Short atrioventricular delay pacing therapy in young and old patients with hypertrophic obstructive cardiomyopathy: good long-term results and a low need for reinterventions.

Aims: Examination of long-term results following different treatments in hypertrophic obstructive cardiomyopathy (HOCM) in a complete geographical cohort. Methods and results: HOCM patients attending during 2002-13 in all 10 hospitals in the West Götaland Region, Sweden, were identified (n = 251), follow-up 14.4 (±8.9) years (mean ± SD), 121 managed medically, 42 treated with myectomy and 88 with short atrioventricular (AV) delay pacing as first interventional procedure. Post-intervention follow-up was 12.9 ± 8.7 years and 12.2 ± 5.0 years, respectively. Both intervention treatments improved New York Heart Association (NYHA) class and outflow gradients significantly. Patients treated with pacing were older (median age 64 vs. 43 years, P < 0.001). Freedom from disease-related death post-procedure at 5, 10, and 20 years were 93%, 80%, 56% vs. 93%, 93%, 57% in pacing and myectomy groups, respectively (log-rank P = 0.43). Survival after diagnosis was not different in patients just treated conservatively (P = 0.51 pacing/conservative; P = 0.39 myectomy/conservative). Reintervention for outflow gradients in patients ≥18 years at procedure occurred in 3.5% in pacing group and 15.6% in myectomy group (P = 0.007). Pacing therapy was equally effective in patients aged 13-64 years (n = 44), as in patients ≥65 years (n = 44): resting gradient pre-procedure and at last follow-up were median (IQR) 65 (71) and 12 (20) mmHg for <65 year-olds (P < 0.001), and 75 (64) and 14 (38) mmHg, respectively, for ≥65 year-olds (P < 0.001). New York Heart Association class improved significantly in both age ranges to 1.6 ± 0.6 and 1.8 ± 0.7, respectively (P < 0.001; P < 0.001). Conclusion: Short AV delay pacing provided lasting satisfactory relief of symptoms and outflow obstruction in the majority of patients, with low risk of requiring reintervention. Our findings support the view that pacing therapy should be considered a valid option to treat patients with HOCM.

Factors associated with excess female mortality in obstructive hypertrophic cardiomyopathy.

BACKGROUND: Several studies have reported excess female mortality in patients with hypertrophic cardiomyopathy, but the cause is unknown. AIMS: To compare risk-factors for disease-related death in both sexes in a geographical cohort of patients with obstructive hypertrophic cardiomyopathy (oHCM). METHODS AND RESULTS: Data-bases in all ten hospitals within West Götaland Region yielded 250 oHCM-patients (123 females, 127 males). Mean follow-up was 18.1 y. Risk-factors for disease-related death were evaluated by Cox-hazard regression and Kaplan-Meier survival-curves, with sex-comparisons of distribution of risk-factors and therapy in total and age-matched (n = 166) groups. At diagnosis females were older, median 62 y vs. 51 y, (P < 0.001), but not different in outflow-gradients and median NYHA-class. However, septal hypertrophy was more advanced: 10.6 [IQR = 3.2] vs. 9.6 [2.5] mm/m2 BSA; P = 0.002. Females had higher disease-related mortality than males (P = <0.001), with annual mortality 2.9% vs. 1.5% in age-matched groups (P = 0.010 log-rank). For each risk-category identified (NYHA-class ≥ III, outflow-gradient ≥50 mmHg), a higher proportion of females died (P = 0.0004; P = 0.001). Calcium-blocker therapy was a risk-factor (P = 0.005) and was used more frequently in females (P = 0.034). A beta-blocker dose above cohort-median reduced risk for disease-related death in both males (HR = 0.32; P = 0.0040) and in females (HR = 0.49; P = 0.020). Excess female deaths occurred in chronic heart-failure (P = 0.001) and acute myocardial infarctions (P = 0.015). Fewer females received beta-blocker therapy after diagnosis (64% vs. 78%, P = 0.018), in a smaller dose (P = 0.007), and less frequently combined with disopyramide (7% vs. 16%, P = 0.048). CONCLUSION: Addressing sex-disparities in the timing of diagnosis and pharmacological therapy has the potential to improve the care of females with oHCM.

Morbidity and resource usage after myectomy- or pacing-treatment in hypertrophic obstructive cardiomyopathy: A case-control study.

BACKGROUND: Treatment of left ventricular outflow-obstruction (LVOTO) in hypertrophic obstructive cardiomyopathy (HOCM) by short atrio-ventricular delay pacing has long-term hemodynamic results that are not inferior to myectomy, but publications comparing long-term morbidity following those treatments are lacking. METHODS: A search for HOCM-patients attending all ten hospitals in the West Götaland Region, Sweden, from 2002 through 2013, identified 251 patients (42 treated with myectomy, 88 with pacing and 121 conservatively). As the age at procedure was significantly lower in the myectomy-group compared to the pacing-group, morbidity was compared by case-control methodology, matching patients for age, maximal wall thickness and LVOT-gradient. We found 31 pairs who constituted the comparison-groups. Post-intervention median follow-up was 15.4 and 10.4 years in pacing- and myectomy-group, respectively. Post-procedural and long-term complications and re-interventions, length of stay, and cost of hospitalization were documented. RESULTS: Both treatments improved New York Heart Association class and LVOT-gradients significantly. There were fewer peri-procedural complications in the pacing-group compared to myectomy-group (3.2% and 35.5% p < 0.001). During follow-up pacemaker was implanted in 35.5% of myectomy-group for atrio-ventricular block, 9.7% peri-operatively, and 25.8% during late-follow-up. Furthermore, the pacing group had a superior freedom from all re-interventions, 90.3% versus 61.3% in myectomy-group (p = 0.003). Pacing patients had a shorter in-hospital stay (median 4 [IQR = 2] days) compared to myectomy 11 [7] days; P < 0.001). The mean cost of hospitalization was 74,000 ± 16,000 SEK for pacing and 310,000 ± 180,000 SEK for myectomy, p < 0.001. CONCLUSION: Pacing is a simple and reliable treatment for drug-refractory HOCM-patients with low rate of complications and costs.

Factors influencing long-term heart failure mortality in patients with obstructive hypertrophic cardiomyopathy in Western Sweden: probable dose-related protection from beta-blocker therapy.

Objective: In order to avoid effects of referral bias, we assessed risk factors for disease-related mortality in a geographical cohort of patients with hypertrophic obstructive cardiomyopathy (HOCM), and any therapy effect on survival. Methods: Diagnostic databases in 10 hospitals in the West Götaland Region yielded 251 adult patients with HOCM (128 male, 123 female). Case notes were reviewed for clinical data and ECG and ultrasound findings. Beta-blockers were used in 71.3% of patients from diagnosis (median metoprolol-equivalent dose of 125 mg/day), and at latest follow-up in 86.1%; 121 patients had medical therapy alone, 88 short atrioventricular delay pacing and 42 surgical myectomy. Mean follow-up was 14.4±8.9 (mean±SD) years. Primary endpoint was disease-related death, and secondary endpoint heart failure deaths. Results: There were 65 primary endpoint events. Independent risk factors for disease-related death on multivariate Cox hazard regression were: female sex (p=0.005), age at diagnosis (p<0.001), outflow gradient ≥50 mm Hg at diagnosis (p=0.036) and at follow-up (p=0.001). Heart failure caused 62% of deaths, and sudden cardiac death 17%. Late independent predictors of heart failure death were: female sex (p=0.003), outflow gradient ≥50 mm Hg at latest follow-up (p=0.032), verapamil/diltiazem therapy (p=0.012) and coexisting hypertension (p=0.031), but not other comorbidities. Neither myectomy nor pacing modified survival, but early and maintained beta-blocker therapy was associated with dose-dependent reduction in disease-related mortality in the multivariate model (p=0.028), and final dose was also associated with reduced heart failure mortality (p=0.008). Kaplan-Meier survival curves analysed in initial dose bands of 0-74, 75-149 and ≥150 mg metoprolol/day showed 10-year freedom from disease-related deaths of 83.1%, 90.7% and 97.0%, respectively (ptrend=0.00008). Even after successful relief of outflow obstruction by intervention, there was survival benefit of metoprolol doses ≥100 mg/day (p=0.01). Conclusions: In population-based HOCM cohorts heart failure is a dominant cause of death and on multivariate analysis beta-blocker therapy was associated with a dose-dependent cardioprotective effect on total, disease-related as well as heart failure-related mortality.