Thomas G. DiSalvo

Apoptosis in Myocytes in End-Stage Heart Failure

BACKGROUND Heart failure can result from a variety of causes, including ischemic, hypertensive, toxic, and inflammatory heart disease. However, the cellular mechanisms responsible for the progressive deterioration of myocardial function observed in heart failure remain unclear and may result from apoptosis (programmed cell death). METHODS We examined seven explanted hearts obtained during cardiac transplantation for evidence of apoptosis. All seven patients had severe chronic heart failure: four had idiopathic dilated cardiomyopathy, and three had ischemic cardiomyopathy. DNA fragmentation (an indicator of apoptosis) was identified histochemically by in situ end-labeling as well as by agarose-gel electrophoresis of end-labeled DNA. Myocardial tissues obtained from four patients who had had a myocardial infarction one to two days previously were used as positive controls, and heart tissues obtained from four persons who died in motor vehicle accidents were used as negative controls for the end-labeling studies. RESULTS Hearts from all four patients with idiopathic dilated cardiomyopathy and from one of the three patients with ischemic cardiomyopathy had histochemical evidence of DNA fragmentation. All four myocardial samples from patients with dilated cardiomyopathy also demonstrated DNA laddering, a characteristic of apoptosis, whereas this was not seen in any of the samples from patients with ischemic cardiomyopathy. Histological evidence of apoptosis was also observed in the central necrotic zone of acute myocardial infarcts, but not in myocardium remote from the infarcted zone. Rare isolated apoptotic myocytes were seen in the myocardium from the four persons who died in motor vehicle accidents. CONCLUSIONS Loss of myocytes due to apoptosis occurs in patients with end-stage cardiomyopathy and may contribute to progressive myocardial dysfunction.

Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness

CONTEXT Pulmonary artery catheters (PACs) have been used to guide therapy in multiple settings, but recent studies have raised concerns that PACs may lead to increased mortality in hospitalized patients. OBJECTIVE To determine whether PAC use is safe and improves clinical outcomes in patients hospitalized with severe symptomatic and recurrent heart failure. DESIGN, SETTING, AND PARTICIPANTS The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) was a randomized controlled trial of 433 patients at 26 sites conducted from January 18, 2000, to November 17, 2003. Patients were assigned to receive therapy guided by clinical assessment and a PAC or clinical assessment alone. The target in both groups was resolution of clinical congestion, with additional PAC targets of a pulmonary capillary wedge pressure of 15 mm Hg and a right atrial pressure of 8 mm Hg. Medications were not specified, but inotrope use was explicitly discouraged. MAIN OUTCOME MEASURES The primary end point was days alive out of the hospital during the first 6 months, with secondary end points of exercise, quality of life, biochemical, and echocardiographic changes. RESULTS Severity of illness was reflected by the following values: average left ventricular ejection fraction, 19%; systolic blood pressure, 106 mm Hg; sodium level, 137 mEq/L; urea nitrogen, 35 mg/dL (12.40 mmol/L); and creatinine, 1.5 mg/dL (132.6 micromol/L). Therapy in both groups led to substantial reduction in symptoms, jugular venous pressure, and edema. Use of the PAC did not significantly affect the primary end point of days alive and out of the hospital during the first 6 months (133 days vs 135 days; hazard ratio [HR], 1.00 [95% confidence interval {CI}, 0.82-1.21]; P = .99), mortality (43 patients [10%] vs 38 patients [9%]; odds ratio [OR], 1.26 [95% CI, 0.78-2.03]; P = .35), or the number of days hospitalized (8.7 vs 8.3; HR, 1.04 [95% CI, 0.86-1.27]; P = .67). In-hospital adverse events were more common among patients in the PAC group (47 [21.9%] vs 25 [11.5%]; P = .04). There were no deaths related to PAC use, and no difference for in-hospital plus 30-day mortality (10 [4.7%] vs 11 [5.0%]; OR, 0.97 [95% CI, 0.38-2.22]; P = .97). Exercise and quality of life end points improved in both groups with a trend toward greater improvement with the PAC, which reached significance for the time trade-off at all time points after randomization. CONCLUSIONS Therapy to reduce volume overload during hospitalization for heart failure led to marked improvement in signs and symptoms of elevated filling pressures with or without the PAC. Addition of the PAC to careful clinical assessment increased anticipated adverse events, but did not affect overall mortality and hospitalization. Future trials should test noninvasive assessments with specific treatment strategies that could be used to better tailor therapy for both survival time and survival quality as valued by patients.

Prediction of hospital readmission for heart failure: development of a simple risk score based on administrative data

OBJECTIVES The purpose of this study was to develop a convenient and inexpensive method for identifying an individuals risk for hospital readmission for congestive heart failure (CHF) using information derived exclusively from administrative data sources and available at the time of an index hospital discharge. BACKGROUND Rates of readmission are high after hospitalization for CHF. The significant determinants of rehospitalization are debated. METHODS Administrative information on all 1995 hospital discharges in New York State which were assigned International Classification of Diseases-9-Clinical Modification codes indicative of CHF in the principal diagnosis position were obtained. The following were compared among hospital survivors who did and did not experience readmission: demographics, comorbid illness, hospital type and location, processes of care, length of stay and hospital charges. RESULTS A total of 42,731 black or white patients were identified. The subgroup of 9,112 patients (21.3%) who were readmitted were distinguished by a greater proportion of blacks, a higher prevalence of Medicare and Medicaid insurance, more comorbid illnesses and the use of telemetry monitoring during their index hospitalization. Patients treated at rural hospitals, those discharged to skilled nursing facilities and those having echocardiograms or cardiac catheterization were less likely to be readmitted. Using multiple regression methods, a simple methodology was devised that segregated patients into low, intermediate and high risk for readmission. CONCLUSIONS Patient characteristics, hospital features, processes of care and clinical outcomes may be used to estimate the risk of hospital readmission for CHF. However, some of the variation in rehospitalization risk remains unexplained and may be the result of discretionary behavior by physicians and patients.

Socioeconomic status as an independent risk factor for hospital readmission for heart failure

The management of heart failure is characterized by high rates of hospital admission as well as rehospitalization after inpatient treatment of this disorder, whereas skillful medical care may reduce the risk of hospital admission. The purpose of this study was to examine the relation between income (as a measure of socioeconomic status) and the frequency of hospital readmission among a large and diverse group of persons treated for heart failure. We analyzed administrative discharge data from 236 nonfederal acute-care hospitals in New York State, involving 41,776 African-American or Caucasian hospital survivors with International Classification of Diseases, Ninth Revision, Clinical Modification codes for heart failure in the principal diagnosis position between January 1 and December 31, 1995. Household income was derived from postal ZIP codes and census data. We found that patients residing in lower income neighborhoods were more often women or African-Americans, had more comorbid illness, had higher use of Medicaid insurance, and were more often admitted to rural hospitals. There was a stepwise decrease in the crude frequency of readmission from the lowest quartile of income (23.2%) to the highest (20.0%) (p <0.0001 for Mantel-Haenszel chi-square test for trend across all quartiles; p <0.0001 for comparison between quartiles 1 and 4). After adjustment for baseline differences and process of care, income remained a significant predictor, with an increase in the risk of readmission noted in association with lower levels of income (adjusted odds ratio for quartile 1:4 comparison, 1.18; 95% confidence interval, 1.10 to 1.26, p <0.0001). We conclude that lower income patients hospitalized for treatment of heart failure in New York differ from higher income patients in important clinical and demographic comparisons. Even after adjustment for these fundamental differences and other potential confounding factors, lower income is a positive predictor of readmission risk.

Influence of race and gender on care process, resource use, and hospital-based outcomes in congestive heart failure

Race and gender are important determinants of certain clinical outcomes in cardiovascular disease. To examine the influence of race and gender on care process, resource use, and hospital-based case outcomes for patients with congestive heart failure (CHF), we obtained administrative records on all 1995 New York State hospital discharges assigned ICD-9-CM codes indicative of this diagnosis. The following were compared among black and white women and men: demographics, comorbid illness, care processes, length of stay (LOS), hospital charges, mortality rate, and CHF readmission rate. We identified 45,894 patients (black women, 4,750; black men, 3,370; white women, 21,165; white men, 16,609). Blacks underwent noninvasive cardiac procedures more often than whites; procedure and specialty use rates were lower among women than among men. After adjusting for other patient characteristics and hospital type and location, we found race to be an important determinant of LOS (black, 10.4 days; white, 9.3 days; p = 0.0001), hospital charges (black,

Hospital Outcomes in Major Teaching, Minor Teaching, and Nonteaching Hospitals in New York State

13,711; white,

Geriatric patients with acute myocardial infarction: Cardiac risk factor profiles, presentation, thrombolysis, coronary interventions, and prognosis

11,074; p = 0.0001), mortality (black-to-white odds ratio = 0.832; p = 0.003), and readmission (black-to-white odds ratio = 1.301; p = 0.0001). Gender was an important determinant of LOS (women, 9.8 days; men, 9.2 days; p = 0.0001), hospital charges (women,

Biopsy-induced flail tricuspid leaflet and tricuspid regurgitation following orthotopic cardiac transplantation

11,690; men,

Outcome following isolated tricuspid valve replacement

11,348; p = 0.02), and mortality (women-to-men odds ratio = 0.878; p = 0.0008). We conclude that race and gender influence care process and hospital-based case outcomes for patients with CHF.

Cellular and molecular remodeling in a heart failure model treated with the β-blocker carteolol

PURPOSE The possible benefit that hospital teaching status may confer in the care of patients with cardiovascular disease is unknown. Our purpose was to determine the effect of hospital teaching status on in-hospital mortality, use of invasive procedures, length of stay, and charges in patients with myocardial infarction, heart failure, or stroke. SUBJECTS AND METHODS We analyzed a New York State hospital administrative database containing information on 388 964 consecutive patients who had been admitted with heart failure (n = 173 799), myocardial infarction (n = 121 209), or stroke (n = 93 956) from 1993 to 1995. We classified the 248 participating acute care hospitals by teaching status (major, minor, nonteaching). The primary outcomes were standardized in-hospital mortality ratios, defined as the ratio of observed to predicted mortality. RESULTS Standardized in-hospital mortality ratios were significantly lower in major teaching hospitals (0.976 for heart failure, 0.945 for myocardial infarction, 0.958 for stroke) than in nonteaching hospitals (1.01 for heart failure, 1.01 for myocardial infarction, 0.995 for stroke). Standardized in-hospital mortality ratios were significantly higher for patients with stroke (1.06) but not heart failure (1.0) or myocardial infarction (1.06) in minor teaching hospitals than in nonteaching hospitals. Compared with nonteaching hospitals, use of invasive cardiac procedures and adjusted hospital charges were significantly greater in major and minor teaching hospitals for all three conditions. The adjusted length of stay was also shorter for myocardial infarction in major teaching hospitals and longer for stroke in minor teaching hospitals. CONCLUSION Major teaching hospital status was an important determinant of outcomes in patients hospitalized with myocardial infarction, heart failure, or stroke in New York State.