William H. Spencer

Alcohol Septal Ablation for the Treatment of Hypertrophic Obstructive Cardiomyopathy: A Multicenter North American Registry

OBJECTIVESnThe purpose of the study is to identify the predictors of clinical outcome (mortality and survival without repeat septal reduction procedures) of alcohol septal ablation for the treatment of patients with hypertrophic obstructive cardiomyopathy.nnnBACKGROUNDnAlcohol septal ablation is used for treatment of medically refractory hypertrophic obstructive cardiomyopathy patients with severe outflow tract obstruction. The existing literature is limited to single-center results, and predictors of clinical outcome after ablation have not been determined. Registry results can add important data.nnnMETHODSnHypertrophic obstructive cardiomyopathy patients (N = 874) who underwent alcohol septal ablation were enrolled. The majority (64%) had severe obstruction at rest, and the remaining had provocable obstruction. Before ablation, patients had severe dyspnea (New York Heart Association [NYHA] functional class III or IV: 78%) and/or severe angina (Canadian Cardiovascular Society angina class III or IV: 43%).nnnRESULTSnSignificant improvement (p < 0.01) occurred after ablation (~5% in NYHA functional classes III and IV, and 8 patients in Canadian Cardiovascular Society angina class III). There were 81 deaths, and survival estimates at 1, 5, and 9 years were 97%, 86%, and 74%, respectively. Left anterior descending artery dissections occurred in 8 patients and arrhythmias in 133 patients. A lower ejection fraction at baseline, a smaller number of septal arteries injected with ethanol, a larger number of ablation procedures per patient, a higher septal thickness post-ablation, and the use beta-blockers post-ablation predicted mortality.nnnCONCLUSIONSnVariables that predict mortality after ablation, include baseline ejection fraction and NYHA functional class, the number of septal arteries injected with ethanol, post-ablation septal thickness, beta-blocker use, and the number of ablation procedures.

Follow-up of alcohol septal ablation for symptomatic hypertrophic obstructive cardiomyopathy the Baylor and Medical University of South Carolina experience 1996 to 2007.

OBJECTIVESnThis study sought to determine the long-term outcome of alcohol septal ablation (ASA).nnnBACKGROUNDnThere are inadequate data on the long-term outcome of ASA for symptomatic hypertrophic obstructive cardiomyopathy (HOCM).nnnMETHODSnSix hundred and twenty-nine patients were enrolled consecutively (1996 to 2007) and 98.4% (n = 619) underwent ASA with 92% follow-up in 2007. Evaluation included deaths, procedural complications, pacemaker requirement, repeat ASA, and myectomy/valve surgery. Follow-up parameters included angina (Canadian Cardiovascular Society score), dyspnea (New York Heart Association functional class), exercise time, and echocardiographic indices (septal thickness, ejection fraction, resting and provoked gradients).nnnRESULTSnEthanol (2.6 +/- 1.0 ml) was injected into 1.3 +/- 0.5 septal arteries, inducing a septal infarct. Complications included death 1% (n = 6), permanent pacemaker requirement 8.2% (n = 52), coronary dissection 1.3% (n = 8), and worsening mitral regurgitation 0.3% (n = 2). The mean follow-up was 4.6 +/- 2.5 years (range: 3 months to 10.2 years). During follow-up, New York Heart Association functional class decreased from 2.8 +/- 0.6 to 1.2 +/- 0.5 (p < 0.001); Canadian Cardiovascular Society angina score 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 (p < 0.001) min. The resting and provoked left ventricular outflow tract gradients decreased progressively (p < 0.001) and remained low during follow-up. The septal thickness decreased from 2.1 +/- 0.5 cm to 1.0 +/- 0.1 cm (p < 0.001) and the ejection fraction decreased from 68 +/- 9% to 62 +/- 3% (p < 0.001). The survival estimates at 1, 5, and 8 years were 97%, 92%, and 89%, respectively.nnnCONCLUSIONSnThe initial benefits of ASA were maintained during follow-up.

Implantable Cardioverter-Defibrillator Therapy for Primary Prevention of Sudden Death After Alcohol Septal Ablation of Hypertrophic Cardiomyopathy

OBJECTIVESnThe purpose of this study was to examine the effects of alcohol septal ablation (ASA) on ventricular arrhythmias among patients with obstructive hypertrophic cardiomyopathy (HCM), as measured by appropriate implantable cardioverter-defibrillator (ICD) discharges.nnnBACKGROUNDnAlcohol septal ablation is an effective therapy for patients with symptomatic HCM. However, concern has been raised that ASA may be proarrhythmic secondary to the iatrogenic scar created during the procedure. The impact of ASA on ventricular arrhythmias has not been well described.nnnMETHODSnThis prospective study included 123 consecutive patients with obstructive HCM who underwent ASA and had an ICD implanted for primary prevention of sudden cardiac death (SCD). The ICDs were implanted based on commonly accepted risk factors for SCD in the HCM population. Data from ICD interrogations during routine follow-up were collected.nnnRESULTSnNine appropriate ICD shocks were recorded over a mean follow-up of 2.9 years in the cohort, which had a mean of 1.5 +/- 0.9 risk factors for SCD. Using Kaplan-Meier survival analysis, the estimated annual event rate was 2.8% over 3-year follow-up. There were no significant differences in the incidence of risk factors between patients who did and did not receive appropriate shocks.nnnCONCLUSIONSnThe annual rate of appropriate ICD discharges after ASA is low and less than that reported previously for primary prevention of SCD in HCM. This suggests that ASA is not proarrhythmic. Traditional SCD risk factors did not predict ICD shocks in this cohort.

Sustained Ventricular Tachycardia Following Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy

A 49‐year‐old man with a history of hypertrophic obstructive cardiomyopathy (HOCM) presented in sustained monomorphic ventricular tachycardia (SMVT) 8 days post‐alcohol septal ablation. A dual chamber implantable cardioverter defibrillator ICD was implanted and the patient experienced another episode of VT 3 weeks later, which was terminated by an ICD shock. This case demonstrates probable scar‐induced reentrant VT post‐alcohol septal ablation, a likely rare but hypothesized complication of this procedure.

Electrocardiographic Findings After Alcohol Septal Ablation Therapy for Obstructive Hypertrophic Cardiomyopathy

Ablation of the septal myocardium with alcohol in patients with obstructive hypertrophic cardiomyopathy has been shown to improve symptoms, reduce ventricular outflow gradients, and improve cardiac function. 1,2 Acute electrocardiographic changes in a small group of patients have been reported. 3,4 Later changes have not been evaluated. This study presents 165 patients who underwent ablation therapy and preand post-procedure electrocardiography. ••• One hundred sixty-five consecutive patients treated for symptomatic obstructive hypertrophic cardiomyopathy with alcohol septal reduction therapy underwent pre- and post-procedure electrocardiography. All patients had symptoms refractory to medical therapy and resting gradients of 40 mm Hg or a dobutamineprovoked gradient 60 mm Hg using 5 to 20 g/kg/ min of dobutamine. Almost all patients were classified as having New York Heart Association class III or IV symptoms before the procedure. More details of the procedure have been reported in an earlier publication. 5 Resting 12-lead electrocardiograms were obtained before the procedure and then 2 to 286 days after ablation therapy. All electrocardiograms were reviewed independent of outcomes by 2 observers. Electrocardiograms were reviewed for Q waves, repolarization abnormalities, conduction abnormalities, QRS morphology, arrhythmias, left atrial enlargement, and left ventricular hypertrophy. Romhilt-Estes point system criteria were used to diagnose left ventricular hypertrophy. 6 The median follow-up period was 3 months (mean 60 days). Of the initial 190 patients, 25 (13%) had paced rhythms from prior placed pacemakers as a method of treatment for hypertrophic cardiomyopathy (which was unsuccessful) and were excluded from the study. The most common finding at baseline in the remaining 165 patients (Figure 1) was left ventricular hypertrophy (82 patients, 50%). Left atrial enlargement was also seen in 67 patients (41%) at baseline. Forty-nine patients (30%) were found to have significant Q waves at baseline. Most Q waves (30 of 49, 61%) were found in the septal precordial leads. Atrial fibrillation or atrial flutter was found in 8 patients (5%) before alcohol ablation. The most common conduction abnormality was left anterior fasicular block (17 patients, 10%). Six patients (4%) had right bundle branch block and 6 (4%) had left bundle branch block. First-degree atrioventricular block was noted in 9 patients (6%).

Release of matrix metalloproteinases following alcohol septal ablation in hypertrophic obstructive cardiomyopathy

OBJECTIVESnThis study examined plasma levels of certain matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) species before and after alcohol-induced myocardial infarction (MI) in patients with hypertrophic obstructive cardiomyopathy (HOCM).nnnBACKGROUNDnMatrix metalloproteinases contribute to tissue remodeling, and endogenous control of MMP activity is achieved by the concordant release and binding of TIMPs. Animal models of MI have demonstrated a role for MMP activation in myocardial remodeling. However, the temporal relationship of MMP and TIMP release following a controlled myocardial injury in humans remains unknown.nnnMETHODSnPlasma levels for the gelatinases MMP-2 and MMP-9, and for the collagenases MMP-8 and MMP-13, as well as TIMP-1 profiles were examined (by enzyme-linked immunosorbent assay) at baseline and serially up to 60 h following alcohol injection into the septal perforator artery in order to induce an MI in 51 patients with HOCM (age 55 +/- 2 years).nnnRESULTSnPlasma creatine kinase (MB isoform), indicating myocardial injury, increased 2,150% 18 h post-MI (p < 0.05). Plasma MMP-9 increased by over 400% and MMP-8 by over 100% from baseline values by 12 h post-MI (p < 0.05 vs. baseline). A similar temporal profile was not observed for MMP-2 and MMP-13. In addition, a concomitant increase in plasma TIMP-1 levels did not occur post-MI. As a result, MMP/TIMP stoichiometry (MMP-9/TIMP-1 ratio) increased significantly post-MI, suggestive of reduced TIMP-1 mediated MMP-9 inhibition, which would potentially enhance extracellular myocardial remodeling.nnnCONCLUSIONSnThese unique results demonstrated that induction of a controlled myocardial injury in humans, specifically through alcohol-induced MI, caused species- and time-dependent perturbations of MMP/TIMP stoichiometry that would facilitate myocardial remodeling in the early post-MI setting.

T wave alternans for ventricular arrhythmia risk stratification.

Identifying patients at high risk of sudden cardiac death is an important goal, given the magnitude of this problem. In this regard, T wave alternans (TWA) is a heart-rate–dependent measure of arrhythmia vulnerability. The predictive accuracy of this test is maximal at heart rates between 100 and 120 bpm, which are usually achieved with exercise or atrial pacing. TWA has been shown to predict inducibility of ventricular tachycardia with programmed stimulation and to predict spontaneous arrhythmic events. This test has been applied to diverse populations, including patients with coronary artery disease, nonischemic cardiomyopathy, congestive heart failure, and status post implantable defibrillators. Despite these encouraging results, the role of TWA to guide clinical therapy still must be better elucidated.