Guideline-based Global Approach to the Management of Faints and Falls in a Dedicated Outpatient Facility
Conditions: Syncope, Fall
Sponsor: Istituto Auxologico Italiano

The Faint & Fall Observational Study                                                                              Clinical Investigational Plan 
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Guideline-based global approach to the management of faints and falls in a 
dedicated outpatient facility  
 
The Faint & Fall Study  
 
Clinical Investigation Plan (CIP) 
Clinical coordinating Investigator:   Michele Brignole  
Dipartimento di Scienze Cardiovascolari, Neurologiche e 
Metaboliche, IRCCS Istituto Auxologico Italiano,  
Tel: 320 4391422 
e-mail: mbrignole@outlook.it 
 
Statistical analysis:  
Davide Soranna  
 
Direzione Scientifica 
           IRCCS Istituto Auxologico Italiano 
 
 
 
Version 3 del 7/1/2020 
 

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Table of contents 
1- Background………………………………………………………………………………………………………………    
3 
2- Aim of the study ……………………………………………………………………………………………………….  
3 
3- Study design …………………………………………………………………………………………………………….  
3 
4- Study objectives ………………………………………………………………………………………………………   
5 
5- Sample size ……………………………………………………………………………………………………………..  
5 
6- References ………………………………………………………………………………………………………………  
5 
7- Appendix …………………………………………………………………………………………………………………   
7 
 
 
 
 

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1. Background.  
 
Transient loss of consciousness (or its colloquial synonymous "faint") is a term that encompasses all 
disorders characterized by self-limited loss of consciousness, irrespective of the mechanism. 
Syncope is the most frequent cause of transient loss of consciousness. By including the mechanism 
of unconsciousness, i.e. transient global cerebral hypoperfusion, the current syncope definition of 
the European Society of Cardiology excludes other causes such as epileptic seizures and certain 
common syncope mimics, such as psychogenic pseudosyncope (1). Falls are very frequent in the 
older people. A variety of risk factors, i.e., abnormalities of gait, balance and lower limb joints, 
cognitive status, visual status, environmental hazard and drug interaction predispose patients to fall 
(2). If unwitnessed falls are not due to mechanical slips or trips (i.e. are unexplained or 
nonaccidental), it is likely that the patient experienced a syncopal event and displayed lack of 
awareness for loss of consciousness (1,2). Age-related memory impairment or more established 
forms of cognitive impairment are frequently associated with poor recall and therefore the lack of 
an accurate history of events (the so called “retrograde amnesia”). Management of falls in such 
circumstances is the same as that for syncope. In addition, it has been hypothesized that 
cardiovascular disorders are responsible for up to 77% of patients presenting with a fall related to 
unexplained loss of consciousness (3). Thus, the evaluation of faints and falls frequently overlap in 
older people. Owing to the heterogeneous etiology of faints and falls, their management is by 
necessity multidisciplinary, involving cardiologists, internists, geriatricians, neurologists, 
physiatrists, orthopedics, oculists, etc.  
There is a gap between the best available scientific evidence provided by guidelines on 
syncope (1) and falls (2) and the need for the dissemination of these concepts into clinical practice. 
The multidisciplinary nature of faint and falls is the major barrier to the dissemination of guidelines 
and to a comprehensive management that covers all the aspects of faints and falls.  The absence of 
a systematic global approach to faints and falls incurs higher health and social care costs, 
unnecessary hospitalizations and diagnostic procedures, prolongation of hospital stays, lower 
diagnostic rates, and higher rates of misdiagnoses and symptom recurrence. 
 
2. Aims of the study.  
To assess the effectiveness (adherence) of a patient flow pathway and cost of a guideline-based 
global approach to the management of faints and falls in patients referred to dedicated 
multidisciplinary outpatient facilities. We will considerer the following endpoints: 
 
Primary-endpoint: 
I. Point and interval prevalence estimation of patients with unexplained falls (            ), among 
those who underwent fall diagnostic assessment at initial presentation (           ), and then 
moved to faint pathway for prosecution of diagnostic assessment (Figure 1), and its 
determinants. 
 
 

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Secondary endpoints:  
I. 
Point and interval estimate of the agree proportion between initial presentation and final 
diagnosis in patients initially assigned to faint and those with unexplained falls. 
II. 
Descriptive comparison between patients initially assigned to faint and those with 
unexplained falls in terms of diagnostic assessment and adherence rate to the 
recommendations of the guidelines (see appendix). 
III. 
Descriptive cost analysis of the faint and fall protocol (costs of investigations per patient). 
 
Moreover, all previous analysis will be performed also for predefined age subgroups (≥75, 74-65 and 
64-40 years). 
 
3. Study design  
Prospective observational study  
 
Inclusion criteria 
- Consecutive patients aged ≥40 years referred to the Faint & Fall Clinics for assessment of an 
episode of faint or fall. The possible hospitals to recruit patients are Istituto Auxologico 
Italiano and Ospedale di Careggi, University of Florence. The patients will be recruited from 
the second half of 2020 and the recruitment will continue until to the achievement of the 
sample size (defined below).  
 
Exclusion criteria: 
- Patients with age <40 years 
- Patients with incidental fall 
- Patients with an established diagnosis of syncope  
- Patients in whom syncope and fall are secondary symptoms of severe underlying 
comorbidities (e.g: acute myocardial infarction, pulmonary embolism, acute haemorrage) 
 
A screening log of excluded patients (Faint & Fall Registry) will be collected. 
 
Patients’ flow 
Each included patient will undergo to the faint and fall protocol, to assess the effectiveness of a 
patients’ flow pathways (shown in the figure 1) developed in accordance with the most recent 
guidelines on syncope of the European Society of cardiology (1) and of guidelines on falls of the 
American and British Geriatrics Societies (2). The detailed flow pathway is described in the 
Appendix. 
 
 
 

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Figure 1. Schematic description of the patients’ flow pathways in the Faint & Fall multidisciplinary outpatient 
clinics  
Abbreviations: OI=orthostatic hypotension; PPS=psychogenic pseudosyncope 
 
 
 
4 Sample size 
 
A sample size of 340 produces a two-sided 95% confidence interval with a width equal to 10% when 
the prevalence of unexplained falls is 30% (sample size calculated with software PASS 14 Power 
Analysis 
and 
Sample 
Size 
Software 
(2015). 
NCSS, 
LLC. 
Kaysville, 
Utah, 
USA, 
ncss.com/software/pass.). 
This sample size will allow to calculate an interval estimate of the agree proportion between initial 
presentation and final diagnosis in patients initially assigned to unexplained falls with a width 
varying from 0.12 to 0.19 assuming a prevalence of agree varying from 0.9 to 0.6. Analogously, a 
sample of 100 unexplained faint will guarantee the same coverage.  
 
 
 

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5 Statistical analysis 
 
Continuous data will be summarized by means of mean value and standard deviation (SD) if the 
variable follows a Normal distribution or median and interquartile range in case of non Normal 
distribution. Categorical data will be summarized by means of absolute and relative frequencies.  
For primary endpoint we will calculate the proportion of unexplained fall and its 95% interval 
confidence through normal approximation method. The same calculation will be carried out for the 
agree proportion between initial presentation and final diagnosis in patients initially assigned to 
faint and those with unexplained falls. Finally, to detect the determinants of unexplained falls at 
initial presentation we will apply a linear discriminant analysis [5]. 
 
6 References 
 
1. Brignole M, Moya A, de Lange FJ, et al., ESC guidelines for the diagnosis and management of 
syncope, Eur Heart J. 2018; 39: 1883–1948. 
 
2.Panel on Prevention of Falls in Older Persons. Summary of the updated American Geriatrics 
Society/British Geriatrics Society clinical practice guideline for prevention of falls in older persons. J 
Am Geriatr Soc 2011; 59:148–157. 
 
3. Davies AJ, Kenny RA. Falls presenting to the accident and emergency department: types of 
presentation and risk factor profile. Age Ageing. 1996; 25: 362-366. 
 
4. Daccarett M, Brignole M, Malasana G, Sherwood R, Jatter T, Hamdan M. Journal of Primary Care 
& Community Health 2011; 2: 173-180 
 
5. George C. J. Fernandez. Discriminant Analysis, A Powerful Classification Technique in Data Mining. 
SUGI 27 
 
 
 
 

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7 Appendix 
 
A) Fall assessment 
 
A1. Definitions. 
 
Incidental fall is defined as any fall related to high velocity action or sports, contact or high-risk 
activities, or a state of intoxication.  
 
Accidental fall is defined as any fall due to slipping or tripping. Tripping included stumbling, 
catching feet on objects, stepping into curbs, twisting of ankle or knee joint, becoming tangled up 
in a walker, or falling because the walker or cane hit an object (ie, furniture, doorframe) or part of 
the person (ie, leg, foot, shoe).  
 
Nonaccidental fall is defined as a fall occurring in the absence of the above criteria. A 
nonaccidental fall is further categorized as explained or unexplained depending on whether the 
physician concluded a clear cause-effect relationship between a risk factor or an inherent disease 
and the fall itself. In a patient presenting for fall who has a history of previous syncope/s is likely 
that that the fall was syncopal.  
Remark. If a risk factor or disease is present but the cause-effect relationship with the fall is 
unlikely or uncertain, the fall is considered unexplained (i.e. “syncope likely”) and the patient 
isfurtherly evaluated in the syncope pathway  
 
 
A2. Multifactorial fall risk assessment 
 
Potential risk factors are defined according to the recently published guidelines (2). 
Risk factor for fall are assessed in all patients with accidental and non-accidental falls(primary end-
point). A falls risk assessment is not considered necessary for older persons reporting only a single 
fall without reported or demonstrated difficulty or unsteadiness in walking or standing. 
 
a) Gait, balance, and lower limb joint abnormalities are considered a risk factor if there 
was usage of an assistive device without physical therapy, abnormal muscle strength, diminished 
proprioception, and impaired cortical, cerebellar, or extrapyramidal function, or a known walking 
deviation.  
Gait and balance assessment includes foot and footwear problems. 
The test for gait or balance is the Short Physical Performance Battery (SPPB) (Figure 2). The short 
physical performance battery (SPPB) [Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace 
RB. Lower-extremity function in persons over the age of 70 years as a predictor of subsequent 
disability. N Engl J Med.1995; 332: 556–61] combines a balance test in three positions of 
increasing difficulty, 4-m gait speed and a repeated chair-standing test (Fig. 2). By comparing the 
timings recorded with those obtained in a reference population, the result of each test is 
converted into a score, which ranges from 0 (poor performance) to 4 (optimal performance), so 
that thefinal score of the battery ranges between 0 and 12. 
 
b) Drug interaction. The strongest risk associations occur with psychotropic medications, including 
serotonin reuptake inhibitors, and polypharmacy. Drug interaction is recognized as a risk factor if 

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the patient was taking 9 or more medications, 2 or more medications from the same class (Fick 
DM, Cooper JW, Wade WE, Waller JL, Maclean JR,Beers MH. Updating the Beers criteria for 
potentially inappropriate medication use in older adults: results of a US consensuspanel of experts. 
Arch Intern Med. 2003; 163: 2716-2724).  
The presence of orthostatic hypotension (spontaneous or drug-induced)  requires full 
cardiovascular autonomic assessment (refer to syncope evaluation) 
 
c) Cognitive status is considered to be abnormal if there was impairment in activities of daily living.  
 
d) Visual status is considered a risk factor if bilateral visual acuity was less than20/40 with or 
without corrective lenses, development of cataracts, macular degeneration, glaucoma, and other 
conditions that would suggest an effect on risk of falling 
 
e) Environmental hazards is considered a risk factor if there was inadequate lighting, rugs or loose 
carpets, inadequate bathroom safety equipment, stairs at home, bathroom on a different level of 
the living room, or lack of elevated toilet seat.  
 
 
 
 
Evaluation of functional status
Ungar-Marchionni Eds: Cardiac management  in the frail elderly. Springer 2017 
SC Cardiologia Lavagna 
Cognome:……………………………..
Nome………………………………..….
Data di nascita:…..…………………
Test di Fragilità fisica
(Presenza di fragilità: 
tempo di camminata >5sec)
Gait speed test:………sec
(v.n. <5 sec)
Data:…………………………
Firma…………………………………….   
Test di performance fisica 
Totale punti: …………..
(v.n >10 punti)
Punti….
Punti….
Punti….
Punti….
Punti….
 
 
 
Figure 2. Short Physical Performance Battery (SPPB) test 

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A3. Fall risk assessment in frail patients at risk of fall 
 
- 
BRASS score 
- 
HFRM score 
- 
MORSE score 
 

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A4. Multifactorial interventions 
 
Education and information programs should be considered part of a multifactorial intervention. 
Only the adjusted subset of interventions that target the risk factors that have been identified 
through a fall risk factor assessment are prescribed (secondary end-point): 
 
a) Reduction in medications, particularly psychoactive medications(strong evidence) 
Psychoactive medications (e.g., sedative hypnotics, anxiolytics, antidepressants) and 
antipsychotics (e.g.,new antidepressants or antipsychotics) should be minimized or withdrawn, 
with appropriate tapering if indicated. 
A reduction in the total number of medications or dose of individual medications should be 
pursued. All medications should be reviewed and minimized or withdrawn 
The presence of orthostatic hypotension requires full cardiovascular autonomic assessment 
(refer to syncope pathway for diagnosis and treatment) 
 
b) Adaptation or modification of home environment (strong evidence):Home environment 
assessment and intervention performed by a healthcare professional in order to mitigate 
identified hazards in the home: adequate lighting, rugs or loose carpets, adequate bathroom 
safety equipment, stairs at home, bathroom on a different level of the living room, or elevated 
toilet seat. 
 
c) Exercise, particularly balance, strength, and gait training (strong evidence)prescribed by 
qualified health professionals or fitness instructors 
 
d) Management of foot problems and footwear (weak evidence).Advise to walk with shoes of low 
heel height and high surface contact area 
 
e) Management of visual deficits, especially cataract surgery(strong evidence). Advise not to wear 
multifocal lenses while walking, particularly on stairs (weak evidence). Insufficent evidence for 
other  vision interventions 
 
f) Vitamin D supplement of at least 800 IU per day in patients with proven vitamin D deficiency in 
order to reduce the fracture rate (high evidence) 
 
g) Management of postural  hypotension (spontaneous or drug-induced) (high evidence). Require  
full cardiovascular autonomic assessment (refer to syncope pathway for diagnosis and 
treatment) 
 
Dementia.  There is insufficient evidence to recommend for or against multifactorial or single 
interventions to prevent falls in older persons with known dementia 
 
 
 
 
 

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B) Faint assessment 
 
Patients with unexplained fall perform the same evaluation as for faint 
 
B1. Initial evaluation 
 
To all: 
    - history  
    - physical examination (including standing BP)  
    - standard ECG 
    - echocardiogram (if SHD is suspected) 
 
The initial evalution should be able to classify the patient in one of the following cathegories 
(primary end-point): 
- 
Certain or highly likely diagnosis (if class I diagnostic criteria are met) 
- 
Cardiac likely, to be confirmed by tests 
- 
Cardiac unlikely, reflex or orthostatic hypotension likely to be confirmed by tests 
- 
No diagnosis (unexplained syncope), to be investigated by tests 
- 
Non-syncopal faint 
 
B2. Early evaluation 
In selected cases (when appropriate):  
- basic CV autonomic function tests (if OH or NMS are suspected): 
- 3 min active standing test 
-  Valsalva manoeuvre and deep breathing 
- carotid sinus massage (in pts >40 years) 
- tilt testing 
- ambulatory BP monitoring 
- prolonged ECG home monitoring (if arrhythmia is suspected) 
- blood tests (pO2 & gas analysys, haematocrit & blood  cells count, troponin, d-dimer) 
- exercise test (if syncope had occurred during physical effort) 
 
 
B3. Subsequent evalution 
 
When indicated, in accordnce with the recommendations of ESC guidelines on syncope (secondary 
end-point): 
- Home evideo recording 
- Implantable loop recorder 
- Electrophysiological study 
- Coronary angiography 
 
B4. Faint prevention therapy and follow-up 
When indicated, in accordance with the recommendations of ESC guidelines on syncope 
(secondary end-point) (Figure 3): 

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Treatment of syncope: General principles
Diagnostic evaluation
Unpredictable 
or high-
frequency
Reflex and 
Orthostatic Intolerance 
Unexplained and 
high risk of SCD
Consider
risk/benefit of
ICD therapy
Consider
specific
therapy or 
delayed
treatment
(guided by ECG 
documentation)
Cardiac
i.e., CAD, 
DCM, 
HCM,
ARVC,
Long QT
Brugada S.
Predictable or 
low-frequency
Cardiac 
arrhythmias
Structural 
(cardiac or 
cardiopulmonary)
Education, 
reassurance
avoidance of
triggers
usually
sufficient
Specific
therapy of the 
culprit
arrhythmia
Treatment of
underlying
disease
ESC Guidelines on Syncope – Version 2018
 
 
Figure 3