Clinical and Functional Correlates of Early Microvascular Dysfunction After Heart Transplantation
ABSTRACT BACKGROUND: -Microvascular dysfunction is emerging as a strong predictor of outcome in heart transplant recipients. At this time, the determinants and consequences of early microvascular dysfunction are not well established. The objective of the study was to determine risk factors and functional correlates associated with early microvascular dysfunction in heart transplant recipients. METHODS AND RESULTS: -Sixty-three heart transplant recipients who had coronary physiology assessment, right heart catheterization and echocardiography performed at the time of their first annual evaluation were included in the study. Microvascular dysfunction was assessed using the recently described index of microcirculatory resistance (IMR). The presence of microvascular dysfunction, pre-defined by an IMR > 20, was observed in 46% of patients at 1 year. A history of acute rejection and undersized donor hearts were associated with microvascular dysfunction at 1 year with an OR=4.0 (1.3-12.8) and OR=3.6 (1.2-11.1), respectively. Patients with microvascular dysfunction had lower cardiac index (3.1 ± 0.7 vs. 3.5 ± 0.7 L/min/m(2), p=0.02), and mild graft dysfunction measured by echocardiography-derived left and right myocardial performance indices [(0.54 ± 0.09 vs. 0.43 ± 0.09, p< 0.01) and (0.47 ± 0.14 vs. 0.32 ± 0.05, p< 0.01), respectively]. Microvascular dysfunction was also associated with a higher likelihood of death, graft failure or allograft vasculopathy at 5 years post transplant (hazard ratio of 2.52, 95% confidence interval between 1.04 and 5.91). CONCLUSIONS: -A history of acute rejection during the first year and smaller donor hearts were identified as risk factors for early microvascular dysfunction. Microvascular dysfunction assessed using IMR at 1 year was also associated with worse graft function and possibly worse clinical outcomes.
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ABSTRACT: Endothelial progenitor cells (EPCs) are implicated in protection against vascular disease. However, studies using angiography alone have reported conflicting results when relating EPCs to epicardial coronary artery disease (CAD) severity. Moreover, the relationship between different EPC types and the coronary microcirculation is unknown. We therefore investigated the relationship between EPC populations and coronary epicardial and microvascular disease. Thirty-three patients with a spectrum of isolated left anterior descending artery disease were studied. The coronary epicardial and microcirculation were physiologically interrogated by measurement of fractional flow reserve (FFR), index of microvascular resistance (IMR) and coronary flow reserve (CFR). Two distinct EPC populations (early EPC and late outgrowth endothelial cells [OECs]) were isolated from these patients and studied ex vivo. There was a significant inverse relationship between circulating OEC levels and epicardial CAD severity, as assessed by FFR and angiography (r = 0.371, p = 0.04; r = -0.358, p = 0.04; respectively). More severe epicardial CAD was associated with impaired OEC migration and tubulogenesis (r = 0.59, p = 0.005; r = 0.589, p = 0.004; respectively). Patients with significant epicardial CAD (FFR<0.75) had lower OEC levels and function compared to those without hemodynamically significant stenoses (p<0.05). In contrast, no such relationship was seen for early EPC number and function, nor was there a relationship between IMR and EPCs. There was a significant relationship between CFR and OEC function. EPC populations differ in regards to their associations with CAD severity. The number and function of OECs, but not early EPCs, correlated significantly with epicardial CAD severity. There was no relationship between EPCs and severity of coronary microvascular disease.PLoS ONE 04/2014; 9(4):e93980. DOI:10.1371/journal.pone.0093980 · 3.53 Impact Factor
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ABSTRACT: Background Implementation of reliable noninvasive testing for screening cardiac allograft vasculopathy (CAV) is of critical importance. The most widely used modality, dobutamine stress echocardiography (DSE), has moderate sensitivity and specificity. The aim of this study was to assess the potential role of serial coronary flow reserve (CFR) assessment together with DSE for predicting CAV. Methods A total of 90 studies were performed prospectively over 5 years in 23 consecutive heart transplant recipients who survived >1 year after transplantation. Assessment of CFR with transthoracic Doppler echocardiography, DSE, coronary angiography, and endomyocardial biopsy was performed annually. Results of CFR assessment and DSE were compared with angiographic findings of CAV. Results Acute cellular rejections were excluded by endomyocardial biopsies. CAV was detected in 17 of 90 angiograms. Mean CFR was similarly lower in both mild (CAV grade 1) and more severe (CAV grades 2 and 3) vasculopathy, but wall motion score index became higher in parallel with increasing grades of vasculopathy. Any CAV by angiography was detected either simultaneously with or later than CFR impairment, yielding 100% sensitivity for CFR. The combination of CFR and DSE increased the specificity of the latter from 64.3% to 87.2% without compromising sensitivity (77.8%). Conclusions CFR is very sensitive for detecting CAV and increases the diagnostic accuracy of DSE, raising the potential for patient management tailored to risk modification and to avoid unnecessary angiographic procedures.Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 01/2014; DOI:10.1016/j.echo.2014.01.020 · 3.99 Impact Factor
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ABSTRACT: To evaluate the diagnostic performance of multiparametric cardiovascular magnetic resonance (CMR) for detecting cardiac allograft vasculopathy (CAV) using contemporary invasive epicardial artery and microvascular assessment techniques as reference standards, and to compare the performance of CMR with that of angiography. CAV continues to limit the long-term survival of heart transplant recipients. Coronary angiography has a class I recommendation for CAV surveillance and annual or biannual surveillance angiography is performed routinely in most centers. All transplant recipients referred for surveillance angiography at a single UK center over a 2-year period were prospectively screened for study eligibility. Patients prospectively underwent coronary angiography followed by coronary intravascular ultrasound, fractional flow reserve and index of microcirculatory resistance. Within one month patients underwent multiparametric CMR, including assessment of regional and global ventricular function, absolute myocardial blood flow quantification and myocardial tissue characterization. In addition, 10 healthy volunteers underwent CMR. Forty-eight patients were recruited; median 7.1 years (IQR 4.6-10.3) since transplantation. CMR myocardial perfusion reserve was the only independent predictor of both epicardial (β = -0.57, p<0.001) and microvascular disease (β = -0.60, p<0.001) on stepwise multivariable regression. CMR myocardial perfusion reserve significantly outperformed angiography for detecting moderate CAV (AUC 0.89 (0.79-1.0) v 0.59 (0.42-0.77), p=0.01) and severe CAV (AUC 0.88 (0.78-0.98) v 0.67 (0.52-0.82), p=0.05). CAV, including epicardial and microvascular components, can be detected more accurately using non-invasive CMR-based absolute myocardial blood flow assessment than with invasive coronary angiography, the current clinical surveillance technique.Journal of the American College of Cardiology 12/2013; 63(8). DOI:10.1016/j.jacc.2013.07.119 · 15.34 Impact Factor