High-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and risk of incident heart failure in patients with CKD: the Chronic Renal Insufficiency Cohort (CRIC) Study.

High-sensitivity troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) strongly predict heart failure (HF) in the general population. However, the interpretation of levels of these biomarkers as predictors of HF is uncertain among patients with CKD. Here, we investigated whether hsTnT and NT-proBNP are associated with incident HF among patients with CKD. In a prospective cohort analysis, we studied 3483 people with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study recruited from June of 2003 to August of 2008 who were free of HF at baseline. We used Cox regression to examine the association of baseline levels of hsTnT and NT-proBNP with incident HF after adjustment for demographic factors, traditional cardiovascular risk factors, markers of kidney disease, pertinent medication use, and mineral metabolism markers. At baseline, hsTnT levels ranged from ≤5.0 to 738.7 pg/ml, and NT-proBNP levels ranged from ≤5 to 35,000 pg/ml. Compared with those who had undetectable hsTnT, participants in the highest quartile (>26.5 pg/ml) had a significantly higher rate of HF (hazard ratio, 4.77; 95% confidence interval, 2.49 to 9.14). Similarly, compared with those in the lowest NT-proBNP quintile (<47.6 pg/ml), participants in the highest quintile (>433.0 pg/ml) experienced a substantially higher rate of HF (hazard ratio, 9.57; 95% confidence interval, 4.40 to 20.83) [corrected]. In conclusion, hsTnT and NT-proBNP were strongly associated with incident HF among a diverse cohort of individuals with mild to severe CKD. Elevations in these biomarkers may indicate subclinical changes in volume and myocardial stress that subsequently contribute to clinical HF.

Heart Failure in Non-Caucasians, Women, and Older Adults: A White Paper on Special Populations From the Heart Failure Society of America Guideline Committee.

The presentation, natural history, clinical outcomes, and response to therapy in patients with heart failure differ in some ways across populations. Women, older adults, and non-Caucasian racial or ethnic groups compose a substantial proportion of the overall heart failure population, but they have typically been underrepresented in clinical trials. As a result, uncertainty exists about the efficacy of some guideline-directed medical therapies and devices in specific populations, which may result in the under- or overtreatment of these patients. Even when guideline-based treatments are prescribed, socioeconomic, physical, or psychologic factors may affect non-Caucasian and older adult patient groups to a different extent and affect the application, effectiveness, and tolerability of these therapies. Individualized therapy based on tailored biology (genetics, proteomics, metabolomics), socioeconomic and cultural considerations, and individual goals and preferences may be the optimal approach for managing diverse patients. This comprehensive approach to personalized medicine is evolving, but in the interim, the scientific community should continue efforts focused on intensifying research in special populations, prescribing guideline-directed medical therapy unless contraindicated, and implementing evidence-based strategies including patient and family education and multidisciplinary team care in the management of patients.

Advanced (stage D) heart failure: a statement from the Heart Failure Society of America Guidelines Committee.

We propose that stage D advanced heart failure be defined as the presence of progressive and/or persistent severe signs and symptoms of heart failure despite optimized medical, surgical, and device therapy. Importantly, the progressive decline should be primarily driven by the heart failure syndrome. Formally defining advanced heart failure and specifying when medical and device therapies have failed is challenging, but signs and symptoms, hemodynamics, exercise testing, biomarkers, and risk prediction models are useful in this process. Identification of patients in stage D is a clinically important task because treatments are inherently limited, morbidity is typically progressive, and survival is often short. Age, frailty, and psychosocial issues affect both outcomes and selection of therapy for stage D patients. Heart transplant and mechanical circulatory support devices are potential treatment options in select patients. In addition to considering indications, contraindications, clinical status, and comorbidities, treatment selection for stage D patients involves incorporating the patient's wishes for survival versus quality of life, and palliative and hospice care should be integrated into care plans. More research is needed to determine optimal strategies for patient selection and medical decision making, with the ultimate goal of improving clinical and patient centered outcomes in patients with stage D heart failure.

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.

Guanylyl cyclase (GC)-A and GC-B activities in ventricles and cardiomyocytes from failed and non-failed human hearts: GC-A is inactive in the failed cardiomyocyte.

Cardiomyocytes release atrial natriuretic peptide (ANP) and B-type natriuretic peptide to stimulate processes that compensate for the failing heart by activating guanylyl cyclase (GC)-A. C-type natriuretic peptide is also elevated in the failing heart and inhibits cardiac remodeling by activating the homologous receptor, GC-B. We previously reported that GC-A is the most active membrane GC in normal mouse ventricles while GC-B is the most active membrane GC in failing ventricles due to increased GC-B and decreased GC-A activities. Here, we examined ANP and CNP-specific GC activity in membranes obtained from non-failing and failing human left ventricles and in membranes from matched cardiomyocyte-enriched pellet preparations. Similar to our findings in the murine study, we found that CNP-dependent GC activity was about half of the ANP-dependent GC activity in the non-failing ventricular and was increased in the failing ventricle. ANP and CNP increased GC activity 9- and 5-fold in non-failing ventricles, respectively. In contrast to the mouse study, in failing human ventricles, ANP-dependent activity was unchanged compared to non-failing values whereas CNP-dependent activity increased 35% (p=0.005). Compared with ventricular membranes, basal GC activity was reduced an order of magnitude in membranes derived from myocyte-enriched pellets from non-failing ventricles. ANP increased GC activity 2.4-fold but CNP only increased GC activity 1.3-fold. In contrast, neither ANP nor CNP increased GC activity in equivalent preparations from failing ventricles. We conclude that: 1) GC-B activity is increased in non-myocytes from failing human ventricles, possibly as a result of increased fibrosis, 2) human ventricular cardiomyocytes express low levels of GC-A and much lower levels or possibly no GC-B, and 3) GC-A in cardiomyocytes from failing human hearts is refractory to ANP stimulation.

Chronic kidney disease and prevalent atrial fibrillation: the Chronic Renal Insufficiency Cohort (CRIC).

BACKGROUND: The epidemiology of atrial fibrillation (AF) has been mainly investigated in patients with end-stage renal disease, with limited data on less advanced chronic kidney disease (CKD) stages. METHODS: A total of 3,267 adult participants (50% non-Hispanic blacks, 46% women) with CKD from the Chronic Renal Insufficiency Cohort were included in this study. None of the study participants had been on dialysis. Those with self-identified race/ethnicity other than non-Hispanic black or white (n = 323) or those without electrocardiographic data (n = 22) were excluded. Atrial fibrillation was ascertained by a 12-lead electrocardiogram and self-report. Age-, sex-, and race/ethnicity-specific prevalence rates of AF were estimated and compared between subgroups. Cross-sectional associations and correlates with prevalent AF were examined using unadjusted and multivariable-adjusted logistic regression analysis. RESULTS: The mean estimated glomerular filtration rate was 43.6 (+/-13.0) mL/(min 1.73 m(2)). Atrial fibrillation was present in 18% of the study population and in >25% of those > or =70 years old. In multivariable-adjusted models, 1-SD increase in age (11 years) (odds ratio 1.27, CI 95% 1.13-1.43, P < .0001), male [corrected] sex (0.80, 0.65-0.98, P = .0303), smoking (former vs never) (1.34, 1.08-1.66, P = .0081), history of heart failure (3.28, 2.47-4.36, P < .001), and history of cardiovascular disease (1.94, 1.56-2.43, P < .0001) were significantly associated with AF. Race/ethnicity, hypertension, diabetes, body mass index, physical activity, education, high-sensitivity C-reactive protein, total cholesterol, and alcohol intake were not significantly associated with AF. An estimated glomerular filtration rate <45 mL/(min 1.73 m(2)) was associated with AF in an unadjusted model (1.35, 1.13-1.62, P = .0010), but not after multivariable adjustment (1.12, 0.92-1.35, P = .2710). CONCLUSIONS: Nearly 1 in 5 participants in Chronic Renal Insufficiency Cohort, a national study of CKD, had evidence of AF at study entry, a prevalence similar to that reported among patients with end-stage renal disease and 2 to 3 times of that reported in the general population. Risk factors for AF in this CKD population do not mirror those reported in the general population.

Corin variant associated with hypertension and cardiac hypertrophy exhibits impaired zymogen activation and natriuretic peptide processing activity.

Corin is a cardiac serine protease that acts as the pro-atrial natriuretic peptide (ANP) convertase. Recently, 2 single-nucleotide polymorphisms (SNPs) (T555I and Q568P) in the human corin gene have been identified in genetic epidemiological studies. The minor I555/P568 allele, which is more common in African Americans, is associated with hypertension and cardiac hypertrophy. In this study, we examined the effect of T555I and Q568P amino acid substitutions on corin function. We found that corin frizzled-like domain 2, where T555I/Q568P substitutions occur, was required for efficient pro-ANP processing in functional assays. Mutant corin lacking this domain had 30+/-5% (P<0.01) activity compared to that of wild type. Similarly, corin variant T555I/Q568P had a reduced (38+/-7%, P<0.01) pro-ANP processing activity compared to that of wild type. The variant also exhibited a low activity (44+/-15%, P<0.05) in processing pro-brain natriuretic peptide (BNP). We next examined the biochemical basis for the loss of activity in T555I/Q568P variant and found that the zymogen activation of the corin variant was impaired significantly, as indicated by the absence of the activated protease domain fragment. This finding was confirmed in human embryonic kidney (HEK)293 cells and murine HL-1 cardiomyocytes. Thus, our results show that the corin gene SNPs associated with hypertension and cardiac hypertrophy impair corin zymogen activation and natriuretic peptide processing activity. Our data suggest that corin deficiency may be an important mechanism in hypertensive and heart diseases.

Natriuretic peptides and the genomics of left-ventricular hypertrophy.

Left-ventricular hypertrophy (LVH) is one of the strongest independent predictors of cardiovascular morbidity and mortality in the general population. Although hypertension and obesity are well-established, independent risk factors for the development of LVH, they explain less than 25% to 50% of the variance of left ventricular mass (LVM) in humans. A substantial body of evidence suggests that there is a genetic basis to the observed inter-individual variability in the susceptibility to the development of LVH. Given the continuous relationship between LVM and cardiovascular morbidity and mortality, elucidating the genetic determinants of inter-individual differences in the susceptibility to LVH is of considerable public health importance. It promises the opportunity to identify high-risk individuals for targeted intervention and may identify novel therapeutic targets for improved prevention and treatment strategies.

Blacks and whites have a similar prevalence of reduced left ventricular ejection fraction in the general population: the Dallas Heart Study (DHS).

BACKGROUND: The objective of the study was to evaluate racial differences in the prevalence of left ventricular (LV) dysfunction. Few data compare the relative frequency of reduced LV ejection fraction (EF) (LVEF) in blacks and whites. Because of the higher prevalence of risk factors for heart failure in blacks, including hypertension, obesity, and LV hypertrophy, we hypothesized that LV dysfunction would also be more common in this ethnic group. METHODS: In the DHS, a probability-based sample of Dallas County, we performed cardiac magnetic resonance imaging on 1335 black and 858 white participants aged 30 to 67 years to measure LVEF and volumes. We compared the prevalence of reduced LV EF and distribution of ventricular volumes in the 2 ethnic groups. RESULTS: The prevalence of a reduced LVEF, whether defined as < 50%, < 55%, or < 60%, did not appear to be different between black versus white women (P > or = .7 for each) or men (P > or = .4 for each). Similar findings were seen using a recently defined sex-specific threshold (men < 55% and women < 61%) for low EF (P = .1). Mean LV end-diastolic and end-systolic volumes indexed to body surface area were also comparable in black and white men (P > or = .3) and women (P > or = .1). CONCLUSIONS: Despite having a higher prevalence of risk factors for heart failure, blacks as compared with whites did not have a higher prevalence of reduced LVEF in the general population.

Systolic time ratio by impedance cardiography to distinguish preserved vs impaired left ventricular systolic function in heart failure.

Left ventricular ejection fraction (EF) is used to assess patients with heart failure (HF); however, frequent measurements are not cost-effective. Impedance cardiography (ICG) is a low-cost, noninvasive test that measures systolic time intervals and may be a method for detecting impaired vs intact EF. This study evaluated the relationship between EF by echocardiography or gated nuclear ventriculography and systolic time ratio (STR) by ICG in outpatients with chronic HF. A retrospective chart review identified 52 patients with EF and STR measured within 2 weeks. There was an inverse correlation between STR and EF (r=-0.54; P<.001). The area under the receiver operating characteristic curve for STR to identify reduced EF was 0.86. An EF < or =50% and STR > or =0.50 demonstrated 93% sensitivity and 85% specificity. STR was able to distinguish intact (>50%) from impaired EF (< or =50%). STR by ICG has the potential to be a reliable method to monitor ventricular function in chronic HF.

Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension.

BACKGROUND: The natriuretic peptide system contributes to blood pressure regulation. Atrial and brain natriuretic peptides are cleaved into smaller biologically active molecules by corin, a transmembrane serine protease expressed in cardiomyocytes. METHOD AND RESULTS: This genotype-phenotype genetic association study included replication samples and genomic control to correct for population stratification. Sequencing of the human corin gene identified 2 nonsynonymous, nonconservative single nucleotide polymorphisms (Q568P and T555I) in near-complete linkage disequilibrium, thus describing a single minor I555 (P568) corin gene allele. This allele was present in the heterozygote state in &12% of blacks but was extremely rare in whites (<0.5% were homozygous for the minor allele). In our primary population sample, the Dallas Heart Study, after adjustment for potential confounders, including population stratification, the corin I555 (P568) allele remained independently associated with increased risk for prevalent hypertension (odds ratio, 1.63; 95% CI, 1.11 to 2.38; P=0.013). The corin I555 (P568) allele also was associated with higher systolic blood pressure in subjects not using antihypertensive medication in unadjusted (133.7+/-20.7 versus 129.4+/-17.4 mm Hg; P=0.029) and adjusted (132.5+/-1.6 versus 128.9+/-0.6 mm Hg; P=0.029) analyses. The independent association of the minor corin allele with increased risk for prevalent hypertension was confirmed in the Multi-Ethnic Study of Atherosclerosis (odds ratio, 1.50; 95% CI, 1.09 to 2.06; P=0.014). In addition, the association of the minor corin I555 (P568) allele with higher systolic blood pressure was confirmed in adjusted analysis in the Chicago Genetics of Hypertension Study (125.8+/-1.9 versus 121.4+/-0.7 mm Hg; P=0.03). CONCLUSIONS: The corin I555 (P568) allele is common in blacks and is associated with higher blood pressure and an increased risk for prevalent hypertension.

Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study.

BACKGROUND: The association between higher body mass index (BMI) and lower B-type natriuretic peptide (BNP) level is thought to be mediated by expression of the natriuretic peptide clearance receptor (NPR-C) in adipose tissue. To explore this association, we tested 2 hypotheses: (1) that N-terminal (NT)-proBNP, which is not believed to bind NPR-C, would not be associated with BMI and (2) that lower BNP would be more closely associated with fat mass than with lean mass. METHODS AND RESULTS: Measurements of BNP, NT-proBNP, and body composition by direct dual energy x-ray absorptiometry (DEXA) were performed in 2707 subjects from the Dallas Heart Study. The associations between obesity and low BNP (<4 ng/L) or low NT-proBNP (lowest sex-specific quartile) were evaluated with multivariable logistic regression models stratified by sex and adjusted for age, race/ethnicity, hypertension, left ventricular mass, and end-diastolic volume. Higher BMI was independently associated with lower BNP and NT-proBNP (all P<0.001). When BMI was replaced with both DEXA-derived lean and fat mass, greater lean mass, but not fat mass, was associated with low BNP and NT-proBNP levels. CONCLUSIONS: In a large, population-based cohort, we confirm the previously described association between higher BMI and lower BNP and demonstrate a similar inverse association between BMI and NT-proBNP. Interestingly, both BNP and NT-proBNP are more closely associated with lean mass than with fat mass. These findings do not support the hypothesis that the lower BNP levels seen in obesity are driven by enhanced BNP clearance mediated via NPR-C.

Efficacy of angiotensin-converting enzyme inhibition in reducing progression from asymptomatic left ventricular dysfunction to symptomatic heart failure in black and white patients.

OBJECTIVES: This study was undertaken to determine whether enalapril had comparable efficacy in black and white patients with asymptomatic left ventricular dysfunction (ALVD) in preventing the development of symptomatic heart failure (HF). BACKGROUND: Recent studies have suggested that black patients with HF due to systolic dysfunction may derive less benefit than white patients with HF when treated with the same medication. METHODS: This is a post hoc analysis of the 4,054 black and white participants of the Studies of Left Ventricular Dysfunction Prevention Trial. RESULTS: Randomization to enalapril was associated with a comparable reduction in the relative risk of the development of symptomatic HF in black (relative risk [RR] 0.67, 95% confidence interval [CI] 0.49, 0.92, p = 0.01) and white patients (RR 0.61, 95% CI 0.53, 0.70, p < 0.001). Treatment with enalapril was also associated with a comparable reduction in the risk of the development of HF requiring medical therapy and the composite end point of death or development of HF in black and white patients. Black as compared with white patients with ALVD were at increased risk of the development of symptomatic HF (RR 1.81, 95% CI 1.51, 2.17, p < 0.001) despite adjustment for available measures of disease severity. CONCLUSIONS: Despite the increased absolute risk in black patients compared with white patients for the progression of ALVD, enalapril was equally efficacious in reducing the risk of progression of ALVD in these two ethnic groups.

Increased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years: the Cardiovascular Health Study.

OBJECTIVES: Our aim in this study was to determine whether increased left ventricular mass (LVM) is a risk factor for the development of a reduced left ventricular ejection fraction (LVEF). BACKGROUND: Prior studies have shown that increased LVM is a risk factor for heart failure but not whether it is a risk factor for a low LVEF. METHODS: As part of the Cardiovascular Health Study, a prospective population-based longitudinal study, we performed echocardiograms upon participant enrollment and again at follow-up of 4.9 +/- 0.14 years. In the present analysis, we identified 3,042 participants who had at baseline a normal LVEF and an assessment of LVM (either by electrocardiogram or echocardiogram), and at follow-up a measurable LVEF. The frequency of the development of a qualitatively depressed LVEF on two-dimensional echocardiography, corresponding approximately to an LVEF <55%, was analyzed by quartiles of baseline LVM. Multivariable regression determined whether LVM was independently associated with the development of depressed LVEF. RESULTS: Baseline quartile of echocardiographic LVM indexed to body surface area was associated with development of a depressed LVEF (4.8% in quartile 1, 4.4% in quartile 2, 7.5% in quartile 3, and 14.1% in quartile 4 [p < 0.001]). A similar relationship was seen in the subgroup of participants without myocardial infarction (p < 0.001). In multivariable regression that adjusted for confounders, both baseline echocardiographic (p < 0.001) and electrocardiographic (p < 0.001) LVM remained associated with development of depressed LVEF. CONCLUSIONS: Increased LVM as assessed by electrocardiography or echocardiography is an independent risk factor for the development of depressed LVEF.

Relation of lower hematocrit to progression from asymptomatic left ventricular dysfunction to symptomatic heart failure (from the Studies of Left Ventricular Dysfunction Prevention trial).

The relation between hematocrit and progression from asymptomatic left ventricular (LV) systolic dysfunction to symptomatic heart failure (HF) was examined in 2,821 patients from the Studies of Left Ventricular Dysfunction Prevention trial. Patients in the lowest hematocrit quartile (hematocrit < or = 40%) were at increased risk for the development of HF symptoms (hazard ratio [HR] 1.79, 95% confidence interval [CI] 1.37 to 2.34), first HF hospitalization (HR 2.35, 95% CI 1.52 to 3.62), and death or the development of HF symptoms (HR 1.60, 95% CI 1.28 to 1.99) compared with patients in the highest hematocrit quartile (hematocrit > 46%).

Third heart sound and elevated jugular venous pressure as markers of the subsequent development of heart failure in patients with asymptomatic left ventricular dysfunction.

PURPOSE: To determine the independent prognostic value of a third heart sound (S(3)) and elevated jugular venous pressure in patients with asymptomatic left ventricular dysfunction. METHODS: We performed a post hoc analysis of 4102 participants from the Studies of Left Ventricular Dysfunction (SOLVD) prevention trial. In that trial, participants with asymptomatic or minimally symptomatic left ventricular dysfunction (New York Association class I or II, left ventricular ejection fraction < or =0.35, no treatment for heart failure) were allocated randomly to enalapril or placebo and followed for a mean (+/- SD) of 34 +/- 14 months. The presence of an S(3) and elevated jugular venous pressure was ascertained by physical examination at study enrollment. We used multivariate proportional hazards models to determine whether these physical examination findings were associated with the development of heart failure, a prespecified endpoint of the SOLVD prevention trial. RESULTS: At baseline, 209 subjects (5.1%) had an S(3) and 70 (1.7%) had elevated jugular venous pressure. Heart failure developed in 1044 subjects (25.5%). After adjusting for other markers of disease severity, an S(3) was associated with an increased risk of heart failure (relative risk [RR] = 1.38; 95% confidence interval [CI]: 1.09 to 1.73; P = 0.007) and the composite endpoint of death or development of heart failure (RR = 1.34; 95% CI: 1.09 to 1.64; P = 0.005). Elevated jugular venous pressure was also associated with these outcomes in multivariate models. CONCLUSION: The physical examination provides prognostic information among patients with asymptomatic or minimally symptomatic left ventricular dysfunction.

Effects of diabetes mellitus and ischemic heart disease on the progression from asymptomatic left ventricular dysfunction to symptomatic heart failure: a retrospective analysis from the Studies of Left Ventricular Dysfunction (SOLVD) Prevention trial.

BACKGROUND: Emerging data suggest that diabetes mellitus is a risk factor for the progression of established heart failure only in those patients with ischemic cardiomyopathy. Whether diabetes mellitus is a risk factor for the progression from asymptomatic left ventricular systolic dysfunction to symptomatic heart failure in patients with left ventricular dysfunction of an ischemic cause is not known. METHODS: We performed a retrospective analysis of 2821 patients with asymptomatic left ventricular systolic dysfunction from the Studies of Left Ventricular Dysfunction (SOLVD) Prevention trial. We used adjusted survival analysis to examine the effects of ischemic heart disease and diabetes mellitus on 3 prespecified study end points: (1) development of heart failure (HF) symptoms, (2) HF hospitalization, and (3) death or development of symptoms. RESULTS: There is a statistically significant interaction between the cause of left ventricular systolic dysfunction and diabetes mellitus on the risk of development of heart failure symptoms (P = .020). Patients with ischemic cardiomyopathy and diabetes had an increased risk of progression to symptomatic heart failure (HR = 1.56, P < .001), hospitalization for heart failure (HR = 2.16, P < .001), and death or development of symptoms (HR = 1.50, P < .001), compared with patients with ischemic cardiomyopathy without diabetes. In contrast, diabetes was not associated with an increased risk of reaching these end points in patients with nonischemic cardiomyopathy. CONCLUSIONS: Diabetes mellitus is a risk factor for the progression from asymptomatic left ventricular systolic dysfunction to symptomatic heart failure, but this risk appears to be confined to those patients with ischemic cardiomyopathy.

Beta-blocker therapy in patients with heart failure in the urban setting: moving beyond clinical trials.

BACKGROUND: Despite their known benefits, beta-blockers (BBL) are not yet widely prescribed for heart failure, especially in the primary care setting. We wanted to identify patient characteristics that could guide primary care physicians in deciding whether they or a cardiologist should initiate BBL. A second objective was to determine the tolerability of BBL in clinical practice. METHODS: A retrospective chart review was conducted on a consecutive series of 551 patients with systolic dysfunction referred to a heart failure clinic in an urban public hospital. Patient responses to BBL were stratified into three categories: favorable (improvement of left ventricular ejection fraction by serial echocardiography), unfavorable (development of decompensated heart failure), or neither. Tolerability of BBL was assessed by the need to permanently discontinue BBL. RESULTS: Of 551 patients, 363 (66%) tolerated BBL. Among patients who had BBL initiated in the clinic, 48 had a favorable response, 34 had an unfavorable response, and 57 had neither a favorable or unfavorable response, as defined. A lower systolic blood pressure and higher diuretic dose were associated with development of decompensated heart failure as compared to improvement of ejection fraction. CONCLUSIONS: A majority of patients with heart failure in an urban public hospital can tolerate BBL. Easily measurable characteristics such as lower systolic blood pressure and higher diuretic dose may assist primary care physicians in triaging patients for referral to cardiologists for beta-blocker initiation.

Potential contributing factors to noncompliance with dietary sodium restriction in patients with heart failure.

BACKGROUND: Although sodium restriction is considered essential in the management of patients with chronic heart failure (CHF), there are no data available regarding patients awareness of and ability to comply with the sodium restriction guideline. METHODS: Between May 1999 and August 2000, 50 patients referred to the Parkland Memorial Hospital CHF clinic were assessed by a registered dietitian for (1) awareness of the sodium restriction guideline, (2) ability to read the sodium content from a Nutrition Facts label, and (3) ability to sort 12 food containers, all bearing a Nutrition Facts label, into high- and low-sodium groups. A global measure of dietary sodium knowledge was calculated ("sodium knowledge score," range 0-10). These tests were repeated after the patient completed one or more educational sessions (mean 2.8 +/- 1.5) with the dietitian. RESULTS: The proportion of patients aware of the sodium restriction guideline was 14% at baseline and 42% at follow-up (P <.01). The proportion of patients able to read the sodium content from the Nutrition Facts label was 58% at baseline and 92% at follow-up (P <.01). The sodium knowledge score was 3.8 +/- 3.4 at baseline and 5.8 +/- 3.2 at follow-up (P <.01). The proportion of subjects who achieved a perfect sodium knowledge score of 10 was 8% at baseline and 26% at follow-up (P <.05). The number of food containers sorted accurately was 10.6 +/- 1.5 at baseline and 11.3 +/- 1.1 at follow-up, P =.09. CONCLUSIONS: On referral to a specialty CHF clinic, many patients had severe deficiencies in their knowledge base regarding dietary sodium intake that would preclude compliance with the sodium restriction guideline. Directed education focusing on sodium intake corrected many of these deficiencies.

Development of a depressed left ventricular ejection fraction in patients with left ventricular hypertrophy and a normal ejection fraction.

The progression from concentric left ventricular (LV) hypertrophy to heart failure has not been well defined. Of 159 predominantly hypertensive African-American patients with LV hypertrophy and a normal ejection fraction (EF), 28 (18%) developed a reduced EF after a median follow-up of approximately 4 years. Risk factors for this outcome included a history of coronary artery disease, pulmonary edema seen on a chest x-ray, or a subsequent myocardial infarction.