F Fabbri

Safety and efficacy of early aggressive versus cholesterol-driven lipid-lowering strategies in heart transplantation: a pilot, randomized, intravascular ultrasound study.

BACKGROUND Statins are recommended in heart transplantation regardless of lipid levels. However, it remains unknown whether dosing should be maximized or adjusted toward a pre-defined cholesterol threshold. METHODS This pilot, randomized, open-label study compares an early maximal dose of fluvastatin (80 mg/day) with a strategy based on 20 mg/day subsequently titrated to target low-density lipoproteins (LDL) <100 mg/dl. Efficacy outcomes consisted of achieving an LDL level of <100 mg/dl at 12 months after transplant, and change in intracoronary ultrasound parameters. RESULTS Fifty-two patients were randomized. Overall safety, and efficacy in achieving LDL targets (13 [50%] vs 14 [54%]; p = 0.8) were comparable between study arms, but 17 (65%) patients needed a dose increase in the titrated-dosing arm. Early LDL levels and average LDL burden were lower in the maximal-dosing arm (p < 0.05). Few patients developed an increase in maximal intimal thickness of >0.5 mm, with numerical prevalence in the titrated-dosing arm (3 [12.5%] vs 1 [5%]; p = 0.3). Intimal volume increased in the titrated-dosing (p < 0.01) but not in the maximal-dosing arm (p = 0.1), which accordingly showed a higher prevalence of negative remodeling (p = 0.02). CONCLUSIONS Despite being as effective as the titrated-dosing approach in achieving LDL <100 mg/dl at 12 months after transplant, the maximal-dose approach was associated with a more rapid effect and with potential advantages in preventing pathologic changes in graft coronary arteries.

Reproducibility of IVUS measurements in heart transplant recipients: Increased quality of data by using dedicated software for image analysis

Cardiac allograft vasculopathy (CAV) is the major cause limiting long term graft survival after heart transplantation (HT), and is characterized by changes in coronary artery geometry, such as intimal thickening and vessel remodeling. Given the limited strategies available to reduce its impact on outcome, early diagnosis of CAV - for which intravascular ultrasound (IVUS) is the gold standard - is crucial to appropriately modulate therapy and to reduce contributing risk factors. However, a highly reproducible image-analysis method is required to capture the complex mechanisms beyond CAV-related changes in coronary geometry.