👤 Karianne Backx

The clinical outcomes of noncompaction cardiomyopathy (NCCM) range from asymptomatic to heart failure, arrhythmias, and sudden cardiac death. Genetics play an important role in NCCM. This study investigated the correlations among genetics, clinical features, and outcomes in adults and children diagnosed with NCCM. A retrospective multicenter study from 4 cardiogenetic centers in the Netherlands classified 327 unrelated NCCM patients into 3 categories: 1) genetic, with a mutation in 32% (81 adults; 23 children) of patients; 2) probably genetic, familial cardiomyopathy without a mutation in 16% (45 adults; 8 children) of patients; or 3) sporadic, no family history, without mutation in 52% (149 adults; 21 children) of patients. Clinical features and major adverse cardiac events (MACE) during follow-up were compared across the children and adults. MYH7, MYBPC3, and TTN mutations were the most common mutations (71%) found in genetic NCCM. The risk of having reduced left ventricular (LV) systolic dysfunction was higher for genetic patients compared with the probably genetic and sporadic cases (p = 0.024), with the highest risk in patients with multiple mutations and TTN mutations. Mutations were more frequent in children (p = 0.04) and were associated with MACE (p = 0.025). Adults were more likely to have sporadic NCCM. High risk for cardiac events in children and adults was related to LV systolic dysfunction in mutation carriers, but not in sporadic cases. Patients with MYH7 mutations had low risk for MACE (p = 0.03). NCCM is a heterogeneous condition, and genetic stratification has a role in clinical care. Distinguishing genetic from nongenetic NCCM complements prediction of outcome and may lead to management and follow-up tailored to genetic status. Show less

An important mechanism by which physical activity reduces the risk of cardiovascular disease is through regulating plasma lipids. We investigated whether low-intensity exercise modulates lipid metabolism and the transcription factors peroxisome proliferator-activated receptor gamma (PPARgamma) and liver X receptor alpha (LXRalpha) responsible for controlling reverse cholesterol transport (RCT). Thirty-four sedentary adults, mean age 45.6 +/- 11.1 yr, participated in an 8-wk low-intensity exercise program consisting of walking 10,000 steps, three times a week. Subjects were randomly allocated to either an exercise group or a sedentary control group, and serum lipid or lipoprotein concentrations were determined. Compared with controls, there was a significant decrease in total cholesterol (preexercise, 5.73 +/- 1.39 mmol x L; postexercise, 5.32 +/- 1.28 mmol x L) and a significant increase in HDL (preexercise, 1.46 +/- 0.47 mmol x L; postexercise, 1.56 +/- 0.50 mmol x L) after the exercise program. There was a significant increase in serum oxidized LDL (oxLDL) concentrations in the exercise group before and after exercise (0 wk, 554 +/- 107 ng x mL; 4 wk, 698 +/- 134 ng x mL; 8 wk, 588 +/- 145 ng x mL). A significant increase in leukocyte mRNA expression for PPARgamma (4 wk, 1.8 +/- 0.9-fold; 8 wk, 4.3 +/- 1.9-fold) was observed, which was reinforced by increased PPARgamma DNA-binding activity postexercise (preexercise, 0.22 +/- 0.09 OD units; postexercise, 1.13 +/- 0.29 OD units). A significant increase in gene expression was observed for the oxLDL scavenger receptor CD36 (4 wk, 3.8 +/- 0.6-fold; 8 wk, 2.7 +/- 0.5-fold) and LXRalpha (8 wk, 3.5 +/- 0.8-fold). Two LXRalpha-regulated genes involved in RCT, namely, ATP-binding cassette transporters A1 and GI (ABCA1 and ABCG1, respectively), were significantly up-regulated postexercise (8 wk: ABCA1, 3.46 +/- 0.56-fold; ABCG1, 3.06 +/- 0.47-fold). We propose that the net effect of these changes may be to increase oxLDL uptake, to stimulate RCT, and thus to promote clearance of proatherogenic lipids from the vasculature, ultimately contributing to the cardiovascular benefits of low-intensity aerobic exercise. Show less