Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart.

Human heart failure is associated with a diminished contractile response to beta-adrenergic agonists. We hypothesized that alterations in the activity of a guanine nucleotide-binding regulatory protein (G protein) might be partially responsible for this abnormality. We therefore measured the activity of G proteins in failing human myocardium utilizing bacterial toxin-catalyzed ADP ribosylation. The activity of a 40,000-mol wt pertussis toxin substrate (alpha G40) was increased by 36% in failing human hearts when compared with nonfailing controls. In contrast, there was no change in the level of the stimulatory regulatory subunit (Gs). The increased activity in alpha G40 was associated with a 30% decrease in basal as well as 5'-guanylyl imidodiphosphate-stimulated adenylate cyclase activity. These data suggest that increased alpha G40 activity is a new marker for failing myocardium and may account at least in part for the diminished responsiveness to beta 1-adrenergic agonists in the failing human heart.

Clinical profiles of four large pedigrees with familial dilated cardiomyopathy: preliminary recommendations for clinical practice.

OBJECTIVES: This study aimed to characterize the clinical profile of familial dilated cardiomyopathy (FDC) in the families of four index patients initially diagnosed with idiopathic dilated cardiomyopathy (IDC) and to provide clinical practice recommendations for physicians dealing with these diseases. BACKGROUND: Recent evidence indicates that approximately one-half of patients diagnosed with IDC will have FDC, a genetically transmissible disease, but the clinical profile of families screened for FDC in the U.S. has not been well documented. Additionally, recent ethical guidelines suggest increased responsibilities in caring for patients with newly found genetic cardiovascular disease. METHODS: After identification of four families with FDC, we undertook clinical screening including medical history, physical examination, electrocardiogram and echocardiogram. Diagnostic criteria for FDC-affected status of asymptomatic family members was based on left ventricular enlargement (LVE). Subjects with confounding cardiovascular diagnoses or body mass indices >35 were excluded. RESULTS: We identified 798 living members from the four FDC pedigrees, and screened 216 adults and 129 children (age <16 years). Twenty percent of family members were found to be affected with FDC; 82.8% of those affected were asymptomatic. All four pedigrees demonstrated autosomal dominant patterns of inheritance. The average left ventricular end-diastolic dimension was 61.4 mm for affected and 48.4 mm for unaffected subjects, with an average age of 38.3 years (+/- 14.6 years) for affected and 32.1 years for unaffected subjects. The age of onset for FDC varied considerably between and within families. Presenting symptoms when present were decompensated heart failure or sudden death. CONCLUSIONS: We propose that with a new diagnosis of IDC, a thorough family history for FDC should be obtained, followed by echocardiographic-based screening of first-degree relatives for LVE, assuming their voluntary participation. If a diagnosis of FDC is established, we suggest further screening of first-degree relatives, and all subjects with FDC undergo medical treatment following established guidelines. Counseling of family members should emphasize the heritable nature of the disease, the age-dependent penetrance and the unpredictable clinical course.

The somatostatin receptor SSTR1 is coupled to phosphotyrosine phosphatase activity in CHO-K1 cells.

Somatostatin receptors are abundantly expressed on a variety of human endocrine and epithelial tumors. The ability of these receptors to couple to effector pathways that inhibit the growth of these tumor cells has prompted the use of somatostatin agonists in the treatment of human neoplasms. It has been demonstrated that somatostatin stimulates a phosphotyrosine phosphatase in human tumor cells through a receptor-mediated process. This stimulation may counteract the growth-promoting properties of growth factors and the receptor tyrosine kinases that they activate. The recent cloning and characterization of distinct somatostatin receptor subtypes raise the possibility that different receptor subtypes mediate distinct effector pathways. To determine whether cloned somatostatin receptors could mediate coupling to phosphotyrosine phosphotyrosine phosphatase activity, we examined phosphatase activity after somatotostatin activation of the rat somatostatin receptors SSTR1 and SSTR2 after their stable expression in heterologous Chinese Hamster Ovary (CHO-K1) cells. We found that stimulation of SSTR1 cells was capable of increasing phosphotyrosine phosphatase activity, despite the coupling of both receptors to the inhibition of adenylyl cyclase in these cells. This activation was characterized by an EC50 of 70 nM and was sensitive to pertussis toxin. In addition, we demonstrate that activation of phosphotyrosine phosphatase activity in pituitary cell lines correlates with the endogenous expression of the SSTR1 gene within these cells.

Managed care and outcomes of hospitalization among elderly patients with congestive heart failure.

BACKGROUND: Little was known about the impact of the health maintenance organization-managed care on patients hospitalized for congestive heart failure. Understanding this issue is important with regards to the increasing prevalence of congestive heart failure among the elderly population as well as the growing enrollment of Medicare beneficiaries in managed care. OBJECTIVE: To examine the impact of the health maintenance organization-managed care on the outcomes of hospitalization among patients with congestive heart failure. PATIENTS AND METHODS: We analyzed the Oregon hospital discharge data set. Study subjects were all patients with congestive heart failure aged 65 years or older (N=5821) discharged from hospitals in 1995 and classified into 6 insurance groups: managed care, Medicare, Medicaid, commercial or private insurance, self-pay, and other. RESULTS: The percentage of patients admitted to hospitals via emergency departments was significantly higher in the managed care patients (69%) than in other health insurance coverage groups (29.0%-58.5%; P<.001). After adjusting for age, sex, and comorbidity, the managed care patients experienced a similar length of hospital stay (3.6 days) as the commercial or private insurance patients (3.7 days; P = .67), but a shorter length of hospital stay than the Medicare patients (4.0 days; P<.001), self-pay patients (4.5 days; P<.001), and other patients (4.8 days; P<.001). No difference in the in-hospital mortality rate was seen among the insurance groups (P = .37). The readmission rate was slightly higher in managed care patients (9.1%) than in commercial insurance patients (6.8%) and Medicare patients (7.5%). The differences, however, were not statistically significant after adjusting for the confounding factors (P = .59). CONCLUSIONS: Our results suggest no association between managed care and poor short-term outcomes of hospitalization in patients with congestive heart failure. Attention, however, needs to be paid to the increased use of emergency departments by managed care patients.

Treatment of central nervous system fungal infection with ketoconazole.

Two patients with fungal infection of the central nervous system (coccidioidal meningitis and cerebral histoplasmomas) were treated with ketoconazole for 30 months. Both responded to dosages substantially less than those described previously for similar infections. Neither patient experienced any significant adverse effects from the prolonged therapy.

Factors influencing knowledge of and adherence to self-care among patients with heart failure.

BACKGROUND: Patient education has been shown to be a key component in comprehensive heart failure management. Few data, however, are available regarding patients' knowledge of and adherence to self-care recommendations for the disease. OBJECTIVES: To assess the knowledge level of and adherence to self-care among patients with heart failure and to determine associated factors. METHODS: We conducted a needs-assessment survey among new patients visiting a heart failure clinic from April 1997 through June 1998. Multiple linear regression analysis was used to assess the factors predictive of patients' knowledge level and adherence behaviors. RESULTS: Of the 113 patients surveyed, 77% were referred by cardiologists and 60% had New York Heart Association class III or IV status. Two thirds of the patients reported receiving information or advice about self-care from health care providers. When asked how much they knew about congestive heart failure, however, 37% said "a little or nothing," 49% said "some," and only 14% said "a lot." Approximately 40% of the patients did not recognize the importance of weighing themselves daily and 27% weighed themselves twice a month or less often. Although 80% of the patients knew they should limit their salt intake, only one third always avoided salty foods. Additionally, 25% of the patients did not appreciate the risk of alcohol use and 36% believed they should drink a lot of fluids. The multiple linear regression analysis indicated that a higher knowledge score was associated with being married, prior hospitalization, and having received both advice and information about self-care from physicians or nurses. A poor adherence behavior score was associated with being unmarried, lower perceived self-efficacy, a lack of knowledge about self-care, and no prior hospitalization. CONCLUSIONS: We observed a gap between patients receiving and absorbing or retaining information on self-care for congestive heart failure supplied by health care providers. Self-care education needs to be directed to outpatients in addition to inpatients.

The somatostatin receptors SSTR1 and SSTR2 are coupled to inhibition of adenylyl cyclase in Chinese hamster ovary cells via pertussis toxin-sensitive pathways.

Somatostatin exerts multiple effects throughout the body by binding to specific somatostatin receptors. Two classes of somatostatin receptors, SRIF1 and SRIF2, have been distinguished biochemically and pharmacologically. Two cDNAs have been recently isolated that encode somatostatin receptors 1 and 2 (SSTR1 and SSTR2, respectively). The pharmacological characteristics of receptors expressing these cDNAs resemble those of the SRIF2 and SRIF1 classes of somatostatin receptors, respectively. We stably expressed the rat homologs of both receptors in Chinese hamster ovary (CHO) cells (type K1). These transfected cell lines recognized the endogenous ligands SS14 and SS28 with high affinity, whereas the synthetic analog MK678 identified only SSTR2. In preparations of CHO-SSTR1 or CHO-SSTR2 cells, SS14 and SS28 inhibited forskolin-stimulated adenylyl cyclase activity by approximately 35%, with ED50 values in the nanomolar range. The adenylyl cyclase inhibition was dependent upon the guanine nucleotide GTP and could be ablated with pertussis toxin preincubation. The present data indicate that SSTR1 and SSTR2 are coupled to inhibition of adenylyl cyclase via pertussis toxin- sensitive G-proteins.

Pharmacologic and hemodynamic effects of combined beta-agonist stimulation and phosphodiesterase inhibition in the failing human heart.

STUDY OBJECTIVES: We measured the individual and combined effects of the beta-agonist dobutamine and the phosphodiesterase inhibitor enoximone both in vitro and in vivo in the failing human heart. DESIGN: This was an unblinded, prospective study. SETTING AND PATIENTS: The in vitro measurements were performed on 20 hearts obtained from subjects with end-stage biventricular failure and from seven normal hearts. The in vivo measurements were performed in eight subjects with class IV heart failure. INTERVENTIONS AND MEASUREMENTS: The in vitro measurements of enoximone, dobutamine, and the combination of these agents were phosphodiesterase activity using a sarcoplasmic reticulum-enriched preparation, cyclic adenosine monophosphate (cAMP) accumulation using particulate fractions, and tension response using isolated right ventricular trabeculae. The dose response to dobutamine, the combination of enoximone and dobutamine, and the combination of nitroprusside and dobutamine were measured in vivo using invasive hemodynamic monitoring. RESULTS: In vitro, enoximone exhibited dose-dependent inhibition of phosphodiesterase activity. The addition of enoximone to dobutamine resulted in an upward and leftward shift of the dobutamine dose-response curve for both cAMP production and contractile response. In vivo, enoximone significantly shifted the dobutamine dose-response curves for cardiac index, left ventricular stroke work index, and heart rate upward and to the left; and shifted the dobutamine dose-response curves for right atrial, pulmonary arterial, and pulmonary wedge pressures downward and to the right. CONCLUSIONS: Enoximone exerts favorable effects on cardiac performance that are additive to those produced by dobutamine. These effects are mediated by increasing cellular cAMP concentrations through independent, additive mechanisms.

Heart transplantation in patients with previous cardiac operations. Excellent clinical results.

A significant proportion of potential transplant recipients have undergone previous cardiac procedures and may be subject to an increased risk because of technical and other factors inherent in a reoperation. Between December 1985 and June 1991, 155 orthotopic heart transplantations were carried out in 146 patients. Eighty-five transplantations (54.8%) were carried out as the initial cardiac operation (group I); 61 operations (45.2%) were performed in patients who had previous nontransplant cardiac operations (group II). Preoperative variables including hemodynamic indexes, renal function, and status on the waiting list were similar between these groups; however, group II patients tended to be older than group I patients (51.9 +/- 10.7 versus 47.7 +/- 11.6 years, respectively; p < 0.05) and were more likely to have ischemic heart disease (80.3% versus 34.1%) than were those in group I. Significantly longer cardiopulmonary bypass time (127.6 +/- 44.7 minutes versus 108.2 +/- 18.8 minutes, p < 0.01) and duration of operation (448.1 +/- 120.9 minutes versus 353.2 +/- 85.1 minutes, p < 0.01) was found in group II. Operative mortality in group I was 4.7% and in group II was 6.6% (p > 0.9). Group I actuarial survival at 1 year and 5 years was 87.1% +/- 3.6% and 72.9% +/- 6.2%, respectively. Group II actuarial survival was 85.3% +/- 4.5% and 76.0% +/- 6.6%, respectively, for the same time periods. In spite of the greater technical challenge implied by previous cardiac operations, no significant survival differences occurred between these groups (p > 0.9). However, patients undergoing a second cardiac transplantation (n = 9) were identified as a high-risk subset with operative mortality of 22.8% and 1-year survival of only 33.3% +/- 15.7% (p < 0.0003). Cardiac transplantation in patients who have undergone previous nontransplant cardiac operations can be carried out without compromising immediate or long-term outcome.

Low-dose enoximone in subjects awaiting cardiac transplantation. Clinical results and effects on beta-adrenergic receptors.

During a 3-year period we administered enoximone, a phosphodiesterase inhibitor with positive inotropic and vasodilator properties, to 73 pretransplantation patients with end-stage heart failure who exhibited a clinical requirement for additional inotropic support. The clinical course and myocardial beta-adrenergic receptor status in the explanted hearts of these 73 patients was compared with results in 113 concurrently listed pretransplantation patients not requiring additional inotropic support. Only three patients required cessation of enoximone because of adverse effects, all from exacerbation of ventricular arrhythmias. Sixty-six of 73 (90.4%) enoximone-treated patients ultimately underwent cardiac transplantation a mean of 39.2 +/- 6.6 days (range 1 to 221 days) after starting enoximone, whereas seven patients (9.6%) died awaiting cardiac transplantation. The respective 1-, 3-, and 6-month pretransplantation survival rates of patients treated with enoximone calculated from their time on the waiting list for transplantation were 88.0%, 82.5%, and 82.5% compared with 92.1%, 83.8%, and 76.2% in control patients not receiving enoximone (all p = not significant). In 25 patients who received enoximone, ventricular myocardial beta-adrenergic receptors were measured at the time of transplantation and compared with values in failing ventricles from 52 pretransplantation patients not exposed to enoximone. Compared with ventricular myocardium of patients not given enoximone or intravenous beta-adrenergic agonists, total beta-adrenergic receptor (beta 1 plus beta 2) density was not decreased in patients treated with enoximone or enoximone plus intravenous beta-adrenergic agonists, but was decreased by 31% (p less than 0.05) in patients given intravenous beta-adrenergic agonists alone. Additionally, patients treated with enoximone had higher myocardial beta 2-adrenergic receptor densities than respective subgroups treated without (28% higher, p less than 0.01) or with (65% higher, p less than 0.01) intravenous beta-adrenergic agonists. Finally, isoproterenol- or calcium-mediated contractile responses in isolated right ventricular preparations from 14 patients treated with enoximone were similar to values in control patients not exposed to enoximone or intravenous beta-adrenergic agonists, suggesting that enoximone-related beta-adrenergic subsensitivity or damage to the contractile apparatus does not occur.

Distribution and declines in cardiac allograft radionuclide left ventricular ejection fractions in relation to late mortality.

BACKGROUND: Cardiac allograft left ventricular ejection fraction (LVEF) is an important measure of left ventricular systolic function. Despite widespread use of LVEF after transplantation, its normal range and prognostic value in cardiac allografts has not been defined. METHODS: We conducted a retrospective cohort study among 292 consecutive adult heart transplant patients. Left ventricular ejection fractions were performed at 1, 3, 12, 24, and 48 months after transplantation using radionuclide ventriculography. Endomyocardial biopsies assessed rejection, right heart catheterization assessed loading conditions, and angiography assessed allograft coronary artery disease. We used Cox proportional hazards model to examine the predictive value of LVEF on late mortality. RESULTS: Of the patients who survived > or =4 years, the mean allograft LVEF decreased 4.7 units at 3 months, from 63.8 to 59.7; an additional 4.1 units at 12 months, from 59.7 to 55.6 (p < 0.001); and remained stable afterward. These changes were not associated with concurrent changes in loading conditions, episodes of rejection, or development of allograft coronary artery disease. Left ventricular ejection fraction lower than the 95% normal limit (<40%) at 12 months was inversely associated with risk for late cardiac mortality (relative risk = 3.5, 95% confidence interval = 1.0-12.2), while controlling for recipient age, sex, donor age, and rejection episodes. CONCLUSIONS: The cardiac-allograft LVEF frequently decreases in the first year after transplantation. The 95th percentile of allograft LVEF value (<40%) at Year 1 predicts late cardiac mortality among transplant recipients.

ABO-incompatible heart transplantation: a special case for the A2 donor.

Limited clinical experience concerning heart transplantation across ABO blood group barriers suggests a high incidence of hyperacute rejection and poor patient outcome. Reported is a case of the short-term survival of an ABO-mismatched cardiac graft without evident adverse immunologic effects. A 41-year-old man with blood type O underwent heart transplantation receiving a blood type A2 donor organ. Cyclosporine-based immunosuppression was augmented with daily plasmapheresis and OKT3 therapy. Circulating anti-A antibodies were reduced quickly and held to a very low level with this regimen. The patient remained hemodynamically stable until retransplantation 4 days later. The explanted heart showed no evidence of cellular infiltrate or antibody deposition. Long-term success with the use of type A2 organs in type O recipients has been shown in select series with other types of solid organ transplants. Although this patient underwent retransplantation early, the lack of rejection phenomena gives evidence that the relatively low antigenicity of the A2 subtype may allow planned heart transplantation across this blood group barrier, either as a bridge or on a permanent basis.

Late infection in cardiac allograft recipients: profiles, incidence, and outcome.

Infection continues to cause substantial morbidity and mortality after heart transplantation. Studies focusing on this problem have concentrated on the early posttransplant period, and it is uncertain to what extent infection continues to add to morbidity later after transplantation. Fifty-four patients surviving at least 1 year after heart transplantation made up the study population in this study, and they were surveyed for infections beyond 1 year. In this group there were 15 infections, an incidence of 0.3 infections per patient or 0.016 infections per patient-months of follow-up. Only nine of these infections necessitated hospitalization; two, however, were fatal. Actuarial risk of all late infections and late infections necessitating hospitalization was 13% and 6%, respectively, at 2 years. As expected, bacterial infections made up the largest group (60%), followed by viral disease (27%). Two patients had pulmonary infections, one with Aspergillus and one with Pneumocystis. These data demonstrate that although rates of infection in heart recipients continue to exceed those in the general population, the rates are considerably lower than those in what is seen early after heart transplantation. Despite this, the more unusual infectious agents associated with immune compromise continue to be present.

Recurrence of sarcoidosis in a cardiac allograft: control with augmented corticosteroids.

Sarcoidosis of the heart is an unusual but previously reported indication for heart transplantation. It is clear that sarcoidosis is a systemic disease, but in spite of this, recurrence in the cardiac allograft has not been previously noted. The case presented here is that of a 34-year-old male in whom cardiac sarcoidosis recurred in the allograft 6 months after heart transplantation.

Methotrexate for the treatment of patients with multiple episodes of acute cardiac allograft rejection.

Of 142 cardiac allograft recipients who underwent transplantation from December 1985 to January 1991, four women and seven men (mean age, 41 +/- 14 years) required multiple (10.5 +/- 3.3) courses of antirejection treatment over a total follow-up period of 30 +/- 15 months. The underlying heart disease was cardiomyopathy in six patients and coronary disease in five patients. These patients were treated with methotrexate (10 mg/wk for 6 weeks). Rejection treatment before methotrexate therapy included six courses of OKT3, one course of antithymocyte globulin, 33 courses of high-dose steroids, and 45 courses of low-dose steroids for the entire group. The average number of rejection treatments per patient before methotrexate therapy was 8.7 +/- 3.5 treatments or 0.90 +/- 0.51 treatments per month of follow-up. After methotrexate therapy the average number of rejection treatments fell to 1.7 +/- 1.1 treatments or 0.11 +/- 0.08 treatments per month of follow-up (p = 0.0002). Seven patients responded to a single course of methotrexate therapy; three patients required two courses (second course, 20 mg/wk for 6 weeks), and one patient required three courses of methotrexate therapy. The only complication associated with methotrexate therapy was one patient in whom cytomegalovirus interstitial pneumonitis developed while on therapy. Methotrexate was well tolerated and appeared to be effective in halting repeated episodes of rejection in this subset of patients who have had multiple episodes of acute rejection.

Prolonged cytomegalovirus infection with viremia is associated with development of cardiac allograft vasculopathy.

Several reports have suggested an association between cytomegalovirus infection and the subsequent development of cardiac allograft vasculopathy. The difficulties in interpreting these studies include the variety of methods used for the diagnosis of cytomegalovirus infection and variable criteria for the diagnosis of cardiac allograft vasculopathy. To determine whether specific aspects of cytomegalovirus infection are risk factors for cardiac allograft vasculopathy, the patient population of the Oregon Cardiac Transplant Program was analyzed for the following variables: cytomegalovirus infection, primary cytomegalovirus infection, and persistent cytomegalovirus infection for 4 or 6 months documented by either blood or urine cultures and persistent cytomegalovirus viremia for 4 months. In the 129 patients available for analysis, there was no higher incidence of cardiac allograft vasculopathy in patients with or without cytomegalovirus infection, nor was there a higher incidence of cardiac allograft vasculopathy in primary cytomegalovirus infection. There was a nonstatistically significant trend toward an increased incidence of cardiac allograft vasculopathy in patients with persistent cytomegalovirus infection as assessed by cultures positive for infection in either blood or urine. There was, however, a significant increase in the incidence of cardiac allograft vasculopathy in patients who had persistent viremia for at least 4 months compared with those without this finding (47% vs 18%, respectively; p = 0.012). In our population persistent cytomegalovirus viremia and presumably long-term exposure of the allograft coronary tree to cytomegalovirus is associated with cardiac allograft vasculopathy.

The specificity of normal qualitative angiography in excluding cardiac allograft vasculopathy.

It has been frequently stated that qualitative coronary angiography is insensitive in the diagnosis of cardiac allograft vasculopathy because the disease can be diffuse without observable luminal irregularities. However, the specificity of otherwise normal qualitative coronary angiography for excluding cardiac allograft vasculopathy has not been prospectively studied. Accordingly, 28 patients who underwent transplantation from June 23, 1989 to July 9, 1990 underwent coronary angiography within 3 weeks (predischarge) after transplantation and at 1 year. Twenty-one of these patients who had both normal 1-year qualitative coronary angiography and predischarge angiograms adequate for analysis served as the study cohort. Cross-section luminal diameters (average, 14.3 per angiogram) were measured at the same branch points on each pair of angiograms in the right anterior oblique view. Seventeen of the 21 patients had no change in average luminal diameters, while the remaining four patients had consistent narrowing in all vessels and in all segments. In these four patients, the mean fall in luminal diameter was 20% +/- 2%. The specificity of normal qualitative angiography in predicting absence of cardiac allograft vasculopathy is 81%. In conclusion, qualitative angiography usually predicts the absence of cardiac allograft vasculopathy. However, 15% to 20% of patients will have diffuse disease not detected by a normal study.

Was the decreasing trend in hospital mortality from heart failure attributable to improved hospital care? The Oregon experience, 1991-1995.

OBJECTIVE: To assess the trend in risk-adjusted hospital mortality from heart failure. STUDY DESIGN: Oregon hospital discharge data from 1991 through 1995 were analyzed. PATIENTS AND METHODS: A total of 29,530 hospitalizations because of heart failure in elderly patients (age > or = 65 years) were identified from International Classification of Diseases, 9th Revision, codes 428.0-428.9. The logistic regression and life table analyses were used to assess the risk-adjusted trend in hospital mortality from heart failure. RESULTS: From 1991 through 1995, 1757 (5.9%) patients with heart failure died in the hospital; 920 (52.4%) of them died within 3 days. The percentage of patients discharged to skilled nursing facilities increased from 6.1% in 1991 to 9.8% in 1995 (P value for trend < .001), whereas the percentage of patients discharged directly to home decreased from 69.2% in 1991 to 62.4% in 1995 (P value for trend < .001). The mean length of stay decreased from 5.15 days in 1991 to 3.97 days in 1995. The age- and sex-standardized mortality rate decreased by 33.8% from 7.4 in 1991 to 4.8 in 1995 (P value for trend < .01). Additional adjustment for comorbidity using multiple logistic regression revealed a greater reduction of 41.0% in the mortality rate (odds ratio = 0.59; 95% confidence interval = 0.50, 0.69) and a reduction of 46.0% in the 3-day mortality rate (odds ratio = 0.54; 95% confidence interval = 0.43, 0.67) across the 5-year period. Life table analysis showed consistently lower cumulative mortality rates during the first week after admission in 1995 compared with those in 1991 (P < .001). CONCLUSION: There was a decreasing trend over time in the risk-adjusted hospital mortality rates from heart failure, which was not an artifact of decreasing length of stay. Our findings raised the possibility of improved hospital care for heart failure in Oregon.

Clinical outcomes, quality of life, and cost outcomes after cardiac transplantation.

Cardiac transplantation improves survival in patients with advanced heart failure, especially those who are dependent on intravenous inotropic support or mechanical assistance. However, cardiac transplantation remains a treatment modality rather than a curative procedure, and thus, necessitates long-term care and indefinite immunosuppression. Although quality of life is improved for most cardiac transplant recipients, concerted effort is necessary for long-term care and follow-up of the transplanted heart. The economics of cardiac transplantation are receiving increased scrutiny, especially because of the increasing pretransplant hospital expenditures that have resulted from transplantation in more patients in the hospital who require intravenous inotropic support or mechanical devices. This shift ultimately is related to the reduced supply of donors relative to the demand. The ultimate impact of managed care on cardiac transplantation is not clear, but it probably will continue to reduce expenditures in the near term.

Genetic Counseling and Screening Issues in Familial Dilated Cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDC), a treatable condition characterized by left ventricular dilatation and systolic dysfunction of unknown cause, has only recently been recognized to have genetic etiologies. Although familial dilated cardiomyopathy (FDC) was thought to be infrequent, it is now believed that 30-50% of cases of IDC may be familial. Echocardiographic and electrocardiographic (ECG) screening of first-degree relatives of individuals with IDC and FDC is indicated because detection and treatment are possible prior to the onset of advanced, symptomatic disease. However, such screening often creates uncertainty and anxiety surrounding the significance of the results. Furthermore, FDC demonstrates incomplete penetrance, variable expression, and significant locus and allelic heterogeneity, making genetic counseling complex. The provision of genetic counseling for IDC and FDC will require collaboration between cardiologists and genetics professionals, and may also improve the recognition of FDC, the availability of support services, and overall outcomes for patients and families.