Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy

Alcohol Septal Ablation: Historical Considerations

Alcohol septal ablation was first reported by Ulrich Sigwart in 1995. Sigwart had made the seminal observation that the degree of LVOT obstruction in patients with HCM responded favorably to ischemia caused by temporary balloon occlusion of a major septal artery, but that it returned to baseline after balloon deflation. In this first report, in three cases he was able to successfully and durably reduce the LVOT obstruction by inducing targeted necrosis of the basal interventricular septum via selective injection of alcohol into a septal artery and achieve sustained relief of symptoms that had previously been refractory to medical management. The conceptual approach is illustrated in Figure 14–1 . In subsequent reports of early experience with alcohol septal ablation in relatively small case series, successful LVOT gradient reduction and improvement in symptoms was demonstrated, although it was associated with a relatively high incidence (30% to 40%) of high-degree AV block, requiring PPM insertion. After the initial series of patients, a technical advance was recognized, whereby intraprocedural contrast echocardiographic mapping of the perfusion territory of the candidate septal artery was incorporated into the procedure, allowing more selective and precise localization of the target territory appropriate for ablation. This was associated with reduction in the rate of complications, including AV block. Since its introduction, alcohol septal ablation has been used successfully worldwide to treat a large number of severely symptomatic patients with HCM and LVOT obstruction, including patients who have undergone a previously unsuccessful surgical myectomy.

Outcomes

With respect to procedural success and outcomes, several studies have confirmed that significant reduction of the LVOT gradient and improvement of symptoms are accomplished by alcohol septal ablation in 90% or more of patients. Recent meta-analysis and reports with longer-term follow-up periods have supported immediate, short-term and sustained long-term gradient reduction and symptomatic improvement after alcohol septal ablation. Despite the absence of randomized trial data, comparisons of contemporary case series suggest that the symptomatic improvements after alcohol septal ablation appear similar to those reported after myectomy, although alcohol septal ablation is associated with a somewhat higher posttreatment LVOT gradient and higher risk of PPM implantation. A systematic review of 42 published studies analyzing results from 2959 patients undergoing alcohol septal ablation from 1996 to 2005, with an average follow-up time of about 1 year, reported a sustained reduction of the resting LVOT gradient from 65 mmHg to 16 mmHg and of the provoked LVOT gradient from 125 mmHg to 32 mmHg, associated with a significant improvement in exercise capacity and New York Heart Association (NYHA) functional class (from a mean of 2.9 to 1.2).

Long-term follow-up data from a substantial number of patients undergoing alcohol septal ablation have been reported from several centers since 2008. Welge et al reported that for 347 patients who underwent alcohol septal ablation at one center in Germany, at a follow-up period of over nearly 5 years 89% were symptomatically improved with NYHA class I or II symptoms, 74% were free of LVOT obstruction at rest, and 60% did not exhibit any provocable LVOT obstruction. Fernandes and colleagues reported long-term outcomes of alcohol septal ablation performed in 629 patients at two centers in the United States from 1996 to 2007. The mean follow-up period was 4.6 ± 2.5 years and ranged from 3 months to 10.2 years. In that series, there appeared to be a progressive decline in the LVOT gradient over the long-term follow-up period, with the mean resting gradient at baseline of 77 ± 31 mmHg decreasing to 26 ± 27 mmHg at 3 months, 20 ± 24 mmHg at 1 year, and less than 10 mmHg in those tested after 5 years (p < 0.001). During follow-up study, NYHA functional class decreased from the baseline of 2.8 ± 0.6 to 1.2 ± 0.5 (p < 0.001); Canadian Cardiovascular Society (CCS) angina class decreased from 2.1 ± 0.9 to 1.0 ± 0 (p < 0.001); and exercise time increased from 4.8 ± 3.3 to 8.2 ± 1.0 minutes (p < 0.001) ( Figure 14–2 ). The survival estimates were favorable at 1, 5, and 8 years at 97%, 92%, and 89%, respectively. The rate of new pacemakers required for high-degree heart block was 9.7%. Within this cohort, 14% underwent repeat alcohol septal ablation and 4% underwent myectomy for unsatisfactory initial results. Sorajja et al reported outcomes from 138 patients who underwent alcohol septal ablation at the Mayo Clinic from 1999 to 2006. In that series, the 4-year survival rate free of death and severe NYHA class III/IV symptoms after alcohol septal ablation was 76.4%, and 71 patients (51%) became asymptomatic. They noted, however, from a nonrandomized comparison, that the rate of procedural complications appeared higher than in age- and gender-matched patients who had undergone septal myectomy at the Mayo Clinic, especially among younger patients. Jensen and colleagues recently reported long-term outcomes of alcohol septal ablation among 279 patients with HCM, many of whom had significant comorbidities, performed from 1999 to 2010 in four Scandinavian centers. In their experience, the median LVOT gradient at rest was reduced by alcohol septal ablation from 58 to 12 mmHg at 1-year (p < 0.001), and the gradient provoked by Valsalva maneuver was reduced from 93 to 21 mmHg (p < 0.001). The proportion of patients with NYHA class III/IV symptoms was reduced from 94% to 21% (p < 0.001), and the proportion of patients with syncope was reduced from 18% to 2% (p < 0.001). In-hospital mortality was low at 0.3%. The 1-, 5- and 10-year survival rates were 97%, 87%, and 67%, respectively (p < 0.06 vs. an age- and sex-matched background population).

A report of a large-scale North American registry has provided additional important information from a multicenter experience involving 874 patients undergoing alcohol septal ablation at nine centers from 2000 to 2010. Before the procedure nearly 80% of patients had NYHA class III or IV heart failure symptoms; 43% of patients had CCS class III or IV angina; and 29% reported syncope. After the procedure, there was significant symptomatic improvement, with fewer than 5% of patients having NYHA class III or IV heart failure, less than 1% of patients having CCS class III angina (none had class IV), and only 2.9% of patients with syncope. Among the patients in the registry, survival estimates at 1, 5, and 9 years were 97%, 86%, and 74%, respectively. The authors noted that the overall survival rate at 1 year after alcohol septal ablation (97% vs. 98%) was similar to that seen in a disease-free general population, and survival at 1, 5, and 9 to 10 years appeared better after alcohol septal ablation compared with patients reported in other series, who had HCM and did not undergo septal reduction therapy.

Despite the high success rate of alcohol septal ablation, a small proportion (<10%) of patients may not achieve adequate hemodynamic or clinical response. Among several potential causes, insufficient necrosis and thinning of the basal septal hypertrophy may be the most common etiology. Patients who undergo alcohol septal ablation and are found at follow-up study to have significant residual LVOT gradients, and unrelieved or recurrent symptoms may benefit from a second septal reduction procedure. Among patients in the reported series, approximately 6% to 14% underwent repeat alcohol septal ablation, with reportedly favorable hemodynamic and symptomatic outcomes, and 2% to 3% underwent surgical myectomy, also with favorable outcomes but a possibly higher risk of postoperative pacemaker requirement caused by AV block, compared with patients undergoing myectomy without a prior history of septal ablation. It should be noted, however, that in the North American registry, multivariate analysis suggested that repeat alcohol septal ablation procedures may be associated with higher long-term mortality risk.