Class 1C antiarrhythmic drugs in atrial fibrillation and coronary artery disease

Class 1C antiarrhythmic drugs (AAD) are effective first-line agents for atrial fibrillation (AF) treatment. However, these agents commonly are avoided in patients with known coronary artery disease (CAD), due to known increased risk in the post-myocardial infarction population. Whether 1C AADs are safe in patients with CAD but without clinical ischemia or infarct is unknown. Reduced coronary flow capacity (CFC) on positron emission tomography (PET) reliably identifies myocardial regions supplied by vessels with CAD causing flow limitation.To assess whether treatment with 1C AADs increases mortality in patients without known CAD but with CFC indicating significantly reduced coronary blood flow.In this pilot study, we compared patients with AF and LVEF ≥50% who were treated with 1C AADs, to age-matched AF patients without 1C AAD treatment. No patient had clinically evident CAD (i.e., reversible perfusion defect, known ≥70% epicardial lesion, PCI, CABG, or myocardial infarction). All patients had PET-based quantification of stress myocardial blood flow (sMBF) and CFC. Death was assessed by clinical follow-up and SSDI search.78 patients with 1C AAD exposure were matched to 78 controls. Over a mean follow-up of 2.0 years, the groups had similar survival (p=0.54). Among patients with CFC indicating the presence of occult CAD (i.e., reduced CFC involving ≥50% of myocardium), 1C-treated patients had survival similar to (p=0.44) those not treated with 1C agents.In a limited population of AF patients with preserved LV function and PET CFC indicating occult CAD, treatment with 1C AADs appears not to increase mortality. A larger study would be required to confidently assess safety of these drugs in this context. This article is protected by copyright. All rights reserved

T-peak to T-end interval for prediction of ventricular tachyarrhythmia and mortality in a primary prevention population with systolic cardiomyopathy

The electrocardiographic T-wave peak to T-wave end interval (Tpe) correlates with dispersion of ventricular repolarization (DVR). Increased DVR increases propensity toward electrical reentry that can cause ventricular tachyarrhythmia. The baseline rate-corrected Tpe (Tpec) has been shown to predict ventricular tachyarrhythmia and death in multiple patient populations but not among cardiomyopathic patients undergoing insertion of an implantable cardioverter-defibrillator (ICD) for primary prevention.The purpose of this study was to assess the risk stratification ability of the Tpec in patients with systolic cardiomyopathy without prior ventricular tachyarrhythmia (ie, the primary prevention population).We performed prospective follow-up of 305 patients (73% men; left ventricular ejection fraction [LVEF] 23 ± 7%) with LVEF ≤35% and an ICD implanted for primary prevention. Baseline ECGs were analyzed with automated algorithms. Endpoints were ventricular tachycardia (VT)/ventricular fibrillation (VF), death, and a combined endpoint of VT/VF or death, assessed by device follow-up and Social Security Death Index query.The average Tpec was 107 ± 22 ms. During device clinic follow-up of 31 ± 23 months, 82 patients (27%) had appropriate ICD therapy for VT/VF, and during mortality follow-up of 49 ± 21 months, 91 patients (30%) died. On univariable analysis, Tpec predicted VT/VF, death, and the combined endpoint of VT/VF or death (P < .05 for each endpoint). Multivariable analysis included univariable predictors among demographics, clinical data, laboratory data, medications used, and electrocardiography parameters. After correction, Tpec remained predictive of VT/VF (hazard ratio [HR] per 10-ms increase 1.16, P = .009), all-cause mortality (HR per 10 ms 1.13, P = .05), and the combined endpoint (HR per 10 ms 1.17, P = .001).Tpec independently predicts both VT/VF and overall mortality in patients with systolic dysfunction and ICDs implanted for primary prevention

Natural history and implantable cardioverter-defibrillator implantation after revascularization for stable coronary artery disease with depressed ejection fraction

Background Following revascularization, most payors require 3 months of medical therapy, followed by left ventricular ejection fraction (LVEF) reassessment, before implantable cardioverter-defibrillator (ICD) implantation possibly contributing to incomplete follow-up and suboptimal utilization of ICD therapy. The natural history of these patients, and their fate regarding ICD implantation, is unknown. Hypothesis We hypothesized that a waiting period after revascularization for stable CAD results in missed opportunities to provide care with regard to ICD implantation. Methods We followed patients with LVEF ≤ 35% and no ICD who underwent revascularization (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI]) for stable CAD. Follow-up used chart review and scripted telephone interviews. Results Among 3164 revascularized patients (2198 [69%] PCI, 966 [31%] CABG), only 62 (2%; 33 [53%] male, age 67 ± 12 y, LVEF 28% ± 6%) had stable CAD, depressed LVEF, and no ICD. Over 35 ± 19 months, 35 (56%) of these 62 patients were no longer candidates for ICD based on improved LVEF, 14 (23%) received an ICD, 5 (8%) declined ICD despite physician recommendation, 3 (5%) were not offered ICD despite continued eligibility, 2 (3%) died, 1 (2%) was not a candidate due to substance abuse, and 1 (2%) had ICD implantation temporarily deferred. Only 1 (2%) was lost to follow-up. Conclusions Following revascularization for stable CAD with depressed LVEF, ≥50% of patients' ventricular function improved enough to make ICD implantation unnecessary. A waiting period after revascularization prior to ICD implantation appears appropriate and does not significantly negatively impact follow-up or the rate of appropriate ICD implantation

Utility of serial measurement of biomarkers of cardiovascular stress and inflammation in systolic dysfunction

Evidence links markers of systemic inflammation and heart failure (HF) with ventricular arrhythmias (VA) and/or death. Biomarker levels, and the risk they indicate, may vary over time. We evaluated the utility of serial laboratory measurements of inflammatory biomarkers and HF, using time-dependent analysis.We prospectively enrolled ambulatory patients with left ventricular ejection fraction (LVEF) ≤35% and a primary-prevention implanted cardioverter-defibrillator (ICD). Levels of established inflammatory biomarkers [C-reactive protein, erythrocyte sedimentation rate (ESR), suppression of tumourigenicity 2 (ST2), tumour necrosis factor alpha (TNF-α)] and brain natriuretic peptide (BNP) were assessed at 3-month intervals for 1 year. We assessed relationships between biomarkers modelled as time-dependent variables, VA, and death. Among 196 patients (66±14 years, LVEF 23±8%), 33 experienced VA, and 18 died. Using only baseline values, BNP predicted VA, and both BNP and ST2 predicted death. Using serial measurements at 3-month intervals, time-varying BNP independently predicted VA, and time-varying ST2 independently predicted death. C-statistic analysis revealed no significant benefit to repeated testing compared with baseline-only measurement. C-reactive protein, ESR, and TNF-α, either at baseline or over time, did not predict either endpoint.In stable ambulatory patients with systolic cardiomyopathy and an ICD, BNP predicts ventricular tachyarrhythmia, and ST2 predicts death. Repeated laboratory measurements over a year's time do not improve risk stratification beyond baseline measurement alone.Clinicaltrials.gov NCT01892462 (https://clinicaltrials.gov/ct2/show/NCT01892462)

Positron emission tomography absolute stress myocardial blood flow for risk stratification in nonischemic cardiomyopathy

Sudden cardiac death is a substantial cause of mortality in patients with cardiomyopathy, but evidence supporting implantable cardioverter defibrillator (ICD) implantation is less robust in nonischemic cardiomyopathy (NICM) than in ischemic cardiomyopathy. Improved risk stratification is needed. We assessed whether absolute quantification of stress myocardial blood flow (sMBF) measured by positron emission tomography (PET) predicts ventricular arrhythmias (VA) and/or death in patients with NICM.In this pilot study, we prospectively followed patients with NICM (LVEF ≤35%) and an ICD who underwent cardiac PET stress imaging with sMBF quantification. NICM was defined as absence of angiographic obstructive coronary stenosis, significant relative perfusion defects on imaging, coronary revascularization, or acute coronary syndrome. Endpoints were appropriate device therapy for VA and all-cause mortality. Subgroup analysis was performed in patients who had no prior history of VA (i.e., the primary prevention population).We followed 37 patients (60±14 years, 46% male) for 41±23 months. The median sMBF was 1.56 mL/g/min [IQR 1.00-1.82]. Lower sMBF predicted VA, both in the whole population (HR for each 0.1 mL/g/min increase: 0.84, P=0.015) and in the primary prevention subset (n=27; HR for each 0.1 mL/g/min increase: 0.81, P=0.049). Patients with sMBF below the median had significantly more VA than those above the median, both in the whole population (P=0.004) and in the primary prevention subset (P=0.046). Estimated 3-year VA rates in the whole population were 67% among low-flow patients vs. 13% among high-flow patients, and 39% vs. 8% among primary-prevention patients. sMBF did not predict all-cause mortality.In patients with NICM, lower sMBF predicts VA. This relationship may be useful for risk stratification for ventricular arrhythmia and decision-making regarding ICD implantation. This article is protected by copyright. All rights reserved