Unmasking risk in asymptomatic hypertrophic cardiomyopathy: clinical and multimodality imaging determinants of disease progression and adverse outcomes

Background While patients with hypertrophic cardiomyopathy (HCM) often develop symptoms due to dynamic left ventricular outflow tract obstruction (LVOTO), diastolic dysfunction, arrhythmia and ischemia, many patients remain asymptomatic for an extended period before transitioning to a symptomatic state. Objective To identify baseline clinical and multimodality imaging characteristics associated with progression from asymptomatic to symptomatic status in HCM patients and to evaluate their relationship with long-term outcomes. Methods Between 2006-21 896 HCM patients at a tertiary referral center underwent comprehensive echocardiography and multiparametric contrast-enhanced cardiac magnetic resonance (CMR) at baseline. Dynamic LVOTO was assessed by echocardiography. Late gadolinium enhancement (LGE) on CMR was quantified using a signal intensity threshold of ≥6 SD above reference myocardium). Following a comprehensive evaluation, all patients were deemed to be asymptomatic (New York Heart Association [NYHA] Class I) at baseline. Patients with LVOTO ≥30 mm Hg were deemed obstructive. Primary outcome was a composite of mortality, appropriate internal cardioverter defibrillator (ICD) discharge or cardiac transplantation. Results Over a median follow-up of 9.3 years (interquartile range 6.0, 12.5), 242 (27%) patients developed symptoms (185 NYHA Class II and 57 NYHA Class III/IV). Baseline characteristics are shown in Figure 1A, 423 [47%] were nonobstructive and 473 [53%] were obstructive (171 [19%] underwent septal reduction therapies). Patients who developed symptoms were older, more often women, had thicker LV wall and a higher prevalence of LGE (Figure 1A). There were 128 (14%) composite events (115 [13%] deaths, 15 [2%] ICD discharges and 3 [0.3%] transplants). A significantly higher proportion of patients who became symptomatic experienced the primary outcome during follow-up compared with those who remained asymptomatic (68 [28%] vs 60 [9%]; Hazard ratio or HR 3.40, 95% confidence interval or CI 2.40–4.82; p<0.001). In multivariable analysis (adjusted for age and sex), progression to a higher NYHA class (HR 2.30, 95% CI 1.57–3.38; p<0.001) and %LGE burden at baseline (HR 1.04 per unit increase, 95% CI 1.02–1.07; p<0.001) remained independently associated with the primary outcome (both p<0.001). Patients with any LGE who become symptomatic had significantly worse outcomes compared with those who remained asymptomatic and had no LGE (HR 4.45, 95% CI 2.78–7.11; p<0.001; Figure 1B). Conclusions Asymptomatic HCM patients who transition to a symptomatic state are older, more often women, and have a higher LGE burden. Symptom progression and LGE presence confer adverse long-term prognosis, with LGE on CMR providing incremental prognostic value.