Observational, prospective hypertrophic cardiomyopathy registry

P. Manokar

Senior Interventional Cardiology, Kauvery Hospital, Vadapalani, Chennai

Background

HCM is the most common inherited cardiomyopathy (1 in 200), caused by mutations in sarcomeric protein genes (e.g., MYH7, MYBPC3). High variability in phenotype: asymptomatic to SCD or advanced HF.

Fibrosis, myocyte disarray, and arrhythmias are major pathological features. Indian-specific data on genotype, phenotype, and biomarkers is lacking.

Rationale for the Registry

  • Current risk stratification based on limited predictors (LV thickness, VT, syncope). Biomarkers and CMR-based fibrosis are emerging risk tools.
  • Genetic testing provides insight into familial risk and prognosis.
  • No Indian registry combining all three: clinical, genetic, and biomarker data.

Objectives

Primary Objective

To characterize clinical and Echo profiles along with genetic, and biomarker profiles of HCM patients in an Indian tertiary care setting.

Secondary Objectives

To correlate genetic mutations with clinical phenotype and outcomes.

To assess predictive value of fibrosis and biomarkers for adverse cardiac events.

To create a local risk stratification model based on multimodal parameters.

Study Design

  • Study Type: Observational, prospective, single-center registry.
  • Duration: 3 years (with optional follow-up to 5 years).
  • Sample size: 300 patients with diagnosed HCM.
  • Data collected: Clinical, echocardiographic, genetic (NGS), serum biomarkers.

Eligibility Criteria

Inclusion

  • Age 18–65 years.
  • Diagnosis of HCM (LV wall thickness ≥15 mm).
  • No known secondary cause (e.g., HTN, AS).
  • Informed consent provided.

Exclusion

  • Prior septal myectomy/alcohol ablation.
  • Significant coronary artery disease or MI.
  • Advanced renal disease (due to CMR contrast restriction).
  • Pregnancy or inability to comply with protocol.

Investigations and Protocol Flow

  • Clinical Evaluation: Demographics, symptoms, NYHA class, family history.
  • ECG & Holter Monitoring: Rhythm, QT interval, nonsustained VT episodes.
  • Echocardiography: Wall thickness, LVOT gradient, diastolic function, EF.
  • CMR (if feasible): LGE (fibrosis), T1 mapping, ECV fraction.
  • Genetic Testing: NGS of HCM genes (MYH7, MYBPC3, TNNT2, etc.).

Biomarker Analysis

  • Injury: HS-Troponin I.
  • Stress: NT-proBNP.

Data Collection

  • Parameters collected at baseline, optional annual follow-up for:
    • Cardiac events
    • ICD implantation
    • Heart failure hospitalization
    • Arrhythmias

Ethical Considerations

  • IEC-approved informed consent process.
  • Optional genetic counseling for participants.
  • Confidentiality ensured using coded IDs.
  • Data stored in encrypted servers.

Benefits to Participants

  • Contribution to future risk prediction tools for HCM.
  • Family screening insights if mutation is found.

Risks

  • Minimal physical risk (blood draw, contrast allergy).
  • Genetic knowledge may cause anxiety (mitigated with counseling).

Statistical Plan

  • Use of Principal Component Analysis (PCA) to reduce variable dimensionality.
  • Multivariable Cox regression for outcome prediction.
  • Kaplan-Meier curves for event-free survival.
  • Bootstrap for model validation.
  • Missing data handled via multiple imputation.

Expected Outcomes

  • Phenotypic-genotypic correlations in Indian population.
  • Biomarkers and imaging markers predictive of risk.
  • Better risk stratification algorithm for SCD and HF in HCM.
  • Future clinical trial patient selection tool.

Kauverian Bookshelf

Applied Medical Statistics

Journals

Kauvery Hospital
Find Doctor
Book Appointment