Haris Subacius

Association between diabetes mellitus and post-discharge outcomes in patients hospitalized with heart failure: findings from the EVEREST trial.

We evaluated the impact of diabetes mellitus (DM) and diabetic therapy on outcomes in patients with reduced ejection fraction (EF) after hospitalization for heart failure (HF). DM is prevalent in patients hospitalized with HF, yet inconclusive data exist on the post‐discharge outcomes of this patient population.

Early Repolarization Associated With Ventricular Arrhythmias in Patients With Chronic Coronary Artery Disease

Background—Early repolarization, indicated on the standard 12-lead ECG, has recently been associated with idiopathic ventricular fibrillation in patients without structural heart disease. It is unknown whether there is an association between early repolarization and ventricular arrhythmias in the coronary artery disease (CAD) population. Methods and Results—Patients with CAD with implantable cardioverter-defibrillators in the healed phase of myocardial infarction were analyzed. In a case-control design, 60 patients who had ventricular arrhythmic events were matched for age and sex with 60 control subjects. ECGs were analyzed for early repolarization, defined as notching or slurring morphology of the terminal QRS complex or J-point elevation ≥0.1 mV above baseline in at least 2 lateral or inferior leads. Results were adjusted for left ventricular ejection fraction. Overall, early repolarization in 2 or more leads was more common in cases than control subjects (32% versus 8%, P=0.005). Early repolarization was noted more commonly in inferior leads (23% versus 8%, P=0.03), and a trend was noted in leads V4 through V6 (12% versus 3%, P=0.11). Early repolarization was uncommon in leads I and aVL in cases and control subjects (3% versus 0%). Notching was more common in cases than control subjects (28% versus 7%, P=0.008). Slurring and J-point elevation were not associated with ventricular arrhythmias. Conclusions—Early repolarization and, in particular, notching in the inferior leads is associated with increased risk of life-threatening ventricular arrhythmias in patients with CAD, even after adjustment for left ventricular ejection fraction. Our findings suggest early repolarization, and a notching morphology should be considered in a risk prediction model for arrhythmias in patients with CAD.

Sudden Cardiac Death Risk Stratification in Patients With Nonischemic Dilated Cardiomyopathy

OBJECTIVES The purpose of this study was to provide a meta-analysis to estimate the performance of 12 commonly reported risk stratification tests as predictors of arrhythmic events in patients with nonischemic dilated cardiomyopathy. BACKGROUND Multiple techniques have been assessed as predictors of death due to ventricular tachyarrhythmias/sudden death in patients with nonischemic dilated cardiomyopathy. METHODS Forty-five studies enrolling 6,088 patients evaluating the association between arrhythmic events and predictive tests (baroreflex sensitivity, heart rate turbulence, heart rate variability, left ventricular end-diastolic dimension, left ventricular ejection fraction, electrophysiology study, nonsustained ventricular tachycardia, left bundle branch block, signal-averaged electrocardiogram, fragmented QRS, QRS-T angle, and T-wave alternans) were included. Raw event rates were extracted, and meta-analysis was performed using mixed effects methodology. We also used the trim-and-fill method to estimate the influence of missing studies on the results. RESULTS Patients were 52.8 ± 14.5 years of age, and 77% were male. Left ventricular ejection fraction was 30.6 ± 11.4%. Test sensitivities ranged from 28.8% to 91.0%, specificities from 36.2% to 87.1%, and odds ratios from 1.5 to 6.7. Odds ratio was highest for fragmented QRS and TWA (odds ratios: 6.73 and 4.66, 95% confidence intervals: 3.85 to 11.76 and 2.55 to 8.53, respectively) and lowest for QRS duration (odds ratio: 1.51, 95% confidence interval: 1.13 to 2.01). None of the autonomic tests (heart rate variability, heart rate turbulence, baroreflex sensitivity) were significant predictors of arrhythmic outcomes. Accounting for publication bias reduced the odds ratios for the various predictors but did not eliminate the predictive association. CONCLUSIONS Techniques incorporating functional parameters, depolarization abnormalities, repolarization abnormalities, and arrhythmic markers provide only modest risk stratification for sudden cardiac death in patients with nonischemic dilated cardiomyopathy. It is likely that combinations of tests will be required to optimize risk stratification in this population.

Rationale and design for the Defibrillators to Reduce Risk by Magnetic Resonance Imaging Evaluation (DETERMINE) trial.

Background: Cardiac magnetic resonance imaging (CMR) can accurately determine infarct size. Prior studies using indirect methods and CMR to assess infarct size have shown that patients with larger myocardial infarctions have worse prognoses. Implantable cardioverter defibrillators (ICD) have been shown to improve survival among patients with severe left ventricular (LV) dysfunction. However, the majority of cardiac arrests occur in patients with higher ejection fractions.

Contemporary Perioperative Results of Isolated Aortic Valve Replacement for Aortic Stenosis

BACKGROUND Transcatheter aortic valve implantation may become a potential treatment for high-risk patients with aortic stenosis (AS). We analyzed our contemporary series of isolated aortic valve replacement (AVR) for AS to determine implications for patients referred for AVR. METHODS From April 2004 through December 2008, 190 patients (mean age, 68 years; 68% men) underwent isolated AVR for AS. Mean ejection fraction was 0.58. Sixty-one percent underwent minimally invasive AVR and 18% were reoperations. Twenty-one percent were aged 80 years or older, and 34% were in New York Heart Association functional class III-IV. Estimated operative mortality was 3.6%. RESULTS Thirty-day mortality was 0%. One in-hospital death (0.5%) occurred from complications of an esophageal perforation. Reoperation for bleeding occurred in 4.7%. Acute renal failure developed in 2.1%. Actuarial survival was 97% at 1 year and 94% at 3 years. Hospital length of stay was 7.0 days for patients aged 80 and older vs 5.0 days (p < 0.001), and they were less likely to be discharged to home (50% vs 83%, p < 0.001). CONCLUSIONS Contemporary results show that AVR for AS can be performed with low operative mortality and morbidity, although patients aged 80 years and older are at increased risk of prolonged recovery. Transcatheter aortic valve implantation may be an alternative for high-risk patients, but AVR is still appropriate for low-risk patients. The low risk of AVR supports the argument that asymptomatic patients who have a high likelihood of progression of AS may be considered for earlier surgical referral.

Relationship between clinical trial site enrollment with participant characteristics, protocol completion, and outcomes: insights from the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) trial.

OBJECTIVES The study investigated whether the number of participants enrolled per site in an acute heart failure trial is associated with participant characteristics and outcomes. BACKGROUND Whether and how site enrollment volume affects clinical trials is not known. METHODS A total of 4,133 participants enrolled among 359 sites were grouped on the basis of total enrollment into 1 to 10, 11 to 30, and >30 participants per site and were compared for outcomes (cardiovascular mortality or heart failure hospitalization). RESULTS Per-site enrollment ranged from 0 to 75 (median 6; 77 sites had no enrollment). Regional differences in enrollment were noted between North and South America, and Western and Eastern Europe (p < 0.001). Participants from sites with fewer enrollments were more likely to be older and male, have lower ejection fraction and blood pressure as well as worse comorbidity and laboratory profile, and were less likely to be on angiotensin-converting enzyme inhibitors or aldosterone antagonists. During a median follow-up of 9.9 months, 1,700 (41%) participants had an outcome event. Compared to event rate at sites with >30 participants (32%), those with 1 to 10 (51%, hazard ratio [HR]: 1.77, 95% confidence interval [CI]: 1.56 to 2.02) and 11 to 30 (42%, HR: 1.44, 95% CI: 1.28 to 1.62) participants per site groups had worse outcomes. This relationship was comparable across regions (p = 0.43). After adjustment for risk factors, participants enrolled at sites with fewer enrollees were at higher risk for adverse outcomes (HR: 1.26, 95% CI: 1.08 to 1.46 for 1 to 10; HR: 1.22, 95% CI: 1.07 to 1.38 for 11 to 30 vs. >30 participant sites). Higher proportion of participants from site with >30 participants completed the protocol (45.5% for <10, 61.7% for 11 to 30, and 68.4% for sites enrolling >30 participants; p < 0.001). CONCLUSIONS Baseline characteristics, protocol completion, and outcomes differed significantly among higher versus lower enrolling sites. These data imply that the number of participant enrolled per site may influence trials beyond logistics.

Haemoconcentration, renal function, and post-discharge outcomes among patients hospitalized for heart failure with reduced ejection fraction: insights from the EVEREST trial

Haemoconcentration has been studied as a marker of decongestion in patients with hospitalization for heart failure (HHF). We describe the relationship between haemoconcentration, worsening renal function, post‐discharge outcomes, and clinical and laboratory markers of congestion in a large multinational cohort of patients with HHF.

Cardiac magnetic resonance imaging: infarct size is an independent predictor of mortality in patients with coronary artery disease

BACKGROUND Cardiac magnetic resonance imaging (CMR) can accurately determine infarct size. Prior studies using indirect methods to assess infarct size have shown that patients with larger myocardial infarctions have a worse prognosis than those with smaller myocardial infarctions. OBJECTIVES This study assessed the prognostic significance of infarct size determined by CMR. METHODS Cine and contrast CMR were performed in 100 patients with coronary artery disease (CAD) undergoing routine cardiac evaluation. Infarct size was determined by planimetry. We used Cox proportional hazards regression analyses (stepwise forward selection approach) to evaluate the risk of all-cause death associated with traditional cardiovascular risk factors, symptoms of heart failure, medication use, left ventricular ejection fraction, left ventricular mass, angiographic severity of CAD and extent of infarct size determined by CMR. RESULTS Ninety-one patients had evidence of myocardial infarction by CMR. Mean follow-up was 4.8±1.6 years after CMR, during which time 30 patients died. The significant multivariable predictors of all-cause mortality were extent of myocardial infarction by CMR, extent of left ventricular systolic dysfunction, symptoms of heart failure, and diabetes mellitus (P<.05). The presence of infarct greater than or equal to 24% of left ventricular mass and left ventricular ejection fraction less than or equal to 30% were the most optimal cut-off points for the prediction of death with bivariate adjusted hazard ratios of 2.11 (95% confidence interval 1.02-4.38) and 4.06 (95% confidence interval 1.73-9.54), respectively. CONCLUSIONS The extent of myocardial infarction determined by CMR is an independent predictor of death in patients with CAD.

Prognostic value and temporal behavior of the planar QRS-T angle in patients with nonischemic cardiomyopathy.

Background— The planar QRS-T angle can be easily obtained from standard 12-lead ECGs, but its predictive ability is not established. We sought to determine the predictive ability of the planar QRS-T angle in patients with nonischemic cardiomyopathy and to assess QRS-T angle behavior over time. Methods and Results— Baseline QRS-T angles from 455 patients in the Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial were measured. All patients had nonischemic cardiomyopathy, New York Heart Association class I to III heart failure, and nonsustained ventricular tachycardia or frequent ventricular ectopy. The primary end point (a composite of total mortality, appropriate implantable cardioverter-defibrillator shock, or resuscitated cardiac arrest) occurred in 25 of 172 patients (14.5%) with a QRS-T angle ≤90° and in 72 of 283 patients (25.4%) with a QRS-T angle >90° (hazard ratio, 1.93; 95% confidence interval, 1.23 to 3.05; P=0.002). A QRS-T angle >90° remained a significant predictor of the primary end point (P=0.039) after adjustment for treatment group, age, gender, QRS duration, left bundle-branch block, left ventricular ejection fraction, New York Heart Association class III, atrial fibrillation, and diabetes mellitus. The secondary end point (total mortality) occurred in 17 of the 172 patients (9.9%) with a QRS-T angle ≤90° and in 49 of the 283 patients (17.3%) with a QRS-T angle >90° (hazard ratio, 1.79; 95% confidence interval, 1.03 to 3.10; P=0.016). A sample of 152 patients with multiple follow-up ECGs was analyzed to assess temporal QRS-T angle behavior. Changes in the QRS-T angle correlated with changes in left ventricular ejection fraction and QRS duration over time (P<0.001). Conclusions— A planar QRS-T angle >90° is a significant predictor of a composite end point of death, appropriate implantable cardioverter-defibrillator shock, or resuscitated cardiac arrest in nonpaced, mild to moderately symptomatic patients with nonischemic cardiomyopathy with frequent or complex ventricular ectopy. QRS-T angles changed predictably with left ventricular ejection fraction and QRS duration.

Sex differences in outcome after implantable cardioverter defibrillator implantation in nonischemic cardiomyopathy

BACKGROUND Women have been underrepresented in randomized trials of implantable cardioverter defibrillator (ICD) therapy, and limited data suggest that women may not benefit from prophylactic ICD implantation to the same extent as men. In the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, a reduction in all-cause mortality was seen in men (P = .018) but not for women (P = .76). METHODS Sex-specific cumulative probabilities of event-free survival from total, arrhythmic, and noncardiac mortality as well as appropriate shocks were calculated, and log-rank tests were performed. Interaction terms in multivariable Cox proportional hazards models were used to test the hypothesis that the effectiveness of the ICD differed between men and women. RESULTS Among 458 patients (326 men and 132 women) with nonischemic cardiomyopathy enrolled in the DEFINITE trial, the test for an interaction between sex and ICD treatment on total mortality was not significant in unadjusted (P = .11) or in multivariable adjusted (P = .18) analyses. When we examined cause-specific mortality, we found no sex difference in the incidence of arrhythmic death. Instead, we documented a relative excess of noncardiac death among women randomized to the ICD (P = .02) as compared with women randomized to standard medical therapy. With respect to device use, there was a trend for women to have fewer appropriate ICD shocks after multivariable adjustment (P = .06). CONCLUSION Among patients with nonischemic cardiomyopathy enrolled in DEFINITE, we found no conclusive evidence for a sex difference in the effectiveness of the ICD; however, the trial was not adequately powered to detect such interaction effects. Larger studies are required to definitively address whether the benefit of ICD therapy differs between men and women.