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.

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.

Longitudinal Associations Between Neighborhood Physical and Social Environments and Incident Type 2 Diabetes Mellitus: The Multi-Ethnic Study of Atherosclerosis (MESA).

IMPORTANCE: Neighborhood environments may influence the risk for developing type 2 diabetes mellitus (T2DM), but, to our knowledge, no longitudinal study has evaluated specific neighborhood exposures. OBJECTIVE: To determine whether long-term exposures to neighborhood physical and social environments, including the availability of healthy food and physical activity resources and levels of social cohesion and safety, are associated with incident T2DM during a 10-year period. DESIGN, SETTING, AND PARTICIPANTS: We used data from the Multi-Ethnic Study of Atherosclerosis, a population-based cohort study of adults aged 45 to 84 years at baseline (July 17, 2000, through August 29, 2002). A total of 5124 participants free of T2DM at baseline underwent 5 clinical follow-up examinations from July 17, 2000, through February 4, 2012. Time-varying measurements of neighborhood healthy food and physical activity resources and social environments were linked to individual participant addresses. Neighborhood environments were measured using geographic information system (GIS)- and survey-based methods and combined into a summary score. We estimated hazard ratios (HRs) of incident T2DM associated with cumulative exposure to neighborhood resources using Cox proportional hazards regression models adjusted for age, sex, income, educational level, race/ethnicity, alcohol use, and cigarette smoking. Data were analyzed from December 15, 2013, through September 22, 2014. MAIN OUTCOMES AND MEASURES: Incident T2DM defined as a fasting glucose level of at least 126 mg/dL or use of insulin or oral antihyperglycemics. RESULTS: During a median follow-up of 8.9 years (37,394 person-years), 616 of 5124 participants (12.0%) developed T2DM (crude incidence rate, 16.47 [95% CI, 15.22-17.83] per 1000 person-years). In adjusted models, a lower risk for developing T2DM was associated with greater cumulative exposure to indicators of neighborhood healthy food (12%; HR per interquartile range [IQR] increase in summary score, 0.88 [95% CI, 0.79-0.98]) and physical activity resources (21%; HR per IQR increase in summary score, 0.79 [95% CI, 0.71-0.88]), with associations driven primarily by the survey exposure measures. Neighborhood social environment was not associated with incident T2DM (HR per IQR increase in summary score, 0.96 [95% CI, 0.88-1.07]). CONCLUSIONS AND RELEVANCE: Long-term exposure to residential environments with greater resources to support physical activity and, to a lesser extent, healthy diets was associated with a lower incidence of T2DM, although results varied by measurement method. Modifying neighborhood environments may represent a complementary, population-based approach to prevention of T2DM, although further intervention studies are needed.

Short Communication: Coronary Heart Disease Risk by Framingham Risk Score in Hepatitis C and HIV/Hepatitis C-Coinfected Persons.

We compared the Framingham risk score (FRS) for 10-year coronary heart disease (CHD) risk in age- and race-matched hepatitis C virus (HCV)-infected and HCV-uninfected persons: 114,073 HCV-infected (111,436 HCV-monoinfected and 2,637 HIV/HCV-coinfected) and 122,996 HCV-uninfected (121,380 HIV and HCV-uninfected and 1,616 HIV-monoinfected) males without cardiovascular disease, diabetes, or hepatitis B. In unadjusted analyses, FRS was similar between the HCV-infected and HCV-uninfected groups [median (interquartile range, IQR) risk points 13 (10-14) vs. 13 (10-14), p=0.192]. Cholesterol levels were lower and current smoking more prevalent in the HCV groups (both HCV and HIV/HCV) compared with the uninfected groups (p<0.001 for both). Prevalence of non-FRS CHD risk factors, such as substance abuse and chronic kidney disease, in the cohort was high, and differed by HCV and HIV status. Adjusting for age, race/ethnicity, body mass index, chronic kidney disease, drug and alcohol use, and HIV status, HCV infection was associated with minimally lower FRS (ß=-0.095 risk points, p<0.001), suggesting a small but significant difference in 10-year CHD risk estimation in HCV-infected as compared to HCV-uninfected persons when measuring risk by FRS. Given the complex relationship between HCV, HIV, and CHD risk factors, some of which are not captured by the FRS, the FRS may underestimate CHD risk in HCV-monoinfected and HIV/HCV-coinfected persons. HCV- and HIV/HCV-specific risk scores may be needed to optimize CHD risk stratification.

Association of menopause age and N-terminal pro brain natriuretic peptide: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: Menopause age can affect the risk of developing cardiovascular disease (CVD). The purpose of this study was to investigate the associations of early menopause (menopause occurring before age 45 y) and menopause age with N-terminal pro brain natriuretic peptide (NT-proBNP), a potential risk marker of CVD and heart failure. METHODS: Our cross-sectional study included 2,275 postmenopausal women, aged 45 to 85 years and without clinical CVD (2000-2002), from the Multi-Ethnic Study of Atherosclerosis. Participants were classified as having or not having early menopause. NT-proBNP was log-transformed. Multivariable linear regression was used for analysis. RESULTS: Five hundred sixty-one women had early menopause. The median (25th-75th percentiles) NT-proBNP value was 79.0 (41.1-151.6) pg/mL for all participants, 83.4 (41.4-164.9) pg/mL for women with early menopause, and 78.0 (40.8-148.3) pg/mL for women without early menopause. The mean (SD) age was 65 (10.1) and 65 (8.9) years for women with and without early menopause, respectively. No significant interactions between menopause age and ethnicity were observed. In multivariable analysis, early menopause was associated with a 10.7% increase in NT-proBNP levels, whereas each 1-year increase in menopause age was associated with a 0.7% decrease in NT-proBNP levels. CONCLUSIONS: Early menopause is associated with greater NT-proBNP levels, whereas each 1-year increase in menopause age is associated with lower NT-proBNP levels, in postmenopausal women.

Intact skeletal muscle mitochondrial enzyme activity but diminished exercise capacity in advanced heart failure patients on optimal medical and device therapy.

BACKGROUND: A skeletal myopathy, perhaps attributable to neuro-endocrine excitation or disuse, has been described in heart failure (HF) patients, and is thought to contribute to their exercise limitation. Our purpose was to assess biochemical and morphometric characteristics of skeletal muscles of HF patients on optimal HF therapy. A secondary purpose was to explore the effects of clonidine, which interrupts the neuro-endocrine excitation, on these same muscle characteristics. METHODS AND RESULTS: Eleven HF patients (50.8 ± 3.4 years, peak VO2 11.6 ± 2.5 ml/kg/min) underwent two vastus lateralis biopsies (pre/post clonidine). Baseline values were compared to biopsies in 11 age-matched, healthy controls. Scatter plots of individual values for each mitochondrial enzyme revealed almost complete overlap between HF and control groups; mean values, although tending to be greater in controls versus HF patients, were not significantly different. The proportion of type 1 fibers was diminished in 10 of 11 patients. There was no difference in any of the variables after 3 months clonidine versus placebo. CONCLUSION: In HF patients treated with optimal medical and device therapy, characteristic abnormalities of mitochondrial enzyme activity are not found, but muscle fiber type shifts are present. The remaining severe impairment in exercise capacity cannot be attributed to mitochondrial abnormalities.

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.

Epidemiology and risk profile of heart failure.

Heart failure (HF) is a major public health issue, with a prevalence of over 5.8 million in the USA, and over 23 million worldwide, and rising. The lifetime risk of developing HF is one in five. Although promising evidence shows that the age-adjusted incidence of HF may have plateaued, HF still carries substantial morbidity and mortality, with 5-year mortality that rival those of many cancers. HF represents a considerable burden to the health-care system, responsible for costs of more than $39 billion annually in the USA alone, and high rates of hospitalizations, readmissions, and outpatient visits. HF is not a single entity, but a clinical syndrome that may have different characteristics depending on age, sex, race or ethnicity, left ventricular ejection fraction (LVEF) status, and HF etiology. Furthermore, pathophysiological differences are observed among patients diagnosed with HF and reduced LVEF compared with HF and preserved LVEF, which are beginning to be better appreciated in epidemiological studies. A number of risk factors, such as ischemic heart disease, hypertension, smoking, obesity, and diabetes, among others, have been identified that both predict the incidence of HF as well as its severity. In this Review, we discuss key features of the epidemiology and risk profile of HF.

Relation of systolic blood pressure to survival in both ischemic and nonischemic systolic heart failure.

High systolic blood pressure (SBP) is a predictor of survival for patients with heart failure (HF). Whether SBP predicts survival in both ischemic and nonischemic HF has not been well examined. We analyzed 2,178 patients with advanced HF (47.3% ischemic etiology, 75.5% men, 93.5% New York Heart Association class III or IV, age 52 +/- 13, left ventricular ejection fraction 24 +/- 9%) referred to a university center between 1983 and 2006. SBP and invasive hemodynamic variables were recorded after optimization of medical therapy. Patients were divided into SBP quartiles (or=113 mm Hg) based on SBP frequency. Survival free from death or urgent transplant in ischemic versus nonischemic HF was 53.2% versus 61.1% at 2 years. Higher SBP quartile was associated with increased survival in the total cohort and in subgroups of both nonischemic and ischemic HF. On multivariate analysis adjusting for age, left ventricular ejection fraction, cholesterol, gender, diabetes mellitus, pulmonary capillary wedge pressure, cardiac index, New York Heart Association class, beta-blocker use, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use, statin use, and smoking history, relative risk (95% confidence interval) of death or urgent transplant at 2 years for quartile 1 compared with quartile 4 was 1.9 (1.4 to 2.6) in the total cohort, 1.6 (1.1 to 2.5) in nonischemic HF, and 2.4 (1.5 to 3.7) in ischemic HF. In conclusion, SBP predicts HF survival in both ischemic and nonischemic HF independent of other risk factors and invasive hemodynamic variables.

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.

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.

Risk factor paradox in wasting diseases.

PURPOSE OF REVIEW: Emerging data indicate that conventional cardiovascular risk factors (e.g. hypercholesterolemia and obesity) are paradoxically associated with better survival in distinct populations with wasting. We identify these populations and review survival paradoxes and common pathophysiologic mechanisms. RECENT FINDINGS: A 'reverse epidemiology' of cardiovascular risk is observed in chronic kidney disease, chronic heart failure, chronic obstructive lung disease, cancer, AIDS and rheumatoid arthritis, and in the elderly. These populations apparently have slowly progressive to full-blown wasting and significantly greater short-term mortality than the general population. The survival paradoxes may result from the time differential between the two competing risk factors [i.e. over-nutrition (long-term killer but short-term protective) versus undernutrition (short-term killer)]. Hemodynamic stability of obesity, protective adipokine profile, endotoxin-lipoprotein interaction, toxin sequestration of fat, antioxidation of muscle, reverse causation, and survival selection may also contribute. SUMMARY: The seemingly counterintuitive risk factor paradox is the hallmark of chronic disease states or conditions associated with wasting disease at the population level. Studying similarities among these populations may help reveal common pathophysiologic mechanisms of wasting disease, leading to a major shift in clinical medicine and public health beyond the conventional Framingham paradigm and to novel therapeutic approaches related to wasting and short-term mortality.

Relation of loop diuretic dose to mortality in advanced heart failure.

Although loop diuretics are widely used in heart failure (HF), their effect on outcomes has not been evaluated in large clinical trials. This study sought to determine the dose-dependent relation between loop diuretic use and HF prognosis. A cohort of 1,354 patients with advanced systolic HF referred to a single center was studied. Patients were divided into quartiles of equivalent total daily loop diuretic dose: 0 to 40, 41 to 80, 81 to 160, and >160 mg. The cohort was 76% male, with a mean age of 53+/-13 years and a mean ejection fraction of 24+/-7%. The mean diuretic dose equivalence was 107+/-87 mg. The diuretic quartile groups were similar in terms of gender, body mass index, ischemic cause of HF, history of hypertension, and spironolactone use, but the highest quartile was associated with a smaller ejection fraction and lower serum sodium and hemoglobin levels but higher serum blood urea nitrogen and creatinine levels. There was a decrease in survival with increasing diuretic dose (83%, 81%, 68%, and 53% for quartiles 1, 2, 3, and 4, respectively). Even after extensive co-variate adjustment (age, gender, ischemic cause of HF, the ejection fraction, body mass index, pulmonary capillary wedge pressure, peak oxygen consumption, beta-blocker use, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, digoxin use, statin use, serum sodium, blood urea nitrogen, creatinine, hemoglobin, cholesterol, systolic blood pressure, and smoking history), diuretic quartile remained an independent predictor of mortality (quartile 4 vs quartile 1 hazard ratio 4.0, 95% confidence interval 1.9 to 8.4). In conclusion, in this cohort of patients with advanced HF, there was an independent, dose-dependent association between loop diuretic use and impaired survival. Higher loop diuretic dosages identify patients with HF at particularly high risk for mortality.

Epidemiology of dialysis patients and heart failure patients.

The epidemiology of maintenance dialysis patients and heart failure patients has striking similarities. Both groups have a high prevalence of comorbid conditions, a high hospitalization rate, a low self-reported quality of life, and an excessively high mortality risk, mostly because of cardiovascular causes. Observational studies in both dialysis and heart failure patients have indicated the lack of a significant association between the traditional cardiovascular risk factors and mortality, or the existence of a paradoxic or reverse association, in that obesity, hypercholesterolemia, and hypertension appear to confer survival advantages. The time discrepancy between the 2 sets of risk factors, that is, overnutrition (long-term killer) versus undernutrition (short-term killer) may explain the overwhelming role of malnutrition, inflammation, and cachexia in causing the reverse epidemiology, which may exist in more than 20 million Americans. We have reviewed the opposing views about the concept of reverse epidemiology in dialysis and heart failure patients, the recent Die Deutsche Diabetes Dialyze study findings, and the possible role of racial disparities. Contradictory findings on hyperhomocysteinemia in dialysis patients are reviewed in greater details as a possible example of publication bias. Additional findings related to intravenous iron and serum ferritin, calcium, and leptin levels in dialysis patients may enhance our understanding of the new paradigm. The association between obesity and increased death risk in kidney transplanted patients is reviewed as an example of the reversal of reverse epidemiology. Studying the epidemiology of dialysis patients as the archetypical population with such paradoxic associations may lead to the development of population-specific guidelines and treatment strategies beyond the current Framingham cardiovascular risk factor paradigm.

Relationship between anemia, cardiac troponin I, and B-type natriuretic peptide levels and mortality in patients with advanced heart failure.

BACKGROUND: Anemia has been associated with worse symptoms and increased mortality in patients with advanced HF. The association between anemia and biomarkers of increased HF risk is unknown. This study aimed to evaluate the relationship between hemoglobin (Hb), cardiac troponin I (cTnI), B-type natriuretic peptide (BNP), and mortality in patients with advanced heart failure (HF). METHODS: A cohort of 264 patients with advanced HF referred to a single university HF center was analyzed. Hb, cTnI, and BNP levels were drawn at time of initial evaluation. Patients were divided into groups based on the presence or absence of anemia, detectable cTnI (> or = 0.04 ng/mL), and elevated BNP (> or = 485 pg/mL). RESULTS: Mean Hb was 13.0 and the values ranged from 7.7 to 17.9 g/dL. Anemic patients were more likely to have elevated BNP (65.7% vs 47.4%, P = .002). Cardiac troponin I levels were detectable in 50.9% and 46.8% of anemic and non-anemic patients, respectively (P = .3). Anemic patients were at 2.3-fold increased risk of mortality (P = .04). Low Hb, detectable cTnI, and elevated BNP remained independent predictors of mortality on multivariate analysis. Anemia in the setting of detectable cTnI, elevated BNP, or both, was associated with markedly increased mortality. CONCLUSIONS: Anemia is associated with elevated BNP and increased mortality in HF. Furthermore, elevation of the cardiac biomarkers, BNP and cTnI, in patients with HF and anemia identifies patients at particularly high risk of future events.

Survival advantages of obesity in dialysis patients.

In the general population, a high body mass index (BMI; in kg/m(2)) is associated with increased cardiovascular disease and all-cause mortality. However, the effect of overweight (BMI: 25-30) or obesity (BMI: >30) in patients with chronic kidney disease (CKD) undergoing maintenance hemodialysis (MHD) is paradoxically in the opposite direction; ie, a high BMI is associated with improved survival. Although this "reverse epidemiology" of obesity or dialysis-risk-paradox is relatively consistent in MHD patients, studies in CKD patients undergoing peritoneal dialysis have yielded mixed results. Growing confusion has developed among physicians, some of whom are no longer confident about whether to treat obesity in CKD patients. A similar reverse epidemiology of obesity has been described in geriatric populations and in patients with chronic heart failure (CHF). Possible causes of the reverse epidemiology of obesity include a more stable hemodynamic status, alterations in circulating cytokines, unique neurohormonal constellations, endotoxin-lipoprotein interaction, reverse causation, survival bias, time discrepancies among competitive risk factors, and malnutrition-inflammation complex syndrome. Reverse epidemiology may have significant clinical implications in the management of dialysis, CHF, and geriatric patients, ie, populations with extraordinarily high mortality. Exploring the causes and consequences of the reverse epidemiology of obesity in dialysis patients can enhance our insights into similar paradoxes observed for other conventional risk factors, such as blood pressure and serum cholesterol and homocysteine concentrations, and in other populations such as those with CHF, advanced age, cancer, or AIDS. Weight-gaining interventional studies in dialysis patients are urgently needed to ascertain whether they can improve survival and quality of life.

Insulin-treated diabetes is associated with a marked increase in mortality in patients with advanced heart failure.

OBJECTIVES: This study aimed to investigate the effect of diabetes and insulin use on survival in a large cohort of patients with advanced heart failure (HF) of multiple etiologies. BACKGROUND: Although diabetes is a well-known risk factor for both systolic and diastolic dysfunction, the impact of diabetes and insulin treatment on prognosis of patients with HF has not been well studied. METHODS: History of diabetes and insulin treatment was assessed in 554 consecutive patients with advanced systolic HF who presented to a single center for HF management and/or transplant evaluation (mean age 52.0 +/- 13.1 years, ejection fraction 24.6 +/- 7.4). Patients were stratified into 3 groups based on presence or absence of diabetes and insulin use. Differences in patient characteristics and survival were evaluated. RESULTS: There were 132 patients (23.8%) with diabetes; 43 patients (7.8%) were insulin treated and 89 patients (16.1%) were non-insulin-treated patients with diabetes. The groups were similar in sex, smoking history, medication profile, ejection fraction, body mass index, and serum sodium. Survival at 1 year was 89.7% for nondiabetic patients, 85.8% for non-insulin-treated diabetic patients, and 62.1% for insulin-treated diabetic patients (P < .000 01). After Cox multivariate analysis, insulin-treated diabetes was found to be an independent predictor of mortality (hazard ratio 4.30, 95% CI 1.69-10.94) whereas non-insulin-treated diabetes was not (hazard ratio 0.95, 95% CI 0.31-2.93). Similar findings were seen in clinically relevant subgroups. CONCLUSIONS: Insulin-treated diabetes is associated with a significantly worse prognosis in patients with advanced HF. Further investigations into mechanisms for the association of insulin treatment and mortality in patients with HF are warranted.