Health insurance as a requirement to undergo cardiac transplantation: a national survey of transplant program practices.

BACKGROUND: Recent limitations in Medicaid coverage of transplantation in Arizona jeopardized transplantation of potential recipients in that state and called attention to financial barriers inherent in the present organ allocation system. Policies of cardiac transplant centers regarding insurance requirements for transplantation have not been previously assessed. We sought to determine the policies of adult cardiac transplant programs nationwide regarding insurance requirements for evaluation and listing for cardiac transplantation. METHODS: From December 15, 2008 to November 16, 2010, all active adult cardiac transplant programs in the United States were surveyed regarding insurance requirements for evaluation and listing for cardiac transplantation. RESULTS: Surveys were completed by 62 of 101 programs, accounting for 71% of adult cardiac transplants in 2007. Only 2% of recipients were uninsured. Insurance was required by 48% of programs to evaluate and 84% to list for transplantation. For uninsured patients, 81% of programs required a large amount of money upfront (median, $200,000; interquartile range, $10,000-$300,000) to list for transplantation and often (84%) educated patients about fundraising to acquire these resources. CONCLUSIONS: Adult cardiac transplant programs generally require candidates to have adequate health insurance to undergo transplantation. Uninsured patients typically need a significant amount of money upfront to be listed for transplantation and often are advised to fundraise to gather such resources.

Respiratory syncytial virus pneumonia treated with lower-dose palivizumab in a heart transplant recipient.

Respiratory syncytial virus (RSV) is an important community-acquired pathogen that can cause significant morbidity and mortality in patients who have compromised pulmonary function, are elderly, or are immunosuppressed. This paper describes a 70-year-old man with a remote history of heart transplantation who presented with signs and symptoms of pneumonia. Chest computed tomography (CT) imaging demonstrated new patchy ground glass infiltrates throughout the upper and lower lobes of the left lung, and the RSV direct fluorescence antibody (DFA) was positive. The patient received aerosolized ribavirin, one dose of intravenous immunoglobulin, and one dose of palivizumab. After two months of followup, the patient had improved infiltrates on chest CT, improved pulmonary function testing, and no evidence of graft rejection or dysfunction. There are few data on RSV infections in heart transplant patients, but this case highlights the importance of considering this potentially serious infection and introduces a novel method of treatment.

Successful use of the TandemHeart percutaneous ventricular assist device as a bridge to recovery for acute cellular rejection in a cardiac transplant patient.

In this report, we presented a patient who benefited from hemodynamic support with the TandemHeart percutaneous ventricular assist device (pVAD; Cardiac Assist, Inc) implantation in the setting of early acute graft rejection 2 months after orthotopic heart transplant. The TandemHeart initially had been used for temporary hemodynamic assistance during postcardiotomy heart failure and high-risk coronary interventions. More recently, its use in patients with cardiogenic shock from acute myocardial infarction, fulminant myocarditis, and critical aortic stenosis has been reported. To our knowledge, this is one of the first reported cases in which the TandemHeart pVAD served as a successful device for support during acute cardiac transplant rejection.

Long-term follow-up of a heart transplant recipient with documented seroconversion to HIV-positive status 1 year after transplant.

Whether human immunodeficiency virus (HIV) should be an absolute contraindication to heart transplantation has been a topic of recent discussion. There is a paucity of data regarding the expected outcome of heart transplantation in a recipient who is HIV positive. Herein, we report the case and long-term follow-up of a woman who was found to have seroconverted to HIV positive status 1 year after transplant.

Outcomes after emergency department discharge with a primary diagnosis of heart failure.

BACKGROUND: Patients with decompensated chronic heart failure (CHF) are frequently evaluated in emergency departments (ED). The outcomes of such patients after discharge to the outpatient setting from the ED are not well known. Risk factors for return ED visits or subsequent hospital admission after ED discharge for CHF also are not known. METHODS: Charts were reviewed from all 112 patients discharged from the Parkland Memorial Hospital ED with a primary diagnosis of CHF from October to December 1998. A composite end point ("failure of outpatient therapy") was prespecified to be a recurrent ED visit for CHF, hospitalization for CHF, or death at 3 months after the index ED discharge. RESULTS: Within 3 months of the index ED visit, 61% of the study population met the composite end point. The median time to failure of outpatient therapy was 30 days. Univariate analysis of 27 clinical and demographic variables demonstrated the respiratory rate at presentation as the only predictor of failure of outpatient therapy (P =.02). Multivariate analysis of a model with 8 prespecified variables also demonstrated respiratory rate to be the only variable independently associated with an increased risk for the composite end point (odds ratio 1.6, 95% confidence interval 1.1-2.6, for each increase of 5 breaths/min). CONCLUSION: There is a high rate of failure of outpatient therapy (61%) in patients discharged with a primary diagnosis of CHF from an urban county hospital ED. Increased respiratory rate on presentation to the ED may be associated with adverse outcomes after ED discharge for CHF.

Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure.

BACKGROUND: The independent prognostic value of elevated jugular venous pressure or a third heart sound in patients with heart failure is not well established. METHODS: We performed a retrospective analysis of the Studies of Left Ventricular Dysfunction treatment trial, in which 2569 patients with symptomatic heart failure or a history of it were randomly assigned to receive enalapril or placebo. The mean (+/-SD) follow-up was 32+/-15 months. The presence of elevated jugular venous pressure or a third heart sound was ascertained by physical examination on entry into the trial. The risks of hospitalization for heart failure and progression of heart failure as defined by death from pump failure and the composite end point of death or hospitalization for heart failure were compared in patients with these findings on physical examination and patients without these findings. RESULTS: Data on 2479 patients were complete and analyzed. In multivariate analyses that were adjusted for other markers of the severity of heart failure, elevated jugular venous pressure was associated with an increased risk of hospitalization for heart failure (relative risk, 1.32; 95 percent confidence interval, 1.08 to 1.62; P<0.01), death or hospitalization for heart failure (relative risk, 1.30; 95 percent confidence interval, 1.11 to 1.53; P<0.005), and death from pump failure (relative risk, 1.37; 95 percent confidence interval, 1.07 to 1.75; P<0.05). The presence of a third heart sound was associated with similarly increased risks of these outcomes. CONCLUSIONS: In patients with heart failure, elevated jugular venous pressure and a third heart sound are each independently associated with adverse outcomes, including progression of heart failure. Clinical assessment for these findings is currently feasible and clinically meaningful.

Prognostic impact of diabetes mellitus in patients with heart failure according to the etiology of left ventricular systolic dysfunction.

OBJECTIVES: We sought to determine the relative impact of diabetes mellitus on prognosis in ischemic compared with nonischemic cardiomyopathy. BACKGROUND: Ischemic myocardium is characterized by increased reliance on aerobic and anaerobic glycolysis. Because glucose utilization by cardiomyocytes is an insulin-mediated process, we hypothesized that diabetes would have a more adverse impact on mortality and progression of heart failure in ischemic compared with nonischemic cardiomyopathy. METHODS: We performed a retrospective analysis of the Studies Of Left Ventricular Dysfunction (SOLVD) Prevention and Treatment trials. RESULTS: In adjusted analyses, diabetes mellitus was strongly associated with an increased risk for all-cause mortality in patients with ischemic cardiomyopathy, (relative risk [RR] 1.37, 95% confidence interval [CI] 1.21 to 1.55; p < 0.0001), but not in those with nonischemic cardiomyopathy (RR 0.98, 95% CI 0.76 to 1.32; p = 0.98). The increased mortality in patients with ischemic cardiomyopathy compared with nonischemic cardiomyopathy was limited to those with ischemic cardiomyopathy and diabetes mellitus (RR 1.37, 95% CI 1.21 to 1.56; p < 0.0001). When patients with ischemic cardiomyopathy and diabetes mellitus were excluded, there was no significant difference in mortality risk between the ischemic and nonischemic cardiomyopathy groups after adjusted analysis (RR 0.99, 95% CI 0.86 to 1.15; p = 0.99). Previous surgical revascularization identified patients within the cohort with ischemic cardiomyopathy and diabetes mellitus, with improved prognosis. CONCLUSIONS: The differential impact of diabetes on mortality and heart failure progression according to the etiology of heart failure suggests that diabetes and ischemic heart disease interact to accelerate the progression of myocardial dysfunction. Evaluation of the potential for revascularization may be particularly important in patients with ischemic cardiomyopathy and diabetes mellitus.

Early outcome of initiating amiodarone for atrial fibrillation in advanced heart failure.

BACKGROUND: Little information exists about the early outcomes of initiating amiodarone for atrial fibrillation in patients with advanced heart failure. This study assessed the initial rate of success and complications of amiodarone therapy initiated for patients with atrial fibrillation during hospitalization for heart failure. METHODS: We reviewed medical records for 37 consecutive patients with left ventricular ejection fractions

Relationship between right and left-sided filling pressures in 1000 patients with advanced heart failure.

BACKGROUND: Elevated left ventricular filling pressures present a major target of therapy for symptomatic heart failure but are difficult to assess directly. Because the relationship of left- and right-sided pressures remains ill defined in chronic heart failure, this study compared 3 right-sided measurements (right atrial [RA] pressure, pulmonary artery systolic [PAS] pressure, and severity of tricuspid regurgitation [TR]) to the pulmonary capillary wedge (PCW) pressure. METHODS: Hemodynamic measurements and echocardiography were available from 1000 patients undergoing transplant evaluation. Right atrial and PAS pressure, and TR severity were compared to PCW pressure. For 754 patients undergoing repeat measurements, changes in RA and PAS pressures were compared to PCW changes. RESULTS: Right atrial pressure correlated with PCW pressure (r = 0.64), regardless of etiology or TR severity. Right atrial pressure changes correlated with PCW changes (r = 0.62). Discordance was defined as either RA > or = 10 mm Hg despite PCW < 22 mm Hg (6%) or RA < 10 mm Hg despite PCW > or = 22 mm Hg (15%). For detection of PCW > or = 22 mm Hg, positive predictive values were 88% for RA > or = 10 mm Hg, 95% for PAS > or = 60 mm Hg, and 79% for > or = moderate TR. Pulmonary artery systolic pressure correlated very closely with PCW (r = 0.79), and could be estimated as 2 x PCW. Reduction in PAS pressure during therapy was strongly determined by PCW pressure reduction (r = 0.67). CONCLUSIONS: Accurate estimation of RA pressure can potentially guide therapy of left ventricular filling pressures in approximately 80% of chronic heart failure patients without obvious non-cardiac disease. In this population, elevated PAS pressures are largely determined by elevated left-sided filling pressures.

Tailored therapy using dobutamine and nitroglycerin in advanced heart failure.

In 29 patients with advanced heart failure, therapy tailored to hemodynamic goals was attempted using an initial infusion of dobutamine and nitroglycerin (the latter in those with pulmonary hypertension) followed by escalating doses of oral vasodilators. In the 23 patients who were weaned from inodilator therapy, significant improvements in hemodynamic parameters and a low 90-day hospital readmission rate were documented.

Potentiation of beta-adrenergic signaling by gene transfer.

The beta-adrenergic signaling cascade is an important regulator of myocardial function. Numerous abnormalities occur in this pathway and are associated with impaired cardiac contractility in patients with congestive heart failure (CHF). These signaling defects include downregulation of beta-adrenergic receptors (beta ARs) and increased levels of beta-adrenergic receptor kinase (beta ARK), an enzyme that phosphorylates and uncouples only agonist-bound receptors. Our laboratory has been testing the hypothesis that reversal of these beta-adrenergic defects may be able to restore cardiac inotropy to normal in patients with depressed systolic function. Transgenic mice with cardiac overexpression of beta 2ARs or an inhibitor of beta ARK have enhanced cardiac function as compared to wildtype littermates. Adenoviral vectors encoding the beta 2AR or beta ARK inhibitor potentiate beta AR signaling in cultured adult rabbit ventricular myocytes. However, a controversy has developed in the literature regarding whether increasing beta-adrenergic signaling would be beneficial or detrimental for patients with CHF. Those cautioning against this approach note that increased sympathetic activity is dangerous in CHF. Elevated catecholamine levels predict mortality and beta-agonists are not beneficial for survival, while recent studies suggest that beta-antagonists do improve outcome. Supporting these concerns is the demonstration that transgenic mice with cardiac overexpression of Gs alpha and enhanced myocardial responsiveness to isoproterenol develop myocardial fibrosis. This article summarizes this controversy; highlights important differences between overexpression of beta ARs or a beta ARK inhibitor, overexpression of Gs alpha, and administration of beta-agonists; and develops the hypothesis that these strategies may differ in their therapeutic efficacy in treating CHF.

Potentiation of beta-adrenergic signaling by adenoviral-mediated gene transfer in adult rabbit ventricular myocytes.

Our laboratory has been testing the hypothesis that genetic modulation of the beta-adrenergic signaling cascade can enhance cardiac function. We have previously shown that transgenic mice with cardiac overexpression of either the human beta2-adrenergic receptor (beta2AR) or an inhibitor of the beta-adrenergic receptor kinase (betaARK), an enzyme that phosphorylates and uncouples agonist-bound receptors, have increased myocardial inotropy. We now have created recombinant adenoviruses encoding either the beta2AR (Adeno-beta2AR) or a peptide betaARK inhibitor (consisting of the carboxyl terminus of betaARK1, Adeno-betaARKct) and tested their ability to potentiate beta-adrenergic signaling in cultured adult rabbit ventricular myocytes. As assessed by radioligand binding, Adeno-beta2AR infection led to approximately 20-fold overexpression of beta-adrenergic receptors. Protein immunoblots demonstrated the presence of the Adeno-betaARKct transgene. Both transgenes significantly increased isoproterenol-stimulated cAMP as compared to myocytes infected with an adenovirus encoding beta-galactosidase (Adeno-betaGal) but did not affect the sarcolemmal adenylyl cyclase response to Forskolin or NaF. beta-Adrenergic agonist-induced desensitization was significantly inhibited in Adeno-betaARKct-infected myocytes (16+/-2%) as compared to Adeno-betaGal-infected myocytes (37+/-1%, P < 0.001). We conclude that recombinant adenoviral gene transfer of the beta2AR or an inhibitor of betaARK-mediated desensitization can potentiate beta-adrenergic signaling.

Monoclonal antibodies reveal receptor specificity among G-protein-coupled receptor kinases.

Guanine nucleotide-binding regulatory protein (G protein)-coupled receptor kinases (GRKs) constitute a family of serine/threonine kinases that play a major role in the agonist-induced phosphorylation and desensitization of G-protein-coupled receptors. Herein we describe the generation of monoclonal antibodies (mAbs) that specifically react with GRK2 and GRK3 or with GRK4, GRK5, and GRK6. They are used in several different receptor systems to identify the kinases that are responsible for receptor phosphorylation and desensitization. The ability of these reagents to inhibit GRK- mediated receptor phosphorylation is demonstrated in permeabilized 293 cells that overexpress individual GRKs and the type 1A angiotensin II receptor. We also use this approach to identify the endogenous GRKs that are responsible for the agonist-induced phosphorylation of epitope-tagged beta2- adrenergic receptors (beta2ARs) overexpressed in rabbit ventricular myocytes that are infected with a recombinant adenovirus. In these myocytes, anti-GRK2/3 mAbs inhibit isoproterenol-induced receptor phosphorylation by 77%, while GRK4-6-specific mAbs have no effect. Consistent with the operation of a betaAR kinase-mediated mechanism, GRK2 is identified by immunoblot analysis as well as in a functional assay as the predominant GRK expressed in these cells. Microinjection of GRK2/3-specific mAbs into chicken sensory neurons, which have been shown to express a GRK3-like protein, abolishes desensitization of the alpha2AR-mediated calcium current inhibition. The intracellular inhibition of endogenous GRKs by mAbs represents a novel approach to the study of receptor specificities among GRKs that should be widely applicable to many G-protein-coupled receptors.