Background: Diabetes mellitus type 2 (DM2) is a risk factor for developing heart failure but there is no specific therapy for diabetic heart disease. Sodium glucose transporter 2 inhibitors (SGLT2I) are recently developed diabetic drugs that primarily work on the kidney. Clinical data describing the cardiovascular benefits of SGLT2Is highlight the potential therapeutic benefit of these drugs in the prevention of cardiovascular events and heart failure. However, the underlying mechanism of protection remains unclear. We investigated the effect of Dapagliflozin-SGLT2I, on diabetic cardiomyopathy in a mouse model of DM2. Methods: Cardiomyopathy was induced in diabetic mice (db/db) by subcutaneous infusion of angiotensin II (ATII) for 30 days using an osmotic pump. Dapagliflozin (1.5 mg/kg/day) was administered concomitantly in drinking water. Male homozygous, 12-14 weeks old WT or db/db mice (n = 4-8/group), were used for the experiments. Isolated cardiomyocytes were exposed to glucose (17.5-33 mM) and treated with Dapagliflozin in vitro. Intracellular calcium transients were measured using a fluorescent indicator indo-1. Results: Angiotensin II infusion induced cardiomyopathy in db/db mice, manifested by cardiac hypertrophy, myocardial fibrosis and inflammation (TNFα, TLR4). Dapagliflozin decreased blood glucose (874 ± 111 to 556 ± 57 mg/dl, p < 0.05). In addition it attenuated fibrosis and inflammation and increased the left ventricular fractional shortening in ATII treated db/db mice. In isolated cardiomyocytes Dapagliflozin decreased intracellular calcium transients, inflammation and ROS production. Finally, voltage-dependent L-type calcium channel (CACNA1C), the sodium-calcium exchanger (NCX) and the sodium-hydrogen exchanger 1 (NHE) membrane transporters expression was reduced following Dapagliflozin treatment. Conclusion: Dapagliflozin was cardioprotective in ATII-stressed diabetic mice. It reduced oxygen radicals, as well the activity of membrane channels related to calcium transport. The cardioprotective effect manifested by decreased fibrosis, reduced inflammation and improved systolic function. The clinical implication of our results suggest a novel pharmacologic approach for the treatment of diabetic cardiomyopathy through modulation of ion homeostasis.

Absence of early ST segment elevation resolution after angiographically successful primary PTCA identifies patients who are less likely to benefit from the early restoration of flow in the IRA, probably because of microvascular damage and subsequently less myocardial salvage.

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BackgroundThe efficacy of disease management programs in improving the outcome of heart failure patients remains uncertain and may vary across health systems. This study explores whether a countrywide disease management program is superior to usual care in reducing adverse health outcomes and improving well-being among community-dwelling adult patients with moderate-to-severe chronic heart failure who have universal access to advanced health-care services and technologies.MethodsIn this multicenter open-label trial, 1,360 patients recruited after hospitalization for heart failure exacerbation (38%) or from the community (62%) were randomly assigned to either disease management or usual care. Disease management, delivered by multi-disciplinary teams, included coordination of care, patient education, monitoring disease symptoms and patient adherence to medication regimen, titration of drug therapy, and home tele-monitoring of body weight, blood pressure and heart rate. Patients assigned to usual care were treated by primary care practitioners and consultant cardiologists.The primary composite endpoint was the time elapsed till first hospital admission for heart failure exacerbation or death from any cause. Secondary endpoints included the number of all hospital admissions, health-related quality of life and depression during follow-up. Intention-to-treat comparisons between treatments were adjusted for baseline patient data and study center.ResultsDuring the follow-up, 388 (56.9%) patients assigned to disease management and 387 (57.1%) assigned to usual care had a primary endpoint event. The median (range) time elapsed until the primary endpoint event or end of study was 2.0 (0–5.0) years among patients assigned to disease management, and 1.8 (0–5.0) years among patients assigned to usual care (adjusted hazard ratio, 0.908; 95% confidence interval, 0.788 to 1.047). Hospital admissions were mostly (70%) unrelated to heart failure.Patients assigned to disease management had a better health-related quality of life and a lower depression score during follow-up.ConclusionsThis comprehensive disease management intervention was not superior to usual care with respect to the primary composite endpoint, but it improved health-related quality of life and depression. A disease-centered approach may not suffice to make a significant impact on hospital admissions and mortality in patients with chronic heart failure who have universal access to health care.Clinical trial registrationClinicaltrials.gov identifier: NCT00533013. Trial registration date: 9 August 2007. Initial protocol release date: 20 September 2007.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0855-z) contains supplementary material, which is available to authorized users.

AimsEndothelial function is impaired in advanced chronic heart failure (ACHF) patients. We explored a possible association between endothelial function and subsequent mortality risk in ACHF. Methods and resultsWe prospectively assessed brachial flow-mediated dilation (FMD) in 82 consecutive New York Heart Association class IV ischaemic ACHF patients with a mean left ventricular ejection fraction (LVEF) of 22 + 3%. Following overnight fasting and discontinuation of all medications for !12 h, percent increase in FMD (%FMD) and nitroglycerinmediated vasodilation were assessed using linear array ultrasound. All patients were followed for 14 + 2 months for adverse cardiovascular events, including death, hospitalization for CHF exacerbation, or myocardial infarction. Patients were divided into two groups: those with an FMD lesser than or equal to the median %FMD of 4.6% (n ¼ 41) and those with an FMD above the median (n ¼ 41). Both groups were comparable regarding cardiovascular risk factors, LVEF, and concomitant medications. During follow-up, 22 (53.6%) patients with FMD lesser than or equal to the median had composite adverse cardiovascular events compared with only eight patients (19.5%) with FMD above the median (P , 0.01). Furthermore, fiver deaths (12.1%) occurred in patients with FMD lesser than or equal to the median, compared with no deaths in patients with FMD above the median (P , 0.03). Cox regression analyses revealed that FMD was an independent predictor for these events. ConclusionFlow-mediated dilation is associated with increased mortality risk in ischaemic ACHF patients.--

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