Faculty Bibliography

OBJECTIVES: The purpose of this study was to assess whether inotropic contractile reserve (ICR) during dobutamine stress echocardiography (DSE) could risk-stratify patients with human immunodeficiency virus (HIV) cardiomyopathy and predict improvement of left ventricular ejection fraction (LVEF). BACKGROUND: HIV cardiomyopathy is an important cause of heart failure and death. ICR is associated with better survival and improvement of LVEF in patients with ischemic and nonischemic cardiomyopathies. However, the prognostic value of ICR in patients with HIV cardiomyopathy is unknown. METHODS: Patients with HIV cardiomyopathy and a LVEF <45% who were referred for DSE were enrolled. ICR was evaluated by the delta wall motion score index (DeltaWMSI), calculated as the difference between rest and peak WMSI. Patients were followed for cardiac death and change in LVEF on follow-up. RESULTS: Sixty patients (75% men; age, 54 +/- 9 years) with HIV cardiomyopathy (mean LVEF, 28 +/- 11%) formed the study group. After 2.4 +/- 2.1 years, 11 cardiac deaths occurred (event rate of 7.6%/year). A receiver-operating characteristic curve identified a DeltaWMSI of 0.38 as an optimal cut point for the presence of ICR, with a specificity of 88% and a sensitivity of 73% for the prediction of cardiac death. On univariable analysis, the absence of ICR (hazard ratio: 6.6; 95% confidence interval: 1.93 to 22.62; p = 0.003) and New York Heart Association functional class IV (hazard ratio: 7.2; 95% confidence interval: 2.20 to 23.65; p = 0.001) were the only predictors of cardiac death. After 2.1 +/- 1.8 years, 41 patients had a follow-up echocardiogram. LVEF improvement from baseline occurred in 23 patients (56%), more so in patients with ICR than without ICR. A DeltaWMSI of 0.59 predicted improvement in the LVEF with a specificity of 78% and a sensitivity of 74%. CONCLUSIONS: The presence of ICR during DSE can risk-stratify and predict subsequent improvement in LVEF in patients with HIV cardiomyopathy

American College of Cardiology/American Heart Association guidelines for management of patients with ST-segment elevation myocardial infarction (STEMI) recommend culprit artery-only revascularization (CULPRIT) based on safety concerns during noninfarct-related artery intervention. However, the data to support this safety concern are scant. Searches were performed in PubMed/EMBASE/CENTRAL for studies evaluating multivessel revascularization versus CULPRIT in patients with STEMI and multivessel disease (MVD). A multivessel revascularization strategy had to be performed at the time of CULPRIT or during the same hospitalization. Early (</=30-day) and long-term outcomes were evaluated. Among 19 studies (23 arms) that evaluated 61,764 subjects with STEMI and MVD, multivessel revascularization was performed in a minority of patients (16%). For early outcomes, there was no significant difference for outcomes of mortality, MI, stroke, and target vessel revascularization, with a 44% decrease in risk of repeat percutaneous coronary intervention and major adverse cardiovascular events (odds ratio 0.68, 95% confidence interval 0.57 to 0.81) with multivessel revascularization compared to CULPRIT. Similarly, for long-term outcomes (follow-up 2.0 +/- 1.1 years), there was no difference for outcomes of MI, target vessel revascularization, and stent thrombosis, with 33%, 43%, and 53% decreases in risk of mortality, repeat percutaneous coronary intervention, coronary artery bypass grafting, respectively, and major adverse cardiovascular events (odds ratio 0.60, 95% confidence interval 0.50 to 0.72) with multivessel revascularization compared to CULPRIT. In conclusion, in patients with STEMI and MVD, multivessel revascularization appears to be safe compared to culprit artery-only revascularization. These findings support the need for a large-scale randomized trial to evaluate revascularization strategies in patients with STEMI and MVD

OBJECTIVES: To evaluate the cardiovascular outcomes and other outcomes associated with angiotensin receptor blockers. DESIGN: Systematic review of randomised controlled trials with meta-analysis and trial sequential analysis (TSA). Data sources and study selection Pubmed, Embase, and CENTRAL searches for randomised clinical trials, until August 2010, of angiotensin receptor blockers compared with controls (placebo/active treatment) that enrolled at least 100 participants and had a follow-up of at least one year. DATA EXTRACTION: Myocardial infarction, death, cardiovascular death, angina pectoris, stroke, heart failure, and new onset diabetes. RESULTS: 37 randomised clinical trials included 147 020 participants and had a total follow-up of 485 166 patient years. When compared with controls (placebo/active treatment), placebo, or active treatment, angiotensin receptor blockers were not associated with an increase in the risk of myocardial infarction (relative risk 0.99, 95% confidence interval 0.92 to 1.07), death, cardiovascular death, or angina pectoris. Compared with controls, angiotensin receptor blockers were associated with a reduction in the risk of stroke (0.90, 0.84 to 0.98), heart failure (0.87, 0.81 to 0.93), and new onset diabetes (0.85, 0.78 to 0.93), with similar results when compared with placebo or with active treatment. Based on trial sequential analysis, there is no evidence even for an average 5.0-7.5% (upper confidence interval 5-11%) relative increase in myocardial infarction (absolute increase of 0.3%), death, or cardiovascular death with firm evidence for relative risk reduction of stroke (at least 1%, average 10%) (compared with placebo only), heart failure (at least 5%, average 10%), and new onset diabetes (at least 4%, average 10%) with angiotensin receptor blockers compared with controls. CONCLUSIONS: This large and comprehensive analysis produced firm evidence to refute the hypothesis that angiotensin receptor blockers increase the risk of myocardial infarction (ruling out even a 0.3% absolute increase). Compared with controls, angiotensin receptor blockers reduce the risk of stroke, heart failure, and new onset diabetes

Background: Intravenous (IV) Beta-blockade is currently not routinely recommended in the early management of patients with acute coronary syndromes (ACS)-even for patients without obvious contraindications. We performed a systematic review of the medical literature to determine if early IV beta-blockade improves the risk of in-hospital ventricular tachyarrhythmias (ventricular tachycardia/fibrillation) in patients with ACS. Methods: The authors searched the PubMed and EMBASE databases for randomized controlled trials and controlled clinical trials from 1965 through 2009. Intervention included intravenous beta-blockers administered within 24 hours of presentation. The comparator included standard medical therapy and/or placebo. The outcome assessed was the risk of development of in-hospital ventricular tachyarrhythmias (both Vtach and Vfib) in the intervention groups versus the comparator groups. The methodological quality of the studies was assessed. In-hospital mortality rates were compared using a forest plot of relative risk (RR; 95% confidence interval [CI]) using a random effect model (Mantel-Haenszel) between beta-blockers and controls. Statistical analysis was done with Review Manager V5.0. Results: Thirteen studies (total N = 114,801) met the inclusion/ exclusion criteria. In-hospital development of ventricular tachycardia/ fibrillation was reduced 1.88% (7.46% Vs 5.58%) with IV beta-blockers, RR = 0.56 (95% CI, 0.46-0.68; p<0.01). Conclusions: This systematic review suggests a benefit with early use of IV beta-blockers in appropriate patients with ACS for preventing development of ventricular tachyarrhythmias. (Table Presented)

Background: Recent clinical trials suggest that in patients already on conventional heart failure therapy the addition of angiotensin receptor blockers (ARBs) or aldosterone antagonists (AA) are reasonable therapeutic options to further reduce the risk of cardiovascular events. However, whether one is preferable over the other is unknown. Methods: PUBMED, EMBASE,and CENTRAL were searched for randomized clinical trials (RCTs), of trials testing either an ARB or an AA in patients with heart failure and reduced systolic function who were on conventional heart failure therapy (including diuretics,beta blockers and angiotensin converting enzyme inhibitors (ACEi)) with follow-up of at least 6-months. Efficacy (death, cardiovascular (CV) death, myocardialinfarction, stroke, heart failure hospitalization, CV death or heart failure hospitalization) and safety (hyperkalemia, hypotension, renal failure) outcomes were compared. Results: We identified 12 RCTs involving 29,514 participants that satisfied our inclusion criteria. When compared with placebo (reference rate ratio 1), the addition of aldosterone antagonists reduced death from all causes (rate ratio (RR) = 0.80, 95% Credibility Interval (CrI)0.64-0.97), cardiovascular death (RR = 0.79; 95% CrI 0.65-0.94) and heart failure hospitalization (RR = 0.73; 95% CrI 0.56- 0.93) with no difference for other efficacy outcomes. In contrast, the addition of ARBs did not significantly reduce the rate of any of the efficacy outcomes when compared with placebo. Moreover, ARBs but not AA increased the rate of hyper- (Figure presented) hyperkalemia (138% increase), renal failure (126% increase) and hypotension (63% increase). Conclusions: In patients with heart failure and reduced systolic function on conventional medications including ACEi, the risk-benefit ratio favors AA over ARBs

Background: In patients post myocardial infarction and in those with established coronary artery disease (CAD), lower heart rate has been shown to improve long term cardiovascular prognosis. However, how low is low enough and the existence of J-curve relationship has not been proven. Methods: We evaluated 9602 patients, with CAD and a LDL cholesterol level <130 mg/dL, randomized to atorvastatin 80 mg vs. 10 mg, enrolled in the TNT trial. The post-baseline, time-dependent heart rate were categorized into 10 mm Hg increments. The primary outcome was a composite of death from coronary disease, nonfatal myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke. Results: Among the 9602 patients, 886 (9.23%) experienced a primary outcome at 4.9 years (median) of follow-up. The relationship between heart rate and primary outcome followed a J-curve with increased event rates above and below the reference heart rate range, both unadjusted and adjusted (for baseline covariates, treatment effect and LDL levels). A time-dependent, non-linear, multivariate Cox proportional hazard (PH) model identified a nadir of 52.4 bpm where the event rate was lowest (Figure). Similar, non-linear relationship, with higher risk of events at lower heart rate was found for most of the secondary outcomes of all-cause mortality, CV mortality, nonfatal MI, or stroke. (Figure presented) Conclusions: In patients with CAD, a very low heart rate portends an increased risk of future cardiovascular events

Patients with coronary artery calcium (CAC) scores of zero are generally considered not to have atherosclerosis. Recent studies involving computed tomography coronary angiography (CTCA) challenge this assumption. This goal of the present study is to assess the frequency, morphology, location, and the prognosis of patients with plaque detected on CTCA and zero CAC. 1,119 patients (51 +/- 12 years, 52% male) with a zero CAC score during CTCA study were retrospectively identified. The CTCA studies were assessed for the presence, morphology, location and severity of all coronary plaques. All-cause mortality was assessed. The prevalence of coronary plaque was 13% (147 patients). Among the 212 plaques identified 154 (73%) were non-calcified, 28 (13%) were calcified, and 30 (14%) were of mixed morphology. Notably, >/=70% stenosis was noted among only 0.4% of all patients. ROC analysis revealed that coronary artery disease risk factors did not add to the prediction of plaque among our patients. Over a mean follow-up of 2.5 +/- 0.6 years there were 4 deaths (0.4%), all in patients without coronary plaque on CTCA. The presence of coronary plaque is not uncommon among patients with zero CAC scores. These plaques were rarely associated with hemodynamically significant stenoses and were associated with an excellent prognosis. Clinical factors do not appear to be useful in predicting which patients with zero CAC scores have undetected coronary plaque