Increased Regional Epicardial Fat Volume Associated with Reversible Myocardial Ischemia in Patients with Suspected Coronary Artery Disease

Epicardial adipose tissue is a source of pro-inflammatory cytokines and has been linked to the development of coronary artery disease. No study has systematically assessed the relationship between local epicardial fat volume (EFV) and myocardial perfusion defects. We analyzed EFV in patients undergoing SPECT myocardial perfusion imaging combined with computed tomography (CT) for attenuation correction. Low-dose CT without contrast was performed in 396 consecutive patients undergoing SPECT imaging for evaluation of coronary artery disease. Regional thickness, cross-sectional areas, and total EFV were assessed. 295 patients had normal myocardial perfusion scans and 101 had abnormal perfusion scans. Mean EFVs in normal, ischemic, and infarcted hearts were 99.8 ± 82.3 cm3, 156.4 ± 121.9 cm3, and 96.3 ± 102.1 cm3, respectively (P < 0.001). Reversible perfusion defects were associated with increased local EFV compared to normal perfusion in the distribution of the right (69.2 ± 51.5 vs 46.6 ± 32.0 cm3; P = 0.03) and left anterior descending coronary artery (87.1 ± 76.4 vs 46.7 ± 40.6 cm3; P = 0.005). Our results demonstrate increased regional epicardial fat in patients with active myocardial ischemia compared to patients with myocardial scar or normal perfusion on nuclear perfusion scans. Our results suggest a potential role for cardiac CT to improve risk stratification in patients with suspected coronary artery disease

Erratum to: Ventricular assist device implantation improves skeletal muscle function, oxidative capacity, and growth hormone/insulin-like growth factor-1 axis signaling in patients with advanced heart failure

Background: Skeletal muscle dysfunction in patients with heart failure (HF) has been linked to impaired growth hormone (GH)/insulin-like growth factor (IGF)-1 signaling. We hypothesized that ventricular assist device (VAD) implantation reverses GH/IGF-1 axis dysfunction and improves muscle metabolism in HF. Methods: Blood and rectus abdominis muscle samples were collected during VAD implantation and explantation from patients with HF and controls. Clinical data were obtained from medical records, biomarkers measured by enzyme-linked immunosorbent assay (ELISA), and gene expression analyzed by reverse transcription and real-time polymerase chain reaction (RT-PCR). Grip strength was assessed by dynamometry. Oxidative capacity was measured using oleate oxidation rates. Muscle fiber type and size were assessed by histology. Results: Elevated GH (0.27 ± 0.27 versus 3.6 ± 7.7 ng/ml in HF; p = 0.0002) and lower IGF-1 and insulin-like growth factor binding protein (IGFBP)-3 were found in HF (IGF-1, 144 ± 41 versus 74 ± 45 ng/ml in HF, p < 0.05; and IGFBP-3, 3,880 ± 934 versus 1,935 ± 862 ng/ml in HF, p = 0.05). The GH/IGF-1 ratio, a marker of GH resistance, was elevated in HF (0.002 ± 0.002 versus 0.048 ± 0.1 pre-VAD; p < 0.0039). After VAD support, skeletal muscle expression of IGF-1 and IGFBP-3 increased (10-fold and 5-fold, respectively; p < 0.05) accompanied by enhanced oxidative gene expression (CD36, CPT1, and PGC1α) and increased oxidation rates (+1.37-fold; p < 0.05). Further, VAD implantation increased the oxidative muscle fiber proportion (38 versus 54 %, p = 0.031), fiber cross-sectional area (CSA) (1,005 ± 668 versus 1,240 ± 670 μm2, p < 0.001), and Akt phosphorylation state in skeletal muscle. Finally, hand grip strength increased 26.5 ± 27.5 % at 180 days on-VAD (p < 0.05 versus baseline). Conclusion: Our data demonstrate that VAD implantation corrects GH/IGF-1 signaling, improves muscle structure and function, and enhances oxidative muscle metabolism in patients with advanced HF

Patient-specific induced pluripotent stem cells for cardiac disease modeling

WOS: 000464646800009Reprogramming of human somatic cells to induced pluripotent stem cells (iPSCs) via induction of pluripotency genes is one of the most influential scientific breakthroughs during the last decade. Behind this breakthrough is the capacity of iPSCs to self-renew and differentiate into derivatives of all the three germ layers, similar to human embryonic stem cells. Importantly, iPSCs can be generated using somatic cells from healthy donors or patients retaining the genetic and epigenetic make-up of the donor and can be used for regenerative applications without provoking immune rejection. Given their potential use in basic and translational research, iPSCs have become an attractive cell type to create "disease-on-a-dish" models to investigate disease phenotype in vitro, to assess drug response and evaluate cardiac toxicity for drug discovery, and to develop personalized cell therapy for various diseases. Among these diseases, inherited or acquired forms of cardiovascular diseases are the most common reason of mortality worldwide. Cardiac arrhythmias and channelopathies are a distinct group of disorders caused by abnormal ion homeostasis and action potential of cardiomyocytes, accounting for a large subset of hospitalization and sudden cardiac death. Pharmacological, catheter, or medical device implants and surgical approaches have been largely applied in the clinical perspective for symptomatic treatment and to improve the quality of life for patients with arrhythmias and other heart diseases. Recently, stem-cell-based regenerative approaches have been vigorously assessed in clinical trials, and novel stem-cell-based treatments are being evaluated for their potential use to provide lasting recovery. In this book chapter, we focus on the recent progress in the application of iPSC-related research in selected channelopathies and cardiac arrhythmia modeling in vitro and their potential application in the clinical perspective