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BACKGROUND: Allograft adaptation to a foreign circulation is imperfect as noted from persistent limitations to stress. Effective arterial elastance (Ea), a measure of afterload, provides an estimate of aortic impedance. End systolic elastance (Ees) is a load-independent measure of ventricular performance as well as its interaction in the periphery. The ratio (Ea to Ees) characterizes ventricular-vascular coupling; a value close to unity signifies poor mechanical efficiency. The purpose of this investigation was to correlate mechanical efficiency of work with expression of B-type natriuretic peptide BNP, a specific marker of ventricular stress and strain. METHODS: We measured BNP levels in 40 consecutive stable heart transplant recipients free from rejection. In addition, echocardiography was performed to obtain Ea, Ees, and their ratio (Ea to Ees) by the single-beat method. We examined correlates of BNP expression by assessing Ea to Ees, while correcting for mean arterial pressure, body mass index, left ventricular mass index, ejection fraction, and serum creatinine. RESULTS: BNP levels were significantly and positively correlated (r=0.38, P=.05) with an increased Ea to Ees ratio. By multivariable analysis, this relationship persisted independently (t=2.1, P=.04), while the five other measures were insignificant predictors. CONCLUSION: This investigation indicated that the transplanted heart demonstrates poor contractile efficiency and operates at maximal left ventricular work. This is paralleled by a tandem increase in BNP, suggesting that elevation in this stress peptide is at least partly explained by ventriculo-vascular uncoupling in heart transplantation, independent of alterations in blood pressure.

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BACKGROUND: Compared with cyclosporine, tacrolimus-based immunosuppression yields improved metabolic outcomes in heart transplantation. Whether corticosteroid freedom provides incremental metabolic benefits in tacrolimus and mycophenolate mofetil immunoprophylaxis remains uncertain. METHODS: In a prospective trial, 41 heart transplant patients treated with tacrolimus and mycophenolate mofetil underwent steroid weaning immediately after transplantation until weaning was complete. Weaning was interrupted only for treated rejection with or without hemodynamic compromise. Benefits of steroid weaning assessed following the first year included B-type natriuretic peptide (BNP), late infections, lipids, blood pressure, hyperglycemia, and body mass index (BMI). RESULTS: Of this 41 patient cohort (age 53 +/- 9 years, 50% black American, 35% women) followed for a total of 47 +/- 5 months, 25 had corticosteroids discontinued (62%) by an average of 20 +/- 11 months. No differences between the two groups were noted in baseline characteristics. Significant predictors of failure to wean steroids included higher rejection, BNP, and lower dose of mycophenolate mofetil. No significant benefits of steroid weaning were noted on lipids, blood pressure, hyperglycemia, and BMI. However, late infections (after 1 year) requiring hospitalizations were more frequent in the failure to wean group (0.60.4 vs 0 infections/patient/y, P <.001). INFERENCES: Unlike known metabolic benefits of steroid withdrawal with cyclosporine, heart transplant recipients treated with tacrolimus and mycophenolate mofetil demonstrate no incremental metabolic benefits, but instead experience benefits of decreased serious late infections. Furthermore, failure to discontinue corticosteroids in this series is predicted by early allograft rejection, use of lower doses of mycophenolate mofetil, and higher BNP levels suggesting poor cardiac adaptation.

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AIMS: Data on the safety and efficacy of HMG CoA reductase inhibitors in managing dyslipidemia in heart transplant recipients is inadequate. We undertook this study to evaluate the comparative safety and efficacy of simvastatin and pravastatin in lowering lipids in heart transplant recipients. METHODOLOGY: Forty eight patients (38 males) who received heart transplantation between 1995 and 1997, and who had no contraindications to statin therapy or history of myopathy were randomized to receive either pravastatin (n=24) or simvastatin (n=24) for six months. Detailed fasting lipid profiles, hepatic function tests, and serum creatinine phosphokinase were obtained regularly. Baseline and six month characteristics were compared using the unpaired student t test for continuous variables and Chi-square analysis or Fisher's exact test, as appropriate. RESULTS: Baseline total cholesterol levels, LDL cholesterol levels, HDL cholesterol levels, and triglyceride levels were similar in the two groups. At six months, the total cholesterol, LDL cholesterol, and triglyceride levels were greatly reduced in both groups, with greater reductions in the simvastatin group than in the pravastatin group. Only modest increases were noted in HDL cholesterol levels in the two groups. No significant adverse effects were noted, and no complications with drug withdrawals occurred. Patient compliance exceeded 97%. CONCLUSION: Simvastatin and pravastatin are safe and very effective in total cholesterol and LDL cholesterol lowering in heart transplant recipients, with simvastatin being more efficacious than pravastatin in lipid lowering in this group of patients.

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The available evidence suggests that while chronic inotropic support likely exerts a long-term deleterious effect on survival, their use is accompanied by short-term enhancements in symptomatology and decreases in medical resource use, thereby curtailing the overall medical costs. The decision to use chronic parenteral inotropic support should not be made lightly and must be considered only after all evidence based therapeutic options has been investigated thoroughly and tried (Fig. 1). This should include not only hemodynamic monitoring-based drug therapy but [figure: see text] also appropriate consideration for options such as heart transplantation or patient enrollment into large-scale drug trials that seek to answer pertinent issues relating to various aspects of advanced heart failure therapeutics. The use of parenteral inotropic support as a chronic bridge to transplantation is accepted widely but remains controversial in other scenarios. For instance, when refractory congestion or hypoperfusion is exhibited in the absence of any definitive medical or mechanical option, it may be wise to contemplate inotropic support after appropriate informed consent has been obtained from the patient. Lastly, it is of great importance to continually seek ways to transit the patient from this approach to a definitive therapeutic end point, such as with transition to oral beta-blockade, which may be better tolerated in the patient with advanced heart failure using an inotropic umbrella.

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We investigated the relationship of QT dispersion and cardiac allograft vasculopathy in heart transplant recipients. The findings suggest that the development of cardiac allograft vasculopathy is associated with an increase in QT dispersion, suggesting the presence of abnormal repolarization in these patients.

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The differential diagnosis of dyspnea can be overwhelming in the presence of competing diseases. The recent advent of the peptide marker brain natriuretic peptide has ushered in an era of refined diagnostic capability in heart failure. We present a clinical scenario to illustrate the usefulness of this new biomarker assay in directing appropriate therapy for heart failure. (c)2001 CHF, Inc.

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Transmyocardial laser revascularization (TLR) was initially touted as a promising therapeutic alternative for tackling the growing problem of cardiac allograft vasculopathy in late heart transplant survivors. We first described 4- and 8-week observations of application of this surgical technique, in which we professed enthusiasm for TLR in providing symptomatic relief and in reducing ischemic burden. In this report, we present the long-term (24-month) impact of TLR on clinical outcome, channel patency, and recrudescence of ischemic burden. In the long term, surgical TLR provides neither consistent symptomatic improvement nor an ameliorative effect on the natural history of cardiac allograft vasculopathy.

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Electronic home monitoring for chronic heart failure is emerging as an available option to add to our armamentarium as a vital part of the multidisciplinary care process. This investigation describes the early clinical results of a multicenter study that suggests that important trends in medical resource utilization may be attained by the use of this modality. (c)2000 by CHF, Inc.