Effect of Beta-Blocker Dose on Survival After Acute Myocardial Infarction

Beta-blocker therapy after acute myocardial infarction (MI) improves survival. Beta-blocker doses used in clinical practice are often substantially lower than those used in the randomized trials establishing their efficacy

Recovery of Heart Rate Variability and Ventricular Repolarization Indices Following Exercise

BACKGROUND: There is a heightened risk of sudden cardiac death related to exercise and the post-exercise recovery period, but the precise mechanism is unknown. We have demonstrated that sympathoexcitation persists for ≥45 minutes after exercise in normals and subjects with coronary artery disease (CAD). The purpose of this study is to determine whether this persistent sympathoexcitation is associated with persistent heart rate variability (HRV) and ventricular repolarization changes in the post-exercise recovery period. METHODS AND RESULTS: Twenty control subjects (age 50.7±1.4 years), 68 subjects (age 58.2±1.5 years) with CAD and preserved left ventricular ejection fraction (LVEF), and 18 subjects (age 57.6±2.4 years) with CAD and depressed LVEF underwent a 16-minute submaximal bicycle exercise protocol with continuous ECG monitoring. QT and RR intervals were measured in recovery to calculate the time dependent corrected QT intervals (QTc), the QT-RR relationship, and HRV. QTc was dependent on the choice of rate correction formula. There were no differences in QT-RR slopes among the 3 groups in early recovery. HRV recovered quickly in controls, more slowly in those with CAD-preserved LVEF, and to a lesser extent in those with CAD-depressed LVEF. CONCLUSION: Despite persistent sympathoexcitation for the 45 minute recovery period, ventricular repolarization changes do not persist for that long and HRV changes differ by group. Further understanding of the dynamic changes in cardiac parameters after exercise are needed to explore the mechanism of increased sudden cardiac death risk at this time

Improvements in health-related quality of life before and after isolated cardiac operations

Our study compared health-related quality of life (HRQOL) among cardiac surgical patient groups before and after cardiac operations for isolated surgical procedures and examined cardiac surgical patient HRQOL within the context of United States population norms. Of 2524 patients undergoing cardiac operations, 370 underwent isolated procedures (coronary artery bypass grafting, 136; aortic valve repair or replacement, 96; mitral valve repair or replacement, 92; Maze procedures, 46) between April 18, 2004, and June 30, 2008. They completed Short Form 36 questionnaires at baseline, at 3, 6, and 12 months postoperatively, and annually thereafter. Statistical analyses included χ(2), analysis of variance, longitudinal modeling, and longitudinal multivariable analyses. Overall, the 370 cardiac surgical patients were 61.5 ± 11.9 years old, 70% men, and 76% white. Significant baseline differences in HRQOL existed among the cardiac surgical groups. Physical and mental components of the Short Form 36 improved from baseline to within 3 to 6 months postoperatively and remained stable through 3 years for all groups. When demographic and clinical covariates were held constant, the effect of cardiac surgical type on postsurgical HRQOL changes was not significant. HRQOL improves early after cardiac operations and remains relatively constant long-term, independently of procedure type

Persistent Sympathoexcitation Long After Submaximal Exercise in Subjects with and without Coronary Artery Disease

There is an increased risk of cardiac events after exercise, which may, in part, be mediated by the sympathoexcitation that accompanies exercise. The duration and extent of this sympathoexcitation following moderate exercise is unknown, particularly in those with coronary artery disease (CAD). Twenty control subjects (mean age, 51 years) and 89 subjects with CAD (mean age, 58 years) underwent two 16-min bicycle exercise sessions followed by 30-45 min of recovery. Session 1 was performed under physiological conditions to peak workloads of 50-100 W. In session 2, parasympathetic blockade with atropine (0.04 mg/kg) was achieved at end exercise at the same workload as session 1. RR interval was continually recorded, and plasma catecholamines were measured at rest and selected times during exercise and recovery. Parasympathetic effect, measured as the difference in RR interval with and without atropine, did not differ between controls and CAD subjects in recovery. At 30 and 45 min of recovery, RR intervals were 12% and 9%, respectively, shorter than at rest. At 30 and 45 min of recovery, plasma norepinephrine levels were 15% and 12%, respectively, higher than at rest. A brief period of moderate exercise is associated with a prolonged period of sympathoexcitation extending \u3e45 min into recovery and is quantitatively similar among control subjects and subjects with CAD, with or without left ventricular dysfunction. Parasympathetic reactivation occurs early after exercise and is also surprisingly quantitatively similar in controls and subjects with CAD. The role of these autonomic changes in precipitating cardiac events requires further evaluation

One‐Year Landmark Analysis of the Effect of Beta‐Blocker Dose on Survival After Acute Myocardial Infarction

Background Although beta‐blockers are recommended following myocardial infarction (MI), the benefits of long‐term treatment have not been established. The study's aim was to evaluate beta‐blocker efficacy by dose in 1‐year post‐MI survivors. Methods and Results The OBTAIN (Outcomes of Beta‐Blocker Therapy After Myocardial Infarction) registry included 7057 patients with acute MI, with 6077 one‐year survivors. For this landmark analysis, beta‐blocker dose status was available in 3004 patients and analyzed by use (binary) and dose at 1 year after MI. Doses were classified as no beta‐blocker and >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target doses used in randomized clinical trials. Age was 63 to 64 years, and approximately two thirds were men. Median follow‐up duration was 1.05 years (interquartile range, 0.98–1.22). When analyzed dichotomously, beta‐blocker therapy was not associated with improved survival. When analyzed by dose, propensity score analysis showed significantly increased mortality in the no–beta‐blocker group (hazard ratio,1.997; 95% CI, 1.118–3.568; P 0% to 12.5% group (hazard ratio, 1.817; 95% CI, 1.094–3.016; P 25% to 50% group (hazard ratio, 1.764; 95% CI, 1.105–2.815; P 12.5% to 25% dose group. The mortality in the full‐dose group was not significantly higher (hazard ratio, 1.196; 95% CI, 0.687–2.083). In subgroup analyses, only history of congestive heart failure demonstrated significant interaction with beta‐blocker effects on survival. Conclusions This analysis suggests that patients treated with >12.5% to 25% of the target dose used in prior randomized clinical trials beyond 1 year after MI may have enhanced survival compared with no beta‐blocker and other beta‐blocker doses. A new paradigm for post‐MI beta‐blocker therapy is needed that addresses which patients should be treated, for how long, and at what dose