Angiotensin-Neprilysin Inhibition in Black Americans: Data From the PIONEER-HF Trial.

Objectives: This study compared the efficacy and safety of sacubitril/valsartan to enalapril in Black and non-Black Americans with acute decompensated heart failure (ADHF).

Background: Black patients have a different response to treatment with angiotensin-converting enzyme inhibitors compared with other racial and ethnic groups. How Black patients with ADHF respond to sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, is unclear.

Selenium protein identification and profiling by mass spectrometry: A tool to assess progression of cardiomyopathy in a whale model.

Non-ischemic cardiomyopathy is a leading cause of congestive heart failure and sudden cardiac death in humans and in some cases the etiology of cardiomyopathy can include the downstream effects of an essential element deficiency. Of all mammal species, pygmy sperm whales (Kogia breviceps) present the greatest known prevalence of cardiomyopathy with more than half of examined individuals indicating the presence of cardiomyopathy from gross and histo-pathology. Several factors such as genetics, infectious agents, contaminants, biotoxins, and inappropriate dietary intake (vitamins, selenium, mercury, and pro-oxidants), may contribute to the development of idiopathic cardiomyopathy in K.

Implantation of a defibrillator in a patient with an upper airway stimulation device.

The patient is a 62-year-old man with continuous positive airway pressure-intolerant obstructive sleep apnea who was enrolled in a study for a hypoglossal nerve upper airway stimulation device (UAS). Nearly 2.5 years later, he was admitted to the hospital for unstable angina.

Differences in coronary artery disease by CT angiography between patients developing unstable angina pectoris vs. major adverse cardiac events.

Objective: CT angiography (CTA) has prognostic value in patients. But it is unknown whether differences in atherosclerosis by CTA predict the development of unstable angina pectoris (UAP) vs. major adverse cardiac events (MACE).

Coronary CT angiography versus conventional cardiac angiography for therapeutic decision making in patients with high likelihood of coronary artery disease.

Purpose: To assess the efficacy of coronary computed tomographic (CT) angiography for therapeutic decision making in patients with high likelihood of coronary artery disease (CAD)-specifically the ability of coronary CT angiography to help differentiate patients without and patients with a need for revascularization and determine the appropriate revascularization procedure.

Materials And Methods: The study protocol was approved by institutional review board, with written informed consent from all patients. The study was conducted in compliance with HIPAA.

Remodeling of the peripheral cardiac conduction system in response to pressure overload.

How chronic pressure overload affects the Purkinje fibers of the ventricular peripheral conduction system (PCS) is not known. Here, we used a connexin (Cx)40 knockout/enhanced green fluorescent protein knockin transgenic mouse model to specifically label the PCS. We hypothesized that the subendocardially located PCS would remodel after chronic pressure overload and therefore analyzed cell size, markers of hypertrophy, and PCS-specific Cx and ion channel expression patterns.

Coronary CT angiography: image quality, diagnostic accuracy, and potential for radiation dose reduction using a novel iterative image reconstruction technique-comparison with traditional filtered back projection.

Objectives: To compare image noise, image quality and diagnostic accuracy of coronary CT angiography (cCTA) using a novel iterative reconstruction algorithm versus traditional filtered back projection (FBP) and to estimate the potential for radiation dose savings.

Methods: Sixty five consecutive patients (48 men; 59.3 ± 7.

Takotsubo cardiomyopathy in a patient with previously undiagnosed hypertrophic cardiomyopathy with obstruction.

Takotsubo cardiomyopathy (TCM) is usually characterized by left ventricular anteroapical dysfunction in the absence of significant coronary disease commonly precipitated by an emotional or stressful trigger. Hypertrophic cardiomyopathy (HCM) is usually diagnosed on the basis of symptoms, family history, echocardiography, or by the presence of a characteristic murmur. We report a unique case of TCM occurring in a patient with previously undiagnosed HCM with left ventricular outflow tract (LVOT) obstruction who presented with an acute coronary syndrome and ultimately underwent successful alcohol septal ablation.

Differentiation of cardiac Purkinje fibers requires precise spatiotemporal regulation of Nkx2-5 expression.

Nkx2-5 gene mutations cause cardiac abnormalities, including deficits of function in the atrioventricular conduction system (AVCS). In the chick, Nkx2-5 is elevated in Purkinje fiber AVCS cells relative to working cardiomyocytes. Here, we show that Nkx2-5 expression rises to a peak as Purkinje fibers progressively differentiate.

Pulsatile hemodynamic effects of candesartan in patients with chronic heart failure: the CHARM Program.

Background: Abnormal large artery function and increased pulsatile load are exacerbated by excess angiotensin-II acting through the AT1 receptor and contribute to the pathogenesis and progression of chronic heart failure (CHF).

Aims: To evaluate effects of the AT1 receptor blocker candesartan (N = 30) or placebo (N = 34) on pulsatile hemodynamics in participants with CHF in the CHARM program.

Methods And Results: Noninvasive hemodynamics were assessed following 6 and 14 months of treatment and averaged.

The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure.

Background: Despite its high prevalence, optimal therapy for diastolic heart failure (DHF) has not been determined. Alagebrium chloride (ALT-711) is a novel compound that breaks glucose crosslinks and may improve ventricular and arterial compliance.

Methods And Results: A total of 23 patients, mean age 71 years, with stable DHF, ejection fraction (EF) >50%, were enrolled in a 16-week, open-label trial of alagebrium 420 mg per day.

Transcriptional regulation of cardiac conduction system development: 2004 FASEB cardiac conduction system minimeeting, Washington, DC.

The development of the complex network of specialized cells that form the atrioventricular conduction system (AVCS) during cardiac morphogenesis occurs by progressive recruitment within a multipotent cardiomyogenic lineage. Understanding the molecular control of this developmental process has been the focus of recent research. Transcription factors representative of multiple subfamilies have been identified and include members of zinc-finger subfamilies (GATA4, GATA6 HF-1b), skeletal muscle transcription factors (MyoD), T-box genes (Tbx5), and also homeodomain transcription factors (Msx2 and Nkx2.

Function follows form: cardiac conduction system defects in Nkx2-5 mutation.

Mutations of Nkx2-5 cause congenital heart disease and atrioventricular block in man. The altered expression of an electrophysiologic protein regulated by Nkx2-5 was originally presumed to cause the conduction defect, but when no such protein was found, an alternative hypothesis was considered. In pediatric patients, the association of certain cardiac malformations with congenital atrioventricular block suggests that errors in specific developmental pathways could cause both an anatomic and a physiologic defect.

Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system.

Heterozygous mutations of the cardiac transcription factor Nkx2-5 cause atrioventricular conduction defects in humans by unknown mechanisms. We show in KO mice that the number of cells in the cardiac conduction system is directly related to Nkx2-5 gene dosage. Null mutant embryos appear to lack the primordium of the atrioventricular node.

Analysis of the rat connexin 43 proximal promoter in neonatal cardiomyocytes.

Altered transcriptional control is likely to contribute to the down-regulation of connexin 43 (Cx43) expression observed in many forms of heart disease. However, little is known about the factors regulating Cx43 transcription in the heart under (patho)physiological conditions. Therefore, a systematic study of rat Cx43 (rCx43) proximal promoter regulation in rat primary neonatal ventricular cardiomyocytes (NCM) and, for comparison, different cell types was initiated.

His-Purkinje lineages and development.

The heartbeat is initiated and coordinated by a multi-component set of specialized muscle tissues collectively referred to as the pacemaking and conduction system. Over the last few years, impetus has gathered into unravelling the cellular and molecular processes that regulate differentiation and integration of this essential cardiac network. One focus of our collective work has been the developmental history of cells comprising His-Purkinje tissues of the conduction system.

Development of the cardiac pacemaking and conduction system.

The heartbeat is initiated and coordinated by a heterogeneous set of tissues, collectively referred to as the pacemaking and conduction system (PCS). While the structural and physiological properties of these specialized tissues has been studied for more than a century, distinct new insights have emerged in recent years. The tools of molecular biology and the lessons of modern embryology are beginning to uncover the mechanisms governing induction, patterning and developmental integration of the PCS.

Coronary arteriogenesis and differentiation of periarterial Purkinje fibers in the chick heart: is there a link?

In the following review, we outline the cellular ontogeny and time course of coronary artery development within the vertebrate heart. Our eventual focus will be the potential role of arteriogenesis in the differentiation of a subset of specialized conduction cells in the chick heart. We begin by briefly outlining early heart formation, showing how the outermost layer of the looped, tube heart--the epicardium--is of extracardiac origin and provides the progenitor cells to the entire vascular bed.

Differential regulation of the cardiac sodium calcium exchanger promoter in adult and neonatal cardiomyocytes by Nkx2.5 and serum response factor.

Nkx2.5 and serum response factor (SRF) are critically important transcription factors in cardiac morphogenesis. They are also widely expressed in adult cardiomyocytes, but there is little data to indicate their possible role in adult cardiac cells.