Risk of death associated with nesiritide in patients with acutely decompensated heart failure.
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Heart Failure↗
Biomedical subjects
Keith D Aaronson
Publications and source records attributed to Keith D Aaronson.
Prophylactic pacemaker use to allow beta-blocker therapy in patients with chronic heart failure with bradycardia.
BACKGROUND: Although the benefits of beta-blocker therapy for patients with congestive heart failure (CHF) are independent of pretreatment heart rate, patients with chronic systolic heart failure and low resting heart rates are often excluded from beta-blocker therapy. We investigated the effectiveness and cost-effectiveness of prophylactic pacemaker insertion to facilitate beta-blocker use in these patients. METHODS: A Markov model simulated the natural history of a cohort of clinically stable patients with CHF (ejection fraction < or = 35%, mean age 60 years) with resting heart rates of < 68 beat/min. Two strategies were evaluated: (1) conventional therapy (conventional)-the risks for death and hospitalization were derived from the angiotensin-converting enzyme inhibitor arm of the SOLVD treatment trial; and (2) pacemaker insertion with atrial pacing and carvedilol therapy (pacemaker-carvedilol)-risk reductions for death and CHF-related hospitalizations for carvedilol compared with conventional therapy were derived from the US Carvedilol Heart Failure Study. We assumed full carvedilol benefits for 2 years, declining benefits for the next 3 and no additional benefits after 5 years, whereas pacemaker-related adverse events persisted. RESULTS: In the base case, the pacemaker-carvedilol strategy increased mean survival by 1.3 years at an incremental cost of $7800, for an incremental cost-effectiveness of $6100 per year of life saved. Results were most sensitive to theoretical pacing-induced harm, changes in hospitalization cost, and reductions in beta-blocker benefits. CONCLUSION: Prophylactic pacemaker insertion to facilitate beta-blocker treatment in patients with CHF with low resting heart rates has the potential to produce clinical benefits in a highly cost-effective manner.
Adrenergic beta-Antagonists↗
CRT-D therapy in heart failure: how much do NYHA class IV patients benefit?
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Aged↗
Nesiritide--not verified.
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Drug Approval↗
Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure.
BACKGROUND: Renal function is an important prognostic factor for patients with acutely decompensated heart failure (ADHF). We investigated the renal effects of nesiritide as treatment for ADHF. METHODS AND RESULTS: Randomized clinical trials comparing nesiritide with either placebo or active control for ADHF were identified by electronic and manual searches and thorough review of US Food and Drug Administration files available via the website. Worsening renal function was defined as an increase in serum creatinine >0.5 mg/dL. Relative risk across all studies was determined by meta-analysis with Mantel-Haenszel fixed-effects models (RR(MH)). Risk of dialysis and medical intervention for worsening renal function were compared between therapies. Frequency of worsening renal function was determined from 5 randomized studies that included 1269 patients. Use of Food and Drug Administration-approved doses of nesiritide (< or =0.03 microg x kg(-1) x min(-1)) significantly increased the risk of worsening renal function compared with non-inotrope-based control (RR(MH), 1.52; 95% CI, 1.16 to 2.00; P=0.003) or any control therapy, including non-inotrope- and inotrope-based therapies (RR(MH), 1.54; 95% CI, 1.19 to 1.98; P=0.001). Even low-dose nesiritide (< or =0.015 microg x kg(-1) x min(-1)) significantly increased risk (P=0.012 and P=0.006 compared with non-inotrope- and inotrope-based controls, respectively), as did nesiritide administered at any dose up to 0.06 microg x kg(-1) x min(-1) (P=0.002 and P=0.001, respectively). There was no difference in the need for dialysis between therapies. CONCLUSIONS: Nesiritide significantly increases the risk of worsening renal function in patients with ADHF. Whether worsening renal function reflects hemodynamic effect or renal injury is unknown, but the prognostic importance of worsening renal function suggests the need for further investigation in appropriately powered clinical trials.
Creatine↗
Validation of peak exercise oxygen consumption and the Heart Failure Survival Score for serial risk stratification in advanced heart failure.
The Heart Failure Survival Score (HFSS) and peak exercise oxygen consumption (VO2) accurately assess mortality in ambulatory patients who have advanced heart failure and are referred for initial cardiac transplant evaluation. We investigated the prognostic value of the HFSS and peak VO2 when applied serially to these patients. This study included 227 adults (mean age +/- SD 52 +/- 10 years old) who presented for reevaluation >60 days after initial evaluation (352 +/- 238 days). The HFSS was determined from mean arterial blood pressure, heart rate, left ventricular ejection fraction, serum sodium, peak VO2, heart failure etiology, and width of QRS complex. Survival without reevaluation, United Network of Organ Sharing 1 transplant, or left ventricular assist device was determined by the Kaplan-Meier method with censoring at United Network of Organ Sharing 2 transplant. Survival differed by HFSS stratum (p <0.001) and by peak VO2 stratum (p <0.001). Patients whose HFSS or peak VO2 deteriorated from low risk to medium or high risk had lower survival rates than did patients whose values remained at low risk (p <0.01 and p <0.001, respectively). Patients who started at medium or high risk and improved to low risk tended to have higher survival rates than those who remained medium or high risk (p = 0.06 and p <0.16, respectively). Patients who improved to low risk had a 1-year survival rate of 72% for HFSS and peak VO2. However, patients who improved to low risk and were treated with beta blockers had a 1-year survival rate (89% for HFSS and 83% for peak VO2) comparable to that after transplant (84%). Peak VO2 and the HFSS can be successfully used for serial evaluation of mortality risk in ambulatory patients who have advanced heart failure.
Adult↗
Impact of mitral valve annuloplasty on mortality risk in patients with mitral regurgitation and left ventricular systolic dysfunction.
OBJECTIVES: This study was designed to assess effects of mitral valve annuloplasty (MVA) on mortality in patients with mitral regurgitation (MR) and left ventricular (LV) systolic dysfunction. BACKGROUND: Mitral valve annuloplasty improves hemodynamics and symptoms in these patients, but effects on long-term mortality are not well established. METHODS: We retrospectively analyzed consecutive patients with significant MR and LV systolic dysfunction on echocardiography between 1995 and 2002. Cox regression analysis, including MVA as a time-dependent covariate and propensity scoring to adjust for differing probabilities of undergoing MVA, was used to identify predictors of death, LV assist device implantation, or United Network for Organ Sharing-1 heart transplantation. RESULTS: Of 682 patients identified, 419 were deemed surgical candidates; 126 underwent MVA. Propensity score derivation identified age, ejection fraction, and LV dimension to be associated with undergoing MVA. End points were reached in 120 (41%) non-MVA and 62 (49%) MVA patients. Increased risk of end point was associated with coronary artery disease (hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.30 to 2.49), blood urea nitrogen (HR 1.01, 95% CI 1.005 to 1.02), cancer (HR 2.77, 95% CI 1.45 to 5.30), and digoxin (HR 1.66, 95% CI 1.15 to 2.39). Reduced risk was associated with angiotensin-converting enzyme inhibitors (HR 0.65, 95% CI 0.44 to 0.95), beta-blockers (HR 0.59, 95% CI 0.42 to 0.83), mean arterial pressure (HR 0.98, 95% CI 0.97 to 0.99), and serum sodium (HR 0.93, 95% CI 0.90 to 0.96). Mitral valve annuloplasty did not predict clinical outcome. CONCLUSIONS: In this analysis, there is no clearly demonstrable mortality benefit conferred by MVA for significant MR with severe LV dysfunction. A prospective randomized control trial is warranted for further study of mortality with MVA in this population.
Aged↗
Discharge education improves clinical outcomes in patients with chronic heart failure.
BACKGROUND: Although interventions combining patient education and postdischarge management have demonstrated benefits in patients with chronic heart failure, the benefit attributable to patient education alone is not known. We hypothesized that a patient discharge education program would improve clinical outcomes in patients with chronic heart failure. METHODS AND RESULTS: We conducted a randomized, controlled trial of 223 systolic heart failure patients and compared the effects of a 1-hour, one-on-one teaching session with a nurse educator to the standard discharge process. Subjects were contacted by telephone at 30, 90, and 180 days to collect information about clinical events, symptoms, and self-care practices. The primary end point of the study was the total number of days hospitalized or dead in the 180-day follow-up period. Subjects randomized to receive the teaching session (n=107) had fewer days hospitalized or dead in the follow-up period (0 and 10 days, median and 75th percentiles) than did controls (n=116, 4 and 19 days; P=0.009). Patients receiving the education intervention had a lower risk of rehospitalization or death (relative risk, 0.65; 95% confidence interval, 0.45 to 0.93; P=0.018). Costs of care, including the cost of the intervention, were lower in patients receiving the education intervention than in control subjects by 2823 dollars per patient (P=0.035). CONCLUSIONS: The addition of a 1-hour, nurse educator-delivered teaching session at the time of hospital discharge resulted in improved clinical outcomes, increased self-care measure adherence, and reduced cost of care in patients with systolic heart failure.
Aged↗
The prevalence and pattern of complementary and alternative supplement use in individuals with chronic heart failure.
BACKGROUND: There are few data on the prevalence and pattern of complementary and alternative medicine (CAM) supplement use among people with chronic heart failure (CHF). The aim of this survey was to characterize the prevalence, pattern, and reasons for use of CAM supplements among those with CHF. METHODS AND RESULTS: We conducted a cross-sectional survey in 2 groups: CHF patients who had participated in the Hawthorn Extract Randomized Blinded Chronic Heart Failure (HERB CHF) Trial, and CHF patients who attended the University of Michigan's CHF Outpatient Clinic. We received 252 surveys. One third of respondents had used a CAM supplement in the last 6 months. There were 24 different supplements used. Reasons for use included heart problems, anxiety, weight loss, and arthritis. No demographic or behavioral characteristic identified CAM supplement users, although a 50% lower use among HERB CHF participants approached statistical significance (P = .08). CONCLUSION: One third of our CHF patients were taking CAM supplements, several of which may interact negatively with typical heart failure medications. CAM supplement use for weight loss may be underreported. Demographic and behavioral characteristics may not have identified people with CHF who were using CAM supplements.
Adult↗
Brain natriuretic peptide predicts serious cardiac allograft rejection independent of hemodynamic measurements.
BACKGROUND: Serum brain natriuretic peptide (BNP) has been reported to be elevated in heart transplant recipients with both cellular and vascular rejection. Whether BNP can be used to help predict the severity of rejection is not well established. METHODS: We analyzed serial BNP measurements obtained during endomyocardial biopsy procedures in consecutive heart transplant patients occurring >45 days after transplantation. To eliminate potential confounding from prior rejection episodes, we included only observations in which the previous biopsy grade was 0 or 1A. Multivariable linear regression was performed examining the outcome of increasing seriousness of rejection, defined as grade 0 < 1A < 2 < 1B < 3A < vascular rejection. A univariable logistic regression model was performed using log-transformed BNP as a predictor of vascular rejection. RESULTS: There were 77 patients, with 161 separate observations. Median time between transplantation and first assessment was 6.0 months (interquartile range, 2.1, 31.6). Using multivariable linear regression, 3 factors were significantly associated with biopsy score: pulmonary capillary wedge pressure (p < 0.0001), BNP (p = 0.003), and heart rate (p = 0.01). Even after other significant univariable predictors (including pulmonary capillary wedge pressure) were forced into the model, BNP remained a significant predictor of biopsy score (p = 0.02). Log BNP was a significant univariable predictor of vascular rejection, with an odds ratio of 12.55 (per 1 unit increase, 95% confidence interval 3.43-45.84; p = 0.0001) and a model c-statistic of 0.91. CONCLUSIONS: BNP predicts new episodes of serious cardiac allograft rejection, particularly vascular rejection, independent of hemodynamic measurements, and may be a useful part of rejection surveillance.
Adult↗
Effect of oral vitamin E and C therapy on calcineurin inhibitor levels in heart transplant recipients.
BACKGROUND: A recent prospective trial demonstrated that oral vitamins C and E retard the early progression of transplant-associated coronary arteriosclerosis; as a result, a number of centers have added these agents to their maintenance regimens. This study reviewed the impact of vitamin E and C supplementation on calcineurin inhibitor trough concentrations. METHODS: A retrospective chart review of the first 29 heart transplant patients prescribed anti-oxidant agents was performed. Twenty-two patients taking cyclosporin A (CsA) and 7 patients taking tacrolimus were prescribed vitamin C (500 mg twice a day) and vitamin E (400 IU twice a day). Serum chemistries and drug levels were measured before and after vitamin therapy was initiated. RESULTS: The baseline CsA trough concentration (mean +/- SD) was 137 +/- 39 ng/ml and it declined to 99 +/- 54 ng/ml (p = 0.007) after anti-oxidant therapy was initiated. The average percentage decrease in the CsA trough concentration was 30%. No significant changes were seen in the patients taking tacrolimus. CONCLUSIONS: These data demonstrate that supplementation with the anti-oxidant agents vitamin C and vitamin E decreases CsA concentrations but does not appear to effect tacrolimus concentrations. Although more detailed pharmacokinetic analysis is necessary to clarify the exact mechanism of this interaction, physicians who take care of transplant recipients should be aware that more frequent CsA concentration monitoring is warranted after initiating these anti-oxidant agents.
Adult↗
Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure.
BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.
Adrenergic beta-Antagonists↗
Heart failure survival score continues to predict clinical outcomes in patients with heart failure receiving beta-blockers.
BACKGROUND: The Heart Failure Survival Score (HFSS) has been previously shown to effectively risk-stratify patients under evaluation for heart transplantation. However, this model was developed before broad use of beta blockade. We hypothesized that the prognostic tool would retain its ability to risk stratify patients treated with beta-blockers. METHODS: We collected clinical data on 524 consecutive patients referred for heart transplantation from 1994 to 2001. Kaplan-Meier survival analysis and multivariable Cox regression analysis were performed with events defined as death, left ventricular assist device placement, or United Network of Organ Sharing 1 heart transplantation. RESULTS: Kaplan-Meier analysis of the patient population revealed effective discrimination by the survival score both for beta-blocker treated and untreated patients (both p <0.0001). Two-year event-free survival was 94% +/- 2% and 84% +/- 4% for beta-blocker and no beta-blocker patients in the low-risk HFSS strata. Cox proportional hazard modeling showed that HFSS strata (medium risk: HR 2.65, 95% CI 1.75-4.02, p <0.001; high risk: HR 5.51, 95% CI 3.64-8.33, p <0.001) and beta-blocker treatment (HR 0.45, 95% CI 0.31-0.64, p <0.001) were significant predictors of event-free survival. Receiver operating curves (area under the curve) for HFSS strata used to predict 2-year events were similar for beta-blocker treated (0.78 +/- 0.04) and untreated (0.80 +/- 0.03) patients. CONCLUSIONS: The HFSS provides effective risk stratification with or without beta-blocker therapy. Consideration of beta-blocker therapy with survival score strata improves outcome prediction in patients evaluated for heart transplantation.
Adrenergic beta-Antagonists↗
Predicting survival in ambulatory patients with severe heart failure on beta-blocker therapy.
Peak VO(2) and the Heart Failure Survival Score are 2 clinical parameters used to risk stratify patients with heart failure and time listing for cardiac transplantation. The efficacy of these prognostic variables in patients receiving beta-blocker therapy was evaluated.
Adrenergic beta-Antagonists↗
Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation.
OBJECTIVES: We report histological analysis of hearts from patients with end-stage heart disease who were transplanted with autologous skeletal myoblasts concurrent with left ventricular assist device (LVAD) implantation. BACKGROUND: Autologous skeletal myoblast transplantation is under investigation as a means to repair infarcted myocardium. To date, there is only indirect evidence to suggest survival of skeletal muscle in humans. METHODS: Five patients (all male; median age 60 years) with ischemic cardiomyopathy, refractory heart failure, and listed for heart transplantation underwent muscle biopsy from the quadriceps muscle. The muscle specimen was shipped to a cell isolation facility where myoblasts were isolated and grown. Patients received a transplant of 300 million cells concomitant with LVAD implantation. Four patients underwent LVAD explant after 68, 91, 141, and 191 days of LVAD support (three transplant, one LVAD death), respectively. One patient remains alive on LVAD support awaiting heart transplantation. RESULTS: Skeletal muscle cell survival and differentiation into mature myofibers were directly demonstrated in scarred myocardium from three of the four explanted hearts using an antibody against skeletal muscle-specific myosin heavy chain. An increase in small vessel formation was observed in one of three patients at the site of surviving myotubes, but not in adjacent tissue devoid of engrafted cells. CONCLUSIONS: These findings represent demonstration of autologous myoblast cell survival in human heart. The implanted skeletal myoblasts formed viable grafts in heavily scarred human myocardial tissue. These results establish the feasibility of myoblast transplants for myocardial repair in humans.
Aged↗
Impact of serial changes in cardiac hemodynamics on exercise performance in patients with heart failure due to ischemic and nonischemic cardiomyopathy.
Although prior studies have examined the role of central and peripheral hemodynamics on exercise tolerance within populations of patients with heart failure, a clear relation between hemodynamics and exercise has not been demonstrated. This may be due to the inability to control for other factors that may influence exercise performance. To isolate the impact of hemodynamics on exercise, we studied the relation between changes in these factors within individual patients studied on 2 occasions. A consecutive series of 133 ambulatory patients with heart failure were evaluated on 2 separate occasions with right-sided cardiac catheterization and treadmill cardiopulmonary exercise testing. Linear regression models were constructed and correlation coefficients were determined to examine the relation between changes in hemodynamic variables and changes in exercise variables over time for each patient. A significant correlation between peak oxygen consumption (VO(2)) and pulmonary arterial wedge pressure was found for both the first (r = -0.316, p <0.001) and second (r = -0.183, p = 0.029) tests. A stronger inverse correlation between the change in pulmonary arterial wedge pressure and change in peak VO(2) was observed in the study patients (r = -0.470, p <0.001). Similar correlations were found between change in peak VO(2) and changes in pulmonary arterial pressures. Changes in left ventricular filling pressure influence exercise tolerance in patients with heart failure due to left ventricular systolic dysfunction. Interpretation of cardiopulmonary exercise testing for the purpose of determining cardiac transplantation eligibility will be improved with knowledge of left ventricular filling pressure.
Adolescent↗
Patient selection for left ventricular assist device therapy.
Patient selection for left ventricular assist device (LVAD) therapy is the most important process in obtaining a successful outcome. Evaluation requires assessing the appropriateness for device implantation based on need and risk of LVAD implant to the patient. Appropriate patients can be selected without the need for invasive hemodynamic measurements and selection can be based on symptoms, appropriateness of medical therapy, and on the need for inotropic therapy. Assessing the risk of LVAD therapy to the patient requires evaluating the degree of organ dysfunction and technical factors. Patients should be offered the option of LVAD therapy if they meet criteria for need, possess the potential for organ recovery, and have appropriate operative risk.
Heart Failure↗
Treating hypertension: a new chapter. Do whatever it takes to hit your blood-pressure target.
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Angiotensin-Converting Enzyme Inhibitors↗