Hypertrophic Cardiomyopathy With Left Ventricular Systolic Dysfunction

Abstract

Background: The term “end stage” has been used to describe hypertrophic cardiomyopathy (HCM) with left ventricular systolic dysfunction (LVSD), defined as occurring when left ventricular ejection fraction is <50%. The prognosis of HCM-LVSD has reportedly been poor, but because of its relative rarity, the natural history remains incompletely characterized. Methods: Data from 11 high-volume HCM specialty centers making up the international SHaRe Registry (Sarcomeric Human Cardiomyopathy Registry) were used to describe the natural history of patients with HCM-LVSD. Cox proportional hazards models were used to identify predictors of prognosis and incident development. Results: From a cohort of 6793 patients with HCM, 553 (8%) met the criteria for HCM-LVSD. Overall, 75% of patients with HCM-LVSD experienced clinically relevant events, and 35% met the composite outcome (all-cause death [n=128], cardiac transplantation [n=55], or left ventricular assist device implantation [n=9]). After recognition of HCM-LVSD, the median time to composite outcome was 8.4 years. However, there was substantial individual variation in natural history. Significant predictors of the composite outcome included the presence of multiple pathogenic/likely pathogenic sarcomeric variants (hazard ratio [HR], 5.6 [95% CI, 2.3–13.5]), atrial fibrillation (HR, 2.6 [95% CI, 1.7–3.5]), and left ventricular ejection fraction <35% (HR, 2.0 [95% CI, 1.3–2.8]). The incidence of new HCM-LVSD was ≈7.5% over 15 years. Significant predictors of developing incident HCM-LVSD included greater left ventricular cavity size (HR, 1.1 [95% CI, 1.0–1.3] and wall thickness (HR, 1.3 [95% CI, 1.1–1.4]), left ventricular ejection fraction of 50% to 60% (HR, 1.8 [95% CI, 1.2, 2.8]–2.8 [95% CI, 1.8–4.2]) at baseline evaluation, the presence of late gadolinium enhancement on cardiac magnetic resonance imaging (HR, 2.3 [95% CI, 1.0–4.9]), and the presence of a pathogenic/likely pathogenic sarcomeric variant, particularly in thin filament genes (HR, 1.5 [95% CI, 1.0–2.1] and 2.5 [95% CI, 1.2–5.1], respectively). Conclusions: HCM-LVSD affects ≈8% of patients with HCM. Although the natural history of HCM-LVSD was variable, 75% of patients experienced adverse events, including 35% experiencing a death equivalent an estimated median time of 8.4 years after developing systolic dysfunction. In addition to clinical features, genetic substrate appears to play a role in both prognosis (multiple sarcomeric variants) and the risk for incident development of HCM-LVSD (thin filament variants).

Twenty‐year survival following orthotopic heart transplantation in the United States

“…Many diagnoses of obstructive hypertrophic cardiomyopathy are amenable to surgical debulking and ablative therapies with excellent results, and do not result in death, transplantation, or cardiac assist device implantation. In a review of 6793 patients with hypertrophic cardiomyopathy, 553 (8.1%) patients exhibited left ventricular systolic dysfunction with an even smaller subset of these patients requiring OHT 11 . Regardless, this predilection towards younger presentation and lack of other associated comorbidities may explain the greatest age‐adjusted odds of long‐term survival found in this population after OHT.…”

Sex-Related Differences in Protein Expression in Sarcomere Mutation-Positive Hypertrophic Cardiomyopathy

“…Sex-differences in clinical presentation contribute to the phenotypic heterogeneity of HCM. Several large cohort studies observed a higher disease prevalence in men representing 55-65% of the total HCM population (7)(8)(9)(10)(11). At HCM diagnosis, women are on average 9 years older than men (7,12), and at the time of myectomy surgery women are on average 7 years older than men (13).…”

Transthoracic echocardiography of hypertrophic cardiomyopathy in adults: a practical guideline from the British Society of Echocardiography

“…The yield of clinical screening is higher in families where the disease onset has been in childhood (9,10). HCM featuring the so-called dilated-hypokinetic or 'burnt-out' phase (5), or due to specific gene mutations (11)(12)(13), can be associated with only mild increases in wall thickness. Grey Cases Ethnicity, hypertension, renal disease, significant aortic stenosis, increased body mass index and athletic remodelling all influence left ventricular hypertrophy.…”

“…To allow this critical information to be accessed rapidly by the referring clinician, the conclusion for every report in a patient with suspected or confirmed HCM should contain these parameters. Although not in the ESC risk calculator, the presence of left ventricular impairment (5) and an apical aneurysm(25) is also essential to include in the study conclusion as they modify risk of sudden cardiac death. The importance of reporting cardiac rhythm in every echocardiogram report is particularly relevant in HCM as a significant proportion of patients will develop atrial fibrillation.…”

“…As a measure of systolic function, ejection fraction (EF) can be misleading in HCM being normal even when markers of systolic dysfunction such as abnormal regional wall motion and global longitudinal strain(26) (see the section below) are present. Nonetheless, the absolute value helps clinical teams to identify patients in whom systolic dysfunction is likely to develop (50-60%) and those in whom it is overt (<50%) (5). Accurately determining EF using Simpson's biplane, and three-dimensional quantification where possible, and highlighting instances when this measurement is discordant with the systolic function will aid clinical management.…”