Faculty Bibliography

BACKGROUND: Heart failure is among the most common reasons for hospitalizations in the United States. Recent data from Medicare suggest that the number of hospitalizations with a primary diagnosis of heart failure has declined over the past decade. However, heart failure may increase hospitalization rates for related comorbidities and individuals with heart failure are commonly admitted for other reasons. Using a nationally representative sample of hospital admissions, we studied trends in hospitalizations with both a primary and a secondary diagnosis of heart failure. METHODS: We evaluated trends in heart failure hospitalizations from 2001 to 2009 using the Nationwide Inpatient Sample (NIS), the largest all-payer inpatient database in the United States. We included hospitalizations with an International Classification of Diseases, Ninth Revision discharge diagnosis codes of 402.X1, 404.X1, 404.X3, 428.XX in any position; these codes in the primary position are used by The Centers for Medicare & Medicaid Services for reporting heart failure quality measures. Admissions were categorized as either primary heart failure hospitalization, if heart failure was the primary discharge code, or heart failure associated hospitalization, if heart failure was listed as a secondary diagnosis. National estimates of heart failure hospitalizations were calculated using the sampling weights and stratified sample design of the NIS. Yearly hospitalization rateswere determined by dividing the number of hospitalizations by the United States population in a given year. Population estimates were obtained from the United States Census Bureau. RESULTS: The total number of heart failure hospitalizations in the United States increased from 3,900,305 in 2001 to 4,398,376 in 2006 and then decreased to 4,253,937 in 2009. The number of primary heart failure admissions decreased from 1,139,607 in 2001 to 1,087,913 in 2009, while the number of heart failure associated hospitalizations increased from 2,760,698 to 3,166,024 over !

Aldosterone antagonists (or mineralocorticoid receptor antagonists [MRAs]) are guideline-recommended therapy for patients with moderate to severe heart failure (HF) symptoms and reduced left ventricular ejection fraction (LVEF), and in postmyocardial infarction patients with HF. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) trial evaluated the MRA eplerenone in patients with mild HF symptoms. Eplerenone reduced the risk of the primary endpoint of cardiovascular death or HF hospitalization (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.54-0.74, P < .001) and all-cause mortality (adjusted HR 0.76, 95% CI 0.62-0.93, P < .008) after a median of 21 months. Based on EMPHASIS-HF, an MRA is recommended for patients with New York Heart Association (NYHA) Class II-IV symptoms and reduced LVEF (<35%) on standard therapy (Strength of Evidence A). Patients with NYHA Class II symptoms should have another high-risk feature to be consistent with the EMPHASIS-HF population (age >55 years, QRS duration >130 msec [if LVEF between 31% and 35%], HF hospitalization within 6 months or elevated B-type natriuretic peptide level). Renal function and serum potassium should be closely monitored. Dose selection should consider renal function, baseline potassium, and concomitant drug interactions. The efficacy of eplerenone in patients with mild HF symptoms translates into a unique opportunity to reduce morbidity and mortality earlier in the course of the disease.

Cardiac resynchronization therapy (CRT) improves survival, symptoms, quality of life, exercise capacity, and cardiac structure and function in patients with New York Heart Association (NYHA) functional class II or ambulatory class IV heart failure (HF) with wide QRS complex. The totality of evidence supports the use of CRT in patients with less severe HF symptoms. CRT is recommended for patients in sinus rhythm with a widened QRS interval (>/=150 ms) not due to right bundle branch block (RBBB) who have severe left ventricular (LV) systolic dysfunction and persistent NYHA functional class II-III symptoms despite optimal medical therapy (strength of evidence A). CRT may be considered for several other patient groups for whom evidence of benefit is clinically significant but less substantial, including patients with a QRS interval of >/=120 to <150 ms and severe LV systolic dysfunction who have persistent mild to severe HF despite optimal medical therapy (strength of evidence B), some patients with atrial fibrillation, and some with ambulatory class IV HF. Several evidence gaps remain that need to be addressed, including the ideal threshold for QRS duration, QRS morphology, lead placement, degree of myocardial scarring, and the modality for evaluating dyssynchrony. Recommendations will evolve over time as additional data emerge from completed and ongoing clinical trials.

BACKGROUND: Hemoconcentration has been proposed as a putative biomarker of effective decongestion therapy in heart failure patients. The prevalence and clinical correlates of hemoconcentration in hospitalized patients with acute decompensated heart failure (ADHF) have not been previously described. METHODS AND RESULTS: We retrospectively reviewed paired values of hemoglobin at admission and discharge to identify evidence of hemoconcentration in 295 subjects hospitalized with ADHF and determined the association between hemoconcentration and risk of worsening renal function and survival. Subjects with hemoconcentration (n = 75) received higher diuretic doses and demonstrated greater weight loss during hospitalization when compared with subjects without hemoconcentration (median [IQR] loop diuretic dose 180 (120) versus 160 (150) mg, P = .014; mean +/- SD weight loss 4.0 +/- 3.1 versus 2.2 +/- 3.1 kg, P < .001). In univariate analysis, hemoconcentration was associated with increased risk of worsening renal function (odds ratio 2.34, 95% CI 1.27-4.30, P = .006), but decreased risk of all-cause mortality (hazard ratio 0.53, 95% CI 0.29-0.96, P = .035). In multivariate analysis, hemoconcentration remained independently associated with worsening renal function, but not mortality. CONCLUSIONS: Hemoconcentration is significantly associated with increased diuretic dose, greater weight loss, and increased risk of worsening renal function during hospitalization. Hemoconcentration was significantly associated with mortality in univariate analysis, but not in multivariate analysis

OBJECTIVE:To characterize acute (postprandial) and chronic (after a 6-month period of weight loss) effects of a low-carbohydrate vs. a low-fat diet on subclinical markers of cardiovascular disease (CVD) in adults with type 2 diabetes. DESIGN/METHODS:At baseline and 6 months, measures of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule (sICAM) and soluble E-selectin were obtained from archived samples (n = 51) of participants randomized in a clinical trial comparing a low-carbohydrate and a low-fat diet. In a subset of participants (n = 27), postprandial measures of these markers were obtained 3 h after a low-carbohydrate or low-fat liquid meal. Endothelial function was also measured by reactive hyperemic peripheral arterial tonometry during the meal test. Paired t tests and unpaired t tests compared within- and between-group changes. RESULTS:There were no significant differences observed in postprandial measures of inflammation or endothelial function. After 6 months, CRP (mean ± S.E.) decreased in the low-fat arm from 4.0 ± 0.77 to 3.0 ± 0.77 (P = .01). In the low-carbohydrate arm, sICAM decreased from 234 ± 22 to 199 ± 23 (P = .001), and soluble E-selectin decreased from 93 ± 10 to 82 ± 10 (P = .05.) A significant correlation between change in high-density lipoprotein and change in soluble E-selectin (r = -0.33, P = .04) and with the change in ICAM (r = -0.43, P = .01) was observed. CONCLUSIONS:Low-carbohydrate and low-fat diets both have beneficial effects on CVD markers. There may be different mechanisms through which weight loss with these diets potentially reduces CVD risk.

BACKGROUND: Increased iron stores are associated with greater cardiovascular risk in postmenopausal women. Oral contraceptive pill (OCP) use decreases the volume of menstrual blood loss and increases iron stores, but the link between OCP use, iron stores and cardiovascular risk in premenopausal women has not been characterized. STUDY DESIGN: We conducted a cross-sectional study of 23 healthy OCP users to determine the association between type and duration of OCP exposure, iron stores, and vascular endothelial function [flow-mediated dilation (FMD) in the brachial artery]. RESULTS: Median duration of OCP use was 45 months. FMD in the brachial artery was significantly associated with progestin type used (estranes/gonanes vs. drospirenone) and duration of OCP use (both p<.05) but not iron stores. In multivariate analysis, progestin type was the only independent predictor of FMD. CONCLUSIONS: Use of OCP containing drospirenone was independently associated with greater FMD in the brachial artery and, thus, a potentially more favorable cardiovascular risk profile, when compared with use of OCP containing estranes/gonanes

Background- Iron deficiency has been proposed as a potential therapeutic target in heart failure, but its prevalence and association with anemia and clinical outcomes in community-dwelling adults with heart failure have not been well characterized. Methods and Results- Using data from the Third National Health and Nutrition Examination Survey, we evaluated the associations between iron deficiency, hemoglobin, C-reactive protein (CRP), and all-cause and cardiovascular mortality in 574 adults with self-reported heart failure. Iron deficiency was defined in both absolute and functional terms as a ferritin level <100 mug/L or between 100 and 299 mug/L if the transferrin saturation was <20%. Iron deficiency was present in 61.3% of participants and was associated with reduced mean hemoglobin (13.6 versus 14.2 g/dL, P=0.007) and increased mean CRP (0.95 versus 0.63 mg/dL, P=0.04). Over a median of 6.7 years of follow-up, there were 300 all-cause deaths, 193 of which were from cardiovascular causes. In age- and sex-adjusted Cox proportional hazards models, hemoglobin, CRP, and transferrin saturation but not iron deficiency were significantly associated with all-cause and cardiovascular mortality. In multivariate models, hemoglobin remained an independent predictor of cardiovascular mortality, whereas CRP remained an independent predictor of both all-cause and cardiovascular mortality. Conclusions- Iron deficiency is common in heart failure and is associated with decreased hemoglobin and increased CRP. In multivariate analysis, hemoglobin was associated with cardiovascular mortality while CRP was associated with both all-cause and cardiovascular mortality. Iron deficiency was not associated with all-cause or cardiovascular mortality in this cohort