Robbert C. Steggerda

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.

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.

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.

The patient with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is characterised by idiopathic hypertrophy of the left ventricle (LV), sometimes accompanied by hypertrophy of the right ventricle. HCM is estimated to occur in 1:500 subjects in the general population.1 The disease is inherited as an autosomal dominant trait, but about 50% of the patients do not have relatives with HCM, suggesting sporadic mutations, unidentified genes or more complex patterns of heredity. The presentation of the disease is diverse with on the one hand asymptomatic subjects diagnosed through family screening or routine clinical examination, and on the other hand severely symptomatic subjects with impaired LV systolic function. Patients may also present with sudden cardiac death (SCD). The distribution of hypertrophy is also variable; the most common pattern is asymmetrical septal hypertrophy, but other LV morphologies are seen including concentric hypertrophy, apical hypertrophy, and hypertrophy of the LV free wall. About one quarter of patients have obstruction of the left ventricular outflow tract (LVOT); less commonly, dynamic obstruction may occur in the mid LV cavity or at the right ventricular (RV) outflow tract.2 3 Microscopy demonstrates a variety of abnormalities, including myocyte hypertrophy, myocardial fibre disarray (myocytes are not in parallel but lay chaotically intersected), interstitial and perivascular fibrosis, and intimal and medial hypertrophy in intramural arteries leading to narrowing of the microcirculation. These abnormalities are thought to contribute to LV diastolic dysfunction by impairing relaxation and reducing compliance as well as to scarring of the myocardium. Fibrosis and scarring may predispose to ventricular and atrial arrhythmias. Elevated left atrial and LV end diastolic pressures lead to reduced stroke volume, reduced cardiac output, and pulmonary congestion. The cardiomyopathic abnormalities are not confined to the (mostly septal) hypertrophic ventricular segments, and can be demonstrated in non-hypertrophied myocardium. Many patients show diffuse hypertrophy of the LV; in about …

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).

Optimal gradient reduction after alcohol septal ablation: a case report with anatomical and practical determinants.

IntroductionRecent meta-analyses have shown good long-term survivalof patients with hypertrophic obstructive cardiomyopathy(HOCM) after alcohol septal ablation (ASA) comparablewith surgical myectomy. However, gradient reduction afterASA was slightly less favourable [1, 2] and in a single-centre study a higher rate of aborted sudden cardiac deathwas found [3]. The following case report illustrates theimportance of coronary anatomy and infarction location indetermining the outcome after ASA.Case reportA 53-year-old male patient was referred to undergoalcohol septal ablation (ASA) for symptoms due tohypertrophic obstructive cardiomyopathy despite medicaltherapy. His echocardiogram revealed a septal wallthickness of 18 mm, severe systolic anterior motion ofthe mitral valve and a severe posterolaterally directed mitralvalve regurgitation. The gradient in the left ventricularoutflow tract was 54 mmHg at rest and 100 mmHg aftervalsalva manoeuvres.Coronary angiography revealed two septal branches ofwhich the first was very small and could not becannulated. Subsequently, the second branch (S2) wascannulated (Fig. 1) and myocardial contrast echocardiog-raphy(MCE)wasusedtodelineatetheperfusedareaacross the septal contact areaof the mitral valve. However,during probatory inflation of the balloon the invasivelymeasured gradient was only reduced from 60 mmHg to50 mmHg (Fig. 2a and 2b). Also after injection of 2 ml ofalcohol, the gradient remained elevated at 50 mmHg.Therefore, after perseverance, the smaller and moreproximal septal branch was successfully cannulated. Afterprobatory inflation of the balloon, the gradient resolvedcompletely and this septal branch was ablated as well(Fig. 2c). The second ablation resulted in completeresolution of the outflow tract gradient (Fig.2d), but wasoffset by the necessity for pacemaker implantation due tototal AV block. An MRI was performed three days afterthe procedure and revealed an infarction of the entire basalpart of the septum (Fig.3). At three months follow-up theechocardiogram revealed a gradient in the outflow tract ofonly 10 mmHg and the patient no longer experiencedshortness of breath.DiscussionPatients with HOCM can exhibit severely reducedexercise tolerance. A prevalvular obstruction is causedby a thickened protruding septum and systolic anteriormotion of the mitral valve (SAM). Gradient reductioncan be achieved by surgical removal of part of thethickened septum or by ASA. With ASA, alcohol isselectively infused in an appropriate septal branch. Thiscauses infarction and thinning of the septum. Firstprobatory balloon inflation and later myocardial contrastechocardiography (MCE) were introduced for guidanceand selection of the appropriate branch for ASA.

Septal ablation for hypertrophic cardiomyopathy: outcomes in the past, the present and the future

The first descriptions of alcohol septal ablation (ASA) arose around 1994–1995. Based on the findings of a gradient reduction during temporary balloon occlusion of the first septal branch, combined with the long-lasting experience of transcoronary injection of ethanol for cardiac arrhythmia, this method was further developed. During the first procedures, an inflated balloon was temporarily placed in the first septal branch to induce ischaemia. Simultaneous pressure recordings with a catheter in the left ventricle and the aorta were used to observe a reduction of at least 30% of the gradient. When a pressure drop was observed, 96% of ethanol (average 4–6 mL) was injected through the balloon catheter in order to induce a sustained reduction of the gradient. The first reported periprocedural mortality rate in 62 patients was 4%, and permanent pacemaker (PM) implantation was necessary in 38% of all patients. The potential risk of ventricular rhythm disturbances was recognised from the inception of the ASA procedure. An extensive study was published in 1999 by Gietzen et al , including electrophysiological testing and a pathoanatomical study. Surprisingly, electrophysiological induction of sustained ventricular tachycardia (VT) occurred only in 2.6% of patients after the ASA procedure. This was much lower than the 20%–34% reported inducible sustained VT after myocardial infarction. The histological pattern of the alcohol-induced scar showed a different pattern as compared with the one known after myocardial infarction. ‘A well-defined area, characterized by a homogeneous necrosis with contracted fibers encircled by a sharply demarcated scar’ was thus seen in deceased ASA patients.1 This was thought to be the reason why patients after ASA …