Circulation

Background: Patients with heart failure and reduced ejection fraction (HFrEF) will experience multiple hospitalizations for heart failure during the course of their disease. We assessed the efficacy of dapagliflozin on reducing the rate of total (i.e. first and repeat) hospitalizations for heart failure in the Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). Methods: The total number of HF hospitalizations and cardiovascular deaths was examined using the proportional rates approach of Lei-Wei-Ying-Yang (LWYY) and a joint frailty model for each of recurrent HF hospitalizations and time to cardiovascular death...

Background: Sodium/glucose co-transporter 2 (SGLT2) inhibitors exert robust cardioprotective effects against heart failure in diabetes patients and there is intense interest to identify the underlying molecular mechanisms that afford this protection. As the induction of the late component of the cardiac sodium channel current (late-INa ) is involved in the etiology of heart failure, we investigated whether these drugs inhibit late-INa . Methods: Electrophysiological, in silico molecular docking, molecular, calcium imaging and whole heart perfusion techniques were employed to address this question...

Perioperative stroke is a potentially devastating complication in patients undergoing noncardiac, nonneurological surgery. This scientific statement summarizes established risk factors for perioperative stroke, preoperative and intraoperative strategies to mitigate the risk of stroke, suggestions for postoperative assessments, and treatment approaches for minimizing permanent neurological dysfunction in patients who experience a perioperative stroke. The first section focuses on preoperative optimization, including the role of preoperative carotid revascularization in patients with high-grade carotid stenosis and delaying surgery in patients with recent strokes...

Background: Target lesion failure remains an issue with contemporary drug eluting stents. Thus, the dual therapy sirolimus-eluting and CD34+ antibody coated Combo stent (DTS) was designed to further improve early healing. The aim of this study was to investigate whether the DTS is non-inferior to the sirolimus-eluting Orsiro stent (SES) in an all-comers patient population. Methods: The SORT OUT X trial, was a large-scale randomized, multicenter, single-blind, two-arm, non-inferiority trial with registry-based follow-up...

Background: Cardiac hypertrophy is an independent risk factor for heart failure, a leading cause of morbidity and mortality globally. The calcineurin/NFAT (nuclear factor of activated T cells) pathway and the MAPK/Erk (extracellular signal-regulated kinase) pathway contribute to the pathogenesis of cardiac hypertrophy as an inter-dependent network of signaling cascades. However, how these pathways interact remains unclear, and specifically few direct targets responsible for the pro-hypertrophic role of NFAT have been described...

Background: Vein graft failure remains a common clinical challenge. We applied a systems approach in mouse experiments to discovering therapeutic targets for vein graft failure. Methods: Global proteomics and high-dimensional clustering on multiple vein graft tissues were used to identify potential pathogenic mechanisms. The peroxisome proliferator-activated receptors (PPARs) pathway served as an example to substantiate our discovery platform. In vivo mouse experiments with macrophage-targeted PPARα siRNA and the novel, selective activator pemafibrate demonstrate the role of PPARα in the development and inflammation of vein graft lesions...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Background: Accelerated endothelial healing after targeted antiproliferative drug delivery may limit the long-term inflammatory response of drug eluting stents (DES). The novel SupremeTM DES (Supreme) is designed to synchronize early drug delivery within 4-6 weeks of implantation, leaving behind a pro-healing permanent base layer. Whether the Supreme DES is safe and effective in the short term and can improve long term clinical outcomes is not known. Methods: In an international 2:1 randomized single-blind trial, we compared treatment with Supreme DES to durable polymer everolimus-eluting stents (DP-DES) in patients with acute and chronic coronary syndromes...

Background: Left atrial appendage (LAA) occlusion provides an alternative to oral anticoagulation (OAC) for thromboembolic risk reduction in patients with non-valvular atrial fibrillation (NVAF). Since regulatory approval in 2015, the WATCHMAN device has been the only LAA closure device available for clinical use in the United States. The PINNACLE FLX study evaluated the safety and effectiveness of the next-generation WATCHMAN FLX LAA closure device in patients with NVAF in whom OAC is indicated, but who have an appropriate rationale to seek a non-pharmaceutical alternative...

No abstract text is available yet for this article.

Background: The role of epicardial fat (eFat)-derived extracellular vesicles (EVs) in the pathogenesis of atrial fibrillation (AF) has never been studied. We tested the hypothesis that eFat-EVs transmit proinflammatory, profibrotic, and proarrhythmic molecules that induce atrial myopathy and fibrillation. Methods: We collected eFat specimens from patients with (n=32) and without AF (n=30) during elective heart surgery. eFat samples were grown as organ cultures, and the culture medium was collected every two days...

Background: Mutations in tafazzin ( TAZ ), a gene required for biogenesis of cardiolipin, the signature phospholipid of the inner mitochondrial membrane, causes Barth syndrome (BTHS). Cardiomyopathy and risk of sudden cardiac death are prominent features of BTHS, but the mechanisms by which impaired cardiolipin biogenesis causes cardiac muscle weakness and arrhythmia are poorly understood. Methods: We performed in vivo electrophysiology to define arrhythmia vulnerability in cardiac specific TAZ knockout mice...

This statement summarizes evidence that adverse pregnancy outcomes (APOs) such as hypertensive disorders of pregnancy, preterm delivery, gestational diabetes, small-for-gestational-age delivery, placental abruption, and pregnancy loss increase a woman's risk of developing cardiovascular disease (CVD) risk factors and of developing subsequent CVD (including fatal and nonfatal coronary heart disease, stroke, peripheral vascular disease, and heart failure). This statement highlights the importance of recognizing APOs when CVD risk is evaluated in women, although their value in reclassifying risk may not be established...

No abstract text is available yet for this article.

Background: Metabolic alterations provide substrates that influence chromatin structure to regulate gene expression that determines cell function in health and disease. Heightened proliferation of smooth muscle cells (SMC) leading to the formation of a neointima is a feature of pulmonary arterial hypertension (PAH) and systemic vascular disease. Increased glycolysis is linked to the proliferative phenotype of these SMC. Methods: RNA Sequencing was applied to pulmonary arterial (PA) SMC from PAH patients with and without a BMPR2 mutation vs...

Nontraumatic lower-extremity amputation is a devastating complication of peripheral artery disease (PAD) with a high mortality and medical expenditure. There are ≈150 000 nontraumatic leg amputations every year in the United States, and most cases occur in patients with diabetes. Among patients with diabetes, after an ≈40% decline between 2000 and 2009, the amputation rate increased by 50% from 2009 to 2015. A number of evidence-based diagnostic and therapeutic approaches for PAD can reduce amputation risk...

Background: Exercise can induce physiological myocardial hypertrophy (PMH), and former athletes can live 5-6 years longer than nonathletic controls, suggesting a benefit after regression of PMH. We previously reported that regression of pathological myocardial hypertrophy has antihypertrophic effects. Accordingly, we hypothesized that antihypertrophic memory exists even after PMH has regressed, increasing myocardial resistance to subsequent pathological hypertrophic stress. Methods: C57BL/6 mice were submitted to 21 days of swimming training to develop PMH...

Background: High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the safety and efficacy of this approach is uncertain. We investigated whether an early-rule out pathway is safe and effective for patients with suspected acute coronary syndrome. Methods: We performed a stepped-wedge cluster randomized controlled trial in the Emergency Departments of seven acute care hospitals in Scotland. Consecutive patients presenting with suspected acute coronary syndrome between December 2014 and December 2016 were included...

Background: Out-of-hospital cardiac arrest (OHCA) patients who remain comatose after initial resuscitation are at high risk of morbidity and mortality due to the ensuing post cardiac arrest syndrome (PCAS). Systemic inflammation constitutes a major component of PCAS, and interleukin-6 (IL-6) levels are associated with PCAS severity. The IL-6 receptor antagonist tocilizumab could potentially dampen inflammation in PCAS. The objective of the present trial was to determine the efficacy of tocilizumab to reduce systemic inflammation after OHCA of presumed cardiac cause and thereby potentially mitigate organ injury...