Multicenter Prospective Registry of Patients With Hypertrophic Cardiomyopathy
Conditions: Hypertrophic Cardiomyopathy (HCM)
Sponsor: Central State Medical Academy

 
 
Draft v.2  
 
 
 
 
National reGistry of hypeRtrophic 
cArDIomyopathy: regional fEatures,  
geNeTics and course (GRADIENT) 
 
Russian Multicenter Open-label 
Observational Clinical Trial 
 
(Project of the Central State Medical Academy of the Department of 
Presidential Affairs, Almazov National Medical Research Center, and the ESC 
Working Group on Myocardial and Pericardial Diseases) 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
 
ABBREVIATIONS ......................................................................................... 6 
INTRODUCTION ........................................................................................... 7 
2. OBJECTIVE ............................................................................................... 9 
3. STUDY DESIGN AND SELECTION CRITERIA .................................. 10 
3.1 Study type ............................................................................................ 10 
3.2 Inclusion criteria .................................................................................. 10 
3.2.1 HCM Criteria for probands ≥ 18 years based on ECHO or CMR 10 
3.2.2 HCM Criteria for probands/patients with arterial hypertension ... 10 
3.2.3 HCM Criteria for the first-degree relatives ≥ 18 years based on 
ECHO (or CMR) and ECG [21]: ...................................................................... 11 
3.2.4 HCM Criteria for children and adolescents < 18 years................. 11 
3.3 Exclusion criteria ................................................................................. 11 
3.4 Target number of patients .................................................................... 12 
3.5 Sources of HCM patients ..................................................................... 12 
3.6 Stages of study ..................................................................................... 13 
3.6.1 Selection period ............................................................................. 13 
3.6.2 Follow-up ...................................................................................... 13 
3.6.3 Statistics and publications ............................................................. 14 

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3.7 Requirements for investigational site .................................................. 14 
4. STUDY PROCEDURES .......................................................................... 14 
4.1 ENROLLMENT OF PATIENTS ........................................................ 14 
4.1.1 Obtaining of informed consent...................................................... 14 
4.1.2 Obtaining of the clinical data ........................................................ 15 
4.1.3 Instrumental examination .............................................................. 16 
4.1.4 Blood samples collection .............................................................. 17 
4.1.5 Shipment of blood samples for genetic study ............................... 17 
4.2 FOLLOW UP ....................................................................................... 17 
4.3 GENETIC STUDY .............................................................................. 17 
5. ENDPOINTS ............................................................................................. 18 
5.1 Primary endpoint ................................................................................. 18 
5.2 Secondary endpoints ............................................................................ 18 
6. STATISTICS ............................................................................................. 19 
6.1 Data collection ..................................................................................... 19 
6.2 Statistical methods ............................................................................... 19 
6.3 Prognosis .............................................................................................. 20 
6.4 Genome-wide association study (GWAS)........................................... 20 
6.5 Comparison analysis ............................................................................ 21 
6.6 The assessment of examination and treatments .................................. 21 

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6.7 Registration of Patients with transformed diagnosis during follow-up
 .............................................................................................................................. 21 
7. ETHICS ASPECTS ................................................................................... 22 
7.1 Informed consent form ........................................................................ 22 
7.2 Confidentiality ..................................................................................... 22 
8.OWNERSHIP AND FUNDINGS ............................................................. 23 
REFERENCES .............................................................................................. 24 
APPENDICES ............................................................................................... 27 
 
 
 
 

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ABBREVIATIONS 
CAD 
– 
Coronary artery disease 
CMR 
– 
Cardiovascular magnetic resonance 
CRF 
– 
Case report form 
ECG 
– 
Electrocardiogram 
ECHO 
– 
Echocardiogram 
HCM 
– 
Hypertrophic cardiomyopathy 
HF 
– 
Heart failure 
ICD 
– 
Implantable cardioverter-defibrillator 
IVS 
 
Interventricular septum 
LV 
– 
Left ventricular 
SCD 
– 
Sudden cardiac death 
SRT 
– 
Septal reduction therapy 
 
 

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1. INTRODUCTION 
Hypertrophic cardiomyopathy (HCM) is defined as a primary cardiac muscle 
disorder characterized by the development of left ventricular hypertrophy in the 
absence of obvious causes for the observed magnitude of hypertrophy [1]. The 
morphological expression of HCM is confined solely to the heart. Despite the 
success in reducing HCM mortality rates - achieved mostly through the application 
of sudden cardiac death (SCD) risk stratification strategies and interventions for 
SCD prevention [2] - HCM is still associated with: 1) an increased risk of SCD, 
especially in young adults, 2) the progression of heart failure (HF), 3) atrial 
fibrillation (AF), and 4) thromboembolic stroke [3]. All-cause mortality in all age 
cohorts of patients with HCM is still at least twice as high as in same-aged controls 
[4, 5]. 
HCM is the most common inherited cardiac disease. The overall prevalence of 
phenotypically apparent HCM is approximately 1:500 [6], and among those who 
come to medical attention, it is 1:3200 [7]. Significant progress in cardiac imaging 
and increasing availability of genetic analysis suggest a greater number of patients 
with HCM, estimated at 1:200, according to some authors [8]. This means that in 
Russia, with a population of about 140 million people, the number of patients with 
HCM and carriers of pathogenic variants in sarcomere genes is around 700 000, of 
which 280 000 have LV hypertrophy, and 44 000 have a “clinical HCM.”  
The understanding of the genetic architecture of HCM has undergone substantial 
changes over the past 30 years. Initial studies identified sarcomere genes 
containing mutations that explain the Mendelian (monogenic) inheritance of HCM 
[9]. In large segregation studies over the past decade, a few additional non-
sarcomere genes have demonstrated a strong involvement in the development of 
HCM [10, 11]. However, pathogenic mutations associated with HCM genes are 
found in only 60% of patients. Moreover, significant clinical heterogeneity is 
observed among carriers of the same mutation and within members of the same 
family [12], including monozygotic twins [13].  
In recent years, the concept of a more complex genetic architecture of HCM has 
been developed. This includes not only the genes responsible for the primary 
genetic effect but also modifier genes, which contribute to the oligogenic nature of 
inheritance and phenotype formation in genotype-positive patients [14, 15]. 

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The current understanding of the pathogenesis of HCM in patients who do not 
have convincing evidence of a causative genetic defect includes a polygenic trait of 
inherence and phenotype formation under the influence of concomitant diseases, 
such as diastolic arterial hypertension and obesity [15-17]. However, obtaining 
evidence for the modifying role of common genetic variants or environmental 
factors appears even more challenging than identifying new genes. Clearly, large 
case-control GWAS trials in cohorts of patients who meet the clinical criteria for 
HCM are required [18]. 
HCM has been the subject of intensive investigation for over 60 years. However, 
only in the last decade have studies become multicenter, involving large numbers 
of patients and providing the best source of real-world data. Currently, there are 
epidemiological, clinical, and genetic data on patients with HCM from North 
America and Europe, but not from the Russian Federation[2, 4, 5, 19].  
All of the above, along with the recent development of pathogenetic treatment for 
HCM [20], which is likely to improve not only the quality but also the prognosis of 
life, underscores the need for an observational registry of patients with HCM in 
Russian Federation. This registry will help increase knowledge of the 
epidemiology and prevalence of HCM, ultimately improving diagnosis and 
management. To assess the feasibility of new interventions, understanding the 
epidemiological profile of patients with HCM is essential. Clinical characteristics, 
imaging patterns, and outcomes may vary across different geographic regions. 
Completing this registry will enhance our understanding of the disease in Russia, 
and promote measures that modify the natural history of HCM. 
 
 

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2. OBJECTIVE 
This study is envisioned as the very first of its kind in the Russian Federation, 
aiming to provide a comprehensive characterization of the clinical spectrum and 
disease burden, focusing on the epidemiology and progression of HCM in the 
largest cohort of adult and pediatric patients from this region. The objectives 
include understanding the epidemiological profile of Russian population, clarifying 
the origins of clinical heterogeneity in HCM, and analyzing natural history. The 
study seeks to elucidate disease progression, identify contributing clinical factors, 
and explore new as well as previously established associations between genetic 
and acquired determinants and clinical features of HCM, all based on from a 
prospective observational study in the Russian population.  
2.1 The Additional Objectives of the Study are: 
 
 To evaluate the natural progression of HCM in non-operated patients who 
have indications for myectomy and in high-risk patients for SCD, who have 
not been implanted with an ICD. 
 To clarify the relationship between pediatric and adult HCM by constructing 
large pedigrees, including clinically and genetically examined relatives.  
 To evaluate real-world clinical practices, both surgical and therapeutic, in 
the management of LV obstruction. 
 To investigate the impact of comorbidities on phenotypic expression of 
HCM. 
 To establish a group of national HCM experts and centers of excellence. 
 
 

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3. STUDY DESIGN AND SELECTION CRITERIA 
3.1 Study Type 
This is a multicenter observational study (Registry) 
3.2 Inclusion Criteria 
 Any age 
 Signed informed consent form (ICF) for participation in the study, including 
genetic testing  
 Meets the criteria for HCM 
 
3.2.1 HCM Criteria for Probands ≥ 18 Years Based on ECHO or CMR 
• End-diastolic LV wall thickness ≥ 15mm in any segment of the LV 
3.2.2 HCM Criteria for Probands ≥ 18 Years with Arterial Hypertension 
• 1st degree of AH: The same ECHO/CMR criteria as patients without 
AH 
• 2nd and 3rd degrees of AH: 
• Asymmetric LV hypertrophy: the ratio of septum / LV PW ≥ 
 1.5 or apical HCM 
• If asymmetry < 1.5, the wall thickness must be ≥ 20mm 
• For all patients with arterial hypertension, the presence of at least one 
of the following ECG changes is obligatory:  
• Pathological “dagger” Q wave 
• T-wave inversion ≥ 3mm in ≥ 2 adjacent leads  
• Poor R progression / QS / RV1 > RV2 < RV3 in V1-V4  
 

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3.2.3 HCM Criteria for First-degree Relatives ≥ 18 Years Based on ECHO 
or CMR and ECG [21]:   
• End-diastolic LV wall thickness ≥ 13mm in any segment and/or ECG 
changes in the absence of CAD, such as (at least one of the following):  
 
• Quantitative signs of LV hypertrophy* + repolarization changes 
• T wave inversions in at least 2 adjacent leads: ≥ 3mm in V3-V6, 
 I, aVL or ≥ 5mm in II, III, aVF 
• Pathological Q waves (> 25% of R) in at least 2 adjacent leads: II, 
III, aVF (in the absence of left anterior hemiblock) or V1-V4, or I, 
aVL, V5-V6 
*Presence at least one of the following: 
• Sokolow-Lyon index (S in V1 + R in V5 or V6) > 35mm 
• R or S in limb leads ≥ 20mm 
• S in V1 or V2 ≥ 30mm 
• R in V5 or V6 ≥ 30mm  
3.2.4 HCM Criteria for Children and Adolescents < 18 Years 
• End-diastolic LV wall thickness in any segment > 2.5 standard 
deviations (> 2.5 z-score) above the norms for the index gender, age 
and weight (or body surface area) in asymptomatic children/adolescents 
without a family history of HCM  
• End-diastolic LV wall thickness in any segment > 2.0 standard 
deviations (> 2.0 z-score) above the norms for the index gender, age 
and weight (or body surface area) in children/adolescents with a family 
history of HCM or a positive genetic test 
3.3 Exclusion Criteria 
 Uncontrolled arterial hypertension of 2nd – 3rd degree with mild/moderate (< 
20mm) or symmetric LV hypertrophy or a “normal” ECG 
 Hemodynamically significant congenital or acquired valve heart disease  

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 Established diagnosis of metabolic, infiltrative, endocrine, or other diseases 
known as “phenocopies of HCM”  
3.4 Target Number of Patients 
The size of a representative group of patients with HCM, aimed at assessing the 
demographic and clinical characteristics of the disease in the Russian population - 
including the proportion of high-risk patients - was based on the estimated 
prevalence of HCM in the general population as 1:500 [22] and the population of 
the Russian Federation (140 million people). Type I error was set at 5%, and Type 
II error at 20%. The required sample size was 384 patients. To achieve a Type I 
error of 1%, the sample size would need to be 662 patients. 
When planning a prospective observation to assess all-cause mortality, the 
estimated total mortality rate among adults in the Russian Federation was used, set 
at 13.2 per 1000 (averaged data for 2010-2019 from the Federal State Statistics 
Service https://rosstat.gov.ru/folder/12781). The annual mortality rate for patients 
with HCM was estimated at 45.6 per 1000 (data from the Sarcomeric Human 
Cardiomyopathy Registry (SHaRe)). The enrollment period was planned for 3 
years, with a follow-up period of 1 year. Type I error was set at 5%, Type II error 
at 20%. The required number of patients for the analysis of all-cause mortality was 
912 [808-1006]. To achieve a Type I error of 1%, the required number of patients 
for the analysis was 1346 [1200-1492]. 
The group size calculation was performed using the NCSS statistical software 
package (PASS 2021).  
3.5 Sources of HCM Patients 
 Consecutive patients who meet the HCM criteria within enrollment period 
 Patients who have been examined at the participating centers in the past and 
may be invited for enrollment 
 Patients who have been examined at the participanting centers within the last 
year, with all enrolment procedures completed  

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3.6 Stages of Study 
3.6.1 Selection Period 
• Start Date of Enrolment: October 01, 2023 
• End Date of Enrolment: October 01, 2026 
• Definition of Enrollment Date: The date of enrollment will be 
considered the date of the first comprehensive examination at the 
center.  
3.6.2 Follow-up 
• Duration of Follow-up: Each patient will be followed for a minimum of 
one year or until one of the following events occurs:  
 
• Death  
• Heart transplantation 
 
• Start Date of Follow-up: The start date for each patient’s follow-up 
period will be the date of their enrollment visit. 
• End Date of Follow-up: The end date will be defined as one of the 
following: 
 
• The date of the last contact during the study completion 
• The date of death 
• The date of heart transplantation 
The estimated end date of the follow-up period in the study is October 01, 2027. If 
investigational staff and technical resources are available, the follow-up period will 
be extended as long as possible. 
During the follow-up period, all deaths, as well as non-fatal HCM-related events 
and other cardiovascular events, will be recorded. Additionally, information about 
diagnostic procedures and treatment interventions will also be collected during the 
follow-up period. 
Patients lost to follow up will be assessed until the date of their last contact.     

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3.6.3 Statistics and Publications 
The dates for statistical analysis and the preparation of publications are estimated 
to be from October 01, 2027 to October 01, 2029.  
3.7 Requirements for Investigational Site 
 Availability of staff experienced in the management of patients with HCM 
 Ability to examine the patients with suspected HCM referred from the other 
clinics 
 Capacity to recruit at least 20 patients  
 Availability of a state-of-the-art echocardiograph and specialists with 
experience in the diagnosis of HCM and differential diagnostics of other 
causes of LV hypertrophy 
 Ability to perform 12-lead ECGs  
 Capability to collect, store (in a freezer), and ship blood samples to the 
Almazov National Medical Research Center for further genetic testing 
 The study protocol and informed consent form must be approved by the 
local Ethics Committee 
 
4. STUDY PROCEDURES 
4.1 ENROLLMENT OF PATIENTS 
To enroll patients in the study, the following procedures must be followed: 
 Obtain Inform Consent 
 Collect Personal and Family History 
 2D Transthoracic Echocardiogram with Provocation 
 12-lead ECG at Rest  
 24-Hour Holter Monitoring 
 Blood Sample Collection  
 
4.1.1 Obtaining of Informed Consent  
 

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• Each patient ≥ 18 years is required to personally sign an informed 
consent form (ICF) to participate in the observational study, including 
genetic testing component 
• For patients < 18 years, the ICF must be signed by an official 
representative, which may be one of the parents or a legal guardian. In 
addition, individuals aged between 14 and 18 years must personally 
sign the ICF, along with their parent or guardian 
• An example of the ICF is available in Appendix 2 for reference 
• Each investigational site has the rights to use its own version of the 
ICF, approved by the local Ethics Committee.  
4.1.2 Obtaining of the Clinical Data 
The process for obtaining clinical data is as follows: 
 Data Collection: 
• Clinical data will be gathered during the patient’s interview and 
recorded initially in a paper version of a case report form (CRF) titled 
“Visit of Enrollment”.  
• Afterward, the data will be transferred from the paper CRF to an 
electronic version of the CRF. 
 
 Responsibilities of the Center: 
• The responsibility for accurately completing both the paper and 
electronic versions of the CRF lies with the study center conducting the 
enrollment. 
 
 Quality Control: 
• Members of the study working group will oversee the quality control of 
the collecting data. 
• They may communicate with investigators to clarify and issues or 
discrepancies in the CRF. 
 
  CRF Completion Guidelines: 
• Detailed guidelines for completing the CRF are provided in Appendix 5 
for reference.  
 

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 CRF “Visit of Enrollment” Sections: 
The Visit of Enrollment CRF (Appendix 6) will include the following sections: 
• Demographic and epidemiological data 
• Personal and family history of HCM 
• Diagnostic procedures 
• Comorbidities 
• Pharmacological treatment at enrollment 
• Outcomes / follow up visits 
4.1.3 Instrumental Examination 
The following instrumental examinations will be conducted for all enrolled 
patients: 
4.1.3.1 Echocardiography 
All patients will undergo an ECHO investigation at the time of enrollment. The 
specific parameters to be evaluated during the ECHO are detailed in the CRF 
“Echocardiogram” (see Appendix 7).  
4.1.3.2 Electrocardiogram 
A 12-lead ECG will be recorded for all patients while at rest during enrollment. 
The recorded ECG data will be documented in the CRF “Electrocardiogram” (see 
Appendix 8).  The scanned or digital version of the ECG must be uploaded to the 
electronic database of the study to ensure proper storage and accessibility. 
4.1.3.3 24-hour ECG Holter Monitoring  
• Procedure: All patients must provide data from a 24-hour ECG Holter 
monitoring, which can be performed either at the enrolling site or at 
another medical facility, as long as conducted within ± 12 months from 
the enrollment date. 
• Data Recording: the results from the 24-hour ECG monitoring will be 
documented in the CRF titled “24-hour ECG monitoring” (see 
Appendix 9). 

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4.1.4 Blood Samples Collection 
• Procedure: The procedures for collecting and storing blood samples, as 
well as coding patients and biosamples, are detailed in Appendix 2 and 
Appendix 3.  
4.1.5 Shipment of Blood Samples for Genetic Study 
• Shipment Deadline: Blood samples must be shipped to the Almazov 
National Medical Research Center no later than 12 months after 
collection.  
• Courier Service: The shipment must be handled by a courier service 
that is licensed to transport biological material.   
• Shipping Conditions: On the day of shipment, blood samples should be 
removed from the freezer and shipped at room temperature. The 
samples should not be re-frozen after thawing, and cooling is not 
required during transportation. 
• Enrollment Confirmation: Once the blood samples are received at the 
central genetic laboratory, the patient is officially considered enrolled 
in the study.  
4.2 FOLLOW-UP 
 During follow-up period, patients or their relatives will be contacted by 
phone at least once every 12 months  
 At follow-up visits, information regarding the study endpoints, ant medical 
examinations, and interventions that have occurred since the time of 
enrollment will be collected. Investigators are encouraged to make every 
effort to obtain official medical records that document these endpoints and 
any interventions that have taken place.  
 All follow-up data will be recorded in the CRF titled “Follow up” (see 
Appendix 10).  
4.3 GENETIC STUDY 
The genetic study aims to identify the causative genetic variants associated with 
HCM in enrolled patients (probands). The key procedures and stages of the genetic 
analysis are as follows: 

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 The genetic testing will be conducted using new-generation sequencing 
(NGS) with target gene panels.  
 First initial stage of testing will focus on 39 genes (listed in Appendix 11) 
that are most frequently associated with the development of HCM in both 
adults and children. The aim is to identify pathogenic, likely pathogenic, 
or variants of unknown significance (VUS) in genes which could be 
potentially causative for HCM. 
 If no significant genetic variants are found in the initial panel, the gene list 
will be expanded to an extensive cardio panel of 172 genes (and potentially 
more) that are linked to a variety of inherited cardiovascular diseases (see 
Appendix 12).  
 In cases where the extensive panel does not reveal any causative variants, 
whole exome sequencing (WES) may be performed. Additionally, WES 
may be conducted immediately after receiving a negative result from the 39-
gene panel, depending on the clinical features of the disease.  
 If pathogenic, likely pathogenic variants, or high-probability VUSs are 
identified, cascade family screening will be offered. This involved testing 
family members to assess genetic risk and provide further clinical 
interpretation of the results. Patients will receive genetic counseling both 
before and after the genetic study. Counseling will cover the aim and 
significance of the genetic test, the expected results and their potential 
interpretations, the implications of the genetic findings for disease prognosis 
and management.     
 
5. ENDPOINTS 
5.1 Primary endpoint 
The primary endpoint of the study is all-cause mortality (death from any cause). 
5.2 Secondary Endpoints 
The study will collect and analyze information regarding the following nonfatal 
events during the follow-up period. These events will be assessed both 
individually and in combination: 

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1. Appropriate and non-appropriate ICD shocks 
2. Successful resuscitation 
3. Progression of dyspnea to class III/IV according by NYHA 
4. A reduction in LV EF to less than 50% 
5. Hospitalization due to HF requiring parenteral diuretics and/or inotropic 
therapy 
6. LVAD implantation 
7. Heart transplantation or being on the waiting list 
8. Septal reduction therapy 
9. Non-fatal ischemic strokes 
10. New onset AF 
11. New onset non-sustained VT 
12. New onset Sustained VT 
13. New onset syncope (highly likely arrhythmogenic) 
14. Other non-fatal CV events, including but not limited to MI and pulmonary 
embolism. 
 
  6. STATISTICS 
6.1 Data Collection 
All collected data will be entered into a single, study-specific electronic database. 
Given the large number of patients expected to enroll in the study, data should be 
entered after each patient visit – whether the visit is on-site or conducted via 
phone.  
6.2 Statistical Methods 
For all variables the normality of distribution will be checked by Shapiro-Wilks. 
Continuous variables will be expressed as mean ± standard deviation (if normally 
distributed) or as median and interquartile range (IQR) (P25-P75) for non-normally 
distributed data. Student’s t-test (for normally distributed data) or Mann-Whitney 
U test (for non-normally distributed data) will be used for comparisons of 
continuous variables, and Chi-square or Fisher tests for categorical variables. 
Categorical variables will be given as total number and percentages. Correlations 
were assessed by Pearson’s and Spearman’s correlation analysis. Survival curves 

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will be constructed according to the Kaplan-Meier method and comparison will be 
performed using log-rank test. Survival will be assessed by Cox proportional 
hazard regression for time depended variables and by binary logistical regression 
for time independent variables. All p-values will be two-sided, and considered 
significant when < 0,05.  
6.3 Prognosis  
 The prognosis for all-cause mortality will be assessed for the entire cohort of 
patients from the moment of their enrollment.  
 The annual incidence of HCM-related events will be analyzed in subgroups 
of patients who were free from HCM-related events at the time of their 
enrollment. 
 The following covariates will be considered when assessing prognosis: 
assessment: age at diagnosis, age at enrollment, sex, comorbidities, other 
clinical factors 
 The study will compare mortality rates and disease progression between the 
following sarcomere gene variant groups:  
 
• Sarcomere positive group: patients with ≥ 1 pathogenic or likely 
pathogenic variant linked with HCM.  
• Sarcomere VUS group  
• Sarcomere negative group 
 
 If data on a specific endpoint (e.g., new onset AF) are unavailable, the 
patient will be excluded from the analysis of that particular endpoint (e.g., 
“AF and stroke”). However, the patient will still be included in analyses for 
other applicable endpoints.   
6.4 Genome-Wide Association Study (GWAS) 
In the study cohort of patients, an analysis of the effect of common genetic 
variants, identified based on the literature or GWAS, on the course of HCM will be 
conducted. In the study cohort (partially or entirely), genome-wide sequencing 
might be performed to replicate the significance of existing variants and to identify 
new genetic determinants that define the development of the HCM phenotype.   

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6.5 Comparison Analysis 
A comparative analysis of different parameters will be performed across various 
subgroups, categorized by the following characteristics (but not limited to them): 
• Sex 
• Age at first diagnosis 
• Proband or relative status 
• Presence of LV obstruction 
• Morphological type of HCM 
• Presence of comorbidities  
• Presence of mutations or VUSs in sarcomere genes  
 
6.6 Assessment of Examinations and Treatments 
In addition to the clinical and genetic spectrum and endpoints, the rate and type of 
diagnostic and treatment procedures related to HCM will be assessed. 
6.7 Registration of Patients with Transformed Diagnosis during Follow-up   
In cases where the diagnosis of HCM was reconsidered or declined based on the 
results of additional investigations after enrollment, such patients will not be 
included in the prognosis analysis. However, they will be described in the clinical 
and genetic profile of the study population.  
 
 

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7. ETHICAL ASPECTS 
7.1 Informed Consent Form 
Patients meeting all inclusion criteria will be considered eligible for the study. 
Before enrollment, the patient must sign the ICF. The study details should be 
explained to the patient, either orally or in writing. Patients should be informed 
that a blood sample will be collected for genetic testing during the study. 
7.2 Confidentiality 
The data collected during the study and stored in the computer should be protected 
in accordance with the regulations for the protection of personal information. 
Investigators will handle all personal information in compliance with medical 
confidentiality standards and relevant data protection laws. 
The confidentiality of data entered into the database will be ensured by assigning a 
unique identification number to each patient. Simultaneously, all personal 
information and identification lists will be stored at each center in accordance with 
procedures established by relevant personal data protection laws.   
 
 

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8. OWNERSHIP AND FUNDING 
Each investigational group has the right to publish its own data obtained during the 
study.  
The publication or use of data from the other centers may only occur with the 
agreement of the principal investigators from those centers.  
Given the initiative-based nature of this project, each participant is encouraged to 
secure their own funding. Grant applications are encouraged, both individually by 
each center or jointly. Each center may use only its own data for project 
implementation, or by mutual agreement, data from other study participants. When 
using data from other centers, the respective participants must be involved as co-
executors. In these cases, the grant leader will be the head of the center that 
receives the funding. 
The results of the first Russian register of HCM are intended to be published in 
both Russian and international journals. Participation in the project implies 
agreement to follow this protocol and the conditions outlined in section 8.  
 
 

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APPENDICES 
 
1. Leaders of the study and members of working group 
2. Informed consent form  
3. Coding of Patient and genetic tubes 
4. Blood collection and storage guidelines 
5. Guidelines for CRF completion 
6. “Enrollment visit” form 
7. “Echocardiogram” form 
8. “Electrocardiogram” form 
9. “24-hour ECG monitoring” form 
10. “Follow-up visit” form 
11. Target panel of genes associated with HCM (39 genes) 
12. Extensive panel of genes (172 genes and more) 
 
 

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Appendix 1 
 
STEERING COMMITTEE 
Chairman: prof. William McKenna, Institute of Cardiovascular 
Science, University College London, London, UK  
1. Prof. Alexandra Konradi, MD, DSc, Deputy Director General for 
Research, Head of Arterial Hypertension Research Department, Almazov 
National Medical Research Centre, St-Petersburg, Russia 
2. Prof. Michael Arad, professor, scientific researcher of Seidman Lab, 
Dept. of Genetics, Harvard Medical School and HHMI, Boston, USA; 
professor of cardiology at the Institute of Heart Failure and Center for 
Cardiomyopathy and Hereditary Heart Disease, Sheba Medical Centre; 
Associate Professor in the Department of Cardiology, Tel Aviv 
University, Israel 
3. Prof. Iacopo Olivotto, associate professor of cardiology, Head of 
Cardiomyopathies Unit, department of experimental and clinical 
medicine, University of Florence, Italy 
4. Dr. Natalia Sonicheva, cardiologist, secretary of the National Research 
League of Cardiogenetics of Russia 
5. Dr. Juan Pablo Ochoa, cardiologist, Heart Failure and Inherited 
Cardiac Diseases Unit, Hospital Universitario Puerta de Hierro 
Majadahonda, Comunidad de Madrid, Spain. Head of the cardiology 
department at HealthinCode 
LEADERS OF THE PROJECT 
1. Antonis Pantazis, former President of the ESC Working Group on 
Myocardial and Pericardial Diseases; cardiologist at the Cardiovascular 
Research Centre, Royal Brompton and Harefield National Health Service 
Foundation Trust, London, UK. 

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2. Dmitry Zateyshchikov, MD, DSc, professor, head of the department of 
Internal medicine, Cardiology and Functional diagnostics, Central State 
Medical Academy of the Department of Presidential Affairs; head of the 
primary vascular center, Moscow City Clinical Hospital #29; scientific 
researcher, laboratory of genetics, Federal Scientific Clinical Centre of the 
Federal Medical and Biological Agency of Russia, Moscow. 
3. Anna Kostareva, MD, DSc, Director of the Institute of Molecular Biology 
and Genetics, Almazov National Medical Research Centre, St-Petersburg, 
Russia 
4. Olga Moiseeva, MD, DSc, Director of the Heart and Vascular Institute; 
senior scientific researcher in noncoronary myocardial diseases, Almazov 
National Medical Research Centre, St-Petersburg, Russia 
 
WORKING GROUP 
1. Olga Chumakova, MD, PhD, cardiologist, certified specialist in 
echocardiography, assistant professor in the department of Internal 
medicine, Cardiology and Functional diagnostics, Central State Medical 
Academy of the Department of Presidential Affairs; scientific researcher in 
the laboratory of genetics, Federal Scientific Clinical Centre of the Federal 
Medical and Biological Agency of Russia, Moscow. 
2. Sofia Andreeva, MD, cardiologist, Almazov National Medical Research 
Centre, St-Petersburg, Russia 
3. Vadim Zaitsev, MD, cardiologist, Almazov National Medical Research 
Centre, St-Petersburg, Russia 
4. Larisa Minushkina, MD, DSc, cardiologist, professor in the department of 
Internal medicine, Cardiology, and Functional diagnostics, Central State 
Medical Academy of the Department of Presidential Affairs, Moscow 
5. Michael Alekhin, MD, DSc, professor, head of the functional diagnostics 
department, Central Clinical Hospital of Department of Presidential Affairs; 
vice-president of the Russian Association of Specialists in Ultrasound 
Diagnostics in Medicine (RASUDM), Moscow 
6. Tatiana Tipteva, MD, PhD, cardiologist, EACVI certified specialist in 
echocardiography, K+31 Medical center “Petrovsky vorota”, Moscow