Cardiomyopathy: Recent Findings

In 1957, Wallace Brigden published an article on the Lancet, such as uncommon myocardial diseases: the non-coronary cardiomyopathy. In this article, he mentioned that “the term cardiomyopathy is used here to indicate isolated noncoronary myocardial disease.” Then “cardiomyopathy” has become a commonly used term in the cardiovascular field, and has been defined and classified by many researchers and academic societies. The basic concept of cardiomyopathy is a group of diseases with mechanical and/or electrophysiological dysfunction of the ventricles, and cardiomyopathy is distinguished with normal ischemic heart disease, valvular disease, and hypertensive heart disease. It can often cause heart failure and cardiac death. In this chapter, we describe the classification, details, and treatment of cardiomyopathy, and iPS cell from pathological myocardium

Cardiac magnetic resonance imaging-based myocardial strain study for evaluation of cardiotoxicity in breast cancer patients treated with trastuzumab: A pilot study to evaluate the feasibility of the method

Background: Trastuzumab, used to treat breast cancer overexpressing human epidermal growth factor receptor 2, may be cardiotoxic. Cardiac magnetic resonance (CMR) imaging with myocardial strain studies has been used to evaluate subclinical biventricular myocardial changes, however, its clinical utility during chemotherapy has not been evaluated. Methods: The clinical outcomes, CMR and cardiac biomarkers of 9 women aged 62.3 ± 12.6 years with early or locally advanced breast cancer were evaluated at baseline, and at 3, 6 and 12 months after the initiation of trastuzumab. Results: None of the patients developed heart failure or elevated serum cardiac biomarkers. Global left ventricular (LV) peak systolic longitudinal and circumferential strains were significantly decreased at 6 months (longitudinal strains, –21.1 ± 1.7% [baseline] vs. –19.5 ± 1.0% [6 months], p = 0.039, and circumferential strains, –23.4 ± 1.8% [baseline] vs. –21.6 ± 2.5% [6 months], p = 0.036). These changes were analogous to those observed in the LV ejection fraction. Right ventricular (RV) free wall peak systolic circumferential strains were decreased at 6 months (–20.9% ± 2.4% [baseline] vs. –19.1% ± 2.3% [6 months], p = 0.049), whereas RV longitudinal strains and ejection fraction remained unchanged. The LV longitudinal strain was the most reproducible of the 4 peak strain parameters. Conclusions: The LV longitudinal and circumferential strains measured by CMR decreased during trastuzumab therapy, although their predictive value for later heart failure or association with RV parameters was not determined. These techniques may be a useful means of diagnosing and monitoring trastuzumab-related cardiotoxicity

Promyelocytic Leukemia Zinc Finger Protein Activates GATA4 Transcription and Mediates Cardiac Hypertrophic Signaling from Angiotensin II Receptor 2

Background: Pressure overload and prolonged angiotensin II (Ang II) infusion elicit cardiac hypertrophy in Ang II receptor 1 (AT1) null mouse, whereas Ang II receptor 2 (AT2) gene deletion abolishes the hypertrophic response. The roles and signals of the cardiac AT2 receptor still remain unsettled. Promyelocytic leukemia zinc finger protein (PLZF) was shown to bind to the AT2 receptor and transmit the hypertrophic signal. Using PLZF knockout mice we directed our studies on the function of PLZF concerning the cardiac specific transcription factor GATA4, and GATA4 targets. Methodology and Principal Findings: PLZF knockout and age-matched wild-type (WT) mice were treated with Ang II, infused at a rate of 4.2 ng?kg 21?min 21 for 3 weeks. Ang II elevated systolic blood pressure to comparable levels in PLZF knockout and WT mice (140 mmHg). WT mice developed prominent cardiac hypertrophy and fibrosis after Ang II infusion. In contrast, there was no obvious cardiac hypertrophy or fibrosis in PLZF knockout mice. An AT 2 receptor blocker given to Ang II-infused wild type mice prevented hypertrophy, verifying the role of AT2 receptor for cardiac hypertrophy. Chromatin immunoprecipitation and electrophoretic mobility shift assay showed that PLZF bound to the GATA4 gene regulatory region. A Luciferase assay verified that PLZF up-regulated GATA4 gene expression and the absence of PLZF expression in vivo produced a corresponding repression of GATA4 protein. Conclusions: PLZF is an important AT2 receptor binding protein in mediating Ang II induced cardiac hypertrophy throug

Relationship between Soluble (Pro)Renin Receptor and Renin Activity in Patients with Severe Heart Failure

The (pro)renin receptor ((P)RR), which evokes renin activity with prorenin, is secreted extracellularly as soluble (P)RR (s(P)RR) and may participate in tissue renin-angiotensin system (RAS) activity in severe heart failure (HF) patients. The aim of this study was to determine whether s(P)RR is an adequate marker in severe HF patients treated with RAS inhibitors, beta-blockers, and tolvaptan. We enrolled 11 patients with severe HF between May 2013 and June 2014. First of all, furosemide of all patients was changed to tolvaptan with hydrochlorothiazide and then the treatment had been changed according to the patient’s condition. After 1, 3, 6, and 12 months, the variance of s(P)RR, plasma renin activity (PRA), plasma renin concentration (PRC), brain natriuretic peptide (BNP) and their association was investigated. Furosemide was restarted in five patients and two patients suffered cardiac death. PRA/PRC and s(P)RR were unchanged (PRA: 10.7 ± 13.9 to 12.8 ± 8.5 ng/mL/h; PRC: 347.1 ± 577.5 to 148.3 ± 123.8 pg/mL; s(P)RR: 28.2 ± 19.3 to 33.4 ± 22.4 ng/mL) and had no significant correlations (PRA and s(P)RR: p = 0.36; PRC and s(P)RR: p = 0.35). There was a significant positive correlation with a high correlation coefficient (CC) between PRA and PRC (p < 0.0001, CC = 0.76), and a negative correlation with weak CC between BNP and s(P)RR (p = 0.01, CC = −0.45). In conclusion, s(P)RR was always high and had no correlations with disease state and PRA/PRC in severe HF patients

Beneficial effects of canagliflozin in combination with pioglitazone on insulin sensitivity in rodent models of obese type 2 diabetes.

BACKGROUND:Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity. METHODS:Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF) rats. RESULTS:In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity. CONCLUSIONS:Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes