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Biomedical subjects

Paul J Hauptman

Publications and source records attributed to Paul J Hauptman.

At least 19 recordsLinked to original sources
PubMed2006

Use of nesiritide before and after publications suggesting drug-related risks in patients with acute decompensated heart failure.

CONTEXT: The rate of adoption of new therapies for cardiovascular diseases following the publication of favorable clinical trial results has been studied; however, less is known about the rates of de-adoption of a drug when negative studies are published. OBJECTIVE: To evaluate the use of nesiritide before and after March and April 2005 publications in 2 high-impact journals that suggested an increased risk of renal failure and mortality with intravenous nesiritide for acute decompensated heart failure. DESIGN, SETTING, AND PATIENTS: Analysis of a large prospective hospital database, developed for quality and utilization benchmarking, of 491 acute care US hospitals at which 385,627 inpatient admissions occurred with a primary International Classification of Diseases, Ninth Revision (ICD-9) code for heart failure between January and August 2001 (prior to nesiritide release) and January 2004 to December 2005 (before and after publication periods). In addition, any patient admitted who received nesiritide in the absence of a primary or secondary heart failure code was evaluated for potential off-label use of the drug. MAIN OUTCOME MEASURE: Use of nesiritide and other intravenous vasoactive therapy among patients admitted with heart failure. RESULTS: Nesiritide use decreased from a peak of 16.6% (2351 of 14,167 admissions) in March 2005 to 5.6% (611 of 10,822 admissions) in December 2005 (P<.001). Among those patients treated with nesiritide, the mean duration of treatment changed minimally, from 2.3 to 2.1 days. Although the use of inotropes also decreased during the period under study, the changes were more modest; furthermore, of those patients who were prescribed intravenous vasoactive therapy, a higher percentage were prescribed inotropes after publication (3272 [21.5%] of 15 193 patients from January-April 2005 vs 5750 [29.6%] of 19 445 patients from May-December 2005, P<.001). The use of nesiritide, in the absence of an ICD-9 heart failure code, was small. CONCLUSIONS: Rapid de-adoption of nesiritide occurred following 2 publications suggesting risk with the drug. Further analyses are required to evaluate the consequences of these changes on patient outcomes and to anticipate how publications of adverse findings can influence practice.

Aged↗
PubMed2006

Rationale and design of CASPER: compliance and quality of life study comparing once-daily carvedilol CR and twice-daily carvedilol IR in patients with heart failure.

Adherence to a complex medical regimen in patients with chronic heart failure is an important problem. In the Medicare population, patients with heart failure take an average of 7-8 distinct medications that require >11 separate doses on a daily basis. Nonadherence to these regimens accounts for a significant proportion of hospital admissions. Simplification of the medical regimen for patients with heart failure is likely to be associated with improved adherence and, in parallel, may lead to greater satisfaction and potentially improved outcomes. Therefore, the Compliance and Quality of Life Study Comparing Once-Daily Controlled-Release Carvedilol CR and Twice-Daily Immediate-Release Carvedilol IR in Patients with Heart Failure (CASPER) trial has been designed to rigorously test the hypothesis that a once-daily formulation of carvedilol will result in better compliance and increased patient satisfaction relative to the twice-daily formulation. The background, methods, and statistical approaches used in this trial are reviewed in this article.

Adrenergic beta-Antagonists↗
PubMed2006

Fulminant acute cellular rejection with negative findings on endomyocardial biopsy.

We present a case of a heart transplant recipient who had new-onset heart failure, repeatedly unremarkable endomyocardial biopsies, a negative evaluation for humoral rejection, and subsequently autopsy findings of severe sub-epicardial myocyte necrosis with classic cellular rejection. The sub-endocardial layer was free from rejection. The implications for clinical management, in the context of a diagnosis of "biopsy-negative rejection with hemodynamic compromise," include the need to consider intensification of immunosuppression with regimens similar to those used for biopsy-proven rejection.

Acute Disease↗
PubMed2006

Utility of impedance cardiography for the identification of short-term risk of clinical decompensation in stable patients with chronic heart failure.

OBJECTIVES: This study sought to assess the potential utility of impedance cardiography (ICG) in predicting clinical deterioration in ambulatory patients with heart failure (HF). BACKGROUND: Impedance cardiography uses changes in thoracic electrical impedance to estimate hemodynamic variables, but its ability to predict clinical events has not been evaluated. METHODS: We prospectively evaluated 212 stable patients with HF and a recent episode of clinical decompensation who underwent serial clinical evaluation and blinded ICG testing every 2 weeks for 26 weeks and were followed up for the occurrence of death or worsening HF requiring hospitalization or emergent care. RESULTS: During the study, 59 patients experienced 104 episodes of decompensated HF (16 deaths, 78 hospitalizations, and 10 emergency visits). Multivariate analysis identified 6 clinical and ICG variables that independently predicted an event within 14 days of assessment. These included three clinical variables (visual analog score, New York Heart Association functional class, and systolic blood pressure) and three ICG parameters (velocity index, thoracic fluid content index, and left ventricular ejection time). The three ICG parameters combined into a composite score was a powerful predictor of an event during the next 14 days (p = 0.0002). Visits with a high-risk composite score had 2.5 times greater likelihood and those with a low-risk score had a 70% lower likelihood of a near-term event compared with visits at intermediate risk. CONCLUSIONS: These results suggest that when performed at regular intervals in stable patients with HF with a recent episode of clinical decompensation, ICG can identify patients at increased near-term risk of recurrent decompensation.

Adult↗
PubMed2006

Quality of life in advanced heart failure: role of mitral regurgitation.

BACKGROUND: Quality of life is increasingly used as an important end point in clinical trials of treatments for heart failure; thus, relationships between traditional clinical variables and quality of life need to be understood. Baseline data from an ongoing multi-institutional study of a surgically implanted cardiac support device (CorCap, Acorn Cardiovascular, Inc, St Paul, MN) positioned around the heart to halt progression of remodeling in patients with cardiomyopathy provide an opportunity to study the relationship between mitral regurgitation (MR) and quality of life in a group of relatively young patients. OBJECTIVE: The objective of this study was to determine whether the degree of MR correlates with quality of life in patients presenting with significant symptoms of heart failure. METHODS: Baseline MR was assessed by echocardiography and patients were stratified according to whether there was a clinical indication for mitral valve surgery. The effect of heart failure on quality of life was measured by the Minnesota Living with Heart Failure questionnaire (MLHF). The New York Heart Association class, exercise performance measured by peak oxygen consumption and the 6-minute walk test, and the SF-36 physical function measure were analyzed as potential mediating variables. RESULTS: Mean MR grade was 2 +/- 1.5 on a 0-to-4 (worst) scale (n = 260) and ejection fraction averaged 27% +/- 9%. Most patients (82%) had New York Heart Association class III symptoms. Peak oxygen consumption averaged 14.7 +/- 4.3 mL/kg per minute and average walking distance was 348 +/- 83 m. Median (quartile range) SF-36 physical function was 35 (20-50) on a 0-to-100 (best) scale. Median MLHF score was 61 (47.5-77) on a 0-to-105 (worst) scale. The degree of MR and having an indication for mitral valve repair were not associated with the patients' quality of life. Controlling for symptoms and functional measures, older age was independently associated with better quality of life. CONCLUSIONS: The degree of MR was not related to MLHF scores, suggesting that surgery to reduce MR might not have predictable effects on quality of life. Further studies are needed to understand why younger patients reported worse quality of life and how this observation could impact therapy.

Adult↗
PubMed2006

Chronic inotropic therapy in end-stage heart failure.

BACKGROUND: Interventions in advanced heart failure that provide symptom relief and decrease hospital readmission are important. Chronic intravenous inotropic therapy represents a pharmacologic approach that has been advocated for palliative treatment. However, little is known about associated mortality and cost. Therefore, we sought to describe the impact of chronic infusions on resource use and survival. METHODS: Data were reviewed for a 17-state Medicare region from 1995 to 2002. We obtained hospital and outpatient expenditures accrued up to 180 days before and after the initiation of chronic infusions. Health care use was defined by dollars reimbursed for drug and hospitalizations per beneficiary. Average accumulated cost curves were generated for dollars reimbursed for drug and for hospitalizations by days at risk. RESULTS: The mean age of the cohort (n = 331) was 69.1 +/- 11.3 years. Mortality exceeded 40% at 6 months. Reductions in hospital days were observed at all time points. The amounts reimbursed at 30 and 60 days before and after initiation of inotrope favor drug therapy; however, at six months, the amounts reimbursed were greater due to the cost of milrinone. CONCLUSIONS: Chronic intravenous inotrope use was associated with a high mortality. The cost for milrinone was significant, but there was a decrease in expenditures for subsequent hospitalizations. In the absence of appropriately designed clinical trials, the data suggest that the decision to use inotropes, the choice of inotrope, and the duration of treatment should reflect the impact on resource use.

Aged↗
PubMed2006

Digoxin use and digoxin toxicity in the post-DIG trial era.

BACKGROUND: The advent of medical therapies for congestive heart failure that have proven survival benefits, specifically angiotensin-converting enzyme (ACE) inhibitors, beta-adrenergic antagonists, and the aldosterone antagonists, have called into question the use of digoxin for patients with normal sinus rhythm, left ventricular dysfunction, and symptomatic heart failure. This issue appears to have been heightened after the publication of the results of the Digitalis Investigation Group (DIG) Trial in 1997 that did not demonstrate a statistically significant impact of digoxin on mortality. METHODS AND RESULTS: We used data from a large heart failure registry to examine digoxin use at the time of hospital admission for heart failure, a surveillance system for recording toxic drug exposures to describe patterns in digoxin toxicity and industry estimates for the use of digoxin antibody. Digoxin use has decreased significantly from 31.4% in late 2001 to 23.5% in late 2004 (P < .00001) independent of patient age, gender, or baseline creatinine. Conversely, the number of toxic or potentially toxic exposures to digoxin requiring hospitalization has not decreased. CONCLUSION: Digoxin use is decreasing but there has not been a similar decline in cases of toxicity. Further analyses are required to delineate the reasons underlying these trends and the appropriateness of prescribing practices for both digoxin and its antidote.

Aged↗
PubMed2005

Integrating palliative care into heart failure care.

Heart failure is a condition for which both palliative care and hospice care can be appropriate. The disease's increasing prevalence and predilection for elderly patients with significant comorbidity underscore the need to integrate these modes of care with the acute care approach that has dominated heart failure treatment. We propose integration of a palliative care approach early in the course of heart failure treatment and a tiered process for selecting patients for hospice care. A transition of the focus to palliative care rather than mortality reduction should occur over time, when clinical status deteriorates and advanced therapeutic options become inappropriate or ineffective. Failure to respond to the need for palliative care puts at risk the mandate to treat the patient with heart failure during the entire course of illness.

Aged↗
PubMed2005

It is time to stop ignoring malignancy in heart transplantation: a call to arms.

Increasing numbers of patients are surviving more than 5 years after heart transplantation. Despite the dramatic nature of coronary allograft vasculopathy, Cardiac Transplant Research Database data have shown, and International Society for Heart and Lung Transplantation Registry data suggest, that malignancy is the leading cause of death among long-term survivors of heart transplantation. Recommendations on malignancy screening are provided as well as an outline of areas of ongoing uncertainty.

Female↗
PubMed2005

Comparison of two doses and dosing regimens of tolvaptan in congestive heart failure.

Fluid retention and extracellular volume expansion are frequently encountered complications of congestive heart failure (HF) that can cause morbidity and mortality. Tolvaptan (Otsuka) is an orally administered nonpeptide vasopressin (VP) V2 receptor antagonist that inhibits water reabsorption in the kidney by competitively blocking VP binding, resulting in water diuresis without significantly changing total electrolyte excretion. In the 24-hour period following a 30-mg dose of tolvaptan, urine excretion rate increases and declines as plasma concentrations rise and fall; this uneven effect results in 80% of daily urine output in the first 12 hours. Therefore, the current study was designed to assess the pharmacodynamic effects, pharmacokinetics, and clinical safety of tolvaptan 30 mg QD plus placebo versus 15 mg BID over 7 days in patients with NYHA Class II/III heart failure and persistent fluid overload, SBP > or = 90 mm Hg, and a serum creatinine < or = 3.0 mg/dL. Patients were withdrawn from diuretics for 48 hours before randomization. Statistics were performed with ANCOVA for continuous variables and Mantel-Haenszel mean score test stratified by center for categorical variables. Thirty-nine of 40 patients completed days 1 and 7. There were no significant clinical, pharmacokinetic, or pharmacodynamic differences between the dosing regimens over time. Based on these findings, tolvaptan 30 mg was chosen as the comparator for placebo in a large phase 3 survival trial.

Antidiuretic Hormone Receptor Antagonists↗
PubMed2005

The natural history of renal function following orthotopic heart transplant.

BACKGROUND: The outcome of solid organ transplantation has dramatically improved after the introduction of the calcineurin inhibitor cyclosporine. With the increasing longevity of heart transplant recipients, the long-term effects of cyclosporine on renal function have become more evident. The natural history of kidney function following orthotopic heart transplant is not well defined and long-term follow up studies are scant. METHODS: We conducted an observational study on patients who received a heart transplant at Saint Louis University Hospital between January 1, 1983 and December 31, 1988. Patients were followed up for 15 yr or until death whichever occurred first. In order to assess the effect of heart transplantation and cyclosporine exposure on long-term renal function we restricted the statistical analysis to patients who survived the first year post-transplantation. RESULTS: A total of 68 patients received orthotopic heart transplants at Saint Louis University Hospital between 1983 and 1988. Forty-eight (71%) patients survived for more than 1 yr. All patients were treated with cyclosporine based triple immunosuppressive regimen, with gradual cyclosporine dose reduction over time. The mean duration of follow-up was 8 yr. The estimated GFR at 5 and 10 yr post-transplant were significantly lower than estimated GFR at baseline and 1 yr post-transplant. There was no significant difference between estimated GFR at 15 yr and estimated GFR at baseline or 1 yr post-transplant. The cumulative incidence of chronic renal failure (GFR < or = 29 mL/min/1.73 m2) at 5, 10 and 15 yr was 4.2, 10.4 and 12.5%, respectively (p < 0.05). The cumulative incidence of severe chronic renal failure (GFR < or = 15 mL/min/1.73 m2) at 5, 10 and 15 yr was 2.1, 8.3 and 8.3%, respectively. The mortality rate was 8, 37, and 52% at 5, 10, and 15 yr, respectively. The 10 and 15 yr survivors had an estimated GFR at 1 yr post-transplant that was significantly higher than the non-survivors. Age, pre-transplantation estimated GFR, pre-transplantation diabetes and pre-transplantation hypertension are risk factors associated with > or = 10 mL/min/1.73 m2 decrement in estimated GFR. CONCLUSION: Heart transplant survivors beyond the first year post-transplant have a significant decrease in renal function and significant mortality observed over time. Age, pre-transplant GFR, pre-transplant diabetes and pre-transplant hypertension are important risk factors for decrement in renal function.

Adult↗
PubMed2004

Consensus statement: Palliative and supportive care in advanced heart failure.

BACKGROUND: A consensus conference was convened to define the current state and important gaps in knowledge and needed research on "Palliative and Supportive Care in Advanced Heart Failure." EVIDENCE: Evidence was drawn from expert opinion and from extensive review of the medical literature, evidence-based guidelines, and reviews. CONCLUSIONS: The conference identified gaps in current knowledge, practice, and research relating to prognostication, symptom management, and supportive care for advanced heart failure (HF). Specific conclusions include: (1) although supportive care should be integrated throughout treatment of patients with advanced HF, data are needed to understand how to best decrease physical and psychosocial burdens of advanced HF and to meet patient and family needs; (2) prognostication in advanced HF is difficult and data are needed to understand which patients will benefit from which interventions and how best to counsel patients with advanced HF; (3) research is needed to identify which interventions improve quality of life and best achieve the outcomes desired by patients and family members; (4) care should be coordinated between sites of care, and barriers to evidence-based practice must be addressed programmatically; and (5) more research is needed to identify the content and technique of communicating prognosis and treatment options with patients with advanced HF; physicians caring for patients with advanced HF must develop skills to better integrate the patient's preferences into the goals of care.

Counseling↗
PubMed2004

Variability in the clinical status of patients with advanced heart failure.

BACKGROUND: The importance of repeated clinical assessments of patients with heart failure is widely accepted. The frequency of such follow-up is not established and is likely to depend on the natural history and variability of patients' health status and the availability and use of appropriate treatments. METHODS AND RESULTS: We analyzed data from a multicenter prospective cohort study of heart failure outpatients comparing baseline variables including New York Heart Association (NYHA) class, summary score on the Kansas City Cardiomyopathy Questionnaire (KCCQ), and performance on a 6-minute walk test with results of a repeat evaluation at 6 weeks. We also compared patient and physician assessment of change in disease status among patients with advanced symptoms (NYHA class III with a recent antecedent hospitalization or class IV) and those with milder degrees of limitation (NYHA classes I, II, and stable III). Patients with advanced symptoms had greater short-term variability in health status as reflected by the KCCQ summary score and a visual analog scale. A greater proportion of patients with advanced heart failure experienced moderate or greater clinical change. Patient and physician global assessments were congruent with more direct measures of health status. CONCLUSION: Patients with advanced heart failure have greater short-term variability in status, supporting the need for frequent clinical follow-up and appropriate power calculations for clinical trials that are designed to measure meaningful changes over a short period.

Arrhythmias, Cardiac↗