Hypertrophic cardiomyopathy (HCM) is a hereditary cardiovascular condition affecting approximately 1 in 200 to 1 in 500 adults globally. About 70% of these patients present with the obstructive form, known as hypertrophic obstructive cardiomyopathy (HOCM). This phenotype is characterized by dynamic obstruction of the left ventricular outflow tract (LVOT), contributing to symptoms such as dyspnea and exercise intolerance.
Mavacamten is a novel cardiac myosin inhibitor that has demonstrated in randomized clinical trials its ability to reduce LVOT gradients significantly. It also improves patient-centered outcomes including symptoms, exercise capacity, and quality of life for those with HOCM. Despite these promising findings, data reflecting its safety and performance in routine clinical practice, particularly among non-Western populations, remain sparse.
The PERSIA-HOCM study is a prospective, multicenter, observational investigation conducted across 19 cardiovascular referral centers in Iran. It seeks to gather real-world evidence on safety, symptom improvement, and adherence to mavacamten among Iranian patients with symptomatic HOCM. This design enables the evaluation of mavacamten under typical clinical care conditions without intervention beyond standard treatment.
Adult patients (aged 18 years or older) with symptomatic obstructive HCM will be included if they are classified as New York Heart Association (NYHA) functional class II through IV, and exhibit an LVOT gradient equal to or greater than 50 mm Hg at rest or provoked conditions. Patients with a left ventricular ejection fraction (LVEF) below 55%, those with a non-obstructive HCM phenotype, or those who do not provide informed consent will be excluded from participation.
Each participant will be enrolled upon prescription of mavacamten and will provide written informed consent consistent with ethical regulations.
Participants will be followed over a 12-month period with visits scheduled every 4 weeks. Data collected at these visits will include clinical symptoms, NYHA classification, vital signs, and echocardiographic measurements focusing on LVOT gradients and LVEF. Echocardiography assessments will be emphasized at weeks 4, 8, 12, and 24.
Additional data collected include mavacamten dosing information, adjustments, and concurrent pharmacologic therapies. Safety monitoring will be conducted using a predetermined adverse event framework covering mortality, hospitalizations, and major clinical incidents.
At weeks 12 and 48, cardiac biomarkers such as cardiac troponin and N-terminal pro B-type natriuretic peptide (NT-proBNP) will be measured alongside validated quality of life questionnaires.
The study's primary endpoints encompass:
Secondary endpoints include cardiac magnetic resonance imaging (MRI) assessments for myocardial fibrosis, measurement of peak oxygen uptake (VO2 max) as a physical capacity indicator, and evaluation of outcomes based on genotypic variations.
All data analyses will utilize the R software environment (version 4.5.1). Descriptive statistics will summarize baseline characteristics and outcome measures. Paired sample t tests will assess changes within individuals over time, while McNemar’s test will examine changes in categorical variables such as NYHA class.
This analytical approach allows for robust evaluation of real-world mavacamten effects on patient-centered and biomarker endpoints.
The study protocol has been approved by the Research Ethics Committee of Rajaie Cardiovascular, Medical and Research Institute and the Iran National Committee for Ethics in Biomedical Research (Code: IR.RHC.REC.1404.210). All enrolled participants provide written informed consent ensuring voluntary participation and data confidentiality.
Analysis findings will be compiled in reports released every 6 months. Additionally, results will be disseminated through peer-reviewed journal publications and presentations at scientific conferences to inform the global cardiovascular community about mavacamten use in diverse populations.