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We studied 361 patients, to evaluate risk factors for cardiac allograft vasculopathy (CAV) onset and severity/diffusion in heart transplantation (HT). Rejection scores (RS) on endomyocardial biopsy were calculated (first year and whole follow-up). CAV onset was defined as any lesion seen at yearly angiography. A CAV severity/diffusion index was calculated for each patient summing up the scores of all lesions. Cox multivariate analysis included: donor age, sex, and weight; recipient sex, age, pre-HT diagnosis, hypertension, diabetes and hyperlipidemia post-HT; number of treated rejections and RS; and immunosuppressive dosage at 3, 6, and 12 months. CAV frequency was 2% at 1 year, 22% at 5 and 39% at 10 years. Risk factors for CAV onset were older donor age [p < 0.0001, relative risk (RR) = = 9.9], male donor (p < 0.001, RR = = 3.2), high RS for severe (≥ 3A) grades (p < 0.02, RR = = 2.01), high cyclosporine at 3 months (p < 0.02, RR = = 1.9). Risk factors for CAV severity/diffusion were higher donor weight (p < 0.01, RR = = 7.5), high prednisone dosage at 1 year (p < 0.0001, RR = = 21.1), and coronary disease pre-HT (p < 0.002, RR = = 9.7). High RS was an independent predictor for CAV onset, not severity/diffusion. This suggests an immune basis for CAV onset and nonimmune modulation for progression. High RS for severe grades may provide a predictor for patients at risk.

Background-We assessed coronary flow velocity pattern and coronary flow reserve (CFR) by contrast-enhanced transthoracic echocardiography (CE-TTE) as markers of major adverse cardiac events (MACE) related to cardiac allograft vasculopathy (CAV) after heart transplantation (HT). Methods and Results-Deceleration time of diastolic flow velocity (DDT) and CFR were measured in the left anterior descending coronary artery (LAD) by CE-TTE in 66 consecutive HT patients (follow-up 19Ϯ5 months). CFR was calculated as the ratio of hyperemic to basal diastolic flow velocity. Angiographies were analyzed by a qualitative grading system; CAV was defined as changes grade II or higher. MACE were cardiac death, stent implantation, and heart failure. Patients with MACE had higher CAV incidence (Pϭ0.004) and grade (Pϭ0.008), shorter DDT (Pϭ0.006), and lower CFR (Pϭ0.008).A receiver-operating characteristic-derived DDT cutpoint Յ840 ms (area under the curve 0.793; Pϭ0.01) was 75% specific and 86% sensitive for predicting MACE, with positive predictive value (PPV) and negative predictive value (NPV) of 33% and 97%, respectively (Pϭ0.002). A CFR cutpoint of Յ2.6 (area under the curve 0.746; Pϭ0.01) was 62% specific and 91% sensitive for predicting MACE (PPV ϭ32%, NPV ϭ97%) (Pϭ0.001). Patients with CFR Յ2.6 and patients with DDT Յ840 ms had a lower survival free from MACE (Pϭ0.006 and Pϭ0.009, respectively). By Cox regression, only a lower CFR predicted the risk of MACE (relative risk 3.1; 95% CI, 1.26 to 7.9; Pϭ0.01). Conclusions-In

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