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Background: Patients with advanced chronic kidney disease (CKD) have increased risk of myocardial infarction (MI). Silent MIs (SMIs) are common in CKD patients and carry increased mortality risk. The prevalence and prognostic value of SMI in advanced CKD has not been evaluated., Methods: We identified consecutive patients with advanced CKD who were evaluated for renal transplantation at the University of Alabama at Birmingham between June 2004 and January 2006. Clinical MI (CMI) was determined by review of medical records. SMI was defined as ECG evidence of MI without clinical history of MI. The primary end-point was a composite of death, MI, or coronary revascularization censored at time of renal transplantation., Results: The cohort included 1007 patients with advanced CKD aged 48±12years (58% men, 43% diabetes, 75% on dialysis). The prevalence of SMI and CMI was 10.7% and 6.7%, respectively. The only independent predictor of SMI was older age (odds ratio for age ≥50yrs. 2.32, p<0.001). During a median follow-up of 28months, 376 (37%) patients experienced the primary outcome (33% death, 2% MI, 5% coronary revascularization). In a multivariable adjusted Cox-regression model, both SMI (adjusted HR 1.58, [1.13-2.20], p=0.007) and CMI (adjusted HR 1.67 [1.15-2.43], p=0.007) were independently associated with the primary outcome. Further, both SMI (HR 2.37 [1.15-4.88], p=0.02) and CMI (HR 4.02 [1.80-8.98], p=0.001) were associated with increased risk after renal transplantation., Conclusions: SMI is more common than CMI in patients with advanced CKD. Both SMI and CMI are associated with increased risk of future cardiovascular events., (Published by Elsevier B.V.)

Background: The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study demonstrated a low 5-year hard cardiac event rate. We hypothesized that a blunted heart rate response (HRR, maximum percent change) to adenosine, a simple marker of cardiac autonomic neuropathy, will identify a cohort at higher cardiac risk., Methods: In DIAD, 518 participants were randomized to screening adenosine myocardial perfusion imaging (MPI) and had available data. HRR <20% was considered abnormal. The primary endpoint was a composite of nonfatal myocardial infarction and cardiac death., Results: During 4.7 ± 0.9 years of follow-up 15 (3%) participants experienced the primary outcome. Participants with lower HRR experienced more events than those with higher HRR (8%, 3%, 1%, for HRR <20% (n=79), 20-39% (n=182) and ≥ 40% (n=257), respectively, p=0.01). In a Cox proportional regression model that included MPI abnormalities and HRR, both were independently associated with cardiac events (p for model <0.001). HRR <20% was associated with 9-fold increased risk (p=0.007) and moderate/large abnormal MPI was associated with 6-fold increased risk (p=0.004). Participants with both abnormal MPI and HRR (n=8) were at highest risk for cardiac events (38%) whereas those with HRR ≥ 40%, irrespective of MPI abnormalities (n=234), were at extremely low risk (≤1%, log-rank p<0.001)., Conclusions: In DIAD, abnormal HRR to adenosine infusion is an independent predictor of cardiac events. This easily obtained marker of cardiac autonomic neuropathy identifies asymptomatic patients with type 2 diabetes mellitus at increased risk, particularly when associated with abnormal MPI, who may warrant further testing and more aggressive cardiovascular risk factor management., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Chronic kidney disease (CKD) is associated with worse survival in patients with implantable cardiac defibrillators (ICDs). This study examined the association of outcomes with CKD in patients receiving an ICD for primary versus secondary prevention., Methods: The study included 696 patients who underwent ICD placement for clinical reasons (59% primary, 41% secondary prevention) at the University of Alabama at Birmingham between January 2002 and September 2007. CKD was defined as an estimated glomerular filtration rate<60 ml/min/1.73 m(2) but not on dialysis. Outcomes of interest included overall mortality and first appropriate ICD therapy (shocks or anti-tachycardia pacing)., Results: After a follow-up of 50 ± 24 months, 213 patients died (31%) and 111 (16%) received appropriate ICD therapy. Patients with CKD had higher mortality than patients with no CKD in the primary (43% vs. 15%, p<0.001) and secondary prevention (37% vs. 23%, p = 0.003) groups. Patients with CKD were at higher risk of receiving an appropriate ICD therapy than patients without CKD in the primary (p<0.001) but not secondary prevention (p = 0.9) cohort. After adjusting for age, gender and multiple risk factors, CKD was independently associated with all-cause mortality and ICD therapy in the primary prevention group (HR 2.08 [1.34-3.23] and 3.53 [1.75-7.10], p = 0.001 and <0.0001, respectively) but not in the secondary prevention group (HR 1.27 [0.81-2.00], and 0.63 [0.35-1.13], p=0.3 and 0.2, respectively)., Conclusions: CKD is independently associated with increased mortality and appropriate ICD therapy in patients undergoing ICD implantation for primary but not secondary prevention., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Right ventricular ejection fraction (RVEF) < 20% is an independent predictor of poor outcomes in patients with advanced chronic systolic heart failure (HF). The aim of this study was to examine if the adverse effect of abnormally reduced RVEF varies by the receipt of beta-blockers., Methods: In the Beta-Blocker Evaluation of Survival Trial (BEST), 2708 patients with chronic advanced HF and left ventricular ejection fraction < 35%, receiving standard background therapy with renin-angiotensin inhibition, digoxin, and diuretics, were randomized to receive bucindolol or placebo. Of these 2008 had data on baseline RVEF, and 14% (146/1017) and 13% (125/991) of the patients receiving bucindolol and placebo respectively had RVEF < 20%., Results: Among patients in the placebo group, all-cause mortality occurred in 33% and 43% of patients with RVEF ≥ 20% and < 20% respectively (unadjusted hazard ratios {HR}, 1.33; 95% confidence intervals {CI}, 0.99-1.78; p = 0.055 and adjusted HR, 0.99; 95% CI, 0.71-1.37; p = 0.934). Among those receiving bucindolol, all-cause mortality occurred in 28% and 49% of patients with RVEF ≥ 20% and < 20% respectively (unadjusted HR, 2.15; 95% CI, 1.65-2.80; p < 0.001 and adjusted HR, 1.50; 95% CI, 1.08-2.07; p = 0.016). These differences were statistically significant (unadjusted and adjusted p for interaction, 0.016 and 0.053 respectively)., Conclusions: In ambulatory patients with chronic advanced systolic HF receiving renin-angiotensin inhibition, digoxin, and diuretics, RVEF < 20% had no intrinsic association with mortality. However, in those receiving additional therapy with bucindolol, RVEF < 20% had a significant independent association with increased risk of mortality., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Reduced right ventricular ejection fraction (RVEF) is associated with poor outcomes in patients with chronic systolic heart failure (HF). Although most HF patients are older adults, little is known about the relationship between low RVEF and outcomes in older adults with systolic HF., Methods: Of the 2008 Beta-Blocker Evaluation of Survival Trial (BEST) participants with systolic HF (left ventricular ejection fraction ≤ 35%) 822 were ≥ 65 years and had data on baseline RVEF estimated by gated-equilibrium radionuclide ventriculography. Using RVEF ≥ 40% (n = 308) as reference, we examined association of RVEF 30-39% (n = 214), 20-29% (n = 206) and <20% (n = 94) with outcomes using Cox regression models., Results: All-cause mortality occurred in 36%, 40%, 39% and 56% of patients with RVEF ≥ 40%, 30-39%, 20-29% and <20% respectively. Compared with RVEF ≥ 40%, unadjusted hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality associated with RVEF 30-39%, 20-29% and <20% were 1.19 (0.90-1.57; P = 0.220), 1.13 (0.84-1.51; P = 0.423) and 1.97 (1.43-2.73; P<0.001) respectively. Respective multivariable-adjusted HR's (95% CI's) for all-cause mortality were 1.19 (0.88-1.60; P = 0.261), 1.00 (0.73-1.39; P = 0.982) and 1.70 (1.14-2.53; P = 0.009). Adjusted HR's (95% CI's) associated with RVEF <20% (versus ≥ 40%) for cardiovascular mortality and HF mortality were 1.79 (1.17-2.76; P = 0.008) and 1.97 (1.02-3.83; P = 0.045) respectively. RVEF had no independent association with sudden cardiac death, all-cause or HF hospitalization., Conclusions: Abnormally low RVEF is a significant independent predictor of mortality, but not of HF hospitalization, in older adults with systolic HF., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)