Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy.

Loss of Bcl2-associated athanogene 3 (BAG3) is associated with dilated cardiomyopathy (DCM). BAG3 regulates sarcomere protein turnover in cardiomyocytes; however, the function of BAG3 in other cardiac cell types is understudied. In this study, we used an isogenic pair of BAG3-knockout and wild-type human induced pluripotent stem cells (hiPSCs) to interrogate the role of BAG3 in hiPSC-derived cardiac fibroblasts (CFs).

Early genetic screening and cardiac intervention in patients with cardiomyopathies in a multidisciplinary clinic.

Aims: Patients with cardiomyopathies are a heterogeneous group of patients who experience high morbidity and mortality. Early cardiac assessment and intervention with access to genetic counselling in a multidisciplinary Cardiomyopathy Clinic may improve outcomes and prevent progression to advanced heart failure.

Methods And Results: Our prospective cohort study was conducted at a multidisciplinary Cardiomyopathy Clinic with 421 patients enrolled (42.

Subnormothermic Machine Perfusion of Neonatal and Small-Sized Pediatric Donor Hearts.

Donor heart machine perfusion enables avoidance of prolonged cold ischemia, however the optimal temperature is yet to be elucidated. Given that maintenance of temperature beyond ambient levels demands significant energy, we sought to determine the suitability of room-temperature perfusion preservation of neonatal/pediatric-sized (5-20 kg) piglet donor hearts. A custom device was fabricated suitable for this purpose, with continuous readout of perfusion pressure, flow rate, temperature, and oxygen saturation.

Pharmaco-Invasive Strategy With Half-Dose Tenecteplase in Patients With STEMI: Prespecified Pooled Analysis of Patients Aged ≥75 Years in STREAM-1 and 2.

Background: In STREAM-1 (Strategic Reperfusion Early After Myocardial Infarction), excess intracranial hemorrhage occurred in patients aged ≥75 years receiving full-dose tenecteplase as part of a pharmaco-invasive strategy, whereas no further intracranial hemorrhage occurred after halving the tenecteplase dose. In STREAM-2 (Second Strategic Reperfusion Early After Myocardial Infarction), half-dose tenecteplase was an effective and safe pharmaco-invasive strategy in older patients with ST-segment-elevation myocardial infarction presenting within <3 hours, compared with primary percutaneous coronary intervention (PCI). We prespecified evaluating the efficacy and safety of a half-dose versus full-dose pharmaco-invasive strategy and compared the half-dose pharmaco-invasive strategy to primary PCI in patients aged ≥75 years.

Relationship Between Severity of Ischemia and Coronary Artery Disease for Different Stress Test Modalities in the ISCHEMIA Trial.

Background: The relationship between the extent and severity of stress-induced ischemia and the extent and severity of anatomic coronary artery disease (CAD) in patients with obstructive CAD is multifactorial and includes the intensity of stress achieved, type of testing used, presence and extent of prior infarction, collateral blood flow, plaque characteristics, microvascular disease, coronary vasomotor tone, and genetic factors. Among chronic coronary disease participants with site-determined moderate or severe ischemia, we investigated associations between ischemia severity on stress testing and the extent of CAD on coronary computed tomography angiography.

Methods: Clinically indicated stress testing included nuclear imaging, echocardiography, cardiac magnetic resonance imaging, or nonimaging exercise tolerance test.

Mild Permissive Alkalosis Improves Outcomes in Porcine Negative Pressure Ventilation Ex-Situ Lung Perfusion.

Background: Ex-Situ Lung Perfusion (ESLP) employs a membrane deoxygenator and mixed (N/O/CO) or pure sweep gas (CO) to target venous blood gas composition with physiologic pCO and pH. Clinically, mild permissive alkalosis counteracts elevated pulmonary vascular resistance (PVR) to improve perfusion. Increased PVR and pulmonary artery pressure (PAP) during ESLP mirrors rising pro-inflammatory cytokines.

State-of-the-Art Review of Aortic Root Reconstruction: Contemporary Techniques and Challenges.

Aortic root reconstruction operations have undergone substantial evolution with technical modifications, expanding indications, and the need for increasingly complex decision-making. The purpose of this state-of-the-art review is to detail our approach to contemporary aortic root reconstruction operations. First, we review the evolution of root reconstruction procedures over the years and discuss the approach to the aortic root patient for lifetime management of aneurysm and valvular disease in the modern context of management options.

Temporal Trends in the Management Practices of Clinically Important Perioperative Atrial Fibrillation After Noncardiac Surgery.

Background: Clinically important perioperative atrial fibrillation (POAF) is a common cardiac complication after noncardiac surgery. Little is known about how patients with POAF are managed acutely and whether practices have changed over time.

Methods: We conducted an observational substudy of patients who had POAF, were at elevated cardiovascular risk, and were enrolled in the PeriOperative Ischemic Evaluation (POISE)-1, 2 and 3 trials between 2002 and 2021.

Long-term outcomes comparison of Bentall-De Bono-versus valve-sparing aortic root replacement: An updated systematic review and reconstructed time-to-event meta-analysis.

Background: For patients with aortic root dilatation and a structurally normal aortic valve (AV) undergoing composite aortic valve-graft (Bentall-De Bono) versus valve-sparing aortic root replacement (VSARR) procedures there are conflicting data regarding early and long-term benefits. We undertook a study-level meta-analysis to compare the results of both procedures.

Methods: Three databases were assessed, and both randomized trials and observational studies were considered eligible.

Prevention and Management of Cardiovascular Disease in Primary Care: A Comment on the PEER Simplified Lipid Guideline.

Background: In Canada, 2 guidelines provide guidance for the management of dyslipidemia. The Patients, Experience, Evidence, Research simplified lipid guidelines, intended for primary care practitioners, and the Canadian Cardiovascular Society guidelines, intended for all practitioners, are based on differing methodologies with distinct priorities and preferences. The disparate approaches may contribute to confusion among family practitioners and their co-managed patients, with the potential for compromised care, differing standards for training in the fundamentals of lipidology, and differing criteria that might be used in practice audits to evaluate quality of care.

They Deserve to Live: Impact of the Berlin Heart EXCOR on Small Children's Heart Transplant Waitlist in Low-Resource Settings.

In newly emerging economy countries, the shortage of pediatric donor hearts and poor healthcare infrastructure poses a significant challenge. Although mechanical circulatory support (MCS) has been proven effective in enhancing heart transplant waiting list outcomes, economic barriers hinder its widespread adoption. A single-center retrospective study reviewed children under 10 kg on the heart transplant (HTx) list from 2012 to 2023.

Initial cannulation strategy impacts perioperative outcomes of acute type A dissection in high-volume centers.

Objective: We performed an intention-to-treat analysis of initial cannulation strategy to assess the impact on perioperative outcomes in acute type A dissection using multicenter data.

Methods: All patients undergoing surgical repair of acute type A dissection from a multicenter national registry of 9 high-volume aortic centers were analyzed. Cannulation strategies included in the analysis were axillary, femoral, direct aortic, and innominate.

A novel GWAS locus influences microvascular response to mental stress and predicts adverse cardiovascular events.

Excessive peripheral microvascular constriction during acute psychological stress reflects similar changes in coronary blood flow and is a predictor of adverse cardiovascular outcomes. Among individuals with coronary artery disease (CAD), we sought to determine if genetic factors contribute to the degree of microvascular constriction during mental stress. A total of 580 stable CAD individuals from two prospective cohort studies underwent mental stress testing.

Timeliness of reperfusion in ST-segment elevation myocardial infarction and outcomes in Kerala, India: results of the TRUST outcomes registry.

Purpose: Transatlantic guidelines endorse quality metrics for timely reperfusion in patients with ST-elevation myocardial infarction (STEMI). Compliance in low- and middle-income countries (LMICs) is largely unknown.

Study Design: We prospectively evaluated 2928 STEMI patients in Kerala, India, across 16 PCI-capable hospitals who received reperfusion with either primary percutaneous coronary intervention (PPCI) or fibrinolysis.

Elevated Troponin T in Immune-Checkpoint Inhibitor Myositis: A Case of Mistaken Myocarditis.

A patient with metastatic renal cell carcinoma on axitinib and pembrolizumab had elevated high-sensitivity cardiac troponin T and normal high-sensitivity cardiac troponin I with unremarkable cardiac investigations. A noncardiac cause (myositis) was the likely cause for cardiac troponin T elevation. Cardiac troponin I may be a more appropriate marker to support a myocarditis diagnosis with concurrent myositis.

Hospital and Physician Variability in Revascularization Decisions and Outcomes for Patients With 3-Vessel and Left Main Coronary Artery Disease: A Population-Based Cohort Study.

Background: Hospital- and physician-level variation for selection of percutaneous coronary intervention versus coronary artery bypass grafting (CABG) for patients with coronary artery disease has been associated with outcome differences. However, most studies excluded patients treated medically.

Methods And Results: From 2010 to 2019, adults with 3-vessel or left main coronary artery disease at 3 hospitals (A, B, C) in Alberta, Canada, were categorized by treatment with medical therapy, percutaneous coronary intervention, or CABG.

Moderate-Flow Perfusion is Superior to Low-Flow Perfusion in Ex Situ Lung Perfusion.

Background: Full-flow perfusion during prolonged ex situ lung perfusion (ESLP) results in unacceptable pulmonary edema formation. Clinical ESLP at 30% to 50% predicted cardiac output (CO) supports acceptable physiologic outcomes; however, progressive pulmonary edema still develops. Lower flow rates may provide equivalent physiologic preservation with less edema formation due to reduced hydrostatic pressures.