The Colorado Heart Failure Acuity Risk Model: A Mortality Model for Waitlisted Cardiac Transplant Patients.

Background: Currently, there is no mathematical model used nationally to determine the medical urgency of patients on the heart transplant waitlist in the United States. While the current organ distribution system accounts for many patient factors, a truly objective model is needed to more reliably stratify patients by their medical acuity.

Objectives: The aim of the study was to develop risk scores (Colorado Heart failure Acuity Risk Model [CHARM] score) to predict mortality in adults waitlisted for heart transplant.

Long-Term Efficacy and Safety of Acoramidis in ATTR-CM: Initial Report From the Open-Label Extension of the ATTRibute-CM Trial.

Background: In the phase 3 randomized controlled study, ATTRibute-CM, acoramidis, a transthyretin (TTR) stabilizer, demonstrated significant efficacy on the primary endpoint. Participants with transthyretin amyloid cardiomyopathy (ATTR-CM) who completed ATTRibute-CM were invited to enroll in an open-label extension study (OLE). We report efficacy and safety data of acoramidis in participants who completed ATTRibute-CM and enrolled in the ongoing OLE.

Optimizing Triage of Ambulatory Patients With Advanced Heart Failure: 2-Year Outcomes From REVIVAL.

Background: Left ventricular assist device (LVAD) use remains uncommon in advanced heart failure (HF) patients not dependent on inotropes.

Objectives: Before considering a randomized trial comparing a strategy of earlier use of LVAD to continued medical therapy, a better understanding is needed of the clinical trajectory of ambulatory patients with advanced systolic HF on optimal guideline-directed medical therapy (GDMT).

Methods: REVIVAL enrolled 400 patients with advanced ambulatory systolic HF, ≥1 HF mortality risk marker (≥2 HF hospitalizations past year; or HF hospitalization and high natriuretic peptide; or no HF hospitalizations but low peak oxygen consumption, 6-minute walk, serum sodium, HF survival score or Seattle HF model predicted survival), and no LVAD contraindication at 21 LVAD centers from July 2015 to June 2016.

Assessment of Autophagy Markers Suggests Increased Activity Following LVAD Therapy.

Left ventricular reverse remodeling in heart failure is associated with improved clinical outcomes. However, the molecular features that drive this process are poorly defined. Left ventricular assist devices (LVADs) are the therapy associated with the greatest reverse remodeling and lead to partial myocardial recovery in most patients.

Risk of Arrhythmic Death in Patients With Nonischemic Cardiomyopathy: JACC Review Topic of the Week.

Nonischemic cardiomyopathy (NICM) is common and patients are at significant risk for early mortality secondary to ventricular arrhythmias. Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy to decrease sudden cardiac death (SCD) in patients with heart failure and reduced left ventricular ejection fraction. However, in randomized clinical trials comprised solely of patients with NICM, primary prevention ICDs did not confer significant mortality benefit.

Magnitude of troponin elevation in patients with biomarker evidence of myocardial injury: relative frequency and outcomes in a cohort study across a large healthcare system.

Background: Serum troponin levels correlate with the extent of myocyte necrosis in acute myocardial infarction (AMI) and predict adverse outcomes. However, thresholds of cardiac troponin elevation that could portend to poor outcomes have not been established.

Methods: In this cohort study, we characterized all cardiac troponin elevations > 0.

Disruption of Phosphodiesterase 3A Binding to SERCA2 Increases SERCA2 Activity and Reduces Mortality in Mice With Chronic Heart Failure.

Background: Increasing SERCA2 (sarco[endo]-plasmic reticulum Ca ATPase 2) activity is suggested to be beneficial in chronic heart failure, but no selective SERCA2-activating drugs are available. PDE3A (phosphodiesterase 3A) is proposed to be present in the SERCA2 interactome and limit SERCA2 activity. Disruption of PDE3A from SERCA2 might thus be a strategy to develop SERCA2 activators.

Myocardial Injury and Altered Gene Expression Associated With SARS-CoV-2 Infection or mRNA Vaccination.

SARS CoV-2 enters host cells via its Spike protein moiety binding to the essential cardiac enzyme angiotensin-converting enzyme (ACE) 2, followed by internalization. COVID-19 mRNA vaccines are RNA sequences that are translated into Spike protein, which follows the same ACE2-binding route as the intact virion. In model systems, isolated Spike protein can produce cell damage and altered gene expression, and myocardial injury or myocarditis can occur during COVID-19 or after mRNA vaccination.

Mechanisms and significance of tissue-specific MICU regulation of the mitochondrial calcium uniporter complex.

Mitochondrial Ca uptake, mediated by the mitochondrial Ca uniporter, regulates oxidative phosphorylation, apoptosis, and intracellular Ca signaling. Previous studies suggest that non-neuronal uniporters are exclusively regulated by a MICU1-MICU2 heterodimer. Here, we show that skeletal-muscle and kidney uniporters also complex with a MICU1-MICU1 homodimer and that human/mouse cardiac uniporters are largely devoid of MICUs.

Cardiomyocyte-Specific Long Noncoding RNA Regulates Alternative Splicing of the Triadin Gene in the Heart.

Background: Abnormalities in Ca homeostasis are associated with cardiac arrhythmias and heart failure. Triadin plays an important role in Ca homeostasis in cardiomyocytes. Alternative splicing of a single gene produces multiple triadin isoforms.

Indications, Complications, and Outcomes of Cardiac Surgery After Heart Transplantation: Results From the Cash Study.

Background: Allograft pathologies, such as valvular, coronary artery, or aortic disease, may occur early and late after cardiac transplantation. Cardiac surgery after heart transplantation (CASH) may be an option to improve quality of life and allograft function and prolong survival. Experience with CASH, however, has been limited to single-center reports.

HDAC6 modulates myofibril stiffness and diastolic function of the heart.

Passive stiffness of the heart is determined largely by extracellular matrix and titin, which functions as a molecular spring within sarcomeres. Titin stiffening is associated with the development of diastolic dysfunction (DD), while augmented titin compliance appears to impair systolic performance in dilated cardiomyopathy. We found that myofibril stiffness was elevated in mice lacking histone deacetylase 6 (HDAC6).