Potential aetiologies and prognostic implications of worsening renal function in acute decompensated heart failure.

BACKGROUND: One third of patients hospitalized for acute decompensated heart failure (ADHF) develop a worsening renal function (WRF) that is associated with increased in-hospital morbidity and mortality. However, previous investigations have not evaluated the various etiologies of WRF and its impact on prognosis. METHODS: A retrospective chart review was performed of patients admitted with ADHF who had a rise of serum creatinine ≥ 0.3 mg/dl on admission or during their hospital stay. The chart notes were reviewed for the suggested etiology of WRF. Cases were defined as ADHF associated WRF (ADHF-WRF) when there was no other explanation for WRF, plus an objective evidence of hypervolemia. Cases with WRF after 48 hours of a negative fluid balance were classified as diuresis-associated WRF (DA-WRF). RESULTS: ICD-9 codes identified 319 admissions with ADHF complicated with WRF. Fifty admissions were excluded. The most common causes of WRF were ADHF-WRF (43.1%) and DA-WRF (42.8%). Other causes included nephrotoxins (5.9%) and surgery (3.7%). The mortality rate was significantly lower with DA-WRF compared to ADHF-WRF; odds ratio 0.059 (95% CI 0.007 to 0.45, P = 0.006). Readmission at 30 days was higher in cases with ADHF-WRF (42%). CONCLUSIONS: WRF with ADHF is a heterogeneous group, and cases with ADHF-WRF had a higher in-hospital mortality and readmission rates.

Mechanical Aortic Valve Thromboembolism During Pregnancy on Low Molecular Weight Heparin.

A 31-year-old pregnant woman with a mechanical aortic valve developed a thrombus on her mechanical aortic valve due to subtherapeutic low molecular weight heparin dosage. She received intravenous heparin followed by warfarin. low molecular weight heparin dosing in pregnancy should be individualized, considering weight, physiological changes, and adjusted based on levels.

Prospective evaluation of the association between cardiac troponin T and markers of disturbed erythropoiesis in patients with heart failure.

BACKGROUND: Elevated cardiac troponin T is a well-documented marker of cardiomyocyte damage and poor prognosis in patients with heart failure. We prospectively evaluated the relationship between this marker and hematopoietic disturbances in heart failure. METHODS: Data were analyzed from 254 patients in the UNITE-HF Biomarker Registry, a prospective, observational, multicenter study of the clinical and biomarker correlates of anemia in heart failure. Logistic regression modeling assessed relationships between detectable troponin T and indices of hematologic function including anemia and red cell distribution width. RESULTS: Anemia (hemoglobin≤12 g/dL) was present in 65 of the 254 study patients, and detectable troponin T was found in 39. Anemia was a significant independent predictor of detectable troponin T in models that considered a number of clinical characteristics including renal function, functional class, heart rate, and systolic blood pressure (odds ratio 2.57, 95% CI 1.09-6.09, P=.032). Likewise, detectable troponin T was directly and independently related to red cell distribution width in similar multivariable analyses (odds ratio 1.36 per unit increase, 95% CI 1.08-1.71, P=.008). CONCLUSIONS: Anemia and increasing red cell distribution width were independently associated with elevated troponin T, a marker of cardiomyocyte injury or death in patients with heart failure.

Validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure.

BACKGROUND: Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. METHODS AND RESULTS: Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. CONCLUSIONS: Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system.

Factors Predicting the Utilization of Center-Based Cardiac Rehabilitation Program.

Although cardiac rehabilitation (CR) is clearly beneficial to improving patients' physical functioning and reducing heart disease progression, significant proportions of patients do not complete CR programs. To evaluate the prevalence and predictors of completion of a center-based CR program in eligible cardiac patients, existing data collected from electronic medical records were used. To identify the predictors of CR completion, we used principal components analysis (PCA) and an artificial neural network (ANN) module. Among 685 patients, 61.4% (n = 421) completed the program, 31.7% (n = 217) dropped out, and 6.9% (n = 47) were referred but failed to initiate the program. PCA was conducted to consolidate baseline data into three factors-(1) psychosocial factors (depression, anxiety, and quality of life), (2) age, and (3) BMI, which explained 66.8% of the total variance. The ANN model produced similar results as the PCA. Patients who completed CR sessions had greater extremity strength and flexibility, longer six-minute walk distance, more CR knowledge, and a better quality of life. The present study demonstrated that patients who were older, obese, and who had depression, anxiety, or a low quality of life were less likely to complete the CR program.

Prospective evaluation of the association between hemoglobin concentration and quality of life in patients with heart failure.

BACKGROUND: Reduced hemoglobin has been associated with adverse outcomes in heart failure, but the relationship of hemoglobin to health-related quality of life in outpatients with this syndrome has not been well studied. METHODS: We used data from the prospective, observational Study of Anemia in a Heart Failure Population Registry, which randomly selected outpatients with heart failure from specialty or community cardiology clinics. Hemoglobin was determined by finger stick at baseline and during medically indicated follow-up visits. Health-related quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire and the Minnesota Living with Heart Failure Questionnaire at 3-month intervals for 12 months. RESULTS: Adjusted regression analysis demonstrated a significant, direct, linear relationship between hemoglobin and health-related quality of life from baseline through 12 months follow-up on all Kansas City Cardiomyopathy Questionnaire domains (all P < .001) and the Summary and Physical domains of the Minnesota Living with Heart Failure Questionnaire (all P < .05). Adjusted categorical analysis of the change in Kansas City Cardiomyopathy Questionnaire Clinical scores associated with change in hemoglobin from baseline to 6 months also showed a significant relationship between increasing hemoglobin and improved health status (5.9 +/- 1.8 units for a hemoglobin increase of >or=1 g/dL, 0.7 +/- 1.2 units for change in hemoglobin <1 g/dL, and -2.6 +/- 1.4 units for a >or=1 g/dL decrease in hemoglobin, P < .001). CONCLUSIONS: These prospective, observational results indicate that reduced hemoglobin is associated with poorer quality of life in patients with heart failure. Additional studies will be required to establish if this is a cause-and-effect relationship.

Prospective assessment of the occurrence of anemia in patients with heart failure: results from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry.

BACKGROUND: Although a potentially important pathophysiologic factor in heart failure, the prevalence and predictors of anemia have not been well studied in unselected patients with heart failure. METHODS: The Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry prospectively studied the prevalence of anemia and the relationship of hemoglobin to health-related quality of life and outcomes among patients with heart failure. A random selection algorithm was used to reduce bias during enrollment of patients seen in specialty clinics or clinics of community cardiologists with experience in heart failure. In this initial report, data on prevalence and correlates of anemia were analyzed in 1,076 of the 1,082 registry patients who had clinical characteristics and hemoglobin determined by finger-stick at baseline. RESULTS: Overall (n = 1,082), the registry patients were 41% female and 73% white with a mean age (+/-SD) of 64 +/- 14 years (68 +/- 13 years in community and 57 +/- 14 years in specialty sites, P < .001). Among the 1,076 patients in the prevalence analysis, mean hemoglobin was 13.3 +/- 2.1 g/dL (median 13.2 g/dL); and anemia (defined by World Health Organization criteria) was present in 34%. Age identified patients at risk for anemia, with 40% of patients >70 years affected. CONCLUSIONS: Initial results from the STAMINA-HFP Registry suggest that anemia is a common comorbidity in unselected outpatients with heart failure. Given the strong association of anemia with adverse outcomes in heart failure, this study supports further investigation concerning the importance of anemia as a therapeutic target in this condition.

A Phase 2a dose-escalation study of the safety, tolerability, pharmacokinetics and haemodynamic effects of BMS-986231 in hospitalized patients with heart failure with reduced ejection fraction.

AIMS: This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS-986231, a novel second-generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS: Forty-six patients hospitalized with decompensated HFrEF were enrolled into four sequential dose-escalation cohorts in this double-blind, randomized, placebo-controlled Phase 2a study. Patients with baseline pulmonary capillary wedge pressure (PCWP) of ≥20 mmHg and a cardiac index of ≤2.5 L/min/m2 received one 6-h i.v. infusion of BMS-986231 (at 3, 5, 7 or 12 µg/kg/min) or placebo. BMS-986231 produced rapid and sustained reductions in PCWP, as well as consistent reductions in time-averaged pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure and right atrial pressure. BMS-986231 increased non-invasively measured time-averaged stroke volume index, cardiac index and cardiac power index values, and decreased total peripheral vascular resistance. There was no evidence of increased heart rate, drug-related arrhythmia or symptomatic hypotension with BMS-986231. Analyses of adverse events throughout the 30-day follow-up did not identify any toxicities specific to BMS-986231, with the potential exception of infrequent mild-to-moderate headaches during infusion. There were no treatment-related serious adverse events. CONCLUSIONS: BMS-986231 demonstrated a favourable safety and haemodynamic profile in patients hospitalized with advanced heart failure. Based on preclinical data and these study's findings, it is possible that the haemodynamic benefits may be mediated by inotropic and/or lusitropic as well as vasodilatory effects. The therapeutic potential of BMS-986231 should be further assessed in patients with heart failure.

The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome.

BACKGROUND: The clinical significance of HLA-directed antibodies newly detected after transplantation (HT) is controversial. METHODS: Seventy-one HT recipients consented to enroll. Mean follow-up time was 28 months (range 6-48). Panel reactive antibody (PRA) analysis was performed on posttransplant sera (2 weeks, 1, 2, 3, 6, and 12 months and annually thereafter) using Flow-PRA. A mean of 6.9+/-1.2 serum samples per patient were obtained. Severity of cellular rejection was measured using the ISHLT grading system. Coronary angiography and intravascular ultrasound (IVUS) studies were performed annually to evaluate severity of allograft vasculopathy. RESULTS: Twenty-five recipients had newly detected HLA-directed antibodies during the first year postHT. HLA class I antibodies were detected in 18 patients (25.4%), and class II in 11 patients (15.5%). The majority of donor recipient pairs were HLA mismatched (4.6+/-1.2 of the six major HLA antigens). Only mismatches at HLA-A locus had significant association with de novo posttransplant antibody formation. Length of ischemia time was correlated with early and sustained presence of de novo HLA-directed antibodies postheart transplant. Importantly, an association between de novo HLA-directed antibodies and cellular rejection was notes (P=0.0002). De novo HLA class II directed antibodies are also associated with IVUS documented vasculopathy (P<0.002). Finally, death due to allograft failure is associated with the presence of de novo formed HLA class II directed antibodies (P=0.008). CONCLUSIONS: Identifying the formation of de novo HLA-directed antibodies following heart transplantation may predict allograft outcome. This, in turn, may serve as a tool for individualization of immunosuppression protocols in heart transplant recipients.

Relationship between bridging with ventricular assist device on rejection after heart transplantation.

BACKGROUND: Ventricular assist devices (VADs) are commonly used to bridge patients to heart transplantation. Recipients of VADs may develop anti-human histocompatibility leukocyte antigen antibodies, as reflected by elevated panel-reactive antibodies (PRA). The purpose of this study was to evaluate the relationship between bridging with VAD before heart transplantation and development of cellular rejection, humoral rejection, and allograft vasculopathy after transplantation. METHODS: Data on all patients who underwent cardiac transplantation between July 1994 and February 2001 at Rush Presbyterian St Luke's Medical Center were retrospectively reviewed. Data collected included sex, age, etiology of cardiomyopathy, percentage panel reactive antibodies (by cytotoxic method), type and duration of mechanical circulatory support, transfusion history, rejection history (both cellular and humoral) after cardiac transplantation, and development of allograft vasculopathy. Cellular rejection was treated when International Society of Heart and Lung and Transplantation Grade 2 or greater in the first 12 months after transplant and Grade 3 or greater after 12 months and treated with intensification of immunosuppression. Humoral rejection was defined clinically as allograft dysfunction by echocardiography without evidence of cellular rejection on endomyocardial biopsy or allograft vasculopathy. Allograft vasculopathy was defined by presence of any degree of luminal narrowing or pruning of distal vessels by coronary arteriography. Statistical analyses were performed by chi-square test, Fisher's exact test, and Wilcoxon rank sum test, as appropriate. RESULTS: Ninety-eight patients underwent cardiac transplantation during the study period (87 men, mean age 49 years, 46 ischemic etiology). Of these, 48 were bridged with HeartMate VAD (20 patients received vented electric device, 28 received pneumatic device). Nineteen percent of VAD patients had a peak pretransplant PRA > or =10% vs 2% of patients without VAD (p = 0.014). PRA > or =10%, use of VAD, or duration of VAD support did not predict development of humoral rejection. Use of VAD did not predict development of cellular rejection or allograft vasculopathy. VAD use was not associated with sudden death after heart transplantation. In the entire group of 98 patients, neither humoral nor cellular rejection predicted development of allograft vasculopathy. Longer ischemic time correlated with increased cellular rejection and humoral rejection after transplantation (p = 0.01). CONCLUSIONS: Some patients bridged to cardiac transplantation with VADs have increased PRA before heart transplantation, but this does not appear to translate into increased risk of either humoral or cellular rejection after transplantation or development of allograft vasculopathy as detected by coronary angiography.

Clinical significance of left atrial volume in clinical outcomes of heart transplant recipients.

BACKGROUND: Left atrial volume (LAV) is surgically kept enlarged in heart transplant (HT) recipients. On the other hand, LAV has been known an independent predictor of various cardiovascular diseases and is associated with exercise capacity of HT recipients. Thus, we evaluated the hypothesis that LAV is still associated with clinical outcomes in HT recipients whose left atria are artificially enlarged. METHODS: Clinical outcomes over 5 years after HT were retrospectively evaluated in 35 HT recipients who had a LAV measurement with echocardiography at 1 year after HT at the University of Cincinnati Medical Center. The LAV was derived from a stacked disc method using apical 4 and 2 chamber views. RESULTS: The average LAV normalized to body surface area was 38.3 ± 9.9 ml/m(2) (mean ± SD) at 1 year after HT. Two deaths and one drop-out occurred during 5-year follow up. A total of 552 cardiac symptom-related hospitalizations occurred in the recipients. The average time to first hospitalization was 166 ± 279 days and average number of hospitalizations of each recipient was 15 ± 16. The indexed LAV failed to correlate with the time to first hospitalization and number of hospitalizations of each recipient (Spearman's p-value; 0.141 and 0.519 respectively). When the patients were divided to groups of large LAV (n = 17) and small LAV (n = 18) using the cut off value of the mean LAV, no significant difference was noted in mortality, hospitalization, and new onset of atrial fibrillation between the groups. CONCLUSIONS: Although our study is limited by a retrospective study design and relatively small number of patients, our results implicate that LAV is not significantly associated with clinical outcomes in HT recipients over 5 years after HT.

Survival rates are similar between African American and white patients with heart failure.

BACKGROUND: The clinical characteristics of heart failure differ significantly between African American patients and white patients, apparently as a result of differences in the pathobiology of the condition in the races. We investigated the hypothesis that race also influences the survival of patients with heart failure. METHODS: Data from the University of North Carolina Heart Failure Database were analyzed for 853 patients (44% African American, 32% women) who had symptomatic heart failure (New York Heart Association class 2.8 +/- 0.02 [mean +/- SEM]) with a reduced left ventricular ejection fraction of 26% +/- 0.5% and a body mass index of 27 +/- 0.2. Data on vital status were available in 96.4% of these patients, with a mean length of follow-up of 3.8 +/- 0.1 years. RESULTS: An unadjusted univariate proportional-hazards analysis suggested similar survival rates between African American patients and white patients in the study population (relative risk, 0.90; 95% CI, 0.73-1.10; P =.293). Adjusted analysis, taking into account the characteristics shown to be of prognostic importance, demonstrated no difference in survival rate between African American patients and white patients (relative risk,1.12; 95% CI, 0.89-1.42; P =.336). The adjusted relative risk of all-cause mortality in the respective races among patients with heart failure caused by ischemic heart disease was 1.21 (95% CI, 0.80-1.84; P =.367). CONCLUSION: African American and white patients with symptomatic heart failure had similar survival rates in our database.

Sideroblastic anemia due to linezolid in a patient with a left ventricular assist device.

An acquired form of sideroblastic anemia has been described in association with several drugs, especially anti-microbial agents. A case of sideroblastic anemia is presented in a patient with a left ventricular assist device drive-line infection who was receiving linezolid, an antibiotic used for serious infections with gram-positive organisms. This patient's anemia resolved after discontinuation of the drug; he subsequently underwent an uncomplicated orthotopic heart transplant with no recurrence of anemia. As linezolid has been shown to have hematologic side effects, blood count monitoring is recommended in patients receiving this drug for long-term therapy.

Racial differences in patients' potassium concentrations during spironolactone therapy for heart failure.

STUDY OBJECTIVE: To determine whether the effects of spironolactone on potassium homeostasis vary by race by comparing serum potassium concentrations and potassium supplement use in African-American and Caucasian patients receiving spironolactone for heart failure. DESIGN: Retrospective medical record review. SETTING: Two heart failure centers. PATIENTS: Fifty African-American and 67 Caucasian patients with heart failure who were receiving a stable dosage of spironolactone in addition to standard heart failure therapy with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker. MEASUREMENTS AND MAIN RESULTS: Medical records of eligible patients were reviewed by pharmacists and physicians who specialize in heart failure management. No significant differences were observed in diuretic therapy or renal function between racial groups; however, African-Americans were receiving higher doses of ACE inhibitors. African-Americans had lower serum potassium concentrations (4.2 +/- 0.4 vs 4.5 +/- 0.5 mEq/L, p<0.01) and a higher prevalence of potassium supplementation (48% vs 15%, p<0.01). In a subset of patients, spironolactone therapy was associated with a 2-fold greater increase in serum potassium concentration and a 3-fold greater reduction in potassium supplement use among Caucasians than African-Americans. CONCLUSION: Our findings suggest that a large percentage of patients with heart failure, particularly African-Americans, still require potassium supplementation despite treatment with spironolactone and standard vasodilator therapy.

Left atrial thrombus mimicking atrial myxoma on imaging studies in a patient with cardiac transplant.

Left atrial thrombus can develop in patients with atrial fibrillation and/or a dilated left atrium such as seen in patients with heart failure. In cardiac transplant patients with bi-atrial anastomosis, the suture line can be a potential nidus for thrombus formation. These thrombi can be either organized or unstable with ulcerated surfaces. We present a unique case of a left atrial mass in a cardiac transplant patient with features of atrial myxoma on imaging studies but found to be an organized thrombus on histopathology. .

Standardized reporting criteria for studies evaluating suspected acute heart failure syndromes in the emergency department.

Heart failure requiring urgent therapy represents a burgeoning health care burden. Although acute heart failure syndromes are commonly defined as a change in chronic heart failure signs and symptoms requiring urgent therapy, the presentation, development, and response to treatment is highly dependent on individual patient characteristics. This heterogeneity has led to challenges in interpreting widely differing study methods, including eligibility requirements and outcome measures. To improve interpretation of results and translate such information to better patient care, it is essential to present an accurate description of the patient population and study design. Based on existing recommendations and expert consensus, the authors present standardized reporting criteria to improve interpretability of research in this challenging cohort.

Sirolimus-eluting stent fractures leading to restenosis in cardiac allograft vasculopathy.

Cardiac allograft vasculopathy (CAV) is the most common cause of long-term graft failure after heart transplantation. In the absence of a specific treatment for this condition, percutaneous coronary revascularization (PCI) has been the main palliative treatment. Although long-term results are unknown, use of drug-eluting stents (DES) has been shown to have favorable outcome when used in heart transplant patients for treatment of focal lesions in CAV. We report the case of a 77-year-old male who presented with restenosis secondary to DES stent fracture (SF) after treatment of CAV with sirolimus-eluting stents (SES).

Does left atrial volume affect exercise capacity of heart transplant recipients?

BACKGROUND: Heart transplant (HT) recipients demonstrate limited exercise capacity compared to normal patients, very likely for multiple reasons. In this study we hypothesized that left atrial volume (LAV), which is known to predict exercise capacity in patients with various cardiac pathologies including heart failure and hypertrophic cardiomyopathy is associated with limited exercise capacity of HT recipients. METHODS: We analyzed 50 patients [age 57 ±2 (SEM), 12 females] who had a post-HT echocardiography and cardiopulmonary exercise test (CPX) within 9 weeks time at clinic follow up. The change in LAV (ΔLAV) was also computed as the difference in LAV from the preceding one-year to the study echocardiogram. Correlations among the measured parameters were assessed with a Pearson's correlation analysis. RESULTS: LAV (n = 50) and ΔLAV (n = 40) indexed to body surface area were 40.6 ± 11.5 ml·m-2 and 1.9 ± 8.5 ml·m-2·year-1, data are mean ± SD, respectively. Indexed LAV and ΔLAV were both significantly correlated with the ventilatory efficiency, assessed by the VE/VCO2 slope (r = 0.300, p = 0.038; r = 0.484, p = 0.002, respectively). LAV showed a significant correlation with peak oxygen consumption (r = -0.328, p = 0.020). CONCLUSIONS: Although our study is limited by a retrospective study design and relatively small number of patients, our findings suggest that enlarged LAV and increasing change in LAV is associated with the diminished exercise capacity in HT recipients and warrants further investigation to better elucidate this relationship.

Spontaneous left main coronary artery dissection complicated by pseudoaneurysm formation in pregnancy: role of CT coronary angiography.

We report a case of a 26-year-old female, who presented at 34 weeks of an uncomplicated pregnancy with an acute ST elevation anterior wall myocardial infarction. Cardiac catheterization suggested a left main coronary artery dissection with pseudoaneurysm formation. The patient's course was complicated by congestive heart failure. She was initially managed conservatively by a multidisciplinary team including heart failure specialists, obstetricians, and cardiovascular surgeons. 4 days after admission, her LMC was imaged by dual-source 64 slice Cardiac computed tomography, coronary dissection was identified extending to the lumen, and the presence of pseudoaneurysm was confirmed. She underwent subsequently a staged procedure, which included placement of an intra-aortic balloon pump, cesarean section, and coronary artery bypass grafting. This case illustrates the utility of coronary artery CT imaging to assess the complexity and stability of coronary artery dissections, thereby helping to determine the need for, and timing of revascularization procedures.