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Heart transplantation results in complete denervation of the donor heart with loss of afferent and efferent nerve connections. The majority of patients remain completely denervated during the first 6-12 months following transplantation. Evidence of reinnervation is usually found during the second year after transplantation and involve the myocardial muscle, sinoatrial node, and coronary vessels, but remains incomplete and regionally limited many years post-transplant. Restoration of cardiac innervation can improve exercise capacity as well as blood flow regulation in the coronary arteries, and hence improve quality of life. As yet, there is no evidence that the reinnervation process is associated with the occurrence of allograft-related events or survival. [ABSTRACT FROM AUTHOR]

Aims We sought to compare the complementary prognostic value of exercise treadmill testing (ETT) and coronary computed tomographic angiography (CTA) among patients referred for both exams. Methods and results We studied 582 patients without known coronary artery disease (CAD) who were clinically referred for ETT and CTA within 6 months. Patientswere followed for cardiovascular (CV) death, non-fatal myocardial infarction (MI), or late revascularization (.90 days), stratified by Duke Treadmill Score (DTS) and CAD severity (≥50% stenosis). Mean age was 54+13 years (63% male). In median follow-up of 40 months, therewere 3 CV deaths, 7 non-fatal MIs, and 26 late revascularizations. ETTwas inconclusive in 23%, positive in 31%, and negative in 46%.CTAdemonstrated noCADin 37%, nonobstructive CADin 28%, and obstructive CADin 35%. Among low-risk ETT patients (n ¼ 326), therewere 3 MI, 10 late revascularizations, and the frequent presence of non-obstructive (32%, n ¼ 105) and obstructive CAD (27%, n ¼ 88). When present, ETT features (i.e. angina, DTS, ischaemic electrocardiogram changes, and exercise capacity) individually failed to predict CV death/MI after adjustment for Morise score. Conversely, both obstructive CAD [HR 4.9 (1.0-23.3), P ¼ 0.048] and CAD extent by segment involvement score .4 [HR 3.9 (1.0-15.2), P ¼ 0.049] predicted increased risk for CV death or MI. Conclusion Patients with a low-risk ETT have an excellent prognosis at 40 months, despite the frequent presence of non-obstructive (32%) and obstructive (27%) CAD. In patients with an intermediate- to high-risk ETT (DTS ,5), CTA can provide incremental risk stratification for future CV events. [ABSTRACT FROM AUTHOR]

Objectives: This study tested the hypothesis that 4-[18F]fluorophenyltriphenylphosphonium (18F-TPP) is useful for in vivo positron emission tomography (PET) measurement of mitochondrial membrane potential (ΔΨm). Its utility as a blood flow tracer also was evaluated. Background: Tetraphenylphosphonium is useful for in vitro measurement of ΔΨm. In vivo measurement of ΔΨm has potential value in the assessment of heart failure pathophysiology and therapy as well as assessment of myocardial viability and so may be a very useful clinical tool. Methods: Anesthetized swine (N = 6) with a balloon catheter in the left anterior descending coronary artery were studied. Microsphere measurements of myocardial blood flow (MBF) were made after balloon inflation (baseline) and ∼10 min after intravenous administration of adenosine and phenylephrine after which ∼10 mCi 18F-TPP was injected intravenously and dynamic PET data acquisition obtained for 30 min. After the swine were killed, the hearts were sectioned for microsphere measurement of MBF and 18F-TPP measured by well counter in these same samples. PET images provided whole blood and myocardial 18F-TPP concentration for determination of ΔΨm by the Nernst equation, corrected for nonspecific 18F-TPP binding. Microsphere MBF, absolute (ml/min/g) and relative, was compared with PET data (standard uptake value and K1). Results: Nonspecific binding of 18F-TPP overestimated ΔΨm measured by −37 ± 4 mV (mean ± SD). Normal zone ΔΨm of ex vivo samples (−91 ± 11 mV; N = 52; sample weight, 1.07 ± 0.18 g) correlated strongly (R2= 0.93) with normal zone by PET (−81 ± 13 mV). Both ex vivo and PET normal zone ΔΨm, although somewhat lower, compared well with that reported for tritium labeled triphenylphosphonium in normal working Langendorff rat heart (−100 mV). Although the relative MBF by 18F-TPP correlated strongly with relative microsphere MBF (R2= 0.83), there was no correlation between absolute MBF by 18F-TPP and microsphere MBF. Conclusions: 18F-TPP is a promising tracer for noninvasive PET measurement of ΔΨm in living subjects. It is useful as well for assessment of relative but not absolute MBF. [Copyright &y& Elsevier]

Objectives: The authors tested the hypothesis that exercise treadmill testing (ETT)–induced ST-segment elevation (STE) in electrocardiographic lead aVR is an important indicator of significant left main coronary artery (LMCA) or ostial left anterior descending coronary artery (LAD) stenosis. Background: Although STE in lead aVR is an indicator of LMCA or very proximal LAD occlusion in acute coronary syndromes, its predictive power in the setting of ETT is uncertain. Methods: Rest and stress electrocardiograms, clinical and stress test parameters, and single photon-emission computed tomographic myocardial perfusion imaging (MPI) data, when available, were obtained in 454 subjects (378 with MPI) who underwent cardiac catheterization and standard Bruce ETT ≤ 6 months before catheterization. Patients were selected for LMCA or ostial LAD disease (≥50% stenosis) with or without other coronary artery disease (CAD), CAD (≥70% stenosis) without significant LMCA or ostial LAD, or no significant CAD. Univariate followed by multivariate logistic regression analyses of clinical, electrocardiographic, stress test, and single photon-emission computed tomographic MPI variables were used to identify significant correlates of LMCA or ostial LAD stenosis. Bayesian analysis of the data also was performed. Results: LMCA (n = 38) or ostial LAD (n = 42) stenosis occurred in 75 patients (5 patients had both). The remainder had CAD without LMCA or ostial LAD stenosis (n = 276) or no CAD (n = 103). In multivariate analysis, the strongest predictor was stress-induced STE in lead aVR (p < 0.0001, area under the curve 0.82). Both left ventricular ejection fraction (after stress) and percent reversible LAD ischemia on single photon-emission computed tomographic MPI also contributed significantly in multivariate analysis (p < 0.005 and p < 0.05, respectively, areas under the curve 0.60 and 0.64, respectively). Although additional electrocardiographic, stress test, and MPI variables were significant univariate predictors, none was statistically significant in multivariate analysis. At 1-mm STE in lead aVR, sensitivity for LMCA or ostial LAD stenosis was 75%, specificity was 81%, overall predictive accuracy was 80%, and post-test probability increased nearly 3 times from 17% to 45%. Conclusions: Stress (ETT)–induced STE in lead aVR is an important indicator of significant LMCA or ostial LAD stenosis and should not be ignored. [Copyright &y& Elsevier]