Managing Congestion in Heart Failure: Pressure- and Volume- Based. A Mechanistic Study in Patients With HFpEF (MAGIC-HF)
Phase: NA
Conditions: Heart Failure With Preserved Ejection Fraction, Remote Monitoring in Heart Failure
Sponsor: Otto-von-Guericke University Magdeburg

 
1 
Study protocol 
 
 
 
Title 
 
 
 
 
Managing Congestion in Heart Failure: 
Pressure- and Volume- based. 
A mechanistic study in patients with HFpEF 
(MAGIC-HF) 
 
 
 
 
 
 
 
 
Version: 17.12.2024 
 
 

 
2 
INDEX: 
1. 
GENERAL INFORMATION ································································· 3 
2. 
SYNOPSIS ······················································································ 4 
3. 
BACKGROUND AND SIENTIFIC RATIONALE ········································ 6 
4. 
OBJECTIVE AND HYPOTHESIS ·························································· 7 
5. 
PRIMARY AND SECONDARY ENDPOINTS ··········································· 8 
6. 
DURATION OF THE STUDY AND THE PLANNED TESTS ························ 8 
7. 
RESEARCH DESIGN & METHODOLOGY ············································· 9 
8. 
PROJECT TIMELINE & FUTURE PLANS ············································ 11 
9. 
PARTICIPATING DEPARTMENT ······················································· 11 
10. 
INFORMATION & INFORMED CONSENT ··········································· 11 
11. 
SAMPLE SIZE AND STATISTICS ······················································· 11 
12. 
STATISTICAL ANALYSIS PLAN (SAP) ················································ 12 
13. 
SAFEGUARD FOR THE PROTECTION OF PATIENT SAFETY AND 
WELFARE ······························································································ 12 
13.1. ETHICAL ASPECTS ········································································ 13 
14. 
FUNDING ······················································································ 13 
15. 
FINAL REPORT & PUBLIATIONS ······················································ 13 
16. 
INSURANCE ·················································································· 13 
17. 
DATA PROTECTION ······································································· 13 
18. 
REFERENCES ··············································································· 15 
 
 
 
 

 
3 
1. GENERAL INFORMATION 
 
Principal Investigator: 
Tarek Bekfani, Associate Professor, MD, MSc (Oxon.), FESC, FHFA 
 
 
Co-Investigators: 
Alexandar Schmeißer, Prof. Dr. med. 
Thomas Rauwolf, PhD 
Birgit Aßmus, Prof. Dr. med. 
Friedrich Köhler, Prof. Dr. med. 
Stefan Störk, Prof. Dr. med. 
Rüdiger C. Braun-Dullaeus, Prof. Dr. med. FESC, FACC 
William T. Abraham, Prof., MD, FACP, FACC, FAHA, FESC, FRCP 
 
Correspondence: 
Department of Internal Medicine, Division of Cardiology, Angiology 
and Intensive Medical Care, University Hospital Magdeburg, Otto-
von-Guericke University, Magdeburg, Germany 
Tel.: 0391 67 14469 
Fax: 0391 67 13202 
E-Mail: tarek.bekfani@med.ovgu.de 
Signatures 
 
Name, Principal Investigator 
Date 
 
 
 
Name, Local PI in Giessen University Hospital 
Date 
 
 
 
 
 
Name, Local PI in DHZC, Charité, Berlin 
Date 
 
 
 
 
Name, Local PI at the University Hospital Wuerzburg 
Date 
 
  
 

 
4 
2. SYNOPSIS 
 
1. Title of study 
 
 
 
Managing Congestion in Heart Failure: Pressure- and Volume- based. 
A mechanistic study in patients with HFpEF (MAGIC-HF) 
 
2. Hypothesis 
 
 
We hypothesize that remote monitoring (RM) in patients with heart failure (HF) with 
preserved (HFpEF) ejection fraction using a smart scale to measure extracellular and 
total amount of water in different segments of the body in parallel to monitoring 
pulmonary pressure improves the management of congestion in patients with HF. This 
leads as a result to an improvement of NT-pro-BNP and renal function. 
 
3. Objective of the 
study 
 
We plan a mechanistic RM-study in patients with HFpEF, who have the indication for 
RM using CardioMEMSTM. Data transmitted from CardioMEMSTM and from the smart 
scale will be monitored on daily basis in order to understand the mechanism of 
changes taking place during the study duration (6 months) in both pulmonary pressure 
and in volume represented as extracellular and total amount of water in the upper and 
lower extremities as well as in the trunk. This should allow us to reach an euvolemic 
state in patients with HF, which is often an unmet need. 
 
4. Background 
 
In patients with heart failure (HF) the absolute number of hospitalizations and the rates 
of HF readmissions is still high with a significant financial burden associated. As a 
result, reducing readmission rates has become a priority in many of the developed 
countries. Currently 25% of patients with HF are readmitted within one month of 
discharge.  
Achieving and maintaining an euvolemic status through managing congestion is a key 
goal in the management of HF. Thus, close observation of, and rapid response to 
changes of early physiological indicators are essential in achieving or maintaining 
euvolemia. Clinical signs and symptoms of cardiac decompensation are preceded by 
an increase in filling pressures and autonomic adaptation. Furthermore, clinical signs 
and symptoms are neither sensitive nor specific for detecting congestion. We have 
shown in a previous study in patients with HF and sleep apnea increased amounts of 
both extracellular and total amounts of water compared to those with HF but without 
sleep apnea. The increased amount of water was not associated with clinical cardiac 
decompensation. We called this clinically pre-congestion. An increased amount of 
water was associated with worse exercise capacity and with an elevated 
apnea/hypopnea index. 
As such, new means and technologies to improve monitoring of such parameters and 
care delivery are urgently required. Novel technologies of telemedicine or RM such as 
CardioMEMSTM (Abbott Laboratories, Chicago, IL, USA), which is a small sensor 
placed in the pulmonary artery to monitor the pulmonary pressure, represent a possible 
solution to the above-mentioned unmet needs in patients with HF. 
 
However, the principle that volume equals pressure has been challenged recently. 
Based on data from CardioMEMSTM and systems enabling estimation of the 
intravascular volume such as blood volume analysis (BVA-100, Daxor Corporation, 
New York, NY, USA), the current approach of HF-Therapy using diuretics to decongest 
these patients appeared not to be always the best decision. The reason is that some 
of those patients with elevated pulmonary pressure (CardioMEMSTM) appeared to be 
euvolemic or hypovolemic. It was postulated that congestion is a result of changes 
occurring in both volume and pressure.  
 
Additionally, severe congestion is supposed to be associated with inflammation, 
mechanical stress, and endothelial dysfunction. Thus, identifying surrogate biomarkers 
for all of these processes in addition to monitoring volume and pressure simultaneously 

 
5 
and continuously for 6 months would help to better understand congestion and its 
management. 
This is indeed an important concept and a clinically relevant question to characterize 
patients in different phenotypes as following: elevated/low pressure with hypervolemic, 
euvolemic or hypovolemic. Managing congestion in patients with HF might be optimally 
achieved by both monitoring pulmonary pressure and volume status.  
 
5. Number of patients 
 
 20 Patients with HFpEF. Dropout 20%. Total number of patients 25 patients. 
 
6. Number of sites  
 
Four sites. 
- Department of Cardiology and Angiology, University Hospital Magdeburg, 
Germany. 
- Department of Cardiology and Angiology, University Hospital Giessen, Germany 
- Department of Cardiology, Deutsches Herzzentrum der Charité, Berlin, Germany 
- Department of Cardiology, University Hospital Wuerzburg, Germany 
 
7. Length of follow-up 
 
The planned follow-up duration is 6 months  
Time from first patient in to last patient out 12 months. 
 
8. Data to be collected 
 
All patients will get following tests at baseline: Echocardiography (left ventricle 
ejection fraction (LVEF), E/e´, left atrial volume index (LAVI), left atrial strain analysis, 
left ventricle mass index (LVMI), tricuspid annular plane systolic excursion (TAPSE), 
right ventricle strain, inferior vena cava IVC), and blood tests: N-terminal pro-b-type 
natriuretic peptide (NT-proBNP), creatinine, glomerular filtrating rate (GFR), soluble 
suppression of tumorigenicity (sST2) as a surrogate of intravascular congestion, 
carbohydrate antigen 125 (CA 125) and bio-adrenomedullin (bio-ADM) as surrogates 
of tissue congestion (extracellular water). Additionally, ALAT, ASAT, complete blood 
count, and hsCRP will be documented. Evaluation of extracellular and total amounts 
of water volume segmentally (arms, legs, trunk) using the smart scale (Body water 
scale InBody, South Korea) as well as pulmonary pressure (CardioMEMSTM) will be 
done at the same time. 
 
We will gather daily data of pulmonary pressure (CardioMEMSTM) and water volume 
using a smart scale. The evaluation of volume will be based on bioelectric impedance 
analysis (BIA).  
 
Following blood tests will be monitored at weeks 2, 6, 12 and at the final visit: 
NT-proBNP, creatinine and GFR, ALAT, ASAT, hemoglobin, hematocrit, hsCRP, sST2, 
CA 125, and bio-ADM.  
 
Tests and investigations at the final visit: Echocardiography (see above), ALAT, ASAT, 
complete blood count, hsCRP, NT-proBNP, creatinine, GFR, sST2, CA 125, and bio-
ADM. 
9. Primary and 
secondary 
Endpoints 
 
Explorative analyses of: 
• 
NT-pro-BNP  
• 
GFR 
• 
The percentage of patients who have elevated pulmonary pressure but 
are hypo- or euvolemic 
 
 
 

 
6 
3. BACKGROUND AND SIENTIFIC RATIONALE 
 
 
The absolute number of HF-hospitalizations and the rates of HF readmission is still 
high with a significant financial burden associated.1 As a result, reducing readmission 
rates has become a priority in many of the developed countries.2,3 Currently 25% of 
patients with HF are readmitted within one month of discharge and 30% of them within 
90 days.4,5  
Achieving and maintaining an euvolemic status through managing congestion is a key 
goal in the management of HF. As a response to the reduced cardiac output, the 
human body attempts to maintain an effective mean arterial pressure through a series 
of compensatory mechanisms. Over-activation of the sympathetic nervous system and 
renin–angiotensin–aldosterone system are among the earliest pathophysiological 
responses6 along with an increased metabolic rate driven by an active inflammatory 
process. Over the course of days to weeks, the body starts to retain salt and water. 
Paired with a decreased vascular compliance due to vasoconstriction, patients at this 
stage retain fluid, increase cardiac filling pressures, increase interstitial pulmonary 
fluid, and lastly increase weight.7 Severe congestion is supposed to be associated with 
inflammation, mechanical stress, and endothelial dysfunction.8  
Thus, close observation of, and rapid response to changes to early patho-physiological 
indicators are essential in achieving and maintaining euvolemia. However, congestion 
as a clinical marker of cardiac decompensation, which is defined clinically as 
peripheral edema (ankle, sacral, scrotal), jugular vein distention, pleural effusion, or 
ascites,9 is preceded by an increase in filling pressures and autonomic adaptation. 
Furthermore, clinical signs and symptoms are neither sensitive nor specific for 
detecting congestion. Additionally, we have shown in a previous study in patients with 
HF and sleep apnea increased amounts of both extracellular and total amounts of 
water compared to those with HF but without sleep apnea. This increased amount of 
water was not associated with overt clinical cardiac decompensation. We called this 
clinically pre-congestion.10 The amount of water was associated with worse exercise 
capacity and with higher values of apnea/hypopnea index. 
As such, new means and technologies to improve monitoring of such parameters and 
care delivery are urgently needed. Novel technologies of telemedicine or remote 
monitoring (RM) such as CardioMEMSTM (Abbott Laboratories, Chicago, IL, USA) 

 
7 
represents a good solution to the above-mentioned unmet needs in patients with 
HF.11,12 Pulmonary artery-pressure-guided management of patients with HF proved to 
reduce morbidity and mortality in this group of patients. However, the principle that 
volume equals pressure was challenged recently. Based on data from CardioMEMSTM 
and systems enabling estimation of the intravascular volume such as blood volume 
analysis (BVA-100, Daxor Corporation, New York, NY, USA), the current approach of 
HF-therapy using diuretics to decongest these patients appeared not to be always the 
best clinical decision. The reason is that some of those patients with elevated 
pulmonary pressure (CardioMEMSTM) appeared to be euvolemic or hypovolemic.13 It 
was postulated that congestion is a result of changes occurring in both volume and 
pressure.  
 
Currently, there is no study that evaluated continuously and simultaneously both 
volume and pressure in patients with HF. This is indeed an important approach and 
clinically relevant question since this might lead to an adjustment of our practice by 
characterizing or phenotyping congested patients into elevated/low pressure with 
hypervolemic, euvolemic or hypovolemic.  Managing congestion in patients with HF 
might be optimally achieved by both monitoring pulmonary pressure and volume 
status. Additionally, using surrogate biomarkers could be very helpful in better 
understanding congestion and its management.  
 
4. OBJECTIVE AND HYPOTHESIS  
 
4.1 
OBJECTIVE OF THE STUDY 
 
We plan a mechanistic RM-study in patients with HF with preserved ejection 
fraction (HFpEF), who have the indication for RM using CardioMEMSTM. Data 
transmitted from CardioMEMSTM and from the smart scale (BWA) will be monitored on 
daily basis in order to understand the mechanism of changes taking place during the 
study duration (6 months) in both pulmonary pressure and in volume represented as 
extracellular and total amount of water in upper and lower extremities as well as in the 
trunk. This should allow us to reach an euvolemic state in patients with HF, which is 
often an unmet need. This is especially true in patients with HFpEF. 
 

 
8 
4.2  
HYPOTHESIS 
 
 
Pulmonary artery pressure-guided management of HF patients through 
CardioMEMSTM is a well-established and evidenced-based method to reduce mortality 
and hospitalization rate for HF. We hypothesize that expanding RM by using a smart 
scale (BWA) to measure extracellular and total amount of water in different body 
compartments would improve the management of congestion in patients with HF. 
Furthermore, the data of our study will lead to a new paradigm characterizing different 
phenotypes of patients with HFpEF with different pressure-volume constellations. By 
adjusting the HF-management accordingly, an improvement of NT-pro-BNP and renal 
function is expected to occur. 
5. PRIMARY AND SECONDARY ENDPOINTS 
 
In this pilot mechanistic study, we are focusing on understanding the pressure-
volume relationship. Thus, our endpoints will be an explorative analysis of: 
• 
NT-pro-BNP  
• 
GFR 
• 
The percentage of patients who have elevated pulmonary pressure but are 
hypo- or euvolemic. 
NT-pro-BNP will be corrected for BMI by reducing 4% per BMI unit over 25 kg/m2. This 
formular was applied similarly in the Guide-HF-trial. 14,15 
 
6. DURATION OF THE STUDY AND THE PLANNED TESTS 
 
The planed follow-up duration is 6 months. Time from first patient in to last patient 
out will be 12 months. 
 
All patients will get following tests at baseline: Echocardiography (left ventricle 
ejection fraction (LVEF), E/e´, left atrial volume index (LAVI), left atrial strain analysis, 
left ventricle mass index (LVMI), tricuspid annular plane systolic excursion (TAPSE), 
right ventricle strain, inferior vena cava IVC), and blood tests: N-terminal pro-b-type 
natriuretic peptide (NT-proBNP), creatinine, glomerular filtrating rate (GFR), soluble 
suppression of tumorigenicity (sST2) as a surrogate of intravascular congestion, 

 
9 
carbohydrate antigen 125 (CA 125) and bio-adrenomedullin (bio-ADM) as surrogates 
of tissue congestion (extracellular water). Additionally, ALAT, ASAT, complete blood 
count, and hsCRP will be documented. Evaluation of extracellular and total amounts 
of water volume segmentally (arms, legs, trunk) using the smart scale (BWA) as well 
as pulmonary pressure (CardioMEMSTM) will be done daily at the same time. 
 
Following blood tests will be monitored at days 14, 42, 90 and at the final visit: NT-
proBNP, creatinine and GFR, hemoglobin, hematocrit, hsCRP, sST2, CA 125, and 
bio-ADM.  
Blood draw will be 20 ml Blood (Serum and EDTA) in each visit.  
 
Tests and investigations at the final visit: Echocardiography (see above), ALAT, 
ASAT, complete blood count, hsCRP, NT-proBNP, creatinine, GFR, sST2, CA 125, and 
bio-ADM. 
 
Bioelectrical-Impedance Analysis (BIA): It is a non-invasive measurement of the 
body composition, i.e. muscle, fat, water. Measurements will be performed in 
standing positions using (Body water scale InBody, South Korea), which is capable 
to measure body amounts of water in different compartment non-invasively, 
reliably, and objectively based on bioelectric impedance (BIA)-technology. Patients 
who have implanted cardiac devices will be excluded.16 
 
 
7. RESEARCH DESIGN & METHODOLOGY 
 
 
7.1 STUDY DESIGN 
 
MAGIC-HF is a streamlined, prospective, mechanistic, non-randomized, study. 
This study will investigate the value of adding volume-based RM to the well-
established pulmonary artery pressure monitoring in patients with HFpEF in 
understanding the volume-pressure relationship. The study will take place in the 
department of cardiology, University Hospital Magdeburg.  
 
7.2 STUDY POPULATION 
 

 
10 
Inclusion criteria:  
1) 18 years of age or older. 
2) Patients with HFpEF hospitalized for acute decompensated heart failure and require 
treatment with intravenous (IV) diuretics.  
3) signed informed consent.  
Exclusion criteria: 
1) Patients admitted with cardiogenic shock and/or those who required inotropic or 
vasopressor support. 
2) had a history of cardiac transplantation or ventricular assist device (VAD) 
implantation.  
3) had any implanted cardiac device (pacemaker, ICD, CRT-D. 
4) had chronic kidney disease with creatinine clearance < 20 ml/min. 
5) had recent acute MI or CABG within 3 months. 
 
Timetable of the study: All participants will undergo a standardized series of 
assessments as shown in table 1. 
 
Table 1: Timetable of the study 
 
 
 
 
 
 
Day 0 
 
daily 
Day 14 
Day 42 
Day 90 
Day 180 
Informed consent 
x 
 
 
 
 
 
Echocardiography 
x 
 
 
 
 
x 
Body 
composition- 
Water assessment 
x 
x 
x 
x 
x 
x 
CardioMEMSTM-
Measurement 
x 
x 
x 
x 
x 
x 
Blood tests 
x 
 
x 
x 
x 
x 

 
11 
8. PROJECT TIMELINE & FUTURE PLANS 
 
We will be able to begin our study in April 2024. We have previous experience with 
an established HF population. We expect to reach full recruitment by the end of 2024. 
Data will be analyzed immediately with focus on presenting initial results in the annual 
meeting of the European society of Cardiology 2025. We expect to have a full analysis 
for manuscript preparations by June 2025.  
 
9. PARTICIPATING DEPARTMENT 
 
Department: Department of Cardiology and Angiology, University Hospital 
Magdeburg 
Telefon-Nummer: 0391 67 14469 
E-Mail: 
tarek.bekfani@med.ovgu.de 
 
10. INFORMATION & INFORMED CONSENT   
 
Subjects will sign an informed consent before any investigation of the designed study 
will be conducted.  
 
11. SAMPLE SIZE AND STATISTICS 
 
There is not enough prior data to calculate the sample size. Our aim primarily is to 
describe the relationship between pressure-volume as part of the management of HF-
management. We suppose that in this pilot study 20 patients should be sufficient to 
understand this relationship and the mechanism beyond it. With expected 20% drop-
out rate, we intend to recruit 25 patients.  
All data and statistics will be reported as mean ± standard deviation (n ± SD) for 
continuous normally distributed data or as median and interquartile range [25–75%] 
for variables that were not normally distributed, respectively. Categorical data will be 
summarized by percentages. Kaplan-Meier analyses with a log-rank test will be used 
for presenting time-to-event data. Daily measurements of CardioMEMSTM and BWA will 

 
12 
be depicted over the study time. A comparison between events represented by 
increased pulmonary pressure and increased volume higher than the defined cut-off 
for each patient respectively will be performed. The Statistical Package for Social 
Sciences software (SPSS 28, IBM, Armonk, USA) will be used for statistical analysis. 
The chi-squared test will be used to look for trend for categorical variables and Kruskal 
Wallis test will be applied for not normally distributed data, respectively. Analysis of 
variance (ANOVA), Pearson’s or Spearman simple regression will be used as 
appropriate. A two-tailed p-value <0.05 indicates statistical significance. 
 
12. STATISTICAL ANALYSIS PLAN (SAP) 
Here is a summary of SAP: 
Exploratory outcomes: NT-pro-BNP, GFR, and the percentage of patients who 
have elevated pulmonary pressure but are hypo- or euvolemic. 
 
General considerations: The intention- to-treat will be applied.  
 
Data presentation: Kaplan Meier curves will be constructed for time-to-event 
analyses. Log rank test will be used to compare between groups.  
 
Missing data handling: To minimize missing data, all measurements will be taken to 
collect all essential data. Still missing data will be dealt with suing a multiple imputation 
model.  
 
13. SAFEGUARD FOR THE PROTECTION OF PATIENT 
SAFETY AND WELFARE  
 
Participation is entirely voluntary and will in no way effect their care. There is no 
direct benefit to the patients except a strong contribution to science. 
Blood samples will be taken during the outpatient visits at low risk. Adverse events will 
be reviewed on a biweekly basis by a cardiologist otherwise not affiliated with this 
proposal. Serious adverse events will be reported to the Institutional Review Board 
within 24 hours. All patient information will be kept absolutely confidential. 

 
13 
13.1. 
ETHICAL ASPECTS 
 
Prior to the start of the study, all required approvals from the local ethic committee 
will be obtained. The Study fulfills all principles of the Declaration of Helsinki and good 
clinical practice and will adhere to the protocol. The study will be registered at 
clinicaltrials.gov. 
 
14. FUNDING  
 
An application for a research grant from Abbott has been submitted. 
 
15. FINAL REPORT & PUBLIATIONS 
 
Data will be analyzed immediately with focus on presenting initial results in the 
annual meeting of the German Society of Cardiology and European Society of 
Cardiology. We expect to have a full analysis for manuscript preparations by June 
2025. A copy of the final report / publications will be submitted to the ethic commission. 
 
16. INSURANCE 
 
In this clinical study, all study participants are covered by the liability insurance of 
the University Hospital Magdeburg A.ö.R.  
 
17. DATA PROTECTION 
 
During the study, medical findings and personal information will be collected from 
you and written down in your personal study file and/or stored electronically in our 
department for Cardiology and Angiology. In accordance with the currently valid data 
protection regulations (EU Data Protection Regulation/DS-GVO, State Data Protection 
of Saxony-Anhalt), the study data will additionally be stored in pseudonymized form, 
evaluated and, if necessary, passed on to other authorized persons. "Pseudonymized" 
means that no details of clear names or complete birth data are used, but only a 

 
14 
number and/or letter code and your personal data are only known to authorized 
persons in the clinic. The data are secured against unauthorized access from outside.  
All data collected during the clinical study shall be published in anonymous form. 
Records and documents relevant to the study (e.g. informed consent forms) will be 
kept in the University Hospital Magdeburg, Department of Cardiology and Angiology 
for at least 15 years. 
Patient records and other original data must be kept for the longest possible period 
provided by Magdeburg University Hospital A.ö.R. (10 years) and secured against 
unauthorized access. 
 
 
 

 
15 
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