Predictors of heart failure with reduced or mildly reduced ejection fraction development in hypertrophic cardiomyopathy: a single-centre study

Introduction

Heart failure (HF) development represents one of the most prevalent and clinically relevant complications among hypertrophic cardiomyopathy (HCM).

Purpose

To identify clinical and imagological predictors of new-onset HF with left ventricle (LV) reduced/mildy reduced ejection fraction (R/MR EF) in a HCM cohort.

Methods

Single-centre retrospective analysis of a HCM cohort followed at cardiomyopathies clinic of a portuguese tertiary centre. HCM phenocopies were excluded. Data was obtained from electronic medical records. Patients (pts) with HF with preserved EF at baseline were included and then divided into two groups according to follow-up (FUP): group A – new-onset HF with R/MR EF; group B – HF with preserved EF.

Results

A total of 157 HCM pts were included. Over a median FUP of 7 (IQR 9) years, 8.9% developed HF with R/MR EF – group A.

Sex distribution (52.9 % male, p=0.786), age at diagnosis (53±20 years, p=0.501) and diagnostic context (59.7% in routine evaluation, p= 0.055) were similar across groups, as well as cardiovascular (CV) risk factors prevalence. No differences regarding to genotype status (42.5% genotype positive, p=0.758) or LV morphology (75.8% asymmetric septal, p=0.083) were also found.

Atrial fibrillation (AF; 64.3% vs 24.5%, p= 0.003, OR 4.63, CI 95% 1.64-13) was significantly higher in group A, which also had more frequently intraventricular obstruction (57.1% vs 25.7%, p=0.026, OR 3.82, CI 95% 1.24-11.87), higher LV mass (167 ± 50 g vs 153±48 g, p=0.031) and greater posterior wall diameter (13.6±2.7 mm vs 11±1.91 mm p=0.003). No differences were found regarding the presence of late gadolinium enhancement (81.3%, p=0.687) or LV aneurysm (1.9%, p=0.247).

In multivariate logistic regression, when adjusted to sex, age and CV risk factors, AF (adjusted OR 4.6, CI 95% 1.32-15) and IV obstruction (adjusted OR 5.38, CI 95% 1.62-17.9) remained independently associated with R/MR EF development.

Group A experienced a higher incidence of adverse CV events (71.4% vs 25.9%, p<0.001, OR 2.57, CI 95% 1.050-1.426), driven mainly by HF events (21.4% vs 1.4%, p=0.010, OR 8.29, CI 95% 3.32-20.69) and ventricular arrhythmias (21.4% vs 2.1%, p=0.005, OR 6.86, CI 95% 2.57-18.32). At FUP, New York Heart Association functional class was significantly worse in group A [mostly in class II (57.1%) vs class I in group B (61.5%), p=0.011].

Use of HF 4-pilar prognosis modifying therapy in group A was modest at FUP - most under sodium–glucose cotransporter-2 inhibitors and beta-blocker and half on renin-angiotensin-aldosterone system inhibitors.

Conclusions

A non-negligible proportion of pts developed HF with R/MR EF, with AF diagnosis and IV obstruction at baseline as independent predictors. These findings underscore the burden of HF and the importance of early identification of markers of HCM progression to enable timely initiation of targeted therapeuties and potentially mitigate adverse clinical outcomes.