Clinical heart transplantation
Determinants of Coronary Flow Reserve in Heart Transplantation: A Study Performed With Contrast-enhanced Echocardiography

https://doi.org/10.1016/j.healun.2009.02.008Get rights and content

Background

Determination of coronary flow reserve (CFR) is increasingly being used in cardiac allograft vasculopathy (CAV). We aimed to identify determinants of CFR in heart transplantation (HT).

Methods

CFR was measured by transthoracic echocardiography in 119 HT recipients (97 men, 22 women; 50 ± 12 years of age at HT and 8 ± 5 years post-HT). CFR was expressed as the ratio of hyperemic (adenosine infusion at a rate of 0.14 mg/kg) to basal diastolic flow velocity. Rejection scores (RS) on endomyocardial biopsy were calculated. Angiographic CAV was analyzed using a qualitative grading system. The coronary tree was divided into 17 traits and a CAV severity/diffusion index (SDI) was calculated for each patient, summing the scores assigned to all lesions.

Results

Upon multivariate analysis, CFR was related to CAV (p = 0.001), interventricular septum thickness (p = 0.01), ischemic heart disease pre-HT (p = 0.02) and SDI and SDI/segment number (p < 0.0001 and p = 0.003, respectively). In patients without CAV, CFR was related only to RS for severe grades (p = 0.01).

Conclusions

Left ventricular hypertrophy, CAV and its severity/diffusion independently contribute to reduced CFR. In patients without angiographic CAV, CFR was only independently related to RS. Because a high rejection burden is associated with increased risk of CAV, CFR reduction may be an early marker of CAV. Microvascular dysfunction may contribute to the late morbidity and mortality seen in HT.

Section snippets

Study Patients

We studied 119 consecutive HT recipients (97 men, 22 women; median age 55 years at HT, range 9 to 73 years). Median post-HT follow-up at study entry was 8.5 years (range 13 months to 19 years). Our immunosuppression protocol consisted of cyclosporine, azathioprine and steroids (triple therapy), as previously detailed.2, 8 Cytomegalovirus (CMV) serostatus (IgG-positive or IgG-negative) of all donors and recipients was analyzed before HT. The study was approved by the institutional ethics

Baseline Clinical and Diagnostic Features

The baseline features of recipients and donors are shown in Table 1. Echocardiographic regional wall motion abnormalities were not detected. Age and time from HT were comparable in patients with and without abnormal angiography (49 ± 11 vs 51 ± 13 years [p = 0.5] and 8 ± 3 vs 7 ± 3 years [p = 0.4], respectively). Ejection fraction was normal in all patients (73 ± 8%). All patients studied were maintained on a cyclosporine (95%) or tacrolimus (5%) and azathioprine (70%) or mycophenolate

Discussion

This study demonstrates, for the first time, that rejection score is an independent determinant of CFR in HT patients. In addition, recognized determinants of CFR have been confirmed.7

CAV is a diffuse process involving the entire coronary circulation, including microvessels.2 In the present study, CFR impairment in patients with CAV may have been related by hemodynamically significant LAD stenosis. Indeed, it has been shown in several studies that endothelium-dependent and -independent CFR is

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