# The associations among genetic features, late gadolinium enhancement and prognosis in hypertrophic cardiomyopathy

## TL;DR

This study shows that combining genetic testing with heart imaging improves predicting outcomes in patients with hypertrophic cardiomyopathy.

## Contribution

The study demonstrates that combining genetic features and late gadolinium enhancement improves risk stratification in HCM patients with preserved LVEF.

## Key findings

- Patients with both genetic variants and late gadolinium enhancement had the highest risk of adverse events.
- Genetic and imaging markers independently predicted poor outcomes even after adjusting for other factors.
- Risk stratification was significantly improved by combining genotype and LGE data in HCM patients.

## Abstract

To assess the combined prognostic value of genotype and late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM) patients, including those with preserved left ventricular ejection fraction (LVEF).

In 135 HCM patients (age 52.43 ± 11.35 years, 79.26% male), whole-exome sequencing, echocardiography, and cardiac magnetic resonance (CMR) were performed. Major adverse cardiovascular and cerebrovascular events (MACCEs, e.g., cardiac death, progressive heart failure, sustained ventricular tachycardia/ventricular fibrillation, ICDs implantation, stroke, syncope, and atrial fibrillation) were analyzed over a median 15-month follow-up (IQR 9–36 months).

Pathogenic/likely pathogenic variants (G+) were identified in 50 (37%) patients, and LGE (L+) in 54 (40%). L+ patients exhibited worse clinical profiles: higher NYHA III–IV class (37% vs. 11%, P < 0.001), increased heart failure hospitalization (26% vs. 7%, P = 0.003), larger LV end-diastolic volume (median: 135, IQR: 125.25–213.00 vs. median: 126, IQR: 106.00–155.50, P = 0.004), lower LVEF (median: 55%, IQR: 39.75%–62% vs. median: 58%, IQR: 48%–65.5%, P = 0.012), and higher G+ prevalence (52% vs. 28%, P = 0.004). Both L+ (HR = 2.237, 95% CI: 1.178–4.247; P = 0.014) and G+ (HR = 1.872, 95% CI: 1.040–3.371; P = 0.037) independently predicted MACCEs after adjusting for age, NYHA class III–IV, LVOT obstruction and LVEF, adjusting for age, NYHA class III–IV, LVOT obstruction and LVEF. MACCE rates escalated across subgroups: G−/L− (22%), G+/L− (39%), G−/L+ (41%), and G+/L+ (63%) (P = 0.004). Among 89 patients with LVEF ≥150%, G+/L+ had the highest MACCE incidence (80% vs. 17% in G−/L−, P < 0.001).

The combined assessment of genotype and late gadolinium enhancement significantly enhances risk stratification and prognosis prediction in hypertrophic cardiomyopathy patients, including those with preserved left ventricular ejection fraction, providing valuable insights for clinical decision-making.