Max Liebregts

Long-Term Outcomes After Medical and Invasive Treatment in Patients With Hypertrophic Cardiomyopathy

OBJECTIVES The aim of this study was to determine the long-term outcomes (all-cause mortality and sudden cardiac death [SCD]) after medical therapy, alcohol septal ablation (ASA), and myectomy in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND Therapy-resistant obstructive HCM can be treated both surgically and percutaneously. But there is no consensus on the long-term effects of ASA, especially on SCD. METHODS This study included 1,047 consecutive patients with HCM (mean age 52 ± 16 years, 61% men) from 3 tertiary referral centers. A total of 690 patients (66%) had left ventricular outflow tract gradients ≥ 30 mm Hg, of whom 124 (12%) were treated medically, 316 (30%) underwent ASA, and 250 (24%) underwent myectomy. Primary endpoints were all-cause mortality and SCD. Kaplan-Meier graphs and Cox regression models were used for statistical analyses. RESULTS The mean follow-up period was 7.6 ± 5.3 years. Ten-year survival was similar in medically treated patients (84%), ASA patients (82%), myectomy patients (85%), and patients with nonobstructive HCM (85%) (log-rank p = 0.50). The annual rate of SCD was low after invasive therapy: 1.0%/year in the ASA group and 0.8%/year in the myectomy group. Multivariate analysis demonstrated that the risk for SCD was lower after myectomy compared with the ASA group (hazard ratio: 2.1; 95% confidence interval: 1.0 to 4.4; p = 0.04) and the medical group (hazard ratio: 2.3; 95% confidence interval: 1.0 to 5.2; p = 0.04). CONCLUSIONS Patients with obstructive HCM who are treated at referral centers for HCM care have good survival and low SCD risk, similar to that of patients with nonobstructive HCM. The SCD risk of patients after myectomy was lower than after ASA or in the medical group.

A systematic review and meta-analysis of long-term outcomes after septal reduction therapy in patients with hypertrophic cardiomyopathy

OBJECTIVES The aim of this meta-analysis was to compare long-term outcomes after myectomy and alcohol septal ablation (ASA) in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND Surgical myectomy and ASA are both accepted treatment options for medical therapy-resistant obstructive HCM. Previous meta-analyses only evaluated short-term outcomes. METHODS A systematic review was conducted for eligible studies with a follow-up of at least 3 years. Primary outcomes were all-cause mortality and (aborted) sudden cardiac death (SCD). Secondary outcomes were periprocedural complications, left ventricular outflow tract gradient, and New York Heart Association functional class after ≥3 months, and reintervention. Pooled estimates were calculated using a random-effects meta-analysis. RESULTS Sixteen myectomy cohorts (n = 2,791; mean follow-up, 7.4 years) and 11 ASA cohorts (n = 2,013; mean follow-up, 6.2 years) were included. Long-term mortality was found to be similarly low after ASA (1.5% per year) compared with myectomy (1.4% per year, p = 0.78). The rate of (aborted) SCD, including appropriate implantable cardioverter defibrillator shocks, was 0.4% per year after ASA and 0.5% per year after myectomy (p = 0.47). Permanent pacemaker implantation was performed after ASA in 10% of the patients compared with 4.4% after myectomy (p < 0.001). Reintervention was performed in 7.7% of the patients who underwent ASA compared with 1.6% after myectomy (p = 0.001). CONCLUSIONS Long-term mortality and (aborted) SCD rates after ASA and myectomy are similarly low. Patients who undergo ASA have more than twice the risk of permanent pacemaker implantation and a 5 times higher risk of the need for additional septal reduction therapy compared with those who undergo myectomy.

Long-term clinical outcome after alcohol septal ablation for obstructive hypertrophic cardiomyopathy: results from the Euro-ASA registry

AIMS The first cases of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) were published two decades ago. Although the outcomes of single-centre and national ASA registries have been published, the long-term survival and clinical outcome of the procedure are still debated. METHODS AND RESULTS We report long-term outcomes from the as yet largest multinational ASA registry (the Euro-ASA registry). A total of 1275 (58 ± 14 years, median follow-up 5.7 years) highly symptomatic patients treated with ASA were included. The 30-day post-ASA mortality was 1%. Overall, 171 (13%) patients died during follow-up, corresponding to a post-ASA all-cause mortality rate of 2.42 deaths per 100 patient-years. Survival rates at 1, 5, and 10 years after ASA were 98% (95% CI 96-98%), 89% (95% CI 87-91%), and 77% (95% CI 73-80%), respectively. In multivariable analysis, independent predictors of all-cause mortality were age at ASA (P < 0.01), septum thickness before ASA (P < 0.01), NYHA class before ASA (P = 0.047), and the left ventricular (LV) outflow tract gradient at the last clinical check-up (P = 0.048). Alcohol septal ablation reduced the LV outflow tract gradient from 67 ± 36 to 16 ± 21 mmHg (P < 0.01) and NYHA class from 2.9 ± 0.5 to 1.6 ± 0.7 (P < 0.01). At the last check-up, 89% of patients reported dyspnoea of NYHA class ≤2, which was independently associated with LV outflow tract gradient (P < 0.01). CONCLUSIONS The Euro-ASA registry demonstrated low peri-procedural and long-term mortality after ASA. This intervention provided durable relief of symptoms and a reduction of LV outflow tract obstruction in selected and highly symptomatic patients with obstructive HCM. As the post-procedural obstruction seems to be associated with both worse functional status and prognosis, optimal therapy should be focused on the elimination of LV outflow tract gradient.

Validation of the 2014 European Society of Cardiology Guidelines Risk Prediction Model for the Primary Prevention of Sudden Cardiac Death in Hypertrophic Cardiomyopathy

Background—The recently released 2014 European Society of Cardiology guidelines of hypertrophic cardiomyopathy (HCM) use a new clinical risk prediction model for sudden cardiac death (SCD), based on the HCM Risk-SCD study. Our study is the first external and independent validation of this new risk prediction model. Methods and Results—The study population consisted of a consecutive cohort of 706 patients with HCM without prior SCD event, from 2 tertiary referral centers. The primary end point was a composite of SCD and appropriate implantable cardioverter-defibrillator therapy, identical to the HCM Risk-SCD end point. The 5-year SCD risk was calculated using the HCM Risk-SCD formula. Receiver operating characteristic curves and C-statistics were calculated for the 2014 European Society of Cardiology guidelines, and risk stratification methods of the 2003 American College of Cardiology/European Society of Cardiology guidelines and 2011 American College of Cardiology Foundation/American Heart Association guidelines. During follow-up of 7.7±5.3 years, SCD occurred in 42 (5.9%) of 706 patients (ages 49±16 years; 34% women). The C-statistic of the new model was 0.69 (95% CI, 0.57–0.82; P=0.008), which performed significantly better than the conventional risk factor models based on the 2003 guidelines (C-statistic of 0.55: 95% CI, 0.47–0.63; P=0.3), and 2011 guidelines (C-statistic of 0.60: 95% CI, 0.50–0.70; P=0.07). Conclusions—The HCM Risk-SCD model improves the risk stratification of patients with HCM for primary prevention of SCD, and calculating an individual risk estimate contributes to the clinical decision-making process. Improved risk stratification is important for the decision making before implantable cardioverter-defibrillator implantation for the primary prevention of SCD.

Long-Term Outcome of Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy in the Young and the Elderly

OBJECTIVES The aim of this study was to compare outcomes of alcohol septal ablation (ASA) in young and elderly patients with obstructive hypertrophic cardiomyopathy (HCM). BACKGROUND The American College of Cardiology Foundation/American Heart Association guidelines reserve ASA for elderly patients and patients with serious comorbidities. Information on long-term age-specific outcomes after ASA is scarce. METHODS This cohort study included 217 HCM patients (age 54 ± 12 years) who underwent ASA because of symptomatic left ventricular outflow tract obstruction. Patients were divided into young (age ≤55 years) and elderly (age >55 years) groups and matched by age in a 1:1 fashion to nonobstructive HCM patients. RESULTS Atrioventricular block following ASA was more common in elderly patients (43% vs. 21%; p = 0.001), resulting in pacemaker implantation in 13% and 5%, respectively (p = 0.06). Residual left ventricular outflow tract gradient, post-procedural New York Heart Association functional class, and necessity for additional septal reduction therapy was comparable between age groups. During a follow-up of 7.6 ± 4.6 years, 54 patients died. The 5- and 10-year survival following ASA was 95% and 90% in patients age ≤55 years and 93% and 82% in patients age >55 years, which was comparable to their control groups. The annual adverse arrhythmic event rate following ASA was 0.7%/year in young patients and 1.4%/year in elderly patients, which was comparable to their control groups. CONCLUSIONS ASA is similarly effective for reduction of symptoms in young and elderly patients; however, younger patients have a lower risk of procedure-related atrioventricular conduction disturbances. The long-term mortality rate and risk of adverse arrhythmic events following ASA are low, both in young and elderly patients, and are comparable to age-matched nonobstructive HCM patients.

Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy: A Word of Endorsement

Twenty years after the introduction of alcohol septal ablation (ASA) for the treatment of obstructive hypertrophic cardiomyopathy, the arrhythmogenicity of the ablation scar appears to be overemphasized. When systematically reviewing all studies comparing ASA with myectomy with long-term follow-up, (aborted) sudden cardiac death and mortality rates were found to be similarly low. The focus should instead shift toward lowering the rate of reinterventions and pacemaker implantations following ASA because, in this area, ASA still seems inferior to myectomy. Part of the reason for this difference is that ASA is limited by the route of the septal perforators, whereas myectomy is not. Improvement may be achieved by: 1) confining ASA to hypertrophic cardiomyopathy centers of excellence with high operator volumes; 2) improving patient selection using multidisciplinary heart teams; 3) use of (3-dimensional) myocardial contrast echocardiography for selecting the correct septal (sub)branch; and 4) use of appropriate amounts of alcohol for ASA.

Outcome of Alcohol Septal Ablation in Mildly Symptomatic Patients With Hypertrophic Obstructive Cardiomyopathy: A Long‐Term Follow‐Up Study Based on the Euro‐Alcohol Septal Ablation Registry

Background The long‐term efficacy and safety of alcohol septal ablation (ASA) in patients with highly symptomatic hypertrophic obstructive cardiomyopathy has been demonstrated. The aim of this study was to evaluate the long‐term outcomes of mildly symptomatic patients with hypertrophic obstructive cardiomyopathy treated with ASA. Methods and Results We retrospectively evaluated consecutive patients enrolled in the Euro‐ASA registry (1427 patients) and identified 161 patients (53±13 years; 27% women) who were mildly symptomatic (New York Heart Association [NYHA] class II) pre‐ASA. The median (interquartile range) follow‐up was 4.8 (1.7–8.5) years. The clinical outcome was assessed and compared with the age‐ and sex‐matched general population. The 30‐day mortality after ASA was 0.6% and the annual all‐cause mortality rate was 1.7%, which was similar to the age‐ and sex‐matched general population (P=0.62). A total of 141 (88%) patients had resting left ventricular outflow tract gradient at the last clinical checkup ≤30 mm Hg. Obstruction was reduced from 63±32 to 15±19 mm Hg (P<0.01), and the mean NYHA class decreased from 2.0±0 to 1.3±0.1 (P<0.01); 69%, 29%, and 2% of patients were in NYHA class I, II, and III at the last clinical checkup, respectively. Conclusions Mildly symptomatic hypertrophic obstructive cardiomyopathy patients treated with ASA had sustained symptomatic and hemodynamic relief with a low risk of developing severe heart failure. Their survival is comparable to the general population.

Low procedure-related mortality achieved with alcohol septal ablation in European patients

Two thirds of patients with hypertrophic cardiomyopathy (HCM) suffer from a left ventricular obstruction associated with more symptoms and worse prognosis [1] ; [2]. According to American and European Guidelines on HCM, there are two main therapeutic alternatives for treating the left ventricular obstruction: surgical myectomy and alcohol septal ablation (ASA) [1] ; [2]. Both these alternatives are considered safe and effective. However, Panaich et al. have recently demonstrated real world American data from the Nationwide Inpatient Sample (NIS) database showing an almost 6% in-hospital mortality rate associated with surgical myectomy [3]. This study is important because it contradicts lower, previously established post-operative mortality rates, which were estimated to be ~ 1% and were calculated using data from high-volume centers. Importantly, however, current guidelines on HCM have been based only on results of these high-volume centers [1] ; [2]. Along this line, Maron et al. recently found that in five major high-volume HCM centers in North America, the 30-day operative mortality rate was only 0.4% over the past 15 years (n = 3.696, mean age 54 ± 14 years) [4], i.e., one fifteenth of mortality rate reported by Panaich et al. [3]. A recent meta-analysis of long-term outcomes after septal reduction therapy, including 24 studies from tertiary HCM centers around the world, showed that the peri-procedural mortality rate of ASA was 1.3%, compared to 2.5% in patients undergoing myectomy [5]. However, when studies from before the year 2000 were excluded, as Maron et al. suggest [4], these figures became similarly low (1.3% vs. 1.1%, respectively). The same held true for the long-term mortality rates.

Effect of alcohol dosage on long-term outcomes after alcohol septal ablation in patients with hypertrophic cardiomyopathy

The aim of this study is to assess the long‐term effects of alcohol dosage in alcohol septal ablation (ASA) on mortality and adverse arrhythmic events (AAE).

Validation of the HCM Risk-SCD model in patients with hypertrophic cardiomyopathy following alcohol septal ablation

Aims The HCM Risk-SCD model for prediction of sudden cardiac death (SCD) in hypertrophic cardiomyopathy recommended by the 2014 European Society of Cardiology (ESC) guidelines has not been validated after septal reduction therapy. The aim of this study was to validate the HCM Risk-SCD model in patients undergoing alcohol septal ablation (ASA) and to compare its performance to previous models. Methods and result A total of 844 ASA patients without prior SCD event were included. The primary endpoint was a composite of SCD and appropriate implantable cardioverter defibrillator (ICD) therapy, identical to the HCM Risk-SCD endpoint. A distinction between periprocedural (≤30 days) and long-term (>30 days) SCD was made to discern procedure-related adverse arrhythmic events caused by the ASA-induced myocardial infarction from long-term SCD risk. Twenty patients reached the SCD endpoint within the first 30 days. During a follow-up of 6.5 ± 4.2 years, another 46 patients reached the SCD endpoint. The predicted 5-year SCD risk according to the HCM Risk-SCD model was 5.1%, and the observed 5-year SCD risk was 4.0%. The C-statistics for the use of the HCM Risk-SCD model was 0.61 (P = 0.02), the C-statistics for the use of the 2003 American College of Cardiology/ESC guidelines was 0.59 (P = 0.051), and the C-statistic for the use of the 2011 American College of Cardiology Foundation/American Heart Association guidelines was 0.58 (P = 0.054). Maximal left ventricular wall thickness, syncope after ASA, and fulfilling the 2014 ESC recommendations for primary ICD implantation according to the HCM Risk-SCD model, respectively, predicted SCD during long-term follow-up. Conclusion The HCM Risk-SCD model can be used for SCD prediction in patients undergoing ASA.