Big tau aggregation disrupts microtubule tyrosination and causes myocardial diastolic dysfunction: from discovery to therapy.

Background: Amyloid plaques and neurofibrillary tangles, the molecular lesions that characterize Alzheimer's disease (AD) and other forms of dementia, are emerging as determinants of proteinopathies 'beyond the brain'. This study aims to establish tau's putative pathophysiological mechanistic roles and potential future therapeutic targeting of tau in heart failure (HF).

Methods And Results: A mouse model of tauopathy and human myocardial and brain tissue from patients with HF, AD, and controls was employed in this study.

Remote Monitoring of Patients With Heart Failure: A White Paper From the Heart Failure Society of America Scientific Statements Committee.

Background: After several neutral telehealth trials, the positive findings and subsequent Food and Drug Administration approval of an implantable pulmonary arterial pressure monitor (PAPM) led to renewed interest in remote patient monitoring (RPM). Here we seek to provide contemporary guidance on the appropriate use of RPM technology.

Results: Although early trials of external RPM devices suggested benefit, subsequent multicenter trials failed to demonstrate improved outcomes.

Effects of Percutaneous LVAD Support on Right Ventricular Load and Adaptation.

Both operative and hemodynamic mechanisms have been implicated in right heart failure (RHF) following surgical left ventricular assist device (LVAD) implantation. We investigated the effects of percutaneous LVAD (pLVAD; Impella®, Abiomed) support on right ventricular (RV) load and adaptation. We reviewed all patients receiving a pLVAD for cardiogenic shock at our institution between July 2014 and April 2017, including only those with pre- and post-pLVAD invasive hemodynamic measurements.

Effect of Milrinone Infusion on Pulmonary Vasculature and Stroke Work Indices: A Single-Center Retrospective Analysis in 69 Patients Awaiting Cardiac Transplantation.

Background: Although milrinone infusion is reported to benefit left ventricular function in chronic left heart failure, few insights exist regarding its effects on pulmonary circulation and right ventricular function.

Methods: We retrospectively reviewed right heart catheterization data at baseline and during continuous infusion of milrinone in 69 patients with advanced heart failure and analyzed the effects on ventricular stroke work indices, pulmonary vascular resistance and pulmonary arterial compliance.

Results: Compared to baseline, milrinone infusion after a mean 58 ± 61 days improved mean left ventricular stroke work index (1540 ± 656 vs.

Mechanical circulatory support and simultaneous heart-kidney transplantation: An outcome analysis.

Background: Single-donor simultaneous heart-kidney transplantation (SHKT) can significantly improve the survival of those with advanced heart failure and advanced renal insufficiency. Data on pre-transplant use of mechanical circulatory support (MCS) devices and outcomes after SHKT are limited and conflicting.

Methods: Using the United Network for Organ Sharing registry data, we evaluated 749 adults undergoing SHKT after January 1, 2000.

Right ventricular protein expression profile in end-stage heart failure.

Little is known about the right ventricular (RV) proteome in human heart failure (HF), including possible differences compared to the left ventricular (LV) proteome. We used 2-dimensional differential in-gel electrophoresis (pH: 4-7, 10-150 kDa), followed by liquid chromatography tandem mass spectrometry, to compare the RV and LV proteomes in 12 explanted human hearts. We used Western blotting and multiple-reaction monitoring for protein verification and RNA sequencing for messenger RNA and protein expression correlation.

Evolving targeted therapies for right ventricular failure.

Introduction: Although right and left ventricular embryological origins, morphology and cardiodynamics differ, the notion of selectively targeted right ventricular therapies remains controversial.

Areas Covered: This review focuses on both the currently evolving pharmacologic agents targeting right ventricular failure (metabolic modulators, phosphodiesterase type V inhibitors) and future therapeutic approaches including epigenetic modulation by miRNAs, chromatin binding complexes, long non-coding RNAs, genomic editing, adoptive gene transfer and gene therapy, cell regeneration via cell transplantation and cell reprogramming and cardiac tissue engineering.

Expert Opinion: Strategies for adult right ventricular regeneration will require a more holistic approach than strategies for adult left ventricular failure.

Epigenetic regulation in heart failure: part II DNA and chromatin.

Epigenetic regulatory mechanisms play key roles in cardiac development, differentiation, homeostasis, response to stress and injury, and disease. Human heart failure (HF) epigenetic regulatory mechanisms have not been deciphered to date. This 2-part review distills the rapidly evolving research focused on human HF epigenetic regulatory mechanisms.

Right ventricular long noncoding RNA expression in human heart failure.

The expression of long noncoding RNAs (lncRNAs) in human heart failure (HF) has not been widely studied. Using RNA sequencing (RNA-Seq), we compared lncRNA expression in 22 explanted human HF hearts with lncRNA expression in 5 unused donor human hearts. We used Cufflinks to identify isoforms and DESeq to identify differentially expressed genes.

Epigenetic Regulation in Heart Failure: Part I RNA.

Epigenetic regulatory mechanisms play key roles in cardiac development, differentiation, homeostasis, response to stress and injury and disease. Human heart failure epigenetic regulatory mechanisms have not been deciphered to date. This 2-part review distills the rapidly evolving research focused on human heart failure epigenetic regulatory mechanisms.

Right ventricular myocardial biomarkers in human heart failure.

Background: Right ventricular (RV) dysfunction contributes to mortality in chronic heart failure (HF). However, the molecular mechanisms of RV failure remain poorly understood, and RV myocardial biomarkers have yet to be developed.

Methods And Results: We performed RNA sequencing (RNA-seq) on 22 explanted human HF RVs and 5 unused donor human heart RVs (DON RV) and compared results to those recently reported from 16 explanted human LVs We used Bowtie-Tophat for transcript alignment and transcriptome assembly, DESeq for identification of differentially expressed genes (DEGs) and Ingenuity for exploration of gene ontologies.

Perioperative blood product use: a comparison between HeartWare and HeartMate II devices.

Background: The HeartWare (HW) (Framingham, MA) and the HeartMate II (HM II) (Thoratec Inc, Pleasanton, CA) continuous-flow left ventricular assist devices (CF-LVADs) are commonly used to bridge patients to transplantation. We hypothesized that there are differences in perioperative blood product (BP) use and chest tube (CT) output between CF-LVAD types.

Methods: We retrospectively evaluated BP use in 71 patients who were implanted with a CF-LVAD (HM II = 38; HW = 33) by median sternotomy for bridge to transplantation (BTT) indications from 2009 to 2013.

Does renal dysfunction and method of bridging support influence heart transplant graft survival?

Background: Renal insufficiency is common in status 1B patients supported with inotropes or a continuous flow left ventricular device (CF-LVAD) as a bridge to heart transplantation. We evaluated the association of renal function and inotrope versus CF-LVAD support on posttransplant graft survival in status 1B patients.

Methods: The Scientific Registry for Transplant Recipients database was analyzed for posttransplant survival in status 1B patients bridged with inotropes or CF-LVAD who underwent transplantation between 2003 and 2012.

Are peripherally inserted central catheters associated with increased risk of adverse events in status 1B patients awaiting transplantation on continuous intravenous milrinone?

Background: Peripherally inserted central catheters (PICCs) are used to deliver continuous intravenous (IV) milrinone in stage D heart failure (HF) patients awaiting heart transplantation (HT).

Methods: We retrospectively analyzed PICC adverse events (AEs) and associated cost in 129 status 1B patients from 2005 to 2012. End points were HT, left ventricular assist device (LVAD), and death.

Institutional volume of heart transplantation with left ventricular assist device explantation influences graft survival.

Background: There are increasing numbers of patients undergoing orthotopic heart transplantation (OHT) with left ventricular assist device (LVAD) explantation (LVAD explant-OHT). We hypothesized that LVAD explant-OHT is a more challenging surgical procedure compared to OHT without LVAD explantation and that institutional LVAD explant-OHT procedural volume would be associated with post-transplant graft survival. We sought to assess the impact of institutional volume of LVAD explant-OHT on post-transplant graft survival.

Mechanical circulatory support and heart transplantation: donor and recipient factors influencing graft survival.

Background: Mechanical circulatory support is an accepted strategy to bridge patients to heart transplantation (HTx). Among mechanical circulatory support patients who go on to HTx, factors associated with improved graft survival have not been fully elucidated.

Methods: Using the Scientific Registry for Transplant Recipients, we identified adults who were treated with a left ventricular assist device (LVAD) or total artificial heart (TAH) before HTx.

Stem cell therapy for chronic heart failure: an updated appraisal.

Introduction: Significant advances have been made to understand the mechanisms involved in cardiac cell-based therapies. The early translational application of basic science knowledge has led to several animal and human clinical trials. The initial promising beneficial effect of stem cells on cardiac function restoration has been eclipsed by the inability of animal studies to translate into sustained clinical improvements in human clinical trials.

Pulmonary hypertension and right ventricular failure in left ventricular systolic dysfunction.

Purpose Of Review: Pulmonary hypertension and right ventricular failure (RVF) in left ventricular systolic dysfunction (LVSD) is associated with high morbidity and mortality. This review presents an overview of the classification, pathophysiology, natural history, clinical features, prevention and treatment of this common clinical problem with a focus on the most recent studies. Many of the current evidence-based therapeutic agents for pulmonary hypertension in the absence of systolic or diastolic heart failure (e.

Familial evaluation for diagnosis of arrhythmogenic right ventricular dysplasia.

Most sudden cardiac deaths in young athletes are caused by previously undetected inherited cardiac diseases. Here, we report a case of a young male athlete in whom a presumptive diagnosis of hypertrophic cardiomyopathy (HCM) was made following a near sudden cardiac death. Although his imaging studies initially suggested HCM, a detailed clinical and genetic evaluation of the patient and his asymptomatic father led to the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVD) in both.