Late Changes in Maximal Intimal Thickness after Heart Transplant: Prognostic Implications and Risk Factors

PurposeIntravascular ultrasound (IVUS) provides unique prognostic information on allograft vasculopathy progression by detecting increase in maximal intimal thickness (MIT) during the first post-heart transplant (HT) year. Later changes in coronary morphology, their prognostic relevance, and risk factors are however unexplored.Methods and MaterialsWe investigated whether changes in coronary morphology assessed in patients receiving serial IVUS at 1 and 5 years after HT predicted fatal and non-fatal cardiovascular (CV) events. We additionally analyzed the impact of metabolic risk factors on changes in IVUS measurements.Results107 consecutive patients receiving HT between 1999 and 2007 entered the study. During the 11 years of follow-up, incidence of CV death was 8±3% and of CV events was 26±6%. Between year 1 and 5, MIT and intimal volume increased, lumen volume decreased (P<0.001 for all), while vessel volume was unchanged. By Cox’s model, only MIT increase was associated with subsequent CV death (RR=4.2 [1.2-12.1] per mm, P=0.03) and CV events (RR=2.6 [1.1-5.6] per mm; P=0.03). By ROC curves, we found that a MIT change cut-off of 0.35 mm best identified patients at risk for CV death and events (Figure). Among the metabolic parameters, increasing triglycerides and HDL-cholesterol ≤65mg/dl predicted MIT increase ≥ 0.35 mm (P≤0.05).ConclusionsThis study provides the first suggestive evidence that MIT increase represent a relevant prognostic marker also after the first year after HT. In addition, the finding that clinically relevant MIT is predicted by lipid pattern typical of insulin resistance, provide a strong rationale supporting aggressive therapeutic interventions against metabolic abnormalities mid and long-term after HT. Intravascular ultrasound (IVUS) provides unique prognostic information on allograft vasculopathy progression by detecting increase in maximal intimal thickness (MIT) during the first post-heart transplant (HT) year. Later changes in coronary morphology, their prognostic relevance, and risk factors are however unexplored. We investigated whether changes in coronary morphology assessed in patients receiving serial IVUS at 1 and 5 years after HT predicted fatal and non-fatal cardiovascular (CV) events. We additionally analyzed the impact of metabolic risk factors on changes in IVUS measurements. 107 consecutive patients receiving HT between 1999 and 2007 entered the study. During the 11 years of follow-up, incidence of CV death was 8±3% and of CV events was 26±6%. Between year 1 and 5, MIT and intimal volume increased, lumen volume decreased (P<0.001 for all), while vessel volume was unchanged. By Cox’s model, only MIT increase was associated with subsequent CV death (RR=4.2 [1.2-12.1] per mm, P=0.03) and CV events (RR=2.6 [1.1-5.6] per mm; P=0.03). By ROC curves, we found that a MIT change cut-off of 0.35 mm best identified patients at risk for CV death and events (Figure). Among the metabolic parameters, increasing triglycerides and HDL-cholesterol ≤65mg/dl predicted MIT increase ≥ 0.35 mm (P≤0.05). This study provides the first suggestive evidence that MIT increase represent a relevant prognostic marker also after the first year after HT. In addition, the finding that clinically relevant MIT is predicted by lipid pattern typical of insulin resistance, provide a strong rationale supporting aggressive therapeutic interventions against metabolic abnormalities mid and long-term after HT.