Galectin-3 Is Associated with Cardiac Fibrosis and an Increased Risk of Sudden Death.

Background: Myocardial fibrosis is a common postmortem finding among individuals with Sudden Cardiac Death (SCD). Numerous in vivo and in vitro studies have shown that increased galectin-3 (gal3) expression into the myocardium is associated with higher incidence of fibrosis. Although elevated gal3 expression is linked with myocardial fibrosis, its role in predicting the risk of SCD is unknown.

Widespread intracoronary allogeneic cardiosphere-derived cell therapy with and without cyclosporine in reperfused myocardial infarction.

Allogeneic cardiosphere-derived cell (CDC) therapy has been demonstrated to improve myocardial function when administered to reperfused myocardial infarcts. We previously pretreated animals with low-dose cyclosporine immunosuppression to limit allogeneic CDC rejection, but whether it is necessary and, if so, can be initiated at the time of reperfusion remains uncertain. Closed-chest swine ( = 29 animals) were subjected to a 90-min left anterior descending (LAD) coronary artery occlusion.

Myocardial injury, troponin release, and cardiomyocyte death in brief ischemia, failure, and ventricular remodeling.

Troponin released from irreversibly injured myocytes is the gold standard biomarker for the rapid identification of an acute coronary syndrome. In acute myocardial infarction, necrotic cell death is characterized by sarcolemmal disruption in response to a critical level of energy depletion after more than 15 min of ischemia. Although troponin I and T are highly specific for cardiomyocyte death, high-sensitivity assays have demonstrated that measurable circulating levels of troponin are present in many normal subjects.

Neutrophils aid cellular therapeutics by enhancing glycoengineered stem cell recruitment and retention at sites of inflammation.

The efficacy of cell-based therapies relies on targeted payload delivery and enhanced cell retention. In vitro and in vivo studies suggest that the glycoengineering of mesenchymal and cardiosphere-derived cells (CDCs) may enhance such recruitment at sites of injury. We evaluated the role of blood cells in amplifying this recruitment.

Does quantification of [C]meta-hydroxyephedrine and [N]ammonia kinetics improve risk stratification in ischemic cardiomyopathy.

Background: In ischemic cardiomyopathy patients, cardiac sympathetic nervous system dysfunction is a predictor of sudden cardiac arrest (SCA). This study compared abnormal innervation and perfusion measured by [C]meta-hydroxyephedrine (HED) vs [N]ammonia (NH), conventional uptake vs parametric tracer analysis, and their SCA risk discrimination.

Methods: This is a sub-study analysis of the prospective PAREPET trial, which followed ischemic cardiomyopathy patients with reduced left ventricular ejection fraction (LVEF ≤ 35%) for events of SCA.

Positron Emission Tomography Imaging of Regional Versus Global Myocardial Sympathetic Activity to Improve Risk Stratification in Patients With Ischemic Cardiomyopathy.

Background: Current risk assessment approaches fail to identify the majority of patients at risk of sudden cardiac arrest (SCA). Noninvasive imaging of the cardiac sympathetic nervous system using single-photon emission computed tomography and positron emission tomography offers the potential for refining SCA risk assessment. While various [C]meta-hydroxyephedrine quantification parameters have been proposed, it is currently unknown whether regional denervation or global innervation yields greater SCA risk discrimination.

Gaining Efficiency in Clinical Trials With Cardiac Biomarkers: JACC Review Topic of the Week.

The momentum of cardiovascular drug development has slowed dramatically. Use of validated cardiac biomarkers in clinical trials could accelerate development of much-needed therapies, but biomarkers have been used less for cardiovascular drug development than in therapeutic areas such as oncology. Moreover, there are inconsistences in biomarker use in clinical trials, such as sample type, collection times, analytical methods, and storage for future research.

Changes in Field Termination of Resuscitation and Survival Rates After an Educational Intervention to Promote on Scene Resuscitation for Out-of-Hospital Cardiac Arrest.

Background: Emergency medical services (EMS) agencies with higher field termination-of-resuscitation (TOR) rates tend to have higher survival rates from out-of-hospital cardiac arrest (OHCA). Whether EMS agencies can improve survival rates through efforts to focus on resuscitation on scene and optimize TOR rates is unknown.

Objective: The goal of this study was to determine if an EMS agency's efforts to enhance on-scene resuscitation were associated with increased TOR and OHCA survival with favorable neurologic outcome.

Reproducible Quantification of Regional Sympathetic Denervation with [C]meta-Hydroxyephedrine PET Imaging.

Background: Regional cardiac sympathetic denervation is predictive of sudden cardiac arrest in patients with ischemic cardiomyopathy. The reproducibility of denervation scores between automated software programs has not been evaluated. This study seeks to (1) compare the inter-rater reliability of regional denervation measurements using two analysis programs: FlowQuant and Corridor4DM; (2) evaluate test-retest repeatability of regional denervation scores.

MiR-101a loaded extracellular nanovesicles as bioactive carriers for cardiac repair.

Myocardial infarction (MI) remains a major cause of mortality worldwide. Despite significant advances in MI treatment, many who survive the acute event are at high risk of chronic cardiac morbidity. Here we developed a cell-free therapeutic that capitalizes on the antifibrotic effects of micro(mi)RNA-101a and exploits the multi-faceted regenerative activity of mesenchymal stem cell (MSC) extracellular nanovesicles (eNVs).

Quantitative proteomic and phosphoproteomic profiling of ischemic myocardial stunning in swine.

Despite decades of research on the pathophysiology of myocardial stunning, protein changes and/or phosphorylation status underlying alterations in cardiac function/structure remain inadequately understood. Here, we utilized comprehensive and quantitative proteomic and phosphoproteomic approaches to explore molecular mechanisms of myocardial stunning in swine. The closed-chest swine ( = 5 pigs) were subjected to a 10-min left anterior descending coronary artery (LAD) occlusion producing regional myocardial stunning.

Transmural variation in microvascular remodeling following percutaneous revascularization of a chronic coronary stenosis in swine.

Remodeling of the coronary microcirculation is known to occur distal to a chronic coronary stenosis, but the reversibility of these changes and their functional significance on maximum myocardial perfusion before and after revascularization is unknown. Accordingly, swine instrumented with a chronic silastic stenosis on the left anterior descending coronary artery to produce hibernating myocardium underwent percutaneous coronary intervention (PCI; = 8) and were compared with animals with a persistent stenosis ( = 8), as well as sham controls ( = 6). Stenotic animals demonstrated an increased subendocardial arteriolar wall thickness-to-lumen ratio (37.

Structural and Physiological Imaging to Predict the Risk of Lethal Ventricular Arrhythmias and Sudden Death.

Identifying patients at risk of sudden cardiac death remains a major challenge in cardiovascular medicine. Advances in cardiovascular imaging have identified several anatomic and functional variables that can be quantified as continuous variables to predict the risk of developing lethal ventricular tachyarrhythmias in patients with depressed left ventricular (LV) systolic function. Some, such as LV mass, volume, and the dyssynchrony of contraction, can be derived from currently available echocardiographic and nuclear imaging modalities.

Adaptive Reductions in Left Ventricular Diastolic Compliance Protect the Heart From Stretch-Induced Stunning.

Swine subjected to 2 weeks of repetitive pressure overload (RPO) exhibited significant myocyte loss, but left ventricular (LV) systolic function was preserved, and chamber dilatation did not occur. Instead, myocardial remodeling characterized by myocyte hypertrophy and interstitial fibrosis led to a marked reduction in LV diastolic compliance, which protected the heart from stretch-induced myocyte injury and preserved LV ejection fraction without anatomic LV hypertrophy. These results support a novel paradigm that links cardiac adaptations to RPO with the pathogenesis of reduced LV diastolic compliance and may explain how LV stiffening can occur in the absence of sustained hypertension or anatomic hypertrophy.

Nonocclusive multivessel intracoronary infusion of allogeneic cardiosphere-derived cells early after reperfusion prevents remote zone myocyte loss and improves global left ventricular function in swine with myocardial infarction.

Intracoronary cardiosphere-derived cells (icCDCs) infused into the infarct-related artery reduce scar volume but do not improve left ventricular (LV) ejection fraction (LVEF). We tested the hypothesis that this reflects the inability of regional delivery to prevent myocyte death or promote myocyte proliferation in viable myocardium remote from the infarct. Swine ( = 23) pretreated with oral cyclosporine (200 mg/day) underwent a 1-h left anterior descending coronary artery (LAD) occlusion, which reduced LVEF from 61.

The role of heart rate variability, heart rate turbulence, and deceleration capacity in predicting cause-specific mortality in chronic heart failure.

Background: The volume of regional denervated myocardium (D-M) on positron emission tomography has been recently suggested as a strong independent predictor of cause-specific mortality from sudden cardiac arrest (SCA) in chronic heart failure. We sought to evaluate whether ECG indices of global autonomic function predict risk of SCA to a similar degree as regional D-M.

Methods: Subjects enrolled in the Prediction of Arrhythmic Events using Positron Emission Tomography (PAREPET) study were included in this study.

Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction.

Background: After myocardial infarction (MI), inflammatory cells infiltrate the infarcted heart in response to secreted stimuli. Monocytes are recruited to the infarct via CCR2 chemokine receptors along a CCL2 concentration gradient. While infiltration of injured tissue with monocytes is an important component of the reparatory response, excessive or prolonged inflammation can adversely affect left ventricular remodeling and worsen clinical outcomes.