Usefulness of cell-mediated immune function in risk stratification for patients with advanced heart failure.

Although heightened inflammation and autoimmune responses have been well described in patients with heart failure, the role of cell-mediated immune function in the pathogenesis and progression of heart failure is unclear. The aim of our study is to evaluate the prognostic role of cell-mediated immune function in patients with advanced heart failure. METHODS: We studied patients with advanced heart failure referred for evaluation of candidacy for advanced heart failure therapies between 2007 and 2010. Cell-mediated immune response was categorized into 3 groups-low or poor immune response (≤225 ng/mL), moderate or normal immune response (226-524 ng/mL), and strong immune response (≥525 ng/mL)-using a phytohemagglutinin-stimulated T-cell response assay. RESULTS: Out of 368 patients, 41 patients (11.1%) had poor immune function, 258 patients (70.1%) had normal immune function, and 69 patients (18.7%) had strong immune function. The primary outcome of all-cause mortality or cardiac transplantation occurred in 63.4%, 45.3%, and 34.8% in the poor immunity, normal immunity, and strong immune function groups, respectively. In univariate analysis, cell-mediated immune function was strongly associated with the primary outcome (P=.014). Poor immune function portended worse prognosis (hazard ratio=2.18, 95% CI 1.01-4.70, P=.047), and strong immune function was associated with better survival (hazard ratio=0.67, 95% CI 0.43-1.04). However, when adjusted for multiple variables in multivariate analysis, immune function status lost its overall significance to predict primary outcome (P=.11), but the direction to an increased risk of primary outcome was maintained in the poor immune function group. CONCLUSIONS: Poor cell-mediated immune function measured by a clinically available assay could be associated with more adverse long-term prognosis in patients with advanced heart failure.

Usefulness of neutrophil-to-lymphocyte ratio in risk stratification of patients with advanced heart failure.

Elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with increased mortality in patients with acute heart failure (HF) and neoplastic diseases. We investigated the association between NLR and mortality or cardiac transplantation in a retrospective cohort of 527 patients presented to the Cleveland Clinic for evaluation of advanced HF therapy options from 2007 to 2010. Patients were divided according to low, intermediate, and high tertiles of NLR and were followed longitudinally for time to all-cause mortality or heart transplantation (primary outcome). The median NLR was 3.9 (interquartile range 2.5 to 6.5). In univariate analysis, intermediate and highest tertiles of NLR had a higher risk than the lowest tertile for the primary outcome and all-causes mortality. Compared with the lowest tertile, there was no difference in the risk of heart transplantation for intermediate and high tertiles. In multivariate analysis, compared with the lowest tertile, the intermediate and high NLR tertiles remained significantly associated with the primary outcome (hazard ratio [HR] = 1.61, 95% confidence interval [CI] 1.10 to 2.37 and HR = 1.55, 95% CI 1.02 to 2.36, respectively) and all-cause mortality (HR = 1.83, 95% CI 1.07 to 3.14 and HR = 2.16, 95% CI 1.21 to 3.83, respectively). In conclusion, elevated NLR is associated with increased mortality or heart transplantation risk in patients with advanced HF.

Prognosis of morbid obesity patients with advanced heart failure.

Obese patients have been noted to have better prognosis in many conditions including heart failure. We hypothesize that this favorable prognosis for obesity may not be seen in patients with morbid obesity and advanced heart failure. A total of 501 consecutive patients with advanced heart failure referred for heart transplant evaluation to the Cleveland Clinic were studied. Patients were categorized into 3 groups based on their body mass index score as nonobese (≤30 kg/m(2) ), obese (30.1-40 kg/m(2) ), and morbidly obese (≥40 kg/m(2) ). There were fewer cardiovascular risk factors in the morbidly obese group. Unadjusted event-free survival rates were 48.4%, 57.4%, and 28.6% in the nonobese, obese, and morbidly obese groups, respectively (P=.02). In univariate analysis, both the nonobese group (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.09-1.91; P=.01) and the morbidly obese group (HR, 2.46; 95% CI, 1.40-4.30; P=.002) had significantly higher risk of all-cause mortality/transplantation compared with the obese group. This difference persisted in multivariate analysis after adjustment for confounding factors. Our study re-emphasizes the presence of an obesity paradox even in patients with very advanced heart failure. This favorable prognosis, however, may not be relevant in patients with morbidly obesity. Cardiovascular risk factors may not contribute to this phenomenon.

Progressive rise in red cell distribution width is associated with disease progression in ambulatory patients with chronic heart failure.

BACKGROUND: Single red cell distribution width (RDW) assessment is a consistent prognostic marker of poor outcomes in heart failure as well as in other patient cohorts. The objective of this study was to determine the prognostic value of sequential RDW assessment in ambulatory patients with chronic heart failure. METHODS AND RESULTS: We reviewed 6,159 consecutive ambulatory patients with chronic heart failure between 2001-2006 and examined changes in RDW values from baseline to 1-year follow-up. Clinical, demographic, laboratory, and ICD-9 coding data were extracted from electronic health records, and all-cause mortality was followed over a mean follow-up of 4.4 ± 2.4 years. In this study cohort, median baseline RDW was 14.9%. RDW >16% at baseline (18.5% of cohort) was associated with a higher mortality rates than RDW ≤16%. For each +1% increment of baseline RDW, the risk ratio for all-cause mortality was 1.17 (95% confidence interval [CI] 1.15-1.19; P < .0001). At 12-month follow-up (n = 1,601), a large majority of subjects (68% in first tertile, 56% in second tertile of baseline RDW) showed rising RDW and correspondingly higher risk for all-cause mortality (risk ratio for +1% increase in changes in RDW was 1.08 (95% CI 1.03-1.13; P = .001). This effect was independent of anemia status or other baseline cardiac or renal indices, and particularly strong in those with lower baseline RDW. CONCLUSIONS: In our ambulatory cohort of patients with chronic heart failure, baseline and serial increases in RDW were associated with poor long-term outcomes independently from standard cardiac, hematologic, and renal indices.

Meta-analysis of randomized controlled trials of statins versus placebo in patients with heart failure.

Although statins have been shown to improve outcomes in retrospective analyses of patients with heart failure (HF), recent randomized placebo-controlled trials have shown mixed results. The goal of this study was to systematically review randomized trials comparing statins to placebo for HF and compare the impact of different statins. CENTRAL, mRCT, and PubMed were searched for eligible studies that prospectively randomized patients with HF to statins or placebo. Primary end points were all-cause mortality, cardiovascular mortality, hospitalization for worsening HF, adverse drug events, and changes in left ventricular ejection fraction (LVEF). Pooling was performed with random effect methods with summary effect estimates (95% confidence intervals). Ten studies (10,192 patients) with follow-up from 3 to 47 months were included. Three trials randomized patients to rosuvastatin, 1 to simvastatin, and 6 to atorvastatin. Overall, statins did not affect all-cause or cardiovascular mortality but did significantly decrease hospitalization for worsening HF during follow-up (odds ratio [OR] 0.67, p = 0.008). Patients randomized to statins had a significant 4.2% increase in LVEF at follow-up (95% confidence interval 1.3 to 7.1, p = 0.004). Furthermore, post hoc analyses showed heterogeneity among different statins and demonstrated that randomization to atorvastatin significantly decreased all-cause mortality (OR 0.39, p = 0.004), decreased hospitalization for worsening HF (OR 0.30, p <0.000 01), and randomization to atorvastatin and simvastatin led to a significant improvement in LVEF, whereas these benefits were not observed in patients randomized to rosuvastatin. In conclusion, meta-analysis of randomized controlled trials demonstrated that statins are safe and improve LVEF and decrease hospitalization for worsening HF.

Relation of blood urea nitrogen to long-term mortality in patients with heart failure.

Patients with chronic kidney disease and heart failure (HF) have been shown to be at higher risk for major adverse cardiovascular events and death. Recent studies have demonstrated that blood urea nitrogen (BUN) might serve as a powerful predictor of mortality in acutely decompensated HF. The goal of this study was to determine the impact of BUN on long-term mortality in patients with stage B and C HF. Our retrospective analysis included patients undergoing percutaneous intervention with a calculated left ventricular ejection fraction < or =50%. Patients on dialysis or with technically inadequate left ventriculograms were excluded. Chart review was performed and mortality data were obtained. Our population included 444 patients with a mean ejection fraction of 38 +/- 10%, mean age of 59 +/- 11 years, median BUN of 14 mg/dl, and median glomerular filtration rate (GFR) of 81 ml/min/1.73 m(2); 31% had stage C HF, and 33% died during follow-up. Patients with increased BUN (> or =17 mg/dl) and decreased GFR (< or =69 ml/min/1.73 m(2)) had significantly increased long-term mortality on Kaplan-Meier analysis (8-year mortalities of 57% and 55%, respectively). In patients with stage C HF, mortalities at 8 years were 69% and 73% with abnormal BUN and GFR, respectively. Proportional hazard regression analysis demonstrated that BUN and stage C HF were independently associated with increased mortality, whereas GFR was not. In conclusion, we demonstrated that BUN is strongly associated with mortality in patients with stage B and C HF and may serve as a better biomarker than GFR for prognostication.