cho Y, Baranczak A, Helmke S, Teruya S, Horn EM, Maurer MS and Kelly JW. Personalized 
medicine approach for optimizing the dose of tafamidis to potentially ameliorate wild-type 
transthyretin amyloidosis (cardiomyopathy). Amyloid : the international journal of experimental and 
clinical investigation : the official journal of the International Society of Amyloidosis. 2015;22:175-
80. 
82. 
Kubo SH, Schulman S, Starling RC, Jessup M, Wentworth D and Burkhoff D. Development 
and validation of a patient questionnaire to determine New York Heart Association classification. J 
Card Fail. 2004;10:228-35. 
83. 
Schocken DD, Arrieta MI, Leaverton PE and Ross EA. Prevalence and mortality rate of 
congestive heart failure in the United States. J Am Coll Cardiol. 1992;20:301-6. 
84. 
Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I and Reichek N. 
Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J 
Cardiol. 1986;57:450-8. 
85. 
Mor-Avi V, Sugeng L, Weinert L, MacEneaney P, Caiani EG, Koch R, Salgo IS and Lang RM. 
Fast measurement of left ventricular mass with real-time three-dimensional echocardiography: 
comparison with magnetic resonance imaging. Circulation. 2004;110:1814-8. 
86. 
Takeuchi M, Nishikage T, Mor-Avi V, Sugeng L, Weinert L, Nakai H, Salgo IS, Gerard O and 
Lang RM. Measurement of left ventricular mass by real-time three-dimensional echocardiography: 
validation against magnetic resonance and comparison with two-dimensional and m-mode 
measurements. J Am Soc Echocardiogr. 2008;21:1001-5. 
87. 
Garcia MJ, Ares MA, Asher C, Rodriguez L, Vandervoort P and Thomas JD. An index of early 
left ventricular filling that combined with pulsed Doppler peak E velocity may estimate capillary wedge 
pressure. J Am Coll Cardiol. 1997;29:448-54. 

SCAN-MP – Study Protocol v4.0 
 
Page | 47  
88. 
Hoffmann R, Altiok E, Nowak B, Heussen N, Kuhl H, Kaiser HJ, Bull U and Hanrath P. Strain 
rate measurement by doppler echocardiography allows improved assessment of myocardial viability 
inpatients with depressed left ventricular function. J Am Coll Cardiol. 2002;39:443-9. 
89. 
Amundsen BH, Helle-Valle T, Edvardsen T, Torp H, Crosby J, Lyseggen E, Stoylen A, Ihlen 
H, Lima JA, Smiseth OA and Slordahl SA. Noninvasive myocardial strain measurement by speckle 
tracking echocardiography: validation against sonomicrometry and tagged magnetic resonance 
imaging. J Am Coll Cardiol. 2006;47:789-93. 
90. 
Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster 
E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, 
Spencer KT, Tsang W and Voigt JU. Recommendations for cardiac chamber quantification by 
echocardiography in adults: an update from the American Society of Echocardiography and the 
European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015;16:233-70. 
91. 
Carroll JD, Gaasch WH and McAdam KP. Amyloid cardiomyopathy: characterization by a 
distinctive voltage/mass relation. Am J Cardiol. 1982;49:9-13. 
92. 
Laboratories ATSCoPSfCPF. ATS statement: guidelines for the six-minute walk test. Am J 
Respir Crit Care Med. 2002;166:111-7. 
93. 
Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA and 
Wallace RB. A short physical performance battery assessing lower extremity function: association with 
self-reported disability and prediction of mortality and nursing home admission. Journal of 
gerontology. 1994;49:M85-94. 
94. 
Lee S, Abecasis GR, Boehnke M and Lin X. Rare-variant association analysis: study designs 
and statistical tests. Am J Hum Genet. 2014;95:5-23. 
95. 
Finkelstein DM and Schoenfeld DA. Combining mortality and longitudinal measures in clinical 
trials. Stat Med. 1999;18:1341-54. 
96. 
Pocock SJ, Ariti CA, Collier TJ and Wang D. The win ratio: a new approach to the analysis of 
composite endpoints in clinical trials based on clinical priorities. Eur Heart J. 2012;33:176-82. 
97. 
Dungu JN, Papadopoulou SA, Wykes K, Mahmood I, Marshall J, Valencia O, Fontana M, 
Whelan CJ, Gillmore JD, Hawkins PN and Anderson LJ. Afro-Caribbean Heart Failure in the United 
Kingdom: Cause, Outcomes, and ATTR V122I Cardiac Amyloidosis. Circ Heart Fail. 2016;9. 
98. 
Chang ICY, Bois JP, Bois MC, Maleszewski JJ, Johnson GB and Grogan M. 
Hydroxychloroquine-Mediated Cardiotoxicity With a False-Positive (99m)Technetium-Labeled 
Pyrophosphate Scan for Transthyretin-Related Cardiac Amyloidosis. Circ Cardiovasc Imaging. 
2018;11. 
99. 
Quarta CC, Obici L, Guidalotti PL, Pieroni M, Longhi S, Perlini S, Verga L, Merlini G and 
Rapezzi C. High 99mTc-DPD myocardial uptake in a patient with apolipoprotein AI-related 
amyloidotic cardiomyopathy. Amyloid : the international journal of experimental and clinical 
investigation : the official journal of the International Society of Amyloidosis. 2013;20:48-51. 
100. 
Alexander DH, Novembre J and Lange K. Fast model-based estimation of ancestry in unrelated 
individuals. Genome Res. 2009;19:1655-64. 
101. 
Glaudemans AW, van Rheenen RW, van den Berg MP, Noordzij W, Koole M, Blokzijl H, 
Dierckx RA, Slart RH and Hazenberg BP. Bone scintigraphy with (99m)technetium-
hydroxymethylene diphosphonate allows early diagnosis of cardiac involvement in patients with 
transthyretin-derived systemic amyloidosis. Amyloid : the international journal of experimental and 
clinical investigation : the official journal of the International Society of Amyloidosis. 2014;21:35-44. 
102. 
Bokhari S, Shahzad R, Castano A and Maurer MS. Nuclear imaging modalities for cardiac 
amyloidosis. J Nucl Cardiol. 2014;21:175-84. 

SCAN-MP – Study Protocol v4.0 
 
Page | 48  
6. 
APPENDICES 
 
 

SCAN-MP – Study Protocol v4.0 
 
Page | 49  
APPENDIX 1 
HEART FAILURE CLINICAL SCORE 
 
 
 
Clinical Variables 
Score 
Dyspnea/difficulty breathing 
 
Trouble with breathing (shortness of breath) 
 
Hurrying on the level or up slight hill 
1 
At ordinary pace on the level? 
1 
Do you stop for breath when walking at own pace? 
2 
Do you stop for breath after 100 yards on the level? 
2 
Physical examination 
 
Heart rate (beats/min) 
 
91 to 110 
1 
111 + 
2 
Rales/crackles 
 
Either lower lung field 
1 
Either lower and either upper lung field 
2 
Jugulovenous distension 
 
Alone 
1 
Plus edema 
2 
Plus hepatomegaly 
2 
Chest X-ray film 
 
Cephalization of pulmonary vessels 
1 
Interstitial edema 
2 
Alveolar fluid plus pleural fluid 
3 
Interstitial edema plus pleural fluid 
3 
 
 

SCAN-MP – Study Protocol v4.0 
 
Page | 50  
APPENDIX 2 
THE BORG SCALE 
 
 
 
PLEASE, GRADE YOUR LEVEL OF SHORTNESS OF 
BREATH AND FATIGUE ACCORDING TO THIS SCALE: 
0 
Nothing at all 
0.5 
Very, very slight (just noticeable) 
1 
Very slight 
2 
Slight (light) 
3 
Moderate 
4 
Somewhat severe 
5 
Severe (heavy) 
6 
 
7 
Very severe 
8 
 
9 
 
10 
Very, very severe (maximal) 
 
 

SCAN-MP – Study Protocol v4.0 
 
Page | 51  
APPENDIX 3 
NUTRITION FACTS OF A CONTAINER OF A PINT OF 
ICE CREAM 
 
 
 
 
 

SCAN-MP – Study Protocol v4.0 
 
Page | 52  
APPENDIX 4 
CASE REPORT FORMS

Visit: SCR 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – Schedule of Activities – Screening v4.0  
 
 
 
 
 
 
Page 1 of 1 
SCHEDULE OF ACTIVITIES – SCREENING 
Order 
Activity 
Done 
Not 
Done 
Notes 
1 
Informed consent 
 
 
 
2 
Inclusion and Exclusion Criteria 
 
 
 
3 
Demographics and Contact Information 
 
 
 

Visit: BL  
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – Schedule of Activities – Baseline v4.0 
 
 
 
 
 
 
 
Page 1 of 1 
SCHEDULE OF ACTIVITIES – BASELINE 
Order 
Activity 
Done 
Not 
Done 
Notes 
1 
Baseline history 
 
 
 
2 
Medications 
 
 
 
3 
Height and Weight 
 
 
 
4 
Vital signs 
 
 
 
5 
Clinical examination 
 
 
 
6 
Electrocardiogram 
 
 
 
7 
Short physical performance battery 
 
 
 
8 
Six-minute walk test 
 
 
 
9 
Echocardiogram 
 
 
 
10 
IV catheter placement 
 
 
 
11 
Blood/urine samples collection 
 
 
 
 
a. Basic metabolic panel 
 
 
 
 
b. Hepatic function panel 
 
 
 
 
c. NT-proBNP, BNP and Galectin-3 
 
 
 
 
d. Troponin I and T 
 
 
 
 
e. Vitamin A / RBP4 in plasma 
 
 
 
 
f. Vitamin A / RBP4 in urine 
 
 
 
 
g. Prealbumin 
 
 
 
 
h. TTR kinetic stability 
 
 
 
 
i. 
TTR gene sequencing 
 
 
 
 
j. 
Ancestry analysis 
 
 
 
12 
Injection of radioisotope (99mTc-PYP or 
99mTc-HMDP) 
 
 
 
13 
QoL questionnaires 
 
 
 
14 
Health Literacy Questionnaire 
 
 
 
15 
Cardiac Amyloid Scintigraphy scan 
 
 
 

Visit: M6  
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – Schedule of Activities – Month 6 v4.0 
 
 
 
 
 
 
 
Page 1 of 1 
SCHEDULE OF ACTIVITIES – MONTH 6 
Order 
Activity 
Done 
Not 
Done 
Notes 
1 
Weight 
 
 
 
2 
Vital signs 
 
 
 
3 
Medications 
 
 
 
4 
Clinical examination 
 
 
 
5 
Adverse events review 
 
 
 
6 
Electrocardiogram 
 
 
 
7 
Blood/urine samples collection 
 
 
 
 
a. Basic metabolic panel 
 
 
 
 
b. Hepatic function panel 
 
 
 
 
c. NT-proBNP, BNP and Galectin-3 
 
 
 
 
d. Troponin I and T 
 
 
 
 
e. Vitamin A / RBP4 in plasma 
 
 
 
 
f. Vitamin A / RBP4 in urine 
 
 
 
 
g. Prealbumin 
 
 
 
8 
Short physical performance battery 
 
 
 
9 
Six-minute walk test 
 
 
 
10 
QoL questionnaires 
 
 
 

Visit: M12 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – Schedule of Activities – Month 12 v4.0 
 
 
 
 
 
 
 
Page 1 of 1 
SCHEDULE OF ACTIVITIES – MONTH 12 
Order 
Activity 
Done 
Not 
Done 
Notes 
1 
Weight 
 
 
 
2 
Vital signs 
 
 
 
3 
Medications 
 
 
 
4 
Clinical examination 
 
 
 
5 
Adverse events review 
 
 
 
6 
Electrocardiogram 
 
 
 
7 
Blood/urine samples collection 
 
 
 
 
a. Basic metabolic panel 
 
 
 
 
b. Hepatic function panel 
 
 
 
 
c. NT-proBNP, BNP and Galectin-3 
 
 
 
 
d. Troponin I and T 
 
 
 
 
e. Vitamin A / RBP4 in plasma 
 
 
 
 
f. Vitamin A / RBP4 in urine 
 
 
 
 
g. Prealbumin 
 
 
 
 
h. TTR kinetic stability 
 
 
 
8 
Short physical performance battery 
 
 
 
9 
Six-minute walk test 
 
 
 
10 
QoL questionnaires 
 
 
 
11 
Echocardiogram 
 
 
 

Visit: SCR 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – Heart Failure Clinical Score – NHANES Criteria v4.0 
 
 
 
 
 
Page 1 of 1 
HEART FAILURE CLINICAL SCORE – NHANES CRITERIA 
 
Clinical Variables 
Check if 
present 
Dyspnea/difficulty breathing 
 
Trouble with breathing (shortness of breath) 
 
Hurrying on the level or up slight hill 
 1 
At ordinary pace on the level? 
 1 
Do you stop for breath when walking at own pace? 
 2 
Do you stop for breath after 100 yards on the level? 
 2 
Physical examination 
 
Heart rate (beats/min) 
 
91 to 110 
 1 
111 + 
 2 
Rales/crackles 
 
Either lower lung field 
 1 
Either lower and either upper lung field 
 2 
Jugulovenous distension 
 
Alone 
 1 
Plus edema 
 2 
Plus hepatomegaly 
 2 
Chest X-ray film 
 
Cephalization of pulmonary vessels 
 1 
Interstitial edema 
 2 
Alveolar fluid plus pleural fluid 
 3 
Interstitial edema plus pleural fluid 
 3 
Score: 
__ __ 

Visit: SCR 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – Inclusion and Exclusion Criteria v4.0 
 
 
 
 
 
 
 
Page 1 of 1 
INCLUSION AND EXCLUSION CRITERIA 
Inclusion Criteria 
Yes 
No 
1. Black or Hispanic of Caribbean origin. 
 
 
2. Age ≥60 years. 
 
 
3. Diagnosis of heart failure, confirmed by two methods: 
 
 
a. 
Modified criteria utilized by Rich et al. which include a history of acute pulmonary 
edema or the occurrence of at least two of the following that improved with diuretic 
therapy without another identifiable cause: dyspnea on exertion, paroxysmal nocturnal 
dyspnea, orthopnea, bilateral lower extremity edema or exertional fatigue, and 
 
 
b. 
NHANES CHF criteria with a score ≥3. 
 
 
4. Left ventricular septal OR inferolateral wall thickness ≥12 mm. 
 
 
5. Ejection fraction >30% 
 
 
6. Able to understand and sign the informed consent document after the nature of the study 
has been fully explained. 
 
 
 
 
 
Exclusion Criteria 
Yes 
No 
1. Primary amyloidosis (AL) or secondary amyloidosis (AA). 
 
 
2. Prior liver or heart transplantation. 
 
 
3. Active malignancy or non-amyloid disease with expected survival of less than 1 year. 
 
 
4. Heart failure, in the opinion of the investigator, primarily caused by severe left-sided valve 
disease. Note: if valve was repaired, subject no longer with severe valve disease. 
 
 
5. Heart failure, in the opinion of the investigator, primarily caused by ischemic heart disease. 
 
 
6. Ventricular assist device or anticipated within the next 6 months. 
 
 
7. Impairment from stroke, injury or other medical disorder that precludes participation in the 
study. 
 
 
8. Disabling dementia or other mental or behavioral disease. 
 
 
9. Enrollment in a clinical trial not approved for co-enrollment. 
 
 
10. Expected use of continuous intravenous inotropic therapy in the next 6 months. 
 
 
11. High risk for non-adherence as determined by screening evaluation. 
 
 
12. Inability or unwillingness to comply with the study requirements. 
 
 
13. Chronic kidney disease with eGFR <15 mL/min/1.73 m2 or ESRD. 
 
 
14. Weight >350 lb. 
 
 
15. Nursing home resident. 
 
 
16. Other reason that would make the subject inappropriate for entry into this study. 
 
 
Specify: ________________________________________________________ 
 
 

Visit: SCR 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
SCAN-MP – Demographics and Contact Information v4.0 
 
 
 
 
 
 
Page 1 of 4 
DEMOGRAPHICS AND CONTACT INFORMATION 
Demographics 
1. Name 
Last Name: ______________________________ 
First Name: ______________________________ 
2. Gender 
 Male 
 Female 
3. Child Bearing Potential 
If the subject is female is she of childbearing potential? 
 Yes 
 No 
If No, why? (check one reason only) 
 ≥2 yrs 
postmenopausal 
 Bilateral oopherectomy 
 Hysterectomy 
 Other (specify): ________________________________________________________________ 
4. Date of Birth: __ __ / __ __ / __ __ __ __ (mm/dd/yyyy) 
5. Date of Enrollment: __ __ / __ __ / __ __ __ __ (mm/dd/yyyy) 
6. Age at Enrollment: __ __ years 
7. Racial Identity (check all that apply) 
 American Indian/Alaska Native 
 Asian 
 Black or African American 
 Native Hawaiian or Other Pacific Islander 
 White 
 Unknown or Not Reported 
8. Hispanic Origin 
 Yes 
 No 
 Unknown or Not Reported 

Visit: SCR 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
SCAN-MP – Demographics and Contact Information v4.0 
 
 
 
 
 
 
Page 2 of 4 
9. Country of Origin 
 Bahamas 
 El Salvador 
 Honduras 
 Senegal 
 Belize 
 Gambia 
 Ivory Coast 
 St Croix 
 Costa Rica 
 Ghana 
 Jamaica 
 St Lucia 
 Cuba 
 Guinea 
 Nigeria 
 St Maarten 
 Dominican Republic 
 Guyana 
 Panama 
 Trinidad and Tobago 
 Ecuador 
 Haiti 
 Puerto Rico 
 Venezuela 
 Other (specify): ________________________ 
10. Marital Status 
 Married 
 Divorced/separated 
 Widowed 
 Living as married/living with partner 
 Single (never married) 
 Did not answer 
11. Highest level of education 
 Less than high school 
 High school/GED 
 2-year or 4-year college degree 
 Graduate or post-graduate degree 
 Did not answer 
12. Insurance 
 Medicare 
 Medicaid 
 Military/VA 
 Private/Other 
 Self/None 
 
 

Visit: SCR 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
SCAN-MP – Demographics and Contact Information v4.0 
 
 
 
 
 
 
Page 3 of 4 
Contact Information 
1. Primary Address 
Address: ______________________________ 
City, State, Zip Code: ______________________________ 
Home phone number: ( __ __ __ ) __ __ __ - __ __ __ __ 
Mobile phone number: ( __ __ __ ) __ __ __ - __ __ __ __ 
2. Secondary Address (if applicable) 
Address: ______________________________ 
City, State, Zip Code: ______________________________ 
Home phone number: ( __ __ __ ) __ __ __ - __ __ __ __ 
3. Social Security Number (SSN) 
__ __ __ - __ __ - __ __ __ __ 
4. Contacts 
Primary Contact 
Full Name: ______________________________ 
Address: ______________________________ 
City, State, Zip Code: ______________________________ 
Home phone number: ( __ __ __ ) __ __ __ - __ __ __ __ 
Mobile phone number: ( __ __ __ ) __ __ __ - __ __ __ __ 
Secondary Contact 
Full Name: ______________________________ 
Address: ______________________________ 
City, State, Zip Code: ______________________________ 
Home phone number: ( __ __ __ ) __ __ __ - __ __ __ __ 
Mobile phone number: ( __ __ __ ) __ __ __ - __ __ __ __ 
 
 
 

Visit: SCR 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
SCAN-MP – Demographics and Contact Information v4.0 
 
 
 
 
 
 
Page 4 of 4 
5. Primary Care Provider 
Full Name: ______________________________ 
Address: ______________________________ 
City, State, Zip Code: ______________________________ 
Home phone number: ( __ __ __ ) __ __ __ - __ __ __ __ 
Mobile phone number: ( __ __ __ ) __ __ __ - __ __ __ __ 
6. Cardiologist 
Full Name: ______________________________ 
Address: ______________________________ 
City, State, Zip Code: ______________________________ 
Home phone number: ( __ __ __ ) __ __ __ - __ __ __ __ 
Mobile phone number: ( __ __ __ ) __ __ __ - __ __ __ __ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Form Completed by: _________________________________ 

Visit: BL  
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – Baseline History v4.0  
 
 
 
 
 
 
 
 
Page 1 of 2 
BASELINE HISTORY 
Medical History 
Have you ever been told by a doctor, nurse or any other health professional 
that you had any of the following conditions? 
Yes 
No 
1. 
Congestive heart failure 
 
 
2. 
Atrial fibrillation or atrial flutter 
 
 
3. 
Other arrhythmias or irregular heart beat 
 
 
4. 
Coronary artery disease  
 
 
5. 
Myocardial infarction or heart attack 
 
 
6. 
Hypertension  
 
 
7. 
Hyperlipidemia or hypercholesterolemia  
 
 
8. 
Peripheral vascular disease (blockages in the blood vessels or arteries of the 
legs 
 
 
9. 
Stroke  
 
 
10. Chronic kidney disease  
 
 
11. Hyperthyroidism  
 
 
12. Hypothyroidism  
 
 
13. Chronic hepatitis  
 
 
14. Hepatic cirrhosis  
 
 
15. Anemia 
 
 
16. Chronic obstructive pulmonary disease (COPD), chronic bronchitis or 
emphysema 
 
 
17. Asthma 
 
 
18. Osteoarthritis 
 
 
19. Carpal tunnel syndrome 
 
 
20. Spinal stenosis 
 
 
21. Polyneuropathy 
 
 
22. Benign prostatic hypertrophy (BPH) or enlarged prostate  
 
 
23. Gastric or duodenal ulcer  
 
 
24. Cancer (not skin cancer but melanoma)  
 
 
25. Skin cancer (not melanoma)  
 
 
26. Diabetes  
 
 
27. Does subject have an implantable cardioverter defibrillator? 
 
 
28. Does subject have a pacemaker? 
 
 
If ‘Yes’, is this a biventricular pacemaker? 
 
 
 

Visit: BL  
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – Baseline History v4.0  
 
 
 
 
 
 
 
 
Page 2 of 2 
Risk Factors 
1. Do you ever drink beer, wine liquor or any drink containing alcohol? 
Yes 
 
No 
 
Did not answer 
 
(If ‘No’, or ‘Did not answer’, skip to Question 2) 
a. If ‘Yes’, on average how many days per week do you drink alcohol? 
 
<1 per 
week 
 
 1 
 2 
 3 
 4 
 5 
 6 
 7 
Did not 
answer 
 
b. If ‘Yes’, on a typical day when you drink, how many drinks do you have? 
(Consider a ‘drink’ to be a 12 oz. beer, 5 oz. glass of wine, 12 oz. wine 
cooler, 1 ½ oz. shot of liquor or a mixed drink made with 1 shot.) 
__ __ 
c. If ‘Yes’, how many times in the past month have had more than 4 or more 
drinks? 
__ __ 
2. Have you smoked more than 100 cigarettes in your entire life? 
Yes 
 
No 
 
Don’t know 
 
Did not answer 
 
(If ‘No’, skip to Question 4) 
3. Do you now smoke cigarettes every day, some days, or not at all? 
Every day 
 
Some days 
 
Not at all 
 
Did not answer 
 
4. Have any of your blood relative died from early heart disease? 
 
(Early heart disease means <65 years in women and <55 years in men. Blood relatives refer to parents, 
siblings, and children.) 
Yes 
 
No 
 
Did not answer 
 
Hospitalizations 
Were you hospitalized in the last 6 months? 
 Yes 
 No 
If ‘yes’, how many times? 
__ __ 
 
If ‘yes’, how many of these hospitalizations were due to heart failure? 
__ __ 
 

Visit: 
BL  
6M  
12M   
 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
Study ID#: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – Body Weight and Height / Vital Signs / Physical Exam / Laboratory v4.0 
 
 
 
Page 1 of 1 
BODY WEIGHT AND HEIGHT 
1. 
Body Weight: __ __ __ Kg 
2. 
Height: __ __ . __ m 
VITAL SIGNS 
 
Supine 
Standing 
 
 
 
3. 
Blood Pressure (mmHg) 
__ __ __ / __ __ __ 
__ __ __ / __ __ __ 
4. 
Pulse Rate (bpm) 
__ __ __ 
__ __ __ 
5. 
Respiratory Rate (rpm) 
__ __ 
__ __ 
PHYSICAL EXAM 
1. JVP (cm H20) 
 ≤ 5 
 6 - 8 
 ≥ 9 
 
Present 
Absent 
 
 
 
2. Rales 
 
 
3. Gallop S3 
 
 
4. Gallop S4 
 
 
5. Hepatomegaly 
 
 
6. Edema 
 
 
7. NYHA Class as per PI 
 I      II      III      IV 
 
8. Incidental Findings 
 
 
 
 
 
 
 
 
9. Adverse Events 
 
 
 
 
 
LABORATORY 
 
 
 
Incidental Findings 
 
 
 
 
 

Visit: ALL 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
SCAN-MP – Medications v3.5 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
MEDICATIONS 
 
List both prescription and over-the-counter medications the patient is taking. 
Medication 
Dose 
Units 
Route 
Frequency 
Start Date 
Stop Date 
# Times 
Time Interval 
PRN 
1 
 
 
 
 
D    W    M 
 
 
 
2 
 
 
 
 
D    W    M 
 
 
 
3 
 
 
 
 
D    W    M 
 
 
 
4 
 
 
 
 
D    W    M 
 
 
 
5 
 
 
 
 
D    W    M 
 
 
 
6 
 
 
 
 
D    W    M 
 
 
 
7 
 
 
 
 
D    W    M 
 
 
 
8 
 
 
 
 
D    W    M 
 
 
 
9 
 
 
 
 
D    W    M 
 
 
 
10 
 
 
 
 
D    W    M 
 
 
 
11 
 
 
 
 
D    W    M 
 
 
 
12 
 
 
 
 
D    W    M 
 
 
 
13 
 
 
 
 
D    W    M 
 
 
 
14 
 
 
 
 
D    W    M 
 
 
 
15 
 
 
 
 
D    W    M 
 
 
 
16 
 
 
 
 
D    W    M 
 
 
 
17 
 
 
 
 
D    W    M 
 
 
 
18 
 
 
 
 
D    W    M 
 
 
 
19 
 
 
 
 
D    W    M 
 
 
 
20 
 
 
 
 
D    W    M 
 
 
 
21 
 
 
 
 
D    W    M 
 
 
 
22 
 
 
 
 
D    W    M 
 
 
 
23 
 
 
 
 
D    W    M 
 
 
 
24 
 
 
 
 
D    W    M 
 
 
 
25 
 
 
 
 
D    W    M 
 
 
 
 

Visit: 
BL  
6M  
12M   
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – NYHA Functional Class Questionnaire v4.0 
 
 
 
 
 
 
Page 1 of 3 
NYHA FUNCTIONAL CLASS QUESTIONNAIRE 
 
Please Read to Patient: 
“I will be asking you a few questions about your health status. Please, respond to the best of your ability with 
the answer that you feel best describes your health. All answers need to be yours and based on your own 
experience.” (Please ask clinical staff, relatives and other visitors to leave the room if they are with you). 
Questions can be answered as Yes/No or with one of 4 responses: 
Never or none of the time 
Rarely, a little of the time, or on occasion 
Some of the time, a moderate amount of the time 
Frequently, most of the time 
 
Answer all applicable questions. 
1. a. How often do you walk up and down stairs? (8-12 steps) 
 
1 Never 
b. Do you avoid stairs because it makes you tired or short of breath? 
 
 
 
0 No 
1 Yes 
Go to #2 
 
 
 
 
 
 
 
2 Rarely 
c. How often do you get short of breath or tired when you walk up or down 
a flight of stairs at a normal pace under normal conditions? 
 
3 Sometimes 
 
1 Never 
2 Rarely 
3 Sometimes 
4 Frequently 
 
 
4 Frequently 
d. How often do you get short of breath or tired when you walk up or down 
a flight of stairs quickly? 
 
 
 
 
1 Never 
2 Rarely 
3 Sometimes 
4 Frequently 
Go to #2 
 
 
2. 
a. How often do you engage in strenuous work or prolonged exertion at work or play? 
 
1 Never 
b. Do you think you would get short of breath or tired if you engaged in 
these activities? 
 
 
 
0 No 
1 Yes 
Go to #3 
 
 
 
 
 
 
 
2 Rarely 
c. How often do you get short of breath or tired doing strenuous work 
or prolonged exertion? 
 
3 Sometimes 
 
1 Never 
2 Rarely 
3 Sometimes 
4 Frequently 
Go to #3 
 
4 Frequently 
 
 

Visit: 
BL  
6M  
12M   
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – NYHA Functional Class Questionnaire v4.0 
 
 
 
 
 
 
Page 2 of 3 
3. a. How often do you go for walks, either outside or inside, on level ground at a normal pace under 
normal conditions? 
 
1 Never 
b. Do you avoid walks because it will make you short of breath? 
 
 
 
0 No 
1 Yes 
Go to #4 
 
 
 
 
 
 
 
2 Rarely 
c. How often would you get short of breath or tired if you walked less than 
1 block? 
 
3 Sometimes 
 
1 Never 
2 Rarely 
3 Sometimes 
4 Frequently 
 
 
4 Frequently 
d. How often would you get short of breath or tired if you walked more 
than 2 blocks? 
 
 
 
1 Never 
2 Rarely 
3 Sometimes 
4 Frequently 
 
 
 
e. How often would you find yourself walking more slowly than usual? 
 
 
 
1 Never 
2 Rarely 
3 Sometimes 
4 Frequently 
Go to #4 
 
 
4. a. How often do you get short of breath or tired when you are sitting doing nothing or when you are 
sleeping? 
 
 
 
1 Never 
2 Rarely 
3 Sometimes 
4 Frequently 
Go to #5 
 
 
5. a. How often do you walk up hills? 
 
1 Never 
b. Do you avoid walking up hills because it makes you short of breath or 
tired? 
 
 
 
0 No 
1 Yes 
Go to #6 
 
 
 
 
 
 
 
2 Rarely 
c. How often do you get short of breath or tired walking up hills in normal 
weather? 
 
3 Sometimes 
 
1 Never 
2 Rarely 
3 Sometimes 
4 Frequently 
Go to #6 
 
4 Frequently 
 
 
 
 
 
 
 
 
 
 
 

Visit: 
BL  
6M  
12M   
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – NYHA Functional Class Questionnaire v4.0 
 
 
 
 
 
 
Page 3 of 3 
6. a. How often do you go out in the cold/windy or hot/humid weather? 
 
1 Never 
b. Do you avoid cold/windy or hot/humid weather because it makes you 
short of breath or tired? 
 
 
 
0 No 
1 Yes 
Go to #7 
 
 
 
 
 
 
 
2 Rarely 
c. How often do you get short of breath or tired when you go outside in 
the cold, windy or hot, humid weather? 
 
3 Sometimes 
 
1 Never 
2 Rarely 
3 Sometimes 
4 Frequently 
Go to #7 
 
4 Frequently 
 
 
 
7. a. On a scale of 1-10, with 10 being perfectly normal and 1 being near death, how would rate yourself? 
 
 1 
 2 
 3 
 4 
 5 
 6 
 7 
 8 
 9 
 10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Form Completed by: _________________________________ 

Visit: BL   6M   12M 
 
Date: __ __ / __ __ / __ __ __ 
__ 
Time: __ __ : __ __ AM   PM 
 
Study ID#: __ __ __ __ 
 
 
Form Completed by: _________________________________ Investigator’s Signature: _________________________________ 
 
SCAN-MP – Electrocardiogram v4.0 
 
 
 
 
 
 
 
 
Page 1 of 1 
ELECTROCARDIOGRAM 
Quantitative 
Ventricular Rate(bpm) 
________ 
 Total QRS Voltage (mm) ________ 
PR Interval (msec) 
________ 
 Low QRS Voltage 
 Yes  No 
QRS Axis (degrees) 
________ 
 QT Interval (msec) 
________ 
QRS Duration (msec) 
________ 
 QTc Interval (msec) 
________ 
SV1 + RV5 or V6 (mm) 
________ 
  
 
 
  
Overall Assessment 
Rhythm 
 Ventricular Conduction Defect  Yes  No 
 Sinus Rhythm 
 Atrial Fibrillation 
 If yes,  Left Bundle Branch Block 
 Other, specify: __________________________ 
  
 Incomplete Left Bundle Branch Block 
Electrical Pacing on ECG 
 Yes  No 
  
 Left Anterior Hemiblock 
If yes,  Atrial Pacing 
  
 Left Posterior Hemiblock 
 
 Ventricular Pacing 
  
 Right Bundle Branch Block 
 
 Atrial Ventricular Pacing 
  
 Incomplete Right Bundle Branch Block 
ST or T-wave changes 
 Yes  No 
  
 Intraventricular Conduction Delay 
If yes, specify reason: 
 Infarct pattern/Poor R-wave 
progression 
 Yes  No 
A-V Block 
 Yes  No 
 If yes, infarct pattern is observed in this locations: 
If yes,  1st degree 
  
 Anteroseptal 
 
 2nd degree, Type I 
 
 
 Anterior 
 
 2nd degree, Type II 
 
 
 Anterolateral 
 
 3rd degree heart block 
 
 
 Lateral 
 
 Other, specify: ___________________ 
 
 
 Inferior 
 
 
 
 
 Other, specify: ___________________ 

Visit: 
BL  
6M  
12M   
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – SPPB v4.0 
 
 
 
 
 
 
 
 
 
 
Page 1 of 2 
SHORT PHYSICAL PERFORMANCE BATTERY (SPPB) 
1. Balance Tests 
a. Side-by-Side Stand 
If not attempted, select reason: 
1 Tried but unable 
2 Participant could not hold position 
       unassisted 
3 Not attempted, you felt unsafe 
4 Not attempted, participant felt unsafe 
5 Participant unable to understand 
       instructions 
6 Other (specify): ___________________ 
7 Participant refused 
 Held for 10 s 
1 point 
 Not held for 10 s 
 Time: __ . __ __ s 
0 points, go to #2 
 Not attempted 
b. Semi-Tandem Stand 
 Held for 10 s 
1 point 
 Not held for 10 s 
 Time: __ . __ __ s 
0 points, go to #2 
 Not attempted 
 
c. Tandem Stand 
 Held for 10 s 
2 point 
 Held for 3 to 9.99 s 
1 point 
 Held for < than 3 s 
0 points 
 Not attempted 
d. Balance Ordinal Score: ___ (sum points) 
 
 
2. Gait Speed Test 
a. Test #1 
If not attempted, select reason: 
1 Tried but unable 
2 Participant could not walk unassisted 
3 Not attempted, you felt unsafe 
4 Not attempted, participant felt unsafe 
5 Participant unable to understand 
       instructions 
6 Other (specify): ___________________ 
7 Participant refused 
Time for 4-meter: __ __ . __ __ s 
b. Test #2 
Time for 4-meter: __ __ . __ __ s 
c. Walking aid 
 None            Cane            Walker 
d. Record best of the two times 
Best time: __ __ . __ __ s 

Visit: 
BL  
6M  
12M   
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – SPPB v4.0 
 
 
 
 
 
 
 
 
 
 
Page 2 of 2 
 
 
e. Gait ordinal score: ___ 
 
0 Could not do 
 
1 >8.70 s 
 
2 6.21-8.70 s 
 
3 4.82-6.20 s 
 
4 <4.82 s 
 
 
 
3. Repeated Chair Stand Test 
a. Safe to stand five times? 
If not attempted, select reason: 
1 Tried but unable 
2 Participant could not stand unassisted 
3 Not attempted, you felt unsafe 
4 Not attempted, participant felt unsafe 
5 Participant unable to understand 
       instructions 
6 Other (specify): ___________________ 
7 Participant refused 
 Yes              No            
b. If five stands done, record time: 
Time to complete five stands: __ __ . __ __ s 
c. Chair stand ordinal score: ___ 
0 Unable to complete 5 chair stands or 
       completes stands in >60 s 
1 If chair stand time is ≥16.70 s and ≤60 s 
2 If chair stand time is ≥13.70 s and <16.70 s 
 
3 If chair stand time is ≥11.20 s and <13.70 s 
 
4 if chair stand time is <11.20 s 
 
 
 
4. Total Score 
Points: ____ (sum of scores above) 
 
 
 
 
 
 
 
Form Completed by: _________________________________ 

Visit: 
BL  
6M  
12M   
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
 
Form Completed by: _________________________________ 
 
SCAN-MP – Six-Minute Walk Test v4.0 
 
 
 
 
 
 
 
 
Page 1 of 1 
SIX-MINUTE WALK TEST 
PROMPT: “The object of this test is to walk as far as possible for 6 minutes. You will walk back and forth in this 
hallway. You will probably get out of breath or become exhausted. You are permitted to slow down, to stop, 
and to rest as necessary. You may lean against the wall while resting, but resume walking as soon as you are 
able. You will be walking back and forth around the cones. You should pivot briskly around the cones and 
continue back the other way without hesitation.” 
Answer any questions the participant may have. 
PROMPT: “Are you ready to do that? Remember that the object is to walk AS FAR AS POSSIBLE for 6 
minutes, but don’t run or jog. Start now, or whenever you are ready.” 
1. Is participant using an assistive device? 
 No 
 Yes 
If “Yes”… 
 Cane  Walker 
2. Supplemental oxygen during the test? 
 No 
 Yes 
3. Measurements 
 
 
 
 
 
 
Baseline 
End of Test 
 
 
Time 
__ __:__ __ 
__ __:__ __ 
 
 
Heart Rate (bpm) 
__ __ __ 
__ __ __ 
 
 
SpO2% 
__ __ __  
__ __ __ 
 
 
Borg Scale 
 
 
 
 
Dyspnea 
__ __ 
__ __ 
 
 
Fatigue 
__ __ 
__ __ 
 
4. Stopped or paused before 6 minutes? 
 No 
 Yes 
Reason: ____________________________________ 
5. Symptoms at end of exercise (select all that apply): 
 Angina 
 Dizziness 
 Hip pain 
 Leg pain 
 Calf pain 
 Other (specify): _________________________________ 
6. Total distance walked in 6 minutes: __ __ __ meters 
 

Visit: 
BL  
6M  
12M   
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – KCCQ v4.0 
 
 
 
 
 
 
 
 
 
 
Page 1 of 3 
THE KANSAS CITY CARDIOMYOPATHY QUESTIONNAIRE (KCCQ) 
 
The following questions refer to your heart failure and how it may affect your life. Please read and complete 
the following questions. There are no right or wrong answers. Please mark the answer that best applies to you. 
 
1. Heart failure affects different people in different ways. Some feel shortness of breath while others feel 
fatigue. Please indicate how much you are limited by heart failure (shortness of breath or fatigue) in 
your ability to do the following activities over the past 2 weeks. 
Please place an X in one box on each line 
Activity 
Extremely 
Limited 
Quite a 
bit 
Limited 
Moderately 
Limited 
Slightly 
Limited 
Not at all 
Limited 
Limited for 
other reasons 
or did not do 
the activity 
Dressing yourself 
 
 
 
 
 
 
Showering/Bathing 
 
 
 
 
 
 
Walking 1 block on 
level ground 
 
 
 
 
 
 
Doing yardwork, 
housework or carrying 
groceries 
 
 
 
 
 
 
Climbing a flight of 
stairs without stopping 
 
 
 
 
 
 
Hurrying or jogging 
(as if to catch a bus) 
 
 
 
 
 
 
2. Compared with 2 weeks ago, have your symptoms of heart failure (shortness of breath, fatigue or 
ankle swelling) changed? 
My symptoms of heart failure have become… 
Much worse 
 
Slightly worse 
 
Not changed 
 
Slightly better 
 
Much better 
 
I’ve had no 
symptoms over 
the last 2 
weeks 
 
3. Over the past 2 weeks, how many times did you have swelling in your feet, ankles or legs when you 
woke up in the morning? 
Every morning 
 
3 or more times a 
week, but not every 
day 
 
1–2 times a week 
 
Less than once a 
week 
 
Never over the 
past 2 weeks 
 
 
 

Visit: 
BL  
6M  
12M   
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – KCCQ v4.0 
 
 
 
 
 
 
 
 
 
 
Page 2 of 3 
4. Over the past 2 weeks, how much has swelling in your feet, ankles or legs bothered you? 
It has been… 
Extremely 
bothersome 
 
Quite a bit 
bothersome 
 
Moderately 
bothersome 
 
Slightly 
bothersome 
 
Not at all 
bothersome 
 
I’ve had no 
swelling 
 
5. Over the past 2 weeks, on average, how many times has fatigue limited your ability to do what you 
want? 
All of the 
time 
 
Several 
times per 
day 
 
At least once 
a day 
 
3 or more 
times per 
week but not 
every day 
 
1–2 times 
per week 
 
Less than 
once a week 
 
Never over 
the past 2 
weeks 
 
6. Over the past 2 weeks, how much has your fatigue bothered you? 
It has been… 
Extremely 
bothersome 
 
Quite a bit 
bothersome 
 
Moderately 
bothersome 
 
Slightly 
bothersome 
 
Not at all 
bothersome 
 
I’ve had no 
fatigue 
 
7. Over the past 2 weeks, on average, how many times has shortness of breath limited your ability to do 
what you wanted? 
All of the 
time 
 
Several 
times per 
day 
 
At least once 
a day 
 
3 or more 
times per 
week but not 
every day 
 
1–2 times 
per week 
 
Less than 
once a week 
 
Never over 
the past 2 
weeks 
 
8. Over the past 2 weeks, how much has your shortness of breath bothered you? 
It has been… 
Extremely 
bothersome 
 
Quite a bit 
bothersome 
 
Moderately 
bothersome 
 
Slightly 
bothersome 
 
Not at all 
bothersome 
 
I’ve had no 
shortness of 
breath 
 
9. Over the past 2 weeks, on average, how many times have you been forced to sleep sitting up in a chair 
or with at least 3 pillows to prop you up because of shortness of breath? 
Every night 
 
3 or more times a 
week, but not every 
day 
 
1–2 times a week 
 
Less than once a 
week 
 
Never over the past 
2 weeks 
 
10. Heart failure symptoms can worsen for a number of reasons. How sure are you that you know what to 
do, or whom to call, if your heart failure gets worse? 
 
Not at all sure 
 
Not very sure 
 
Somewhat sure 
 
Mostly sure 
 
Completely sure 
 

Visit: 
BL  
6M  
12M   
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – KCCQ v4.0 
 
 
 
 
 
 
 
 
 
 
Page 3 of 3 
11. How well do you understand what things you are able to do to keep your heart failure symptoms from 
getting worse? (for example, weighing yourself, eating a low salt diet, etc.) 
Do not understand 
at all 
 
Do not understand 
very well 
 
Somewhat 
understand 
 
Mostly understand 
 
Completely 
understand 
 
12. Over the past 2 weeks, how much has your heart failure limited your enjoyment of life? 
It has extremely 
limited my 
enjoyment of life 
 
It has limited my 
enjoyment of life 
quite a bit 
 
It has moderately 
limited my 
enjoyment of life 
 
It has slightly 
limited my 
enjoyment of life 
 
It has not limited 
my enjoyment of 
life at all 
 
13. If you had to spend the rest of your life with your heart failure the way it is right now, how would you 
feel about this? 
Not at all satisfied 
 
Mostly dissatisfied 
 
Somewhat satisfied 
 
Mostly satisfied 
 
Completely 
satisfied 
 
14. Over the past 2 weeks, how often have you felt discouraged or down in the dumps because of your 
heart failure? 
I felt that way all of 
the time 
 
I felt that way most 
of the time 
 
I occasionally felt 
that way 
 
I rarely felt that 
way 
 
I never felt that 
way 
 
15. How much does your heart failure affect your lifestyle? Please indicate how your heart failure may 
have limited your participation in the following activities over the past 2 weeks. 
Please place an X in one box on each line 
Activity 
Severely 
limited 
Limited 
quite a 
bit 
Moderately 
limited 
Slightly 
limited 
Did not 
limit at all 
Does not 
apply or did 
not do for 
other reasons 
Hobbies, recreational 
activities 
 
 
 
 
 
 
Working or doing 
household chores 
 
 
 
 
 
 
Visiting family or friends 
out of your home 
 
 
 
 
 
 
Intimate relationships 
with loved ones 
 
 
 
 
 
 
 
 
 
 
 
 
 
Form Completed by: _________________________________ 

Visit: 
BL  
6M  
12M   
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – SF-12v2 v4.0  
 
 
 
 
 
 
 
 
 
Page 1 of 2 
12-ITEM SHORT FORM SURVEY (SF-12v2TM) 
 
This survey asks for your views about your health. This information will help you keep track of how you feel 
and how well you are able to do your usual activities. Answer every question by selecting the answer as 
indicated. If you are unsure about how to answer a question, please give the best answer you can. 
1. In general, would you say your health is: 
Excellent 
1 
Very good 
2 
Good 
3 
Fair 
4 
Poor 
5 
2. The following questions are about activities you might do during a typical day. Does your health now 
limit you in these activities? If so, how much? 
 
Yes, limited 
a lot 
Yes, limited 
a little 
No, not 
limited at all 
a. Moderate activities, such as moving a table, pushing 
a vacuum cleaner, bowling, or playing golf 
1 
2 
3 
b. Climbing several flights of stairs 
1 
2 
3 
3. During the past 4 weeks, how much of the time have you had any of the following problems with your 
work or other regular daily activities as a result of your physical health? 
 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
a. Accomplished less than you 
would like 
1 
2 
3 
4 
5 
b. Were limited in the kind of work 
or other activities 
1 
2 
3 
4 
5 
4. During the past 4 weeks, how much of the time have you had any of the following problems with your 
work or other regular daily activities as a result of any emotional problems (such as feeling depressed or 
anxious)? 
 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
a. Accomplished less than you would like 
1 
2 
3 
4 
5 
b. Did work or other activities less carefully 
than usual 
1 
2 
3 
4 
5 
5. During the past 4 weeks, how much did pain interfere with your normal work (including both work 
outside the home and housework)? 
Not at all 
1 
A little bit 
2 
Moderately 
3 
Quite a bit 
4 
Extremely 
5 

Visit: 
BL  
6M  
12M   
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – SF-12v2 v4.0  
 
 
 
 
 
 
 
 
 
Page 2 of 2 
6. These questions are about how you feel and how things have been with you during the past 4 weeks. 
For each question, please give the one answer that comes closest to the way you have been feeling. 
How much of the time during the past 4 weeks… 
 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
a. Have you felt calm and peaceful? 
1 
2 
3 
4 
5 
b. Did you have a lot of energy? 
1 
2 
3 
4 
5 
c. Have you felt downhearted and 
depressed? 
1 
2 
3 
4 
5 
7. During the past 4 weeks, how much of the time has our physical health or emotional problems interfered 
with your social activities (like visiting friends, relatives, etc.)? 
All of the time 
1 
Most of the time 
2 
Some of the time 
3 
A little of the time 
4 
None of the time 
5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Form Completed by: _________________________________ 

Visit: BL  
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – Health Literacy v4.0 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
 
HEALTH LITERACY 
 
Read to subject: 
“This information is on the back of a container of a pint of ice cream.” 
Questions 
 
 
Answer Correct? 
 
Yes 
No 
1. If you eat the entire container, how many calories will you eat? 
Answer  1,000 is the correct answer 
 
 
 
 
2. If you are allowed to eat 60 g of carbohydrates as a snack, how much ice 
cream could you have? 
Answer Any of the following is correct: 
 1 cup (or any amount up to 1 cup) 
 Half the container 
Note: If patient answers “2 servings,” ask “How much ice cream 
would that be if you were to measure it into a bowl?” 
 
 
 
 
3. Your doctor advises you to reduce the amount of saturated fat in your diet. 
You usually have 42 g of saturated fat each day, which includes 1 serving of 
ice cream. If you stop eating ice cream, how many grams of saturated fat 
would you be consuming each day? 
Answer 33 is the only correct answer 
 
 
 
 
 
 
 
 
4. If you usually eat 2500 calories in a day, what percentage of your daily value 
of calories will you be eating if you eat one serving? 
Answer 10% is the only correct answer 
 
 
 
 
Pretend that you are allergic to the following substances: 
Penicillin, peanuts, latex gloves, and bee stings. 
 
 
5. Is it safe for you to eat this ice cream? 
Answer  No 
 
 
 
 
6. (Ask only if patient responds “no” to question 5): Why not? 
Answer Because it has peanut oil. 
 
 
 
 
Total Correct 
______ 
 

Visit: BL  
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – Trust v4.0 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
 
TRUST 
 
 
Strongly 
Disagree 
Disagree 
Neutral 
Agree 
Strongly 
Agree 
1. I doubt that my doctor really cares about 
me as a person. 
 
 
 
 
 
2. My doctor is usually considerate of my 
needs and puts them first. 
 
 
 
 
 
3. I trust my doctor so much I always try to 
follow his/her advice. 
 
 
 
 
 
4. If my doctor tells me something is so, then 
it must be true. 
 
 
 
 
 
5. I sometimes distrust my doctor’s opinion 
and would like a second one. 
 
 
 
 
 
6. I trust my doctor’s judgments about my 
medical care. 
 
 
 
 
 
7. I feel my doctor does not do everything 
he/she should for my medical care. 
 
 
 
 
 
8. I trust my doctor to put my medical needs 
above all other considerations when 
treating my medical problems.  
 
 
 
 
 
9. My doctor is a real expert in taking care of 
medical problems like mine. 
 
 
 
 
 
10. I trust my doctor to tell me if a mistake was 
made about my treatment. 
 
 
 
 
 
11. I sometimes worry that my doctor may not 
keep the information we discuss totally 
private.  
 
 
 
 
 

Visit: BL  
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – Perceived Discrimination v4.0 
 
 
 
 
 
 
 
 
Page 1 of 1 
 
PERCEIVED DISCRIMINATION 
 
Everyday Discrimination Scale (Short Version) 
In your day-to-day life how often have any of the following things happened to you? 
 
Almost 
everyday 
At least 
once a 
week 
A few 
times a 
month 
A few 
times a 
year 
Less than 
once a 
year 
Never 
1. You are treated with less 
courtesy or respect than 
other people. 
 
 
 
 
 
 
2. You receive poorer 
service than other people 
at restaurants or stores. 
 
 
 
 
 
 
3. People act as if they 
think you are not smart. 
 
 
 
 
 
 
4. People act as if they are 
afraid of you. 
 
 
 
 
 
 
5. You are threatened or 
harassed. 
 
 
 
 
 
 
 
Follow-up Question (Asked only of those answering “A few times a year” or more frequently to at least one 
question.): What do you think is the main reason for these experiences? (check more than one if 
volunteered). 
Recommended options: 
Other possible categories to consider: 
1.  Your Ancestry or National Origins 
1.  A physical disability 
2.  Your Gender 
2.  Your shade of skin color 
3.  Your Race 
3.  Your tribe 
4.  Your Age 
4.  Other (specify):_____________________ 
5.  Your Religion 
 
6.  Your Height 
 
7.  Your Weight 
 
8.  Some other Aspect of Your Physical Appearance 
 
9.  Your Sexual Orientation 
 
10.  Your Education or Income Level 
 

Visit: BL  
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – English Proficiency v4.0 
 
 
 
 
 
 
 
 
Page 1 of 1 
 
ENGLISH PROFICIENCY 
 
 
Poor 
Fair 
Good 
Excellent 
1. How well do you speak English 
 
 
 
 
2. How well do you write English 
 
 
 
 
3. How well do you read English 
 
 
 
 

Visit: BL   12M  
Date: __ __ / __ __ / __ __ __ 
__ 
Time: __ __ : __ __ AM   PM 
 
Study ID#: __ __ __ __ 
 
 
Form Completed by: _________________________________ Investigator’s Signature: _________________________________ 
 
SCAN-MP – Echocardiogram v4.0  
 
 
 
 
 
 
 
 
Page 1 of 1 
ECHOCARDIOGRAM
Dimensions 
Value 
LV End Dias. Internal Dimension (cm) 
 
LV End Sys. Internal Dimension (cm) 
 
LVOT Dimension (cm) 
 
Left Atrial Diameter (cm) 
 
Inferior Vena Cava (cm) 
 
IVC Collapse >50% 
 Yes     No 
Volume / Area 
Value 
LV End-Diastolic Volume (ml) 
(via Simpson's, Devereux and Bi-Plane) 
 
LV End-Systolic Volume (ml) 
(via Simpson's, Devereux and Bi-Plane) 
 
LV Stroke Volume (ml) 
 
LV Ejection Fraction (%) 
 
Cardiac Output (l/min) 
 
LA Volume (ml) 
(via Bi-Plane) 
 
RA Volume (ml) 
(via Bi-Plane) 
 
RV EDA (cm2) 
 
RV ESA (cm2) 
 
RV FAC (%) 
 
Mass / Thickness 
Value 
LV Myocardial Mass End Diastole 
(via Simpson's, Devereux and Bi-Plane) 
 
LV Myocardial Mass End Systole 
(via Simpson's, Devereux and Bi-Plane) 
 
Intraventricular Septal Thickness 
(via 2D) 
 
Posterior Wall Thickness 
(via 2D) 
 
RV Wall Thickness 
(via 2D) 
 
LV Wall Thickness at Mid-Cavity 
(via 2D) 
 
Cardiac Valves 
 
Regurgitation 
 
Normal 
Mild 
Moderate 
Severe 
Aortic 
 
 
 
 
Mitral 
 
 
 
 
Pulmonic 
 
 
 
 
Tricuspid 
 
 
 
 
Wall motion assessment 
 Normal 
 Global hypokinesis 
 Regional wall motion abnormalities 
Abnormal segments: 
 
 
 
Hemodynamic Variables 
Value 
AV Velocity Time Integral (cm) 
(area under curve traced in CW) 
 
Isovolumetric Relaxation Time 
(sec - measured from LVOT in PW) 
 
Isovolumetric Contraction Time 
(sec - measured from LVOT in PW) 
 
Aortic Ejection Time (sec) 
 
LVPEP (sec) 
 
MV Peak E Wave Velocity (cm/sec) 
 
MV Peak A Wave Velocity (cm/sec) 
 
Mitral E/A Ratio 
 
Mitral Deceleration Time (sec) 
 
Mitral Inflow Deceleration Slope 
 
Mitral Wave A Duration (sec) 
 
TV Regurgitant Jet Velocity (cm/sec) 
 
TV Max Pressure Gradient (mmHg) 
 
TV Excursion – TAPSE (cm) 
 
Tissue Doppler 
Value 
MV Lateral Velocity (cm/sec) 
 
MV Septal Velocity (cm/sec) 
 
TV Annular Velocity (cm/sec) 
 
Strain 
Value 
Global Longitudinal Strain 
 
Average Apical Segment Strain 
 
Average Mid-Segment Strain 
 
Average Basal Segment Strain 
 
Incidental Findings 
 
 
 
 
 
 
 
 

Site: BU   Milstein  
 
Visit: BL  
Date of Visit: __ __ / __ __ / __ __ __ __ 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________  
 
SCAN-MP – Cardiac Amyloid Scintigraphy Imaging Sheet v4.0  
 
 
 
 
 
Page 1 of 1 
99mTc-PYP CARDIAC AMYLOID SCINTIGRAPHY Imaging Sheet
Vital signs 
Time collected: __ __ : __ __ (24-hour clock) 
(To be collected before dosing) 
Position:     Sitting    Supine 
Systolic blood pressure: __ __ __ mmHg 
Diastolic blood pressure: __ __ __ mmHg 
Heart rate: __ __ __ bpm 
 
Injection Details 
 99mTc-PYP           99mTc-HMDP 
Injectate lot number: ________________ 
Assay date: __ __ / __ __ / __ __ __ __ (mm/dd/yyyy) 
Assay time: __ __ : __ __ (24-hour clock) 
Assay activity: ________ mCi 
Injection time: __ __ : __ __ (24-hour clock) 
Injection site: 
 Antecubital 
 Hand 
 Other, specify: ________________ 
Residual time: __ __ : __ __ (24-hour clock) 
Residual activity: ________ mCi 
Total injected activity: ________ mCi 
 
Planar Imaging Details 
Imaging start time: __ __ : __ __ (24-hour clock) 
Imaging stop time: __ __ : __ __ (24-hour clock) 
Time between injection and acquisition: (ideally 3 hrs) 
__ __ : __ __ (hh:mm) 
Image duration:  ____________ counts 
(750,000 minimum counts) 
 
 
 
SPECT/CT Imaging Details (if applicable) 
Was SPECT/CT imaging performed?      Yes    
No 
Imaging start time: __ __ : __ __ (24-hour clock) 
Imaging stop time: __ __ : __ __ (24-hour clock) 
Time between injection and acquisition: 
__ __ : __ __ (hh:mm) 
Imaging protocol: 
 SPECT 
 Gated SPECT 
 Gated SPECT/CT 
Type of scan: CTAC scan 
Applied to: Rest 
Tube voltage (kV): 120 
Tube current (mAs): _____ 
Radiation dose (DLP): _____ 
Adverse Reactions (AR) 
Any AR to radiotracer injection?      Yes    No  
If ‘Yes’, please check all that apply: 
 Flushing 
 Itching 
 Hypotension  Skin rash 
 Fever 
 Chest pain 
 Chills 
 Palpitations 
 Nausea 
 Tachycardia 
 Vomiting 
 Shortness of breath 
 Dizziness 
 Other (specify): ___________ 
 
Difficulties with Scan 
Please note any difficulties in obtaining the scan. For example, 
difficulty positioning the participant, participant motion, etc. and 
any action taken to correct it. 
 
 
 
 

Site: BU   CUMC  
 
 
Visit: BL  
Date of Visit: __ __ / __ __ / __ __ __ __ 
Subject ID: __ __ __ __ 
First Reader     Second Reader     Third Reader  
 
Form Completed by: _________________________________ Investigator’s Signature: _________________________________ 
 
SCAN-MP – Cardiac Amyloid Scintigraphy Findings Sheet v4.0  
 
 
 
 
 
Page 1 of 1 
CARDIAC AMYLOID SCINTIGRAPHY Findings Sheet 
Nuclear Findings 
Planar myocardial radiotracer uptake pattern: 
 Absent 
 Diffuse 
 Focal 
 Focal on diffuse 
Semi-quantitative visual grading of radiotracer 
uptake – based on “Planar” images: 
 Grade 0: no uptake and normal bone uptake 
 Grade 1: uptake less than rib uptake 
 Grade 2: uptake equal to rib uptake 
 Grade 3: uptake greater than rib uptake with 
mild/absent rib uptake 
Was SPECT imaging performed?   Yes    No 
If ‘Yes’: 
Semi-quantitative visual grading of radiotracer 
uptake – based on “Planar” and “SPECT” 
images: 
 Grade 0: no uptake and normal bone uptake 
 Grade 1: uptake less than rib uptake 
 Grade 2: uptake equal to rib uptake 
 Grade 3: uptake greater than rib uptake with 
mild/absent rib uptake 
Quantitative 
interpretation 
of 
radiotracer 
uptake: 
H/CL ratio: __ . __ __ 
If SPECT or SPECT/CT done, blood pool activity: 
 Absent    Minimal    Significant 
 
Technical Findings 
Study difficulties: 
 None 
 Participant motion 
 High background 
 Inadequate count density 
 Dose infiltration 
 Delay in imaging 
 Poor labeling 
 Other, specify: ____________________ 
Artifact Findings 
 
 
 
 
 
Incidental Findings 
(Bone findings, hot spots, pleural or pericardial effusion, etc.) 
 
 
 
 
 
Comments 
 
 
 
 
 
Conclusion 
Overall interpretation: 
 Not suggestive of ATTR 
 Strongly suggestive of ATTR 
 Equivocal for ATTR / Possible early ATTR 
Study quality: 
 Uninterpretable 
 Poor 
 Fair 
 Good 
 Excellent 

Visit: 
6M  
12M   
 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – On-Site Follow-Up v4.0 
 
 
 
 
 
 
 
 
Page 1 of 2 
ON-SITE FOLLOW-UP 
1. Was the study visit conducted? 
 Yes 
 No 
a. If no, did the patient drop out of the study?  Yes 
 No 
If yes, date of drop out: 
__ __ / __ __ / __ __ __ __ 
If yes, provide reason subject dropped out, and go to #2: 
 
 
 
 
 
 
 
 
 
 
b. If no, did the subject die? 
 Yes 
 No 
If yes, date of death: 
__ __ / __ __ / __ __ __ __ 
Is death related to study participation?         Definitely     Possibly     Not related 
If yes, provide description/narrative, and go to #2: 
 
 
 
 
 
 
 
 
 
 
c. If no, provide reason subject missed visit: 
 
 
 
 
 
 
 
 
 
 
 
 

Visit: 
6M  
12M   
 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – On-Site Follow-Up v4.0 
 
 
 
 
 
 
 
 
Page 2 of 2 
 
2. Has the patient been hospitalized? 
 Yes 
 No 
If yes, number of hospitalizations: __ __ 
 
If yes, 
 
 
Reason 
Causality 
Hospital 
Date of 
admission 
Date of 
discharge 
HF 
CVA 
Other 
CVD 
1 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
2 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
3 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
4 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
5 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
3. Was the patient seen in the ER? 
 Yes 
 No 
If yes, number of ER visits: 
__ __ 
 
If yes, 
 
 
Reason 
Causality 
Hospital 
Date of 
admission 
Date of 
discharge 
HF 
CVA Other 
CVD 
1 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
2 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
3 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
4 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
5 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
4. Has the patient had any ambulatory 
procedures/interventions (no overnight stay) 
 Yes 
 No 
If yes, number of procedures 
__ __ 
 
If yes, 
 
 

Visit: 
6M  
12M   
 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – On-Site Follow-Up v4.0 
 
 
 
 
 
 
 
 
Page 3 of 2 
 
 
 
 
Reason 
Causality 
Hospital 
Date of 
procedure 
HF 
CVA Other 
CVD 
1 
 
 
 
 
__ __ / __ __ / __ __ 
2 
 
 
 
 
__ __ / __ __ / __ __ 
3 
 
 
 
 
__ __ / __ __ / __ __ 
4 
 
 
 
 
__ __ / __ __ / __ __ 
5 
 
 
 
 
__ __ / __ __ / __ __ 
5. Has the patient been infected with COVID-19? 
 Yes 
 No 
If yes, date of COVID-19 diagnosis: 
__ __ / __ __ / __ __ __ __ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Visit: 
6M  
12M   
 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
SCAN-MP – On-Site Follow-Up v4.0 
 
 
 
 
 
 
 
 
Page 4 of 2 
 
Form Completed by: _________________________________ Investigator’s Signature: _________________________________

Visit: 
6M  
12M   
 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
 
Form Completed by: _________________________________ Investigator’s Signature: _________________________________ 
 
SCAN-MP – Phone Call Follow-Up v4.0 
 
 
 
 
 
 
 
 
Page 1 of 1 
PHONE CALL FOLLOW-UP 
1. Was any data collected? 
 Yes 
 No 
If yes, 
 Phone 
 Chart review 
 Phone and chart review 
If no, reason:  _______________ 
 
If no, deceased? 
 Yes 
 No 
If yes, date of death: 
__ __ / __ __ / __ __ __ __ 
Is death related to study participation?         Definitely     Possibly     Not related 
Description / Narrative: 
 
 
 
 
2. Has the patient been hospitalized? 
 Yes 
 No 
If yes, number of hospitalizations: __ __ 
 
If yes, 
 
 
Reason 
Causality 
Hospital 
Date of 
admission 
Date of 
discharge 
HF 
CVA 
Other 
CVD 
1 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
2 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
3 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
4 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
5 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
3. Was the patient seen in the ER? 
 Yes 
 No 
If yes, number of ER visits: 
__ __ 
 
If yes, 
 
 
 
 
 

Visit: 
6M  
12M   
 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
Study ID#: __ __ __ __ 
 
Form Completed by: _________________________________ Investigator’s Signature: _________________________________ 
 
SCAN-MP – Phone Call Follow-Up v4.0 
 
 
 
 
 
 
 
 
Page 2 of 1 
Reason 
Causality 
Hospital 
Date of 
admission 
Date of 
discharge 
HF 
CVA 
Other 
CVD 
1 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
2 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
3 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
4 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
5 
 
 
 
 
__ __ / __ __ / __ __ 
__ __ / __ __ / __ __ 
4. Has the patient had any ambulatory 
procedures/interventions (no overnight stay) 
 Yes 
 No 
If yes, number of procedures 
__ __ 
 
If yes, 
 
 
 
 
 
 
Reason 
Causality 
Hospital 
Date of 
procedure 
HF 
CVA 
Other 
CVD 
1 
 
 
 
 
__ __ / __ __ / __ __ 
2 
 
 
 
 
__ __ / __ __ / __ __ 
3 
 
 
 
 
__ __ / __ __ / __ __ 
4 
 
 
 
 
__ __ / __ __ / __ __ 
5 
 
 
 
 
__ __ / __ __ / __ __ 
5. Has the patient been infected with COVID-19? 
 Yes 
 No 
If yes, date of COVID-19 diagnosis: 
__ __ / __ __ / __ __ __ __ 
 

Visit: ALL 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________ Investigator’s Signature: _________________________________ 
 
SCAN-MP – Serious Adverse Event v4.0 
 
 
 
 
 
 
 
 
Page 1 of 5 
SERIOUS ADVERSE EVENT 
Part A. Event Type 
1. Type of adverse experience (check all that apply) 
 Hospitalization or prolongation of hospitalization 
(specify reason: _________________________________________) 
 Persistent or significant disability. Date: __ __ / __ __ / __ __ __ __ 
 Life threatening. Date: __ __ / __ __ / __ __ __ __ 
 ER / Urgent Care Visit (specify reason: __________________________________________) 
 Important medical event that represents significant risk or harm to the participant and may 
require medical or surgical intervention to prevent one of the other outcomes (e.g. hospitalization, 
persistent disability, death). Date: __ __ / __ __ / __ __ __ __ 
(Specify event: ____________________________________________________) 
 Death: SKIP TO PART C 
 
Part B. Nonfatal Events 
2. Was the participant hospitalized overnight for this experience? 
 No (Skip to Question 3) 
 Yes, complete the following: 
Hospital Name: 
_______________________________________________ 
Street Address: 
_______________________________________________ 
City: 
_____________________________ 
State: 
_____________________________ 
Zip Code: 
_______________ 
Date participant entered the hospital: __ __ / __ __ / __ __ __ __    Check here if unknown:  
Date participant left the hospital: __ __ / __ __ / __ __ __ __    Check here if unknown/ongoing:  
3. Did the participant receive treatment for the experience in an ER or Urgent Care without being 
hospitalized overnight? 
 No (Skip to Question 4) 
 Yes, Complete the following: 
Institution: 
_______________________________________________ 
Street Address: 
_______________________________________________ 
City: 
_____________________________ 
State: 
_____________________________ 
Zip Code: 
_______________ 
Date of visit __ __ / __ __ / __ __ __ __    Check here if unknown:  

Visit: ALL 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________ Investigator’s Signature: _________________________________ 
 
SCAN-MP – Serious Adverse Event v4.0 
 
 
 
 
 
 
 
 
Page 2 of 5 
4. Describe this adverse experience. What was the condition or symptoms the participant was having? 
What tests or procedures were performed? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. Describe any relevant history, including pre-existing conditions, medications, etc. Skip to Part D when 
finished. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Visit: ALL 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________ Investigator’s Signature: _________________________________ 
 
SCAN-MP – Serious Adverse Event v4.0 
 
 
 
 
 
 
 
 
Page 3 of 5 
Part C. Fatal Events 
6. Date of death: __ __ / __ __ / __ __ __ __    Check here if unknown:  
7. Where did the death occur? 
 In the hospital 
 In the ER 
 Out of hospital (includes DOA, Rehab. Center, Hospice or Nursing Home; Skip to 10) 
 Unknown (Skip to 10) 
8. Hospital or ER Name:      _______________________________________________ 
Street Address: 
_______________________________________________ 
City: 
_____________________________ 
State: 
_____________________________ 
Zip Code: 
_______________ 
Date participant entered the hospital or ER: __ __ / __ __ / __ __ __ __    Check here if unknown:  
9. For out of hospital death cases, including deaths that occur in an ER, skip to 10. 
For hospital deaths only: describe the reason for the hospitalization, the symptoms the participant was 
having, and conditions treated. Also, any events, procedures, or tests that occurred before the 
participant died. (Skip to Part D when finished). Hospital records may be requested by the Central Study 
Coordinator. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Visit: ALL 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________ Investigator’s Signature: _________________________________ 
 
SCAN-MP – Serious Adverse Event v4.0 
 
 
 
 
 
 
 
 
Page 4 of 5 
10. For out-of hospital death (including those that occur in the ER): list the location (including city and state), 
social setting, and type and duration of symptoms. Specific symptoms of interest include: angina; pain or 
discomfort in the chest, left arm, shoulder or jaw; increased fatigue or tiredness; shortness of breath; 
dizziness; palpitations; paralysis; loss of speech. 
Be as specific as possible when reporting information such as the precise location of death, when the 
patient was last seen alive, who last saw the patient alive, and location of those final sightings in relation to 
the site where the participant died. The Central Study Coordinator may request any information about the 
patient’s treatment during the last six months of life. If you need more space, write on the back of this form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Part D. SAE Summary 
11. Outcomes: Indicate any of the specific following conditions that occurred as part of this experience (mark 
all that apply). 
 Arrhythmia, atrial fibrillation or flutter 
 Heart Attack 
 Stroke or TIA 
 New or worsening Heart Failure/Heart Failure Exacerbation 
 Chest pain (hospitalized only) 
 Kidney Failure / Dialysis 
 GI Bleeding 
 Infection 
 Arrhythmia, Ventricular  
 Amputation of part of leg, including toes, because of poor circulation/gangrene 
 Other problems with heart, brain or circulation (specify: ____________________________) 
 
 

Visit: ALL 
Date of Visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
Subject ID: __ __ __ __ 
 
Form Completed by: _________________________________ Investigator’s Signature: _________________________________ 
 
SCAN-MP – Serious Adverse Event v4.0 
 
 
 
 
 
 
 
 
Page 5 of 5 
12. Was this event caused or worsened by enrollment in the study or any of its procedures? 
 No 
 Possibly 
 Definitely 
If possible or definitely, why? 
_______________________________________________________ 
_______________________________________________________ 
13. Investigator Signature (Indicate when reviewed and approved by Clinic PI) 
Signature: _____________________________________________  Date: __ __ / __ __ / __ __ __ __ 
 

Adverse Events Log 
 
Protocol:  ________________________________________________________________                    IRB #:   ______________________________ 
Principal Investigator:  ______________________________________________________                    Site:  ________________________________ 
Subject ID #:  _____________________________________________________________ 
 
 
 
Copyright © 2011, 2012, 2013, 2017 by Clinical Trials Office, Columbia University 
All Rights Reserved 
Page ______ of _______                                                                                                       Version 2.1 June 2017 
 
 
  
Adverse Event 
(Please use medical 
terminology) 
 
Serious 
Adverse 
Event 
 
Date Site Became 
Aware 
 
Start Date 
 
End Date 
- OR - 
Continuing 
 
Severity 
(Grade) 
 
Relatedness to 
Study 
Participation 
 
Outcome 
 
Report to 
External 
Entities  
(If applicable) 
 
 
PI  
Initial  
&  
Date 
 
 
 No 
 Yes * 
 
* Complete 
SAE Form 
 
____/_____/20____ 
(mm/dd/yyyy) 
 
 PI notified 
 
 
 
____/_____/20____ 
(mm/dd/yyyy) 
 
____/_____/20____ 
(mm/dd/yyyy) 
 
 Continuing 
 
  1 - Mild  
  2 - Moderate  
  3 - Severe 
  4 - Life-threatening 
  5 - Death 
   Definitely  
   Probably 
   Possibly  
   Unlikely 
   Not Related 
   Unknown 
 Recovered/Resolved  
 Recovered/Resolved with Sequelae 
 Not Recovered/Not Resolved 
 Fatal 
 Other (specify): __________ 
 
IRB  
 Yes 
 No 
 
FDA 
 Yes 
 No 
 
Sponsor  
 Yes 
 No 
 
 
 No 
 Yes * 
 
* Complete 
SAE Form 
 
____/_____/20____ 
(mm/dd/yyyy) 
 
 PI notified 
 
 
____/_____/20____ 
(mm/dd/yyyy) 
 
____/_____/20____ 
(mm/dd/yyyy) 
 
 Continuing 
 
  1 - Mild  
  2 - Moderate  
  3 - Severe 
  4 - Life-threatening 
  5 - Death 
   Definitely  
   Probably 
   Possibly  
   Unlikely 
   Not Related 
   Unknown 
 Recovered/Resolved  
 Recovered/Resolved with Sequelae 
 Not Recovered/Not Resolved 
 Fatal 
 Other (specify): __________ 
 
IRB  
 Yes 
 No 
 
FDA 
 Yes 
 No 
 
Sponsor  
 Yes 
 No 
 
 
 No 
 Yes * 
 
* Complete 
SAE Form 
 
____/_____/20____ 
(mm/dd/yyyy) 
 
 PI notified 
 
 
____/_____/20____ 
(mm/dd/yyyy) 
 
____/_____/20____ 
(mm/dd/yyyy) 
 
 Continuing 
 
  1 - Mild  
  2 - Moderate  
  3 - Severe 
  4 - Life-threatening 
  5 - Death 
   Definitely  
   Probably 
   Possibly  
   Unlikely 
   Not Related 
   Unknown 
 Recovered/Resolved  
 Recovered/Resolved with Sequelae 
 Not Recovered/Not Resolved 
 Fatal 
 Other (specify): __________ 
 
IRB  
 Yes 
 No 
 
FDA 
 Yes 
 No 
 
Sponsor  
 Yes 
 No