Myocardial Perfusion Changes Following Optimal Medical Treatment in Symptomatic Hypertrophic Cardiomyopathy
Conditions: Hypertrophic Obstructive Cardiomyopathy \(HOCM\)
Sponsor: Medical University of Vienna

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CV027-1201 
Myocardial perfusion changes following optimal medical treatment in 
symptomatic hypertrophic cardiomyopathy 
(Version 3.0 – July 22nd 2025) 
 
Investigators: 
Christopher Mann, Rodi Tosun, Recep Alan, Andreas A. 
Kammerlander, 
Dietrich 
Beitzke, 
Christian 
Loewe, 
Christian Hengstenberg, Thomas A. Zelniker, Daniel Dalos  
 
Correspondence:    
Daniel Dalos, PD, MD, PhD, FESC   
Department of Internal Medicine II, Division of Cardiology 
Medical University of Vienna 
 
 
 
 
Waehringer Guertel 18-20, 1090 Vienna, Austria 
 
 
 
 
Tel: +43-1-40400-46140  
 
 
 
 
Fax:+43-1-40400-42160 
 
 
 
 
daniel.dalos@meduniwien.ac.at 
 
 

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ABSTRACT 
Background: Microvascular dysfunction is a hallmark of hypertrophic obstructive 
cardiomyopathy (HOCM) and can be visualized non-invasively using cardiac magnetic 
resonance (CMR) perfusion imaging. In parallel, the six-minute walk test (6MWT) is an 
established clinical tool to assess submaximal exercise capacity in patients with 
structural heart disease. Despite its widespread use, the relationship between 
objective changes in myocardial perfusion and functional improvements assessed by 
the 6MWT remains insufficiently explored in patients with HOCM on optimal medical 
therapy (OMT). 
 
Aim:This study aims to evaluate whether changes in functional capacity, measured by 
the 6MWT, correlate with changes in myocardial perfusion reserve (MPR) in HOCM 
patients treated with OMT. 
 
Methods: We will include patients diagnosed with obstructive HCM who previously 
underwent clinically indicated CMR perfusion scans for risk stratification. These 
patients are regularly followed in the HCM outpatient clinic of the Medical University of 
Vienna, where standardized 6MWTs are performed in routine care. Approximately one 
year after the baseline CMR, a follow-up CMR will be conducted to assess changes in 
perfusion parameters. This second CMR is clinically justified for improved individual 
risk stratification as recommended by the 2023 ESC Guidelines on Cardiomyopathies. 
 
The primary objective is to assess the correlation between the change in the walking 
distance in the 6MWT and the change in MPR over a one-year interval. Secondary 
endpoints include changes in myocardial blood flow (MBF) at rest and during 

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pharmacological stress. All assessments will be integrated with clinical, 
echocardiographic, and laboratory evaluations. 

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BACKGROUND 
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder 
and demonstrates substantial heterogeneity in terms of morphology, symptoms, and 
prognosis. In its obstructive form (HOCM), left ventricular outflow tract obstruction 
(LVOTO) leads to exertional dyspnea, chest discomfort, syncope, and reduced quality 
of life. Guideline-directed medical therapy includes beta-blockers and calcium channel 
blockers for symptom relief. In patients who remain symptomatic despite this 
background therapy, mavacamten—a first-in-class myosin inhibitor—may be added to 
further alleviate symptoms and complete optimal medical treatment (OMT).(1,2) 
 
Despite OMT, many HOCM patients remain symptomatic. Microvascular dysfunction 
is increasingly recognized as a key pathophysiological contributor to symptom burden 
and disease progression. This dysfunction may precede or accompany structural 
changes such as myocardial fibrosis. CMR imaging with perfusion mapping allows for 
quantitative assessment of myocardial blood flow and perfusion reserve and has 
become an important tool for risk stratification in HOCM.(3,4) 
 
In parallel, the six-minute walk test (6MWT) is routinely used to evaluate functional 
capacity in heart failure and cardiomyopathy populations. The simplicity, 
reproducibility, and cost-effectiveness of this test make it attractive in both clinical and 
research settings. Nevertheless, limited data exist linking objective imaging markers of 
myocardial perfusion with changes in functional performance under real-world OMT in 
HOCM patients. 

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This study therefore seeks to close this knowledge gap by longitudinally correlating 
perfusion metrics derived from serial CMR imaging with routine 6MWT performance in 
patients receiving guideline-conform medical treatment.  

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HYPOTHESIS AND ENDPOINTS 
We hypothesize that improvements in myocardial perfusion, are correlated with 
changes in exercise capacity measured by the 6MWT in HOCM patients on OMT. 
 
Primary Endpoint  
The primary endpoint will be the correlation between MPR changes and changes in 
the performed distance in 6MWT.  
 
Secondary Endpoints 
Secondary endpoints will be the correlation of MPR changes with NT-proBNP and hs-
Troponin-T.  

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STUDY DESIGN AND INCLUSION/EXCLUSION CRITERIA  
This prospective, single-arm, single-centre observational study will include patients 
from the outpatient department of HCM from the Medical University of Vienna, a tertiary 
referral centre. The study will be performed in accordance with the Declaration of 
Helsinki and no study-related procedure will be performed prior to written-informed 
consent.  
The targeted patient population will be as follows:  
• Age > 18 years  
• Women, men, intersex 
• Mostly Caucasians from the metropolitan area of Vienna, but there are no 
ethnical exclusion criteria 
 
Study periods  
Screening and enrolment period: approximately 12 months  
First patient first visit: approximately August 2025 
Last patient last visit: approximately Q2 2027  
 
 
 

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Inclusion criteria 
• 
Age > 18 years 
• 
Willingness to provide written informed consent  
• Diagnosis of obstructive HCM based on ESC 2023 criteria 
• Planned CMR with myccardial perfusion for clinical purposes 
• Receiving guideline-conform OMT 
• Ability and willingness to undergo follow-up imaging and testing 
• Written informed consent 
 
Exclusion criteria 
• Claustrophobia or other contraindication for CMR imaging 
• Significant coronary artery disease and/or prior stent implantation or coronary 
artery bypass graft surgery  
• History of sudden cardiac arrest or sustained ventricular arrhythmia 12 months 
prior to screening 
• Glomerular filtration rate < 30ml/min/m2 
• Significant hepatic impairment defined as 3x upper limit of normal of 
transaminases, total bilirubin, or alkaline phosphatase; hepatic cirrhosis 
• Known allergy to contrast agent  
• Alternative disease causing hypertrophic cardiomyopathy (e.g. cardiac 
amyloidosis, Morbus Fabry)  
• Pregnant women (and women with childbearing potential with desire for 
pregnancy) 
• Breastfeeding women 
• Unwillingness to comply with the study protocol and its procedures 

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CLINICAL AND LABORATORY ASSESSMENT  
Patients will receive complete clinical assessment including detailed prior history 
taking, assessment of current New York Heart Association (NYHA) functional class, 
medication assessment (including optimal background therapy) and 12-lead 
electrocardiogram as well as complete laboratory assessment including serum levels 
of high-sensitive troponin-T and NT-proBNP. Plasma samples of each patient will be 
taken routinely at baseline and at the timepoint of the second MRI.  
Each patient will routinely undergo HCM genotyping analysis, if not performed at the 
timepoint of study inclusion, to explore a possible influence of the genetic background 
on the study measurements.  
 

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CARDIAC MRI 
Patients will undergo baseline and follow-up CMR perfusion imaging (Siemens Avanto 
Fit 1.5 Tesla) including a vasodilator stress test using regadenoson. Beside LV 
function, LV size, LV mass and LV strain parameters, MBF at rest and stress as well 
as MPR will be recorded in addition to left atrial volume index. CMR will be performed 
at baseline and after approx. 1 year.  
The detailed CMR protocol will be as follows: all CMR studies will be analyzed by an 
experienced radiologist and an experienced, CMR-specialized cardiologist. Image 
analysis will be performed using commercially available software (MR Suite, Medis 
Medical Imaging). Perfusion maps (3 short-axis slices per patient) will be generated 
automatically and inline at the time of the scan. The perfusion sequence will be a dual 
sequence technique whereby there is a low-resolution arterial input function acquisition 
and a high-resolution myocardial perfusion acquisition simultaneously. Perfusion will 
be quantified for each pixel of myocardium, and perfusion maps will be generated 
within 90 seconds of the scan. Each pixel will encode the myocardial blood flow (mL·g-
1·min-1). An artificial intelligence tool (Siemens) will perform automatic segmentation 
of the LV cavity and myocardium. It will use a convolution neural net approach to 
delineate the LV cavity and myocardium, excluding myocardial fat and papillary 
muscles. The global MBF will then be calculated automatically as an average of all 
pixels and global MPR as the ratio of stress to rest MBF. Contoured perfusion maps 

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will subsequently visually be inspected by an observer (blinded to other parameters 
and outcome data) for quality control and will be discarded if errors occur.  
 
SAMPLE SIZE CALCULATION  
This study is designed as a single-center, prospective observational analysis in a 
highly specialized outpatient setting. The estimated sample size is based on the 
expected number of patients with hypertrophic obstructive cardiomyopathy (HOCM) 
who have previously undergone clinically indicated stress cardiac MRI and are 
routinely followed in our tertiary care HCM clinic. Based on clinical experience and 
case volume, we anticipate enrolling approximately 20 patients over a 12-month 
period. While this is a relatively small sample, it reflects the real-world availability of 
eligible individuals at our center and is considered sufficient to explore the association 
between myocardial perfusion changes and functional capacity under optimal medical 
therapy. Given the exploratory nature of this study and the targeted patient population, 
the sample size is deemed appropriate for addressing the primary objective.  
Variables  
Variable 
Timepoint(s) 
Data Source 
Age, Sex 
Baseline 
Medical Record 
HCM Genotyping 
Baseline  
Medical Record 
NYHA Functional Class 
Baseline, Follow-up 
Medical Record 
Medication  
Baseline, Follow-up 
Medical Record 
12-lead ECG 
Baseline, Follow-up 
Medical Record 
NT-proBNP 
Baseline, Follow-up 
Medical Record 
High-sensitivity Troponin-T 
Baseline, Follow-up 
Medical Record 
6-Minute Walk Test (6MWT) 
Baseline, Follow-up 
Medical Record 
Left Ventricular Mass (CMR) 
Baseline, Follow-up 
Imaging Data (PACS, Medis 
Suite) 
Left 
Ventricular 
End-Diastolic 
Volume 
(CMR) 
Baseline, Follow-up 
Imaging Data (PACS, Medis 
Suite) 

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Left Ventricular End-Systolic Volume (CMR) 
Baseline, Follow-up 
Imaging Data (PACS, Medis 
Suite) 
Left Atrial Volume Index (CMR) 
Baseline, Follow-up 
Imaging Data (PACS, Medis 
Suite) 
Global Longitudinal Strain (CMR) 
Baseline, Follow-up 
Imaging Data (PACS, Medis 
Suite) 
Myocardial Blood Flow at Rest (CMR) 
Baseline, Follow-up 
Imaging Data (PACS, Medis 
Suite) 
Myocardial Blood Flow during Stress (CMR) 
Baseline, Follow-up 
Imaging Data (PACS, Medis 
Suite) 
Myocardial Perfusion Reserve (CMR) 
Baseline, Follow-up 
Imaging Data (PACS, Medis 
Suite) 
 
STATISTICAL ANALYSIS 
All statistical analyses will be conducted using R software (R Foundation for Statistical 
Computing, Vienna, Austria). A two-sided p-value <0.05 will be considered statistically 
significant. Continuous variables will be presented as mean ± standard deviation or 
median with interquartile range (IQR), depending on the distribution. Categorical 
variables will be summarized using frequencies and percentages. The Shapiro-Wilk 
test will be used to assess the normality of continuous variables. 
The primary objective of this study is to assess whether changes in MPR are correlated 
with changes in functional capacity, as measured by 6MWT. To address this question, 
we will compute the correlation between the change in MPR and the change in 6MWT 
distance from baseline to follow-up. Depending on the data distribution, either 
Pearson’s correlation coefficient (for normally distributed variables) or Spearman’s 
rank correlation coefficient (for non-normally distributed variables) will be applied. 
Results will be visualized using scatterplots with regression lines. 
Additionally, we will assess the relationship between changes in MPR and changes in 
the cardiac biomarkers NT-proBNP and high-sensitivity Troponin-T using correlation 
analysis. If indicated, we will also employ multivariable linear regression models 
adjusted for age and sex to explore these associations further. Structural cardiac 

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parameters derived from cardiac MRI, such as left ventricular mass, left atrial volume 
index, and myocardial strain, will likewise be compared between timepoints using 
paired tests and visualized using boxplots. 
Given the exploratory nature of all secondary and subgroup analyses, no formal 
correction for multiple testing will be applied. These analyses are intended to generate 
hypotheses and provide descriptive insight beyond the primary research question. The 
primary endpoint is based on a single, pre-specified hypothesis and will therefore not 
be subject to multiplicity adjustment. All secondary endpoints will be clearly labeled as 
exploratory, and statistical inferences drawn from these results will be interpreted with 
appropriate caution. 
 
SCIENTIFIC BACKGROUND 
Christopher Mann is a member of the research group from the outpatient department 
of hypertrophic cardiomyopathy of the Division of Cardiology from the Medical 
University of Vienna, directed by Daniel Dalos.    
 

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REFERENCES 
 
1. 
Maron B. J. Clinical Course and Management of Hypertrophic Cardiomyopathy. 
N. Engl. J. Med. 2018; 379: 655–668. 
2. 
Arbelo E. et al. 2023 ESC Guidelines for the management of cardiomyopathies: 
Developed by the task force on the management of cardiomyopathies of the European 
Society of Cardiology (ESC). Eur. Heart J. 2023: doi:10.1093/eurheartj/ehad194. 
3. 
Joy G. et al. Microstructural and Microvascular Phenotype of Sarcomere 
Mutation Carries and Overt Hypertrophic Cardiomyopathy. Circulation. 2023; 148:808-
818.  
4. 
Zhou W. et al. Association of Myocardial Blood Flow Reserve With Adverse Left 
Ventricular Remodeling in Patients With Aortic Stenosis. The Microvascular Disease 
in Aortic Stenosis (MIDAS) Study. JAMA Cardiol. 2022; 7:93-99. 
5. 
Knott KD.et al. The Prognostic Significance of Quantitative Myocardial 
Perfusion - An Artificial Intelligence–Based Approach Using Perfusion Mapping. 
Circulation. 2020; 141:1282-1291.