Myocardial T1 mapping and extracellular volume quantification in patients with left ventricular non-compaction cardiomyopathy.

Aims: From pathophysiological mechanisms to risk stratification and management, much debate and discussion persist regarding left ventricular non-compaction cardiomyopathy (LVNC). This study aimed to characterize myocardial T1 mapping and extracellular volume (ECV) fraction by cardiovascular magnetic resonance (CMR), and investigate how these biomarkers relate to left ventricular ejection fraction (LVEF) and ventricular arrhythmias (VA) in LVNC. Methods and results: Patients with LVNC (n = 36) and healthy controls (n = 18) were enrolled to perform a CMR with T1 mapping. ECV was quantified in LV segments without late gadolinium enhancement (LGE) areas to investigate diffuse myocardial fibrosis. Patients with LVNC had slightly higher native T1 (1024 ± 43 ms vs. 995 ± 22 ms, P = 0.01) and substantially expanded ECV (28.0 ± 4.5% vs. 23.5 ± 2.2%, P < 0.001) compared to controls. The ECV was independently associated with LVEF (ß = -1.3, P = 0.001). Among patients without LGE, VAs were associated with higher ECV (27.7% with VA vs. 25.8% without VA, P = 0.002). Conclusion: In LVNC, tissue characterization by T1 mapping suggests an extracellular expansion by diffuse fibrosis in myocardium without LGE, which was associated with myocardial dysfunction and VA, but not with the amount of non-compacted myocardium.

The Effects of Diabetes Induction on the Rat Heart: Differences in Oxidative Stress, Inflammatory Cells, and Fibrosis between Subendocardial and Interstitial Myocardial Areas.

Diabetic cardiomyopathy (DCM) is characterized by cardiac remodeling and impaired diastolic function that may lead to heart failure. The aim of this study was to evaluate oxidative stress, inflammatory cells, and fibrosis in both subendocardial (SEN) and interstitial (INT) areas of the myocardium. Male Wistar rats were allocated to 2 groups of 9 animals, a control (CT) group and streptozotocin-induced diabetes (DM). After 8 weeks, echocardiography morphometry, protein expression, and confocal microscopy in SEN and INT areas of the left ventricle (LV) were performed. The echocardiographic analysis showed that diabetes induction leads to cardiac dilation, hypertrophy, and LV diastolic dysfunction. As compared to CT, the induction of diabetes increased inflammatory cells and fibrosis in both SEN and INT areas of DM myocardium and increased ROS generation only in SEN. Comparing the SEN and INT areas in the DM group, inflammatory cells and fibrosis in SEN were greater than in INT. In conclusion, diabetic myocardium SEN area, wherein oxidative stress was more pronounced, is more susceptible to cardiac dysfunction than INT area. This finding can be important for the understanding of the heart remodeling process occurring in DCM and perhaps to engender targeted therapies to attenuate or revert DCM-related diastolic dysfunction.

Methotrexate carried in lipid core nanoparticles reduces myocardial infarction size and improves cardiac function in rats.

PURPOSE: Acute myocardial infarction (MI) is accompanied by myocardial inflammation, fibrosis, and ventricular remodeling that, when excessive or not properly regulated, may lead to heart failure. Previously, lipid core nanoparticles (LDE) used as carriers of the anti-inflammatory drug methotrexate (MTX) produced an 80-fold increase in the cell uptake of MTX. LDE-MTX treatment reduced vessel inflammation and atheromatous lesions induced in rabbits by cholesterol feeding. The aim of the study was to investigate the effects of LDE-MTX on rats with MI, compared with commercial MTX treatment. MATERIALS AND METHODS: Thirty-eight Wistar rats underwent left coronary artery ligation and were treated with LDE-MTX, or with MTX (1 mg/kg intraperitoneally, once/week, starting 24 hours after surgery) or with LDE without drug (MI-controls). A sham-surgery group (n=12) was also included. Echocardiography was performed 24 hours and 6 weeks after surgery. The animals were euthanized and their hearts were analyzed for morphometry, protein expression, and confocal microscopy. RESULTS: LDE-MTX treatment achieved a 40% improvement in left ventricular (LV) systolic function and reduced cardiac dilation and LV mass, as shown by echocardiography. LDE-MTX reduced the infarction size, myocyte hypertrophy and necrosis, number of inflammatory cells, and myocardial fibrosis, as shown by morphometric analysis. LDE-MTX increased antioxidant enzymes; decreased apoptosis, macrophages, reactive oxygen species production; and tissue hypoxia in non-infarcted myocardium. LDE-MTX increased adenosine bioavailability in the LV by increasing adenosine receptors and modulating adenosine catabolic enzymes. LDE-MTX increased the expression of myocardial vascular endothelium growth factor (VEGF) associated with adenosine release; this correlated not only with an increase in angiogenesis, but also with other parameters improved by LDE-MTX, suggesting that VEGF increase played an important role in the beneficial effects of LDE-MTX. Overall effects of commercial MTX were minor, and did not improve LV function or infarction size. Both treatments did not induce any toxicity. CONCLUSION: The remarkable improvement in heart function and reduction in infarction size achieved by LDE-MTX supports future clinical trials.