Sex and outcomes after alcohol septal ablation for patients with hypertrophic obstructive cardiomyopathy

Abstract

Hypertrophic obstructive cardiomyopathy (HOCM) is currently treated with septal reduction therapy in severely symptomatic patients who are not responsive to medical treatment. Since its introduction by Dr Ulrich Sigwart in 1995, alcohol septal ablation (ASA) has been increasingly performed across the globe. In fact, after discussion of risks, benefits and alternatives, many patients elect to undergo ASA. There have been several attempts to identify ASA outcome predictors in this patient population and there are concerns about worse outcomes in female patients. This important question is tackled in this issue of the journal by Lawin et al. The authors report on procedural outcomes at 1–4 days and at 6 months after ASA in 1367 patients with HOCM, stratified by sex. In comparison with men, women were older but had similar prevalence of coronary artery disease. Overall, symptomatic status was worse in women with more frequent syncope, and more severe dyspnoea and angina. Despite these differences, there were no apparent differences in medical therapy prior to ASA. Symptoms were corroborated by a significantly shorter 6minute walking distance (6MWD) in women prior to ASA. However, we are not told whether there was a difference in the doses of the drugs used or the combination of medications (eg, betablockers and disopyramide). Importantly, both resting gradients and exerciseinduced gradients (supine bicycle exercise to workload of 75 W for 5 min) were similar between men and women. While the basal septum was slightly thicker in men (on average for the study sample a difference of 1 mm), when indexed to body surface area (BSA), septum thickness was more in women (average difference: 0.7 mm/ m). This occurred because of the smaller BSA in women. Interestingly, despite the similar number of septal vessels occluded and volume of ethanol used in men and women, infarct size as assessed by peak creatine kinase was significantly higher in men. The magnitude of change at 6 months in basal septal thickness, rest and exerciseinduced gradients, and 6MWD was similar between men and women. Likewise, symptomatic improvement was comparable. Complications were similar, with the exception of highgrade atrioventricular (AV) block, the need for permanent pacemakers and vascular complications which occured more frequently in women, and pulmonary embolism which was more common in men. The study has the strengths of a large data set and coming from an experienced referral centre for ASA. It has several limitations acknowledged by the authors including followup being available in only 65% of women and 74% of men, the absence of baseline ECG findings and the short duration of followup. The absence of ECG findings is particularly relevant to understanding the reasons behind the higher incidence of advanced AV block in women. While the results of 6MWD at followup were included, data on exercise tolerance were not available. In general, the findings are similar to other studies showing the effects of successful ASA on symptomatic status and dynamic left ventricular outflow tract (LVOT) gradients. 3 With respect to the comparisons between men and women, the study also has similar findings to others showing the higher risk of permanent AV block in women after ASA. Earlier observations have not shown a sex difference with respect to successful outcome after ASA as defined by LVOT gradient reduction and the need for repeat ablation procedures. Similarly, in the multicentre North American registry and EuroASA registry, sex was not associated with repeat septal reduction therapy or allcause mortality. 3 Likewise, female sex was not associated with a survival difference after surgical myectomy. Going back to the higher risk of heart block in women, the authors hypothesise that a relatively higher amount of ethanol injection may be to blame. However, this did not result in a larger infarction in women as judged by peak CK level. Whether baseline differences in the conduction system (more advanced fibrosis and calcification in the conduction system in women since they were older with mean age of 66 years) could explain the higher incidence of heart block is unknown given the absence of data on baseline ECG findings. Of note, prolonged PR interval and left bundle branch block (LBBB) prior to ASA are major risk factors for advanced AV block after the procedure since ASA results in complete right bundle branch block in more than twothirds of the patients. Interestingly, previous data showed female sex remained an independent predictor of complete heart block after ASA in a multivariable logistic regression analysis that included firstdegree AV block, LBBB and number of septal perforator arteries where ethanol was injected. The operator (and his/her experience) can decrease the risk of advanced AV block by paying attention to several technical aspects of the procedure. Ethanol injection should always be targeted to the culprit septal segments by relying on myocardial contrast echocardiography (MCE) to delineate these segments instead of using probatory balloon occlusion to guide ethanol injection which relies only on gradient reduction to surmise that the cannulation of the correct septal perforator artery was achieved. The reason for this recommendation is based on data showing the use of MCE during ASA results in lower likelihood of complications and higher likelihood of procedural success. In general, the volume of ethanol injected depends on the size of the septal perforator artery but can be modulated by changes that develop in the conduction system during the procedure. Specifically, the operator administers ethanol slowly in the septal artery and looks for the development of highgrade AV block, which if present, signals the need to terminate ethanol injection so as to decrease the chances of developing permanent complete heart block. Aside from the above discussion of outcomes after ASA, the study adds to the existing literature showing the late diagnosis and more advanced symptoms in women with HOCM. The exact reasons for this consistent observation are not well elucidated but the findings in HOCM run parallel to the findings seen in other cardiovascular diseases. Practising cardiologists should have a high index of suspicion of HOCM diagnosis in women with physical examination findings that raise the possibility of dynamic obstruction. Further, with suboptimal response to medical treatment, symptomatic women Department of Cardiology, Methodist DeBakey Heart and Vascular Centre, Houston Methodist, Houston, Texas, USA