Prognostic value of treadmill exercise echocardiography with systolic and diastolic evaluation in patients with hypertrophic cardiomyopathy, and impact of genetic abnormalities in findings and outcome

Background Exercise echocardiography (ExE) may assess left ventricular (LV) systolic and diastolic function, LV outflow tract (LVOT) obstruction and mitral regurgitation (MR). We aimed to assess the impact of these variables for assessing long-term outcome in hypertrophic cardiomyopathy (HCM) patients, and to elucidate if ExE findings and outcome are worse in patients with genetic abnormalities. Methods LV systolic and diastolic function, LVOT gradients, and MR were evaluated during ExE in 368 patients with HCM (age 60±13 years, 42% women). Genetic testing performed in 241 subjects showed pathological results in 97 (40%). Considered composite events were overall death, acute coronary syndrome (ACS), cardiac failure, stroke, defibrillator (DF) implantation, myomectomy/septal ablation, new atrial fibrillation (AF), new syncope, and non-sustained ventricular tachycardia (NSVT). Results Thirty-six patients (10%) had LVOT obstruction at rest (>30 mmHg), and 91 (25%) developed exercise-induced LVOT obstruction (>50 mmHg). Abnormal ExE based on exercise wall motion abnormalities (WMAs) was found in 63 patients (17%). E/e´>14 was observed in 178 patients at rest (48%) and in 180 at exercise (49%). Corresponding figures for significant MR (moderate or severe) were 24 (7%) and 24 (7%).During follow-up of 7.7±3.9 years, 148 patients had a first event, (overall death, 34; ACS, 17; cardiac failure, 6; stroke, 13; DF implantation, 16; myomectomy/septal ablation, 4; new AF, 41; new syncope, 3; and NSVT, 14. Independent predictors of a first event were treatment with nitrates (HR=4.8; 95% CI=1.7-13.8, p=0.004), maximal wall thickness (HR=1.1; 95% CI=1.1-1.2, p<0.001), LVOT obstruction at rest (HR=1.7; 95%CI=1.1-2.8, p=0.01), E/e´ at exercise (HR=1.04; 95%CI=1.01-1.06, p=0.004) and LVEF at peak exercise (HR=0.96; 95% CI=0.94-0.99, p=0.006). Independent predictors of overall death (n=48) were age (HR=1.05; 95% CI=1.02-1.09, p=0.002), WMSI at rest (HR=23.8; 95% CI=1.02-556.5, p=0.049), LVOT obstruction at rest (HR=2.8; 95% CI=1.5-5.3, p=0.001) and achieved workload in metabolic equivalents (HR=0.88; 95% CI=0.80-0.98, p=0.02) Patients with genetic abnormalities were younger, had lower prevalence of hypertension and of treatment with ACEI/ARAII. The presence of abnormal ExE, LV obstruction, significant MR, and raised E/e´ values at either rest or exercise were similar between patients with/without pathological genetic testing. Patients with genetic abnormalities had slightly lower peak LVEF, although within normal limits (p=0.049). A positive genetic testing was not predictive of events. Conclusions A comprehensive ExE assessment provides long-term prognostic information in patients with HCM. Both LV systolic and diastolic function with exercise performed well for this purpose. There were no significant differences regarding the presence/absence of genetic testing abnormalities.Kaplan Meier curves