Lack of usefulness of electron beam computed tomography for detecting coronary allograft vasculopathy.

Fifty-five patients with cardiac allografts were studied by electron beam computed tomography for coronary calcification (EBCT CC) and coronary arteriography, and from the latter, a coronary index was calculated using the size, degree of obstruction, and linear extent of disease of each vessel. There was a significant correlation between EBCT CC score and coronary index, but receiver-operating characteristic (ROC) analysis demonstrated unsatisfactory performance of EBCT CC, and 6 patients had no coronary calcification despite having very abnormal coronary indexes. There are pathologic differences between coronary allograft vasculopathy and atherosclerosis, and correspondingly, EBCT CC has limited usefulness in the cardiac transplant population.

Pulmonary hypertension in type 1 Gaucher's disease: genetic and epigenetic determinants of phenotype and response to therapy.

Type 1 Gaucher's disease (GD) is recognized for striking but unexplained phenotypic diversity. Rarely, severe pulmonary hypertension (PH) may occur in GD but its clinical spectrum, determinants or its response to enzyme replacement therapy (ERT)+/-vasodilators is not known. One hundred and thirty-four consecutive patients with Type 1 GD were screened to estimate right ventricular systolic pressure (RVSP) by Doppler echocardiography. Ninety-four patients were on ERT and 40 were untreated. Eight additional GD patients were studied that represented consecutive tertiary referrals with severe PH. Angiotensin converting enzyme (ACE) gene polymorphisms and acid beta-glucosidase gene (GBA) mutations were determined by DNA analysis. Mild, asymptomatic PH (RVSP>35<50 mmHg) was prevalent in Type 1 GD: 30% in untreated patients and 7.4% among patients receiving ERT (P<0.001). Splenectomy was strongly associated with severe, life-threatening PH: all patients with severe PH (RVSP 50-130 mmHg) were asplenic compared to only 31% of patients with RVSP<50 mmHg (Odds ratio [OR] 28.8, 95% CI 1.6-531.6, P<0.001). Other characteristics of patients presenting with severe PH were poor compliance to ERT (4/9 patients) or no ERT (5/9 patients), a family history of a sib with GD and PH (2/2 patients), an excess of ACE I allele (OR 2.3, 95% CI 1.1-4.9, P=0.034) and an excess of non-N370S GBA mutation (OR 6.0, 95% CI 1.1-33, P=0.003). Severe PH was ameliorated by ERT+/-vasodilators during 4.6+/-4.0 yr (range 1-12 yr) follow-up; three patients were initially considered for lung transplantation but improved such that they are no longer active transplant candidates. Our study reveals a remarkable predisposition for PH in type 1 GD. Progression to severe, life-threatening PH occurs in the presence of additional genetic factors (non-N370S GBA mutation, positive family history, and ACE I gene polymorphism) and epigenetic modifiers (i.e., asplenia and female sex). Splenectomy should be avoided and in high-risk patients, ERT+/-vasodilators/coumadin should be initiated.