Impact of COVID-19 Pandemic on Sex and Racial Disparities in Chest Pain Presentation and Management Through the Emergency Department.

Background: Sex and racial disparities in the presentation and management of chest pain persist, however, the impact of coronavirus disease 2019 (COVID-19) on these disparities have not been studied. We sought to determine whether the COVID-19 pandemic contributed to pre-existing sex and racial disparities in the presentation, management, and outcomes of patients presenting to the emergency department (ED) with chest pain. Methods: We conducted an observational cohort study with retrospective data collection of patients between January 1, 2016, and May 1, 2022. This was a single study conducted at a quaternary academic medical center of all patients who presented to the ED with a complaint of chest pain or chest pain equivalent symptoms. Patient were further segregated into different groups based on sex (male, female), race, ethnicity (Asian, Black, Hispanic, White, and other), and age (18 - 40, 41 - 65, > 65). We compared diagnostic evaluations, treatment decisions, and outcomes during prespecified time points before, during, and after the COVID-19 pandemic. Results: This study included 95,764 chest pain encounters. Total chest pain presentations to the ED fell about 38% during the early pandemic months. Females presented significantly less than males during initial COVID-19 (48% vs. 52%, P < 0.001) and Asian females were least likely to present. There was an increase in the total number of troponins and echocardiograms ordered during peak COVID-19 across both sexes, but females were still less likely to have these tests ordered across all timepoints. The number of coronary angiograms did not increase during peak COVID-19, and females were less likely to undergo coronary angiogram during all timepoints. Finally, females with chest pain were less likely to be diagnosed with acute myocardial infarction (AMI) during all timepoints, while in-hospital deaths were similar between males and females during all timepoints. Conclusions: During COVID-19, females, especially Asian females, were less likely to present to the ED for chest pain. Non-White patients were less likely to present to the ED compared to White patients prior to and during the pandemic. Disparities in management and outcomes of chest pain encounters remained similar to pre-COVID-19, with females receiving less cardiac workup and AMI diagnoses than males, but in-hospital mortality remaining similar between groups and timepoints.

Abnormalities of calcium handling proteins in skeletal muscle mirror those of the heart in humans with heart failure: a shared mechanism?

BACKGROUND: In the failing human heart, abnormalities of Ca(2+) cycling have been described, but there is scant knowledge about Ca(2+) handling in the skeletal muscle of humans with heart failure (HF). We tested the hypothesis that in humans with HF, Ca(2+) cycling proteins in skeletal muscle are abnormal. METHODS AND RESULTS: Ten advanced HF patients (50.4 ± 3.7 years), and 9 age-matched controls underwent vastus lateralis biopsy. Western blot analysis showed that sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)2a, which is responsible for Ca(2+) sequestration into the sarcoplasmic reticulum(SR), was lower in HF versus controls (4.8 ± 0.5 vs 7.5 ± 0.8 AU, P = .01). Although phospholamban (PLN), which inhibits SERCA2a, was not different in HF versus controls, phosphorylation (SER16 site) of PLN, which relieves this inhibition, was reduced (0.8 ± 0.1 vs 3.9 ± 0.9 AU, P = .004). Dihydropyridine receptors were reduced in HF, (2.1 ± 0.4 vs 3.6 ± 0.5 AU, P = .04). We tested the hypothesis that these abnormalities of Ca(2+) handling protein content and regulation were due to increased oxidative stress, but oxygen radical scavenger proteins were not elevated in the skeletal muscle of HF patients. CONCLUSION: In chronic HF, marked abnormalities of Ca(2+) handling proteins are present in skeletal muscle, which mirror those in failing heart tissue. This suggests a common mechanism, such as chronic augmentation of sympathetic activity and autophosphorylation of Ca(2+)-calmodulin-dependent-protein kinase II.

Waist circumference, body mass index, and survival in systolic heart failure: the obesity paradox revisited.

BACKGROUND: Higher body mass index (BMI) is associated with improved heart failure (HF) survival, but the role of waist circumference (WC) in HF outcomes has not been studied. METHODS AND RESULTS: A total of 344 patients with advanced systolic HF had WC and BMI measured at presentation. High WC was defined as ≥88 cm in women and ≥102 cm in men, and high BMI as ≥25 kg/m(2). Two-year urgent heart transplant (UT)-free survival in high vs normal WC groups was 77.9% vs 64.3% (P = .025) and in high vs normal BMI was 89.8% vs 58.2% (P < .001). After multivariable adjustment, normal WC compared with high WC was associated with higher all-cause mortality (risk ratio [RR] 2.76, 95% confidence interval [CI] 1.34-5.71) and higher risk of death/UT (RR 2.14, 95% CI 1.25-3.68). The best outcomes were seen in those with both high WC and high BMI. CONCLUSIONS: High WC, an alternative anthropometric index of obesity more specific to abdominal adiposity, high BMI, and the combination of high WC/high BMI were each associated with improved outcomes in this advanced HF cohort, lending further support for an obesity paradox in HF. The role of body composition in HF survival should be a focus of future investigation.

Statins do not significantly affect muscle sympathetic nerve activity in humans with nonischemic heart failure: a double-blind placebo-controlled trial.

BACKGROUND: Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) have been shown to reduce sympathetic nervous system (SNS) activation in experimental heart failure (HF). However, this potential mechanism of action of statins in HF has not been well studied in humans. METHODS AND RESULTS: Twenty-six patients with nonischemic systolic HF (left ventricular ejection fraction [LVEF] ≤35%) were randomized to atorvastatin (10 mg) or placebo for 3 months. Pre- and posttreatment testing included echocardiography, laboratory assays, quality of life (QOL) questionnaires, and peroneal nerve muscle sympathetic nerve activity (MSNA) via microneurography. Eighteen subjects had technically adequate MSNA tracings before and after treatment. The cohort was 65% male, 81% New York Heart Association functional class II, LVEF 26 ± 6%, and low-density lipoprotein cholesterol (LDL-C) 108 ± 26 mg/dL. Baseline MSNA was 41 ± 2 bursts/min. LDL-C significantly decreased in the atorvastatin (-36.8%) versus the placebo (-0.1%) group (P < .0001). However, there was no significant change in MSNA (-16.2% vs -2.5%), LVEF, B-type natriuretic peptide, or QOL score in the atorvastatin compared with the placebo group. CONCLUSIONS: Short-term statin therapy in patients with nonischemic HF does not result in a significant decrease in SNS activation as measured by MSNA. These findings are consistent with the neutral outcomes of large clinical trials of statins in HF.

Sex Differences in the Association of Body Composition and Cardiovascular Mortality.

Background To determine whether differences in body composition contribute to sex differences in cardiovascular disease (CVD) mortality, we investigated the relationship between components of body composition and CVD mortality in healthy men and women. Methods and Results Dual energy x-ray absorptiometry body composition data from the National Health and Nutrition Examination Survey 1999-2004 and CVD mortality data from the National Health and Nutrition Examination Survey 1999-2014 were evaluated in 11 463 individuals 20 years of age and older. Individuals were divided into 4 body composition groups (low muscle mass-low fat mass-the referent; low muscle-high fat; high muscle-low fat, and high muscle-high fat), and adjusted competing risks analyses were performed for CVD versus non-CVD mortality. In women, high muscle/high fat mass was associated with a significantly lower adjusted CVD mortality rate (hazard ratio [HR], 0.58; 95% CI, 0.39-0.86; P=0.01), but high muscle/low fat mass was not. In men, both high muscle-high fat (HR, 0.74; 95% CI, 0.53-1.04; P=0.08) and high muscle-low fat mass (HR, 0.40; 95% CI, 0.21-0.77; P=0.01) were associated with lower CVD. Further, in adjusted competing risks analyses stratified by sex, the CVD rate in women tends to significantly decrease as normalized total fat increase (total fat fourth quartile: HR, 0.56; 95% CI, 0.34-0.94; P<0.03), whereas this is not noted in men. Conclusions Higher muscle mass is associated with lower CVD and mortality in men and women. However, in women, high fat, regardless of muscle mass level, appears to be associated with lower CVD mortality risk. This finding highlights the importance of muscle mass in healthy men and women for CVD risk prevention, while suggesting sexual dimorphism with respect to the CVD risk associated with fat mass.

Women in Cardiology Twitter Network: An Analysis of a Global Professional Virtual Community From 2016 to 2019.

Background Social media is an effective channel for the advancement of women physicians; however, its use by women in cardiology has not been systematically studied. Our study seeks to characterize the current Women in Cardiology Twitter network. Methods and Results Six women-specific cardiology Twitter hashtags were analyzed: #ACCWIC (American College of Cardiology Women in Cardiology), #AHAWIC (American Heart Association Women in Cardiology), #ilooklikeacardiologist, #SCAIWIN (Society for Cardiovascular Angiography and Interventions Women in Innovations), #WomeninCardiology, and #WomeninEP (Women in Electrophysiology). Twitter data from 2016 to 2019 were obtained from Symplur Signals. Quantitative and descriptive content analyses were performed. The Women in Cardiology Twitter network generated 48 236 tweets, 266 180 903 impressions, and 12 485 users. Tweets increased by 706% (from 2083 to 16 780), impressions by 207% (from 26 755 476 to 82 080 472), and users by 440% (from 796 to 4300), including a 471% user increase internationally. The network generated 6530 (13%) original tweets and 43 103 (86%) amplification tweets. Most original and amplification tweets were authored by women (81% and 62%, respectively) and women physicians (76% and 52%, respectively), with an increase in original and amplification tweets authored by academic women physicians (98% and 109%, respectively) and trainees (390% and 249%, respectively) over time. Community building, professional development, and gender advocacy were the most common tweet contents over the study period. Community building was the most common tweet category for #ACCWIC, #AHAWIC, #ilooklikeacardiologist, #SCAIWIN, and #WomeninCardiology, whereas professional development was most common for #WomeninEP. Conclusions The Women in Cardiology Twitter network has grown immensely from 2016 to 2019, with women physicians as the driving contributors. This network has become an important channel for community building, professional development, and gender advocacy discussions in an effort to advance women in cardiology.

Fluid retention is associated with cardiovascular mortality in patients undergoing long-term hemodialysis.

BACKGROUND: Patients with chronic kidney disease (stage 5) who undergo hemodialysis treatment have similarities to heart failure patients in that both populations retain fluid frequently and have excessively high mortality. Volume overload in heart failure is associated with worse outcomes. We hypothesized that in hemodialysis patients, greater interdialytic fluid gain is associated with poor all-cause and cardiovascular survival. METHODS AND RESULTS: We examined 2-year (July 2001 to June 2003) mortality in 34,107 hemodialysis patients across the United States who had an average weight gain of at least 0.5 kg above their end-dialysis dry weight by the time the subsequent hemodialysis treatment started. The 3-month averaged interdialytic weight gain was divided into 8 categories of 0.5-kg increments (up to > or =4.0 kg). Eighty-six percent of patients gained >1.5 kg between 2 dialysis sessions. In unadjusted analyses, higher weight gain was associated with better nutritional status (higher protein intake, serum albumin, and body mass index) and tended to be linked to greater survival. However, after multivariate adjustment for demographics (case mix) and surrogates of malnutrition-inflammation complex, higher weight-gain increments were associated with increased risk of all-cause and cardiovascular death. The hazard ratios (95% confidence intervals) of cardiovascular death for weight gain <1.0 kg and > or =4.0 kg (compared with 1.5 to 2.0 kg as the reference) were 0.67 (0.58 to 0.76) and 1.25 (1.12 to 1.39), respectively. CONCLUSIONS: In hemodialysis patients, greater fluid retention between 2 subsequent hemodialysis treatment sessions is associated with higher risk of all-cause and cardiovascular death. The mechanisms by which fluid retention influences cardiovascular survival in hemodialysis may be similar to those in patients with heart failure and warrant further research.

Metformin therapy and outcomes in patients with advanced systolic heart failure and diabetes.

BACKGROUND: Although 25% to 44% of patients with heart failure (HF) have diabetes mellitus (DM), the optimal treatment regimen for HF patients with DM is uncertain. We investigated the association between metformin therapy and outcomes in a cohort of advanced, systolic HF patients with DM. METHODS AND RESULTS: Patients with DM and advanced, systolic HF (n = 401) were followed at a single university HF center between 1994 and 2008. The cohort was divided into 2 groups based on the presence or absence of metformin therapy. The cohort had a mean age of 56 +/- 11 years, left ventricular ejection fraction (LVEF) of 24 +/- 7%, with 42% being New York Heart Association (NYHA) III and 45% NYHA IV. Twenty-five percent (n = 99) were treated with metformin therapy. The groups treated and not treated with metformin were similar in terms of age, sex, baseline LVEF, medical history, and baseline glycosylated hemoglobin. Metformin-treated patients had a higher body mass index, lower creatinine, and were less often on insulin. One-year survival in metformin-treated and non-metformin-treated patients was 91% and 76%, respectively (RR = 0.37, CI 0.18-0.76, P = .007). After multivariate adjustment for demographics, cardiac function, renal function, and HF medications, metformin therapy was associated with a nonsignificant trend for improved survival. CONCLUSION: In patients with DM and advanced, systolic HF who are closely monitored, metformin therapy appears to be safe. Prospective studies are needed to determine whether metformin can improve HF outcome.

Body Composition Changes During Traditional Versus Intensive Cardiac Rehabilitation in Coronary Artery Disease.

PURPOSE: Intensive cardiac rehabilitation (CR) was recently approved by Medicare and includes more hours and more focus on nutrition, stress management, and group support than a traditional, exercise-focused CR. The purpose of this study was to compare changes in body composition and cardiovascular (CV) risk factors after intensive versus traditional CR programs in patients with coronary artery disease (CAD). METHODS: We studied 715 patients with CAD who completed a traditional versus intensive CR program at UCLA Medical Center between 2014 and 2018. Markers of CV health, including body composition using bioelectrical impedance analysis, were assessed pre- and post-program participation. RESULTS: In both types of CR programs, body mass index, body fat percentage, blood pressure, and cholesterol levels (total cholesterol and low-density lipoprotein cholesterol) were significantly lower post- compared with pre-program. Exercise capacity was increased in both groups. Intensive CR patients had greater reductions in body mass index, body fat percentage, visceral adipose tissue, and diastolic blood pressure. Traditional CR patients demonstrated greater increases in high-density lipoprotein cholesterol and estimated lean mass. CONCLUSIONS: In patients with CAD, both traditional and intensive CR programs led to improvements in CV risk factors, though the magnitude of the effects of the program differed between the programs. Further studies, including studies analyzing CV outcomes, are needed to help determine optimal CR program choice for CAD patients based on their risk factor and body composition profile.

Reducing cardiovascular risk among people living with HIV: Rationale and design of the INcreasing Statin Prescribing in HIV Behavioral Economics REsearch (INSPIRE) randomized controlled trial.

Cardiovascular disease (CVD) is a major cause of morbidity among people living with HIV (PLWH). Statins can safely and effectively reduce CVD risk in PLWH, but evidence-based statin therapy is under-prescribed in PLWH. Developed using an implementation science framework, INcreasing Statin Prescribing in HIV Behavioral Economics REsearch (INSPIRE) is a stepped-wedge cluster randomized trial that addresses organization-, clinician- and patient-level barriers to statin uptake in Los Angeles community health clinics serving racially and ethnically diverse PLWH. After assessing knowledge about statins and barriers to clinician prescribing and patient uptake, we will design, implement and measure the effectiveness of (1) educational interventions targeting leadership, clinicians, and patients, followed by (2) behavioral economics-informed clinician feedback on statin uptake. In addition, we will assess implementation outcomes, including changes in clinician acceptability of statin prescribing for PLWH, clinician acceptability of the education and feedback interventions, and cost of implementation.

Weekend hospital admission and discharge for heart failure: association with quality of care and clinical outcomes.

BACKGROUND: Although hospital admissions during weekends have been associated with worse quality of care and worse outcomes in some but not all medical conditions, the impact of weekend versus weekday admission and discharge for heart failure (HF) has not been well studied. This study investigates the association of (1) weekend compared to weekday HF admissions and discharges with quality of care and (2) weekend versus weekday HF admissions with length of stay (LOS) and mortality in the hospital. METHODS: Data were analyzed for 81,810 HF admissions at 241 sites participating in Get With the Guidelines (GWTG)-HF from January 2005 to September 2008. The cohort was stratified by weekend versus weekday admission and discharge. Generalized estimating equations adjusted for patient and hospital characteristics and clustering. RESULTS: Mean age was 72 +/- 14 years; left ventricular ejection fraction (LVEF) was 39+/-17%. Inhospital mortality was 3.0% and median LOS 4 days. Weekend admission was associated with decreased odds of LVEF documentation. Weekend discharge was associated with decreased odds of LVEF documentation and completed discharge instructions. Weekend HF admission compared to weekday admission was associated with slightly higher risk-adjusted odds of longer inhospital LOS (1.03 [1.01-1.05] and increased inhospital mortality (1.13 [1.02-1.27]). CONCLUSIONS: Among GWTG-HF hospitals, weekend admission and discharge for HF were associated with similar quality of care in many but not all measures. Risk-adjusted LOS was slightly longer and mortality moderately higher for weekend HF admissions.

The relationship between body mass index and cardiopulmonary exercise testing in chronic systolic heart failure.

BACKGROUND: Cardiopulmonary exercise testing (CPX) in patients with systolic heart failure (HF) is important for determining HF prognosis and helping guide timing of heart transplantation. Although approximately 20% to 30% of patients with HF are obese (body mass index [BMI] >30 kg/m(2)), the impact of BMI on CPX results is not well established. The objective of this study was to assess the relationship between BMI and CPX variables, including peak oxygen uptake (VO(2)) at ventilatory threshold, oxygen pulse, and ventilation-carbon dioxide production ratio. METHODS: Consecutive patients with systolic HF (n = 2,324) enrolled in the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training trial who had baseline BMI recorded were included in this study. Subjects were divided into strata based on BMI: underweight (BMI <18.5 kg/m(2)), normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25.0-29.9 kg/m(2)), obese I (BMI 30-34.9 kg/m(2)), obese II (BMI 35-39.9 kg/m(2)), and obese III (BMI > or = 40 kg/m(2)). RESULTS: Obese III, but not overweight; obese I; or obese II was associated with decreased peak VO(2) (mL kg(-1) min(-1)) compared to normal weight status. Increasing BMI category was inversely related to ventilation/carbon dioxide production (V(E)/V(CO2)) ratio (P < .0001). On multivariable analysis, BMI was a significant independent predictor of peak VO(2) (partial R(2) = 0.07, P < .0001) and V(E)/V(CO2) slope (partial R(2) = 0.03, P < .0001) in patients with chronic systolic HF. CONCLUSIONS: Body mass index is significantly associated with key CPX fitness variables in patients with HF. The influence of BMI on the prognostic value of CPX in HF requires further evaluation in longitudinal studies.

Bioelectrical impedance analysis of body composition and survival in patients with heart failure.

BACKGROUND: Studies have shown that higher body mass index (BMI) is associated with improved prognosis in heart failure (HF), and this is often termed the obesity paradox. HYPOTHESIS: Analysis of body composition may reveal that muscle mass rather than adipose tissue accounts for the obesity paradox. METHODS: Bioelectrical impedance analysis of body composition in 359 outpatients with HF was performed using an In Body 520 body composition scale (Biospace Inc., California). Body fat and lean mass were indexed by height (m2 ). The cohort was stratified by median fat and lean mass indexed by height. RESULTS: The mean age of patients studied was 56 ± 14; mean left ventricular ejection fraction was 38 ± 16%. Patients with higher indexed body fat mass had improved 5-year survival over patients with lower indexed body fat mass (90.2% vs 80.1%, P = 0.008). There was also improved survival in patients with high vs low indexed lean body mass (89.3% vs 80.9%, P = 0.036). On multivariable analysis, higher indexed body fat mass, but not lean body mass, was independently associated with improved survival (HR 0.89, per kg/m2 increase in indexed body fat mass, P = 0.044); however, this was attenuated after adjustment for diabetes. The combination of low lean with low-fat mass was independently associated with poor prognosis. CONCLUSIONS: Our data suggest that higher fat mass-and to a lesser extent higher lean mass-is associated with improved outcomes in HF. Further investigations of specific components of body composition and outcomes in HF are warranted.

Monomorphic Ventricular Arrhythmias in Athletes.

Ventricular arrhythmias are challenging to manage in athletes with concern for an elevated risk of sudden cardiac death (SCD) during sports competition. Monomorphic ventricular arrhythmias (MMVA), while often benign in athletes with a structurally normal heart, are also associated with a unique subset of idiopathic and malignant substrates that must be clearly defined. A comprehensive evaluation for structural and/or electrical heart disease is required in order to exclude cardiac conditions that increase risk of SCD with exercise, such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Unique issues for physicians who manage this population include navigating athletes through the decision of whether they can safely continue their chosen sport. In the absence of structural heart disease, therapies such as radiofrequency catheter ablation are very effective for certain arrhythmias and may allow for return to competitive sports participation. In this comprehensive review, we summarise the recommendations for evaluating and managing athletes with MMVA.

Albumin levels predict survival in patients with systolic heart failure.

BACKGROUND: Hypoalbuminemia is associated with poor prognosis in patients with certain chronic diseases, such as end-stage renal disease and cancer. Although low serum albumin is common in patients with heart failure (HF), the relationship between albumin and HF prognosis has not been well characterized. This study investigated the effect of serum albumin level on survival in patients with advanced HF. METHODS: We analyzed 1726 systolic HF patients (age 52 +/- 13 years, ejection fraction [EF] 23% +/- 7%) followed at a university HF center. Albumin level was determined at initial referral. Patients were divided by into groups based on presence of hypoalbuminemia (< or = 3.4 g/dL). Mean albumin was 3.8 +/- 0.6 g/dL, and 25% of patients had hypoalbuminemia. RESULTS: Patients with and without low albumin levels were similar in age, HF etiology, and EF. Hypoalbuminemia was associated with higher New York Heart Association (NYHA) class, higher serum urea nitrogen, creatinine level, C-reactive protein, and B-type natriuretic peptide but lower levels of sodium, hemoglobin, and cholesterol. In patients with BMI < 25 kg/m(2), 27% had albumin < or = 3.4 g/dL, compared to 22% of those with BMI > or = 25 kg/m(2) (P < .01). One-year survival was 66% in patients with and 83% in those without hypoalbuminemia (P < .0001). Risk-adjusted hazard ratios for 1- and 5-year mortality were 2.2 (1.4-3.3) and 2.2 (1.4-3.2), respectively. CONCLUSIONS: Hypoalbuminemia is common in HF and is independently associated with increased risk of death in HF. Further investigation of pathophysiologic mechanisms underlying hypoalbuminemia in HF is warranted.

Cholesterol levels and in-hospital mortality in patients with acute decompensated heart failure.

BACKGROUND: In chronic heart failure (HF), lower total cholesterol (TC) levels have been associated with increased mortality. However, the relationship between lipid levels and outcomes in acute HF has not been studied. This study investigates the relationship between cholesterol levels and in-hospital mortality in patients hospitalized with acute HF. METHODS: The Get With the Guidelines-Heart Failure registry prospectively collects data on patients hospitalized with HF. We analyzed data on 17,791 patients admitted between January 2005 and June 2007 at 236 participating hospitals who had TC levels recorded. Baseline patient characteristics, treatment regimens, and in-hospital mortality were examined by TC level (mg/dL) quartiles (Q) as follows: Q1 (TC < or =118), Q2 (TC 119-145), Q3 (TC 146-179), and Q4 (TC > or =180). RESULTS: Mean TC level was 150 +/- 47 mg/dL. Patients with lower TC were older and had higher prevalence of ischemic heart disease. Of the patients, 46% were on a lipid-lowering drug, including 58%, 50%, 43%, and 34% of patients in TC Q1 to Q4, respectively. In-hospital mortality in TC Q1 to Q4 was 3.3%, 2.5%, 2.0%, and 1.3%, respectively (P < .0001). On multivariable adjusted analyses, each 10-mg/dL increase in TC level was associated with 4% decreased risk of in-hospital mortality (odds ratio 0.96, 95% CI 0.93-0.98). CONCLUSIONS: In patients hospitalized with HF, lower TC levels independently predict increased in-hospital mortality risk. Further evaluation of optimal cholesterol levels and influence of lipid-lowering medication use on outcomes in this population is warranted.

Nutritional and anti-inflammatory interventions in chronic heart failure.

Currently, there are 5 million individuals with chronic heart failure (CHF) in the United States who have poor clinical outcomes, including high death rates. Observational studies have indicated a reverse epidemiology of traditional cardiovascular risk factors in CHF; in contrast to trends seen in the general population, obesity and hypercholesterolemia are associated with improved survival. The temporal discordance between the overnutrition (long-term killer) and undernutrition (short-term killer) not only can explain some of the observed paradoxes but also may indicate that malnutrition, inflammation, and oxidative stress may play a role that results in protein-energy wasting contributing to poor survival in CHF. Diminished appetite or anorexia and nutritional deficiencies may be both a cause and a consequence of this so-called malnutrition-inflammation-cachexia (MIC) or wasting syndrome in CHF. Neurohumoral activation, insulin resistance, cytokine activation, and survival selection-resultant genetic polymorphisms also may contribute to the prominent inflammatory and oxidative characteristics of this population. In patients with CHF and wasting, nutritional strategies including amino acid supplementation may represent a promising therapeutic approach, especially if the provision of additional amino acids, protein, and energy includes nutrients with anti-inflammatory and antioxidant properties. Regardless of the etiology of anorexia, appetite-stimulating agents, especially those with anti-inflammatory properties such as megesterol acetate or pentoxyphylline, may be appropriate adjuncts to dietary supplementation. Understanding the factors that modulate MIC and body wasting and their associations with clinical outcomes in CHF may lead to the development of nutritional strategies that alter the pathophysiology of CHF and improve outcomes.

Usefulness of B-type natriuretic peptide and cardiac troponin levels to predict in-hospital mortality from ADHERE.

B-type natriuretic peptide (BNP) and cardiac troponin (Tn) I or T have been demonstrated to provide prognostic information in patients with acute coronary syndromes. Whether admission BNP and Tn levels provide additive prognostic value in acutely decompensated heart failure (HF) has not been well studied. Hospitalizations for HF from April 2003 to December 2004 entered into ADHERE were analyzed. BNP assessment on admission was performed in 48,629 (63%) of 77,467 hospitalization episodes. Tn assessment was performed in 42,636 (88%) of these episodes. In-hospital mortality was assessed using logistic regression models adjusted for age, gender, blood urea nitrogen, systolic blood pressure, creatinine, sodium, pulse, and dyspnea at rest. Median BNP was 840 pg/ml (interquartile range 430 to 1,730). Tn was increased in 2,370 (5.6%) of 42,636 HF episodes. BNP above the median and increased Tn were associated with significantly increased risk of in-hospital mortality (odds ratios [OR] 2.09 and 2.41 respectively, each p value <0.0001). Mortality was 10.2% in patients with BNP >or=840/Tn increased compared with 2.2% with BNP <840/Tn not increased (OR 5.10, p <0.0001). After covariate adjustment, mortality risk remained significantly increased with BNP >or=840/Tn not increased (adjusted OR 1.56, 95% confidence interval 1.40 to 1.79, p <0.0001), BNP <840/Tn increased (adjusted OR 1.69, 95% confidence interval 1.17 to 2.45, p = 0.006), and BNP >or=840/Tn increased (adjusted OR 3.00, 95% confidence interval 2.47 to 3.66, p <0.0001). Admission BNP and cardiac Tn levels are significant, independent predictors of in-hospital mortality in acutely decompensated HF. Patients with BNP levels >or=840 pg/ml and increased Tn levels are at particularly high risk for mortality. In conclusion, a multimarker strategy for the assessment of patients hospitalized with HF adds incremental prognostic information.

Potential autonomic nervous system effects of statins in heart failure.

Sympathetic nervous system activation in heart failure, as indexed by elevated norepinephrine levels, higher muscle sympathetic nerve activity and reduced heart rate variability, is associated with pathologic ventricular remodeling, increased arrhythmias, sudden death, and increased mortality. Recent evidence suggests that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy may provide survival benefit in heart failure of both ischemic and nonischemic etiology, and one potential mechanism of benefit of statins in heart failure is modulation of the autonomic nervous system. Animal models of heart failure demonstrate reduced sympathetic activation and improved sympathovagal balance with statin therapy. Initial human studies have reported mixed results. Ongoing translational studies and outcomes trials will help delineate the potentially beneficial effects of statins on the autonomic nervous system in heart failure.

Obesity and the Obesity Paradox in Heart Failure.

Obesity continues to be a public health problem in the general population, and also significantly increases the risk for the development of new-onset heart failure (HF). However, in patients with already-established, chronic HF, overweight and mild to moderate obesity is associated with substantially improved survival compared to normal weight patients; this has been termed the "obesity paradox". The majority of studies measure obesity by body mass index, but studies utilizing less-frequently used measures of body fat and body composition, including waist circumference, waist-hip ratio, skinfold estimates, and bioelectrical impedance analysis also confirm the obesity paradox in HF. Other areas of investigation such as the relationship of the obesity paradox to cardiorespiratory fitness, gender, and race are also discussed. Finally, this review explores various explanations for the obesity paradox, and summarizes the current evidence for intentional weight loss treatments for HF in context.