The economic burden of heart failure.

Heart failure, a major cause of morbidity and mortality among the elderly, is a serious public health problem. As the population ages and the prevalence of heart failure increases, expenditures related to the care of these patients will climb dramatically. As a result, the health care industry must develop strategies to contain this staggering economic burden. Strategies may include adopting approaches for preventing heart failure and implementing new treatment modalities with proven efficacy into large-scale clinical practice. Successful implementation of these strategies will require intensive physician and patient education and development of innovative approaches to fund support services.

Malaligned financial incentives of providers in the treatment of chronic diseases: the case of chronic heart failure.

Fee for activity based payment systems create a matrix of conflicting incentives. Hospitals, desiring to maximize revenues and minimize expenses, seek high patient volume with minimal direct variable expenses. The mix of patients, sought bias towards those whose disease related group (DRG), provide the largest contribution to hospitals fixed costs, are frequently characterized by the DRG with high reimbursements, coupled with both low length of stay and low utilization of expensive resources. Physicians, on the other hand, find hospital environments to be extraordinary practice sites. In the hospital, they can generate practice revenue without paying overhead for hospital resources. The incentives to rapidly discharge patients and reduce utilization of resources which are charged to the hospital's expense line are obscure. Hospital treatment of CHF frequently characterizes this conflict; hospitals are seeking rapid through put of CHF patients who neither require expensive hospital based resources nor demonstrate excessive length of stay. Physicians are not encumbered with immediate concerns about costs during the hospitalization, nor the length of hospitalization. The absence of absolute medical consensus on appropriateness of diagnostic and treatment strategies in this population has allowed significant variation on practice patterns to evolve, and consequently, variation on the contribution to hospital fiscal viability made by each physician. (c)1999 by CHF, Inc.

Cyclophosphamide in cardiac transplant recipients with frequent rejection: a six-year retrospective review.

Allograft rejection remains a major cause of morbidity and mortality. Cyclophosphamide, a nitrogen mustard, is a potent immunosuppressive agent with effects on both T- and B-lymphocytes, and thus may be effective in preventing further cellular and/or humoral rejection in cardiac transplant recipients with recurrent or recalcitrant rejection. We retrospectively reviewed the records of 320 surviving cardiac transplant recipients. Cyclophosphamide was substituted for azathioprine in 28 patients because of frequent allograft rejection. We then reviewed the rejection history of these 28 patients, specifically looking at rejection frequency, type (cellular, vascular or mixed), and treatment. Cyclophosphamide was substituted for azathioprine at an average of 8.4 +/- 2.8 months after transplantation. Despite a 56.0% reduction in prednisone dose (p < 0.001), at least a threefold reduction in rejection frequency (p < 0.001) was observed, while cyclosporine levels were unchanged. Twenty-eight percent of the patients did not experience even mild rejection after beginning therapy with cyclophosphamide, 55% had 1 or 2 subsequent mild or moderate rejection episodes, and only 17% had more than two subsequent episodes of mild or moderate rejection. Overall, the number of treated rejection episodes decreased from 0.37 episodes per patient month with azathioprine to 0.10 episodes per patient month on therapy with cyclophosphamide. Separating the patients into two groups based on the predominant rejection type (cellular vs. vascular) occurring at the time of cyclophosphamide substitution revealed a similar reduction in cellular and vascular rejection in each respective group. While white blood cell count decreased by 16%, cyclophosphamide was not discontinued in any patient due to leukopenia, and no change was noted in hematocrit. Cyclophosphamide appears to be safe and effective in maintenance immunosuppression and may reduce rejection frequency in some patients with frequently occurring allograft rejection without necessitating the augmentation of either corticosteroids or cyclosporine.

Improved long-term survival after heart transplantation predicted by successful early withdrawal from maintenance corticosteroid therapy.

BACKGROUND: Short-term studies suggest that cardiac transplant immunosuppression without maintenance corticosteroids is feasible in selected patients. However, concern exists as to the long-term effects, specifically the possibility of increased morbidity and mortality because of late allograft rejection and allograft coronary artery disease. METHODS: We retrospectively reviewed the records from 441 consecutive heart transplantation procedures done in 416 patients with use of an immunosuppressive protocol that attempted corticosteroid withdrawal within 2 months of transplantation. forty-two patients died or underwent retransplantation during the first 3 months and were excluded from further analysis. Analysis focused on demographic and long-term outcome variables (including death, rejection, retransplantation, and infection). RESULTS: Thirty percent (111) of eligible patients (374) met the definition of successful early steroid withdrawal. Only male gender independently predicted successful withdrawal. Mortality, both short and long term, was significantly lower in patients in whom successful early withdrawal from corticosteroids was achieved than in patients in whom the early attempts failed (1.7% per year versus 4.7% per year; p < 0.0001). The prevalence of late acute allograft rejection (more than 1 year after transplantation) was lower in patients successfully withdrawn from steroid therapy early after transplantation (0.07 pt-yr of follow-up versus 0.15 pt-yr; p = 0.002). Multivariate analysis of the entire group identified incidence of infection (p = 0.001), older age (p = 0.001), failed early steroid withdrawal (p = 0.006), and female gender (p = 0.016) as independent predictors of mortality. CONCLUSIONS: Successful early corticosteroid withdrawal identifies a subgroup of "immunologically privileged" patients with a low risk for long-term mortality and is not associated with an increased prevalence of late rejection or clinically significant coronary artery disease.

Community-based internal medicine residency training--a report on our first two years.

Since August, 1993, internal Medicine Associates Foundation, Inc. of Tupelo and the Department of Medicine, University of Mississippi Medical Center, have been cooperating in a program of community-based Internal Medicine residency training, the first effort of its kind in the state. We are pleased to report the program an unqualified success, for the residents themselves, the participating private physicians, and the Department as a whole. As one of only a handful of ambulatory care private practice relationships in the country (approximately five percent of Internal Medicine departments have such at present), we feel that ours can serve as a model for other programs to emulate. We therefore present a report on our program's background, organizational structure, curriculum, and future plans.

The repetitive histologic pattern of vascular cardiac allograft rejection. Increased incidence associated with longer exposure to prophylactic murine monoclonal anti-CD3 antibody (OKT3).

While vascular cardiac allograft rejection increases morbidity and mortality following transplantation, factors predisposing to its development have not been completely elucidated. To evaluate the influence of the duration of early rejection prophylaxis with the murine monoclonal anti-CD3 antibody (OKT3) on the development of a repetitive histologic pattern of vascular cardiac allograft rejection, endomyocardial biopsies from 344 heart transplant recipients were prospectively evaluated. The influence of clinical characteristics was assessed. Eighty-three patients (24%) developed and 261 patients (76%) did not develop a repetitive histologic pattern of vascular cardiac allograft rejection. The vascular rejection pattern was more common in patients with a positive crossmatch (89% versus 11%, P<0.0001) and OKT3 sensitization (73% versus 27%, P<0.0001), and was positively correlated with the duration of OKT3 treatment (P<0.0001). The correlation persists even after excluding patients with a positive crossmatch or OKT3 sensitization. Patients developing a repetitive histologic pattern of vascular cardiac allograft rejection early after transplantation had decreased allograft survival (P=0.0008). The development of a repetitive histologic pattern of vascular cardiac allograft rejection is positively correlated with the duration of OKT3 treatment. Judicious use of OKT3 in early rejection prophylaxis in cardiac transplantation is warranted.

Implications of the Myocarditis Treatment Trial for clinical practice.

Active myocarditis, a common precursor of dilated cardiomyopathy, is defined as myocardial inflammation and injury in the absence of ischemia. Many agents may cause myocarditis and the exact manifestation of the disease depends on the interplay between the inciting agent and host response. Widespread belief that myocarditis is an autoimmune disorder has led to the possible overuse of endomyocardial biopsy and immunosuppressive agents. Their use is further complicated by the observation that many patients improve with conservative management alone. The Myocarditis Treatment Trial was designed to address the role of immunosuppression in the treatment of myocarditis, define the natural history of the disease, and increase understanding of the immunologic mechanisms involved in the pathogenesis of the disease. Enrollment began in October 1986 and was completed in October 1990 with follow-up completed in 1991. The study failed to show a significant benefit for immunosuppressive agents. Conventional medical regimens should be used to alleviate symptoms and immunosuppressive agents should be reserved for patients with progressive deterioration and biopsy-proven disease.

Exercise capacity after heart transplantation: influence of donor and recipient characteristics.

BACKGROUND: For incompletely understood reasons, cardiac transplant recipients achieve only 60% to 70% of predicted values for maximal exercise capacity. The objective was to determine the characteristics of cardiac transplant recipients that are predictive of exercise capacity. METHODS: One hundred ten patients underwent maximal exercise testing using a modified Naughton protocol 26 +/- 1 months after transplantation. Recipient characteristics, resting hemodynamic variables and exercise parameters were compared using univariate and multivariate analyses. RESULTS: The average maximum heart rate was 85% of predicted, and the average peak oxygen consumption (Vo2) was 17.7 +/- 0.3 ml/kg/min (64% of predicted). Pretransplant status, etiology of heart failure, ischemic time, degree of HLA disparity, cumulative corticosteroid exposure, and number of rejection episodes failed to correlate with any exercise parameter. Older recipient age and female gender were associated with greater values for the proportion of the predicted peak Vo2 (p < 0.001 for age; p = 0.001 for gender). Older donor age was the strongest independent predictor of a decreased chronotropic response (p < 0.001) and was a weak predictor of decreased peak Vo2 (p = 0.014). Even in the multivariate analysis, maintenance prednisone dose negatively impacts exercise duration (p = 0.05), peak Vo2 (p = 0.035) and percent of predicted peak Vo2 (p = 0.032). Of all characteristics tested, pulmonary vascular resistance within 24 hours of exercise most powerfully predicts exercise duration (p = 0.002) and peak Vo2 (p = 0.001). CONCLUSIONS: Female recipients and older recipients have a lower absolute exercise capacity, but achieve a greater proportion of their predicted capacity. Recipients of older donor hearts and those receiving chronic corticosteroids have decreased exercise capacity. Pulmonary vascular resistance is inversely correlated with exercise capacity.

Selection and treatment of candidates for heart transplantation. A statement for health professionals from the Committee on Heart Failure and Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association.

Improved outcome of heart failure in response to medical therapy, coupled with a critical shortage of donor organs, makes it imperative to restrict heart transplantation to patients who are most disabled by heart failure and who are likely to derive the maximum benefit from transplantation. Hemodynamic and functional indexes of prognosis are helpful in identifying these patients. Stratification of ambulatory heart failure patients by objective criteria, such as peak exercise oxygen consumption, has improved ability to select appropriate adult patients for heart transplantation. Such patients will have a poor prognosis despite optimal medical therapy. When determining the impact of individual comorbid conditions on a patient's candidacy for heart transplantation, the detrimental effects of each condition on posttransplantation outcome should be weighed. Evaluation of patients with severe heart failure should be done by a multidisciplinary team that is expert in management of heart failure, performance of cardiac surgery in patients with low left ventricular ejection fraction, and transplantation. Potential heart transplant candidates should be reevaluated on a regular basis to assess continued need for transplantation. Long-term management of heart failure should include continuity of care by an experienced physician, optimal dosing in conventional therapy, and periodic reevaluation of left ventricular function and exercise capacity. The outcome of high-risk conventional cardiovascular surgery should be weighed against that of transplantation in patients with ischemic and valvular heart disease. Establishment of regional specialized heart failure centers may improve access to optimal medical therapy and new promising medical and surgical treatments for these patients as well as stimulate investigative efforts to accelerate progress in this critical area.

Role of beta-adrenergic receptor downregulation in the peak exercise response in patients with heart failure due to idiopathic dilated cardiomyopathy.

The effect of beta-adrenergic receptor downregulation on peak exercise response in patients with heart failure has not been directly investigated. Seventy-two patients with idiopathic dilated cardiomyopathy who had a mean ejection fraction of 23 +/- 1% (mean +/- SEM) and New York Heart Association class II or III symptoms were investigated. Subjects underwent maximal exercise testing on a bicycle or a treadmill, hemodynamic assessment by right heart catheterization, and measurement of total beta-adrenergic receptor density by 125I-iodocyanopindolol binding performed in the right ventricular endomyocardial biopsy tissue and in peripheral lymphocytes. Endomyocardial biopsy beta-adrenergic receptor density (Bmax) was markedly decreased (45 +/- 2 fmol/mg), and significantly lower than lymphocytes Bmax (107 +/- 14 fmol/mg; p < 0.05). By univariate analysis, all exercise variables correlated significantly with biopsy tissue Bmax but not with lymphocyte Bmax. Maximal exercise oxygen consumption (VO2max) yielded the highest correlation with Bmax (r2 = 0.61, p < 0.001). By stepwise regression analysis, VO2 max, delta heart rate x systolic blood pressure, and ejection fraction were all independently related to Bmax. Myocardial beta-adrenergic receptor downregulation is likely to be partially responsible for the reduced chronotropic and inotropic responses to peak exercise in patients with mild to moderate symptomatic heart failure due to idiopathic dilated cardiomyopathy.

Heart transplantation in dilated heart muscle disease and myocarditis.

A detailed analysis of outcome with reference to pre-transplant diagnosis was performed in 14 055 cardiac transplant recipients to determine whether the diagnosis of dilated heart muscle disease predicted survival. Overall survival at one year was greater than 80% in all patients. In general, those with dilated heart muscle disease had a small but significantly improved survival compared to those with other diagnoses. Outcome in women, which is significantly poorer than men, showed similar diagnosis-specific results. Multivariate analysis confirmed the significant difference (P = 0.02) with a minimal reduction in risk (relative risk 0.927). In conclusion, carefully selected patients with dilated heart muscle disease are excellent candidates for cardiac transplantation.

The Myocarditis Treatment Trial: design, methods and patients enrollment.

The Myocarditis Treatment Trial was a multicentre clinical trial conducted to determine the efficacy of immunosuppressive therapy for treatment of biopsy-documented myocarditis, and to improve understanding of the immunological mechanisms in the development of myocarditis. Thirty-one centres screened 2305 patients with unexplained heart failure, and 2233 patients underwent an endomyocardial biopsy which provided adequate tissue for diagnosis. Those with a positive biopsy and a left ventricular ejection fraction (LVEF) less than 45% were randomly assigned to receive immunosuppressive therapy plus conventional drug therapy for congestive heart failure (66 patients) or conventional therapy only (45 patients) for 24 weeks. For 28 additional weeks all patients received conventional therapy only. In addition to diagnostic and clinical data, serum and myocardial tissue for immunological marker analysis and histopathologic evaluation were collected at baseline and at 12, 28 and 52 weeks after randomization. The primary analysis of efficacy was designed as a comparison of the mean increase in LVEF at week 28 between treatment limbs. Secondary objectives were to evaluate survival differences, and changes in the histopathology of the disease and immunological markers. Randomized patients were relatively young (mean age, 42.0 years +/- 13.8 standard deviation (sd) and entered the Trial with a mean LVEF percent of 24.3 +/- 10.1 sd) and mean exercise treadmill duration of 9.4 (+/- 5.3 sd) minutes. The incidence of biopsy-documented myocarditis was low (9.6%). The analyses of outcome and immunological data are reported elsewhere.

Mycotic pseudoaneurysm complicating flap closure of an infected median sternotomy.

False aneurysm, or pseudoaneurysm, formation is a well-recognized complication of cardiac surgery that can occur in the setting of postoperative mediastinitis. We present the first case report of a pseudoaneurysm involving flap closure of the infected mediastinum and discuss the presentation and diagnosis of this life-threatening complication.

Myocarditis and idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDC) accounts for 25% of cases of heart failure in the United States. Understanding the relationship between an inciting event or agent and the development of IDC has progressed only recently. Once IDC has developed, treatment is palliative and little can be done to alter the natural course of the disease. Active myocarditis, a suspected precursor of IDC, is myocardial inflammation and injury without ischemia. The disease ranges from a self-limited flulike illness to one of serious consequence with arrhythmias, heart failure, or death. Many agents have been associated with myocarditis, and the clinical manifestations depend on an interplay between the inciting agent and the host response. The development of a murine model and the expanded use of endomyocardial biopsy using the Dallas criteria have increased our understanding of myocarditis and its sequelae. Therapy consists of managing symptoms using conventional medical regimens for heart failure. Immunosuppressive therapy should be reserved for patients with biopsy-proven disease who have failed conventional therapy. Continued deterioration warrants ventricular assistance and consideration of cardiac transplantation.