Alcohol septal ablation in hypertrophic cardiomyopathy: For which patients?

Percutaneous and surgical therapies for septal reduction for hypertrophic cardiomyopathy have been going head-to-head for the past 20 years with similar outcomes and mortality rates, although contemporary myectomy seems to materialize its superiority. However, on closer analysis, the external validity of studies advocating myectomy does not translate to all centres. The aim of this review was to examine the most recent data on septal reduction therapy and to attempt to phenotype the appropriate patient for each of the two treatments. The key to similar low mortality rates between ventricular septal myectomy and alcohol septal ablation appears to be proper patient selection performed in high volume clinical environments. Furthermore, we analyse the role of mavacampten (the recently approved cardiac myosin inhibitor) in replacing or complementing the two septal reduction therapies.

Living history of medicine: vascular scaffolding, from dream to reality.

Following the launch of balloon angioplasty in 1977, its deficiencies-abrupt occlusion requiring emergency bypass surgery in one in twenty attempts and recurrence in one in three cases-became soon apparent. The attempts to eliminate the element of chance from this otherwise highly attractive technique resulted in the concept of intra-vascular scaffolding. Following the inception of self-expanding mesh stents made from stainless steel and extensive bench testing and animal experiments, the first clinical data were obtained in Switzerland almost 30 years ago in 1986 with promising, albeit not undisputed results. Technical improvements including potent platelet inhibitors have made the technique a cornerstone of catheter-treatment of vascular disease. This paper gives an account of the sometimes difficult beginnings of coronary and non-coronary stenting at the University of Lausanne in Switzerland.

Computed tomography angiography planning identifies the target vessel for optimum infarct location and improves clinical outcome in alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

AIMS: Alcohol septal ablation (ASA) is an established treatment option in hypertrophic obstructive cardiomyopathy (HOCM). ASA is ineffective in some: inaccurate infarct and inability to identify a vessel contribute. We aimed to improve accuracy of infarct using CT angiography guidance and provide a more predictable and satisfactory outcome. METHODS AND RESULTS: Twenty-one successive patients with symptomatic LVOT obstruction refractory to medication underwent CT angiography planning to guide ASA. CT was performed using a dual-source CT system. Alcohol was delivered to the artery identified from CT: in 17/21 this was a sub-branch of a septal artery, in 2/21 the septal vessel was identified from the circumflex artery. Peak gradient improved from 98 (IQR 89.50-111.50) mmHg to 14 (IQR 8.50-22) mmHg (p=0.003). Systolic anterior motion (SAM) improved in 18/20 patients. NYHA class improved by ≥1 in 18/20. Peak VO2 improved from 79.19% of predicted value (±14.01) to 91.62% (±12.02) predicted (p<0.0001). Success at the first procedure is greater with CT guidance, 17/20 vs. 50/75 with traditional methods (pre-CT guidance) (p=0.02); 9/20 had six-month CMR with target septum infarct in all. ASA-related RBBB reduced from 62% to 13% (p=0.0004). CONCLUSIONS: CT angiography planning improves localisation of infarct and procedural success at the first attempt in ASA when compared to traditional methods. Follow-up to six months suggests a symptomatic, functional and haemodynamic improvement.

Adverse events following percutaneous and surgical coronary revascularisation: Analysis of non-MACE outcomes in the Stent or Surgery (SoS) Trial.

OBJECTIVES: To analyse adverse events requiring or prolonging hospitalisation in the Stent or Surgery (SoS) trial. BACKGROUND: Many adverse events following coronary revascularisation are non-major adverse cardiovascular events (non-MACE). Trials comparing percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG) have reported rates of mortality and MACE only. MATERIAL AND METHODS: Comparisons between PCI and CABG groups in the SOS trial were by intention to treat. For patients with non-fatal/non-MACE, number of events per 100 patient years follow-up and duration of hospital stay were assessed. Competing risk analysis was used to illustrate temporal pattern of adverse outcomes. RESULTS: During 2 y median follow up, 1 one or more adverse event occurred in 47.3% (231) of the PCI group and 53% (265) of the CABG group (p=0.086). Non-fatal/non-MACE occurred in 11.9% of the PCI group and 38.6% of the CABG group (p<0.001). Non-fatal/non-MACE per 100 patient years follow-up was 17.49 (PCI) and 35.04 (CABG), rate ratio 2.0, 95% CI 1.7 to 2.4, p<0.001. Cumulative non-fatal/non-MACE associated hospital stays were 1387 and 3287 days in PCI and CABG groups respectively. Median duration of hospitalisation per non-fatal/non-MACE was 5 days (interquartile range 2 to 11.75 days) in the PCI group and 6 days (interquartile range 2 to 12 days) in the CABG group, p=0.245. CONCLUSIONS: CABG had lower cumulative incidence of fatal or MACE outcomes, higher cumulative incidence of non-fatal/non-MACE outcomes, and longer cumulative hospitalisation periods compared to the PCI group.

Treatment of coronary artery disease from the inside: Light at the end of the tunnel?

Surgical treatment of coronary heart disease has shown its life saving benefits in millions of patients for more than half a century. Attempts to create less invasive ways to achieve similar results have attracted great attention since the introduction of balloon angioplasty in 1977. The fascination with such techniques was hampered by a 30% recurrence rate and a 5% rate of abrupt closure, requiring emergency bypass surgery in most instances. Angioplasty lost much of its unpredictability with the introduction of stents in 1986. The use of potent anti-platelet regimes added further safety, but recurrence remained a definite thread until the introduction of anti-mitotic coatings during the early years of this century. Very late thrombosis, however, continues to haunt interventionist and patients. Vanishing poly-lactic acid stents time still fail to exhibit comparable mechanical properties at present. So far bypass surgery has not yet lost its attraction in complicated and diffuse disease, despite its much higher patient discomfort.

Therapeutic management of hypertrophic obstructive cardiomyopathy: alcohol septal ablation or surgical myomectomy?

Hypertrophic cardiomyopathy (HCM) is characterized as left ventricular hypertrophy unexplained by abnormal loading conditions. Approximately 30% of patients with HCM will develop left ventricular outflow obstruction under resting conditions. In the 5-10% of patients with drug-refractory symptoms, surgical septal myectomy has been shown to reduce outflow obstruction and relieve symptoms; however, some patients may be at increased risk for surgery. Since 1994, when alcohol septal ablation was introduced, an increasing number of patients have opted for the percutaneous approach, which aims to mimic the anatomic and hemodynamic effects of surgical septal myectomy. The less-invasive version of septal reduction therapy comes at a price: a larger number of pacemaker implantations and, sometimes, depending on the individual's coronary anatomy, a higher residual gradient. Despite these shortcomings and the absence of randomized trials, alcohol septal ablation has established itself as a viable option for patients with obstructive HCM.

The effect of age on outcomes of coronary artery bypass surgery compared with balloon angioplasty or bare-metal stent implantation among patients with multivessel coronary disease. A collaborative analysis of individual patient data from 10 randomized trials.

OBJECTIVES: This study sought to assess whether patient age modifies the comparative effectiveness of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI). BACKGROUND: Increasingly, CABG and PCI are performed in older patients to treat multivessel disease, but their comparative effectiveness is uncertain. METHODS: Individual data from 7,812 patients randomized in 1 of 10 clinical trials of CABG or PCI were pooled. Age was analyzed as a continuous variable in the primary analysis and was divided into tertiles for descriptive purposes (≤56.2 years, 56.3 to 65.1 years, ≥65.2 years). The outcomes assessed were death, myocardial infarction and repeat revascularization over complete follow-up, and angina at 1 year. RESULTS: Older patients were more likely to have hypertension, diabetes, and 3-vessel disease compared with younger patients (p < 0.001 for trend). Over a median follow-up of 5.9 years, the effect of CABG versus PCI on mortality varied according to age (interaction p < 0.01), with adjusted CABG-to-PCI hazard ratios and 95% confidence intervals (CI) of 1.23 (95% CI: 0.95 to 1.59) in the youngest tertile; 0.89 (95% CI: 0.73 to 1.10) in the middle tertile; and 0.79 (95% CI: 0.67 to 0.94) in the oldest tertile. The CABG-to-PCI hazard ratio of less than 1 for patients 59 years of age and older. A similar interaction of age with treatment was present for the composite outcome of death or myocardial infarction. In contrast, patient age did not alter the comparative effectiveness of CABG and PCI on the outcomes of repeat revascularization or angina. CONCLUSIONS: Patient age modifies the comparative effectiveness of CABG and PCI on hard cardiac events, with CABG favored at older ages and PCI favored at younger ages.

Controversies in cardiovascular medicine. Hypertrophic obstructive cardiomyopathy: alcohol septal ablation.

Alcohol septal ablation (ASA) was introduced in 1994 as an alternative to septal myectomy for patients with hypertrophic obstructive cardiomyopathy and symptoms refractory to medical therapy. This procedure alleviates symptoms by producing a targeted, limited infarction of the upper interventricular septum, resulting in an increase in left ventricular outflow tract (LVOT) diameter, a decrease in LVOT gradient, and regression of the component of LV hypertrophy that is due to pressure overload. Clinical success, with improvement in symptoms and reduction in gradient, is achieved in the great majority of patients with either resting or provocable LVOT obstruction. The principal morbidity of the procedure is complete heart block, resulting in some patients in the requirement for a permanent pacemaker. The introduction of myocardial contrast echocardiography as a component of the ASA procedure has contributed to the induction of smaller myocardial infarctions with lower dosages of alcohol and, in turn, fewer complications. Non-randomized comparisons of septal ablation and septal myectomy have shown similar mortality rates and post-procedure New York Heart Association class for the two procedures.

The effect of internal thoracic artery grafts on long-term clinical outcomes after coronary bypass surgery.

OBJECTIVES: We sought to compare long-term outcomes after coronary bypass surgery with and without an internal thoracic artery graft. METHODS: We analyzed clinical outcomes over a median follow-up of 6.7 years among 3,087 patients who received coronary bypass surgery as participants in one of 8 clinical trials comparing surgical intervention with angioplasty. We used 2 statistical methods (covariate adjustment and propensity score matching) to adjust for the nonrandomized selection of internal thoracic artery grafts. RESULTS: Internal thoracic artery grafting was associated with lower mortality, with hazard ratios of 0.77 (confidence interval, 0.62-0.97; P = .02) for covariate adjustment and 0.77 (confidence interval, 0.57-1.05; P = .10) for propensity score matching. The composite end point of death or myocardial infarction was reduced to a similar extent, with hazard ratios of 0.83 (confidence interval, 0.69-1.00; P = .05) for covariate adjustment to 0.78 (confidence interval, 0.61-1.00; P = .05) for propensity score matching. There was a trend toward less angina at 1 year, with odds ratios of 0.81 (confidence interval, 0.61-1.09; P = .16) in the covariate-adjusted model and 0.81 (confidence interval, 0.55-1.19; P = .28) in the propensity score-adjusted model. CONCLUSIONS: Use of an internal thoracic artery graft during coronary bypass surgery seems to improve long-term clinical outcomes.

Rapid detection of genetic variants in hypertrophic cardiomyopathy by custom DNA resequencing array in clinical practice.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease (1/500) and the most common cause of sudden cardiac death in young people. Pathogenic mutation detection of HCM is having a growing impact on the medical management of patients and their families. However, the remarkable genetic and allelic heterogeneity makes molecular analysis by conventional methods very time-consuming, expensive and difficult to realise in a routine diagnostic molecular laboratory. METHOD AND RESULTS: The authors used their custom DNA resequencing array which interrogates all possible single-nucleotide variants on both strands of all exons (n=160), splice sites and 5'-untranslated region of 12 HCM genes (27 000 nucleotides). The results for 122 unrelated patients with HCM are presented. Thirty-three known or novel potentially pathogenic heterozygous single-nucleotide variants were identified in 38 patients (31%) in genes MYH7, MYBPC3, TNNT2, TNNI3, TPM1, MYL3 and ACTC1. CONCLUSIONS: Although next-generation sequencing will replace all large-scale sequencing platforms for inherited cardiac disorders in the near future, this HCM resequencing array is currently the most rapid, cost-effective and reasonably efficient technology for first-tier mutation screening of HCM in clinical practice. Because of its design, the array is also an appropriate tool for initial screening of other inherited forms of cardiomyopathy.

Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials.

BACKGROUND: Coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) are alternative treatments for multivessel coronary disease. Although the procedures have been compared in several randomised trials, their long-term effects on mortality in key clinical subgroups are uncertain. We undertook a collaborative analysis of data from randomised trials to assess whether the effects of the procedures on mortality are modified by patient characteristics. METHODS: We pooled individual patient data from ten randomised trials to compare the effectiveness of CABG with PCI according to patients' baseline clinical characteristics. We used stratified, random effects Cox proportional hazards models to test the effect on all-cause mortality of randomised treatment assignment and its interaction with clinical characteristics. All analyses were by intention to treat. FINDINGS: Ten participating trials provided data on 7812 patients. PCI was done with balloon angioplasty in six trials and with bare-metal stents in four trials. Over a median follow-up of 5.9 years (IQR 5.0-10.0), 575 (15%) of 3889 patients assigned to CABG died compared with 628 (16%) of 3923 patients assigned to PCI (hazard ratio [HR] 0.91, 95% CI 0.82-1.02; p=0.12). In patients with diabetes (CABG, n=615; PCI, n=618), mortality was substantially lower in the CABG group than in the PCI group (HR 0.70, 0.56-0.87); however, mortality was similar between groups in patients without diabetes (HR 0.98, 0.86-1.12; p=0.014 for interaction). Patient age modified the effect of treatment on mortality, with hazard ratios of 1.25 (0.94-1.66) in patients younger than 55 years, 0.90 (0.75-1.09) in patients aged 55-64 years, and 0.82 (0.70-0.97) in patients 65 years and older (p=0.002 for interaction). Treatment effect was not modified by the number of diseased vessels or other baseline characteristics. INTERPRETATION: Long-term mortality is similar after CABG and PCI in most patient subgroups with multivessel coronary artery disease, so choice of treatment should depend on patient preferences for other outcomes. CABG might be a better option for patients with diabetes and patients aged 65 years or older because we found mortality to be lower in these subgroups.

Randomized, controlled trial of coronary artery bypass surgery versus percutaneous coronary intervention in patients with multivessel coronary artery disease: six-year follow-up from the Stent or Surgery Trial (SoS).

BACKGROUND: The Stent or Surgery Trial is a randomized, controlled trial comparing percutaneous coronary intervention with coronary artery bypass grafting (CABG) for patients with multivessel disease. Initial results at a median follow-up of 2 years showed a survival advantage for patients randomized to CABG. This article reports survival outcome at a median follow-up of 6 years. METHODS AND RESULTS: A total of 988 (n=488 percutaneous coronary intervention, n=500 CABG) patients were randomized at 53 centers during the period from 1996 to 1999. Investigators established survival status from hospital or community medical records or national databases or by direct contact with patients and their relatives. All-cause mortality was compared with hazard ratios and confidence intervals calculated from Cox proportional hazards models. Prespecified subgroup analyses for diabetes mellitus, angina grade, and angiographic severity of coronary disease at baseline were performed with tests for interaction. At a median follow-up of 6 years, 53 patients (10.9%) died in the percutaneous coronary intervention group compared with 34 (6.8%) in the CABG group (hazard ratio 1.66, 95% confidence interval 1.08 to 2.55, P=0.022). Little evidence was found that the treatment effect on mortality differed between subgroups according to baseline angina grade (interaction test P=0.52), the severity of coronary disease (P=0.92), or diabetic status (P=0.15). CONCLUSIONS: At a median follow-up of 6 years, a continuing survival advantage was observed for patients managed with CABG, which is not consistent with results from other stent-versus-CABG studies.