JACC. Heart failure
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JACC. Heart failure · Aug 2021
ReviewDifferential Pathophysiological Mechanisms in Heart Failure With a Reduced or Preserved Ejection Fraction in Diabetes.
Diabetes promotes the development of both heart failure with a reduced ejection fraction and heart failure with a preserved ejection fraction through diverse mechanisms, which are likely mediated through hyperinsulinemia rather than hyperglycemia. Diabetes promotes nutrient surplus signaling (through Akt and mammalian target of rapamycin complex 1) and inhibits nutrient deprivation signaling (through sirtuin-1 and its downstream effectors); this suppresses autophagy and promotes endoplasmic reticulum and oxidative stress and mitochondrial dysfunction, thereby undermining the health of diabetic cardiomyocytes. The hyperinsulinemia of diabetes may also activate sodium-hydrogen exchangers in cardiomyocytes (leading to injury and loss) and in the proximal renal tubules (leading to sodium retention). ⋯ Inhibition of SGLT2 may also lead to a reduction in the activity of sodium-hydrogen exchangers in the kidney (leading to diuresis) and in the heart (attenuating the development of cardiac hypertrophy and systolic dysfunction). Finally, SGLT2 inhibitors reduce the mass and mute the adverse biology of epicardial adipose tissue (and reduce the secretion of leptin), thus explaining the capacity of these drugs to mitigate myocardial inflammation, microcirculatory dysfunction, and fibrosis, and improve ventricular filling dynamics. The pathophysiological mechanisms by which SGLT2 inhibitors may benefit heart failure likely differ depending on ejection fraction, but each represents interference with distinct pathways by which hyperinsulinemia may adversely affect cardiac structure and function.
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JACC. Heart failure · Jun 2021
Rehabilitation Intervention in Older Patients With Acute Heart Failure With Preserved Versus Reduced Ejection Fraction.
This study assessed for treatment interactions by ejection fraction (EF) subgroup (≥45% [preserved EF (HFpEF); vs <45% [reduced EF; (HFrEF)]). ⋯ Among older patients hospitalized with ADHF, compared with HFrEF those with HFpEF had significantly worse impairments at baseline and may derive greater benefit from the intervention. (A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients [REHAB-HF]; NCT02196038).
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JACC. Heart failure · May 2021
Worsening Heart Failure Episodes Outside a Hospital Setting in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial.
This study sought to evaluate the frequency and prognostic implications of urgent heart failure (HF) visits in a large global clinical trial of HF with preserved ejection fraction (HFpEF). ⋯ Like HF hospitalizations, worsening HF events treated in the ambulatory setting are prognostically important in HFpEF. Inclusion of these events in the composite primary endpoint underscores the benefit of sacubitril/valsartan compared with valsartan in PARAGON-HF. (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
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JACC. Heart failure · May 2021
Burden of Heart Failure Signs and Symptoms, Prognosis, and Response to Therapy: The PARAGON-HF Trial.
This study investigated the prognostic importance of heart failure (HF) signs and symptoms in patients with heart failure and preserved ejection fraction (HFpEF), and the effect of sacubitril/valsartan on HF signs and symptoms. ⋯ High burden of HF signs and symptoms, particularly the presence of orthopnea and rales, portends a higher risk for adverse CV events in patients with HF with preserved ejection fraction. Sacubitril/valsartan did not significantly decrease the burden of HF signs and symptoms over time but did reduce exertional dyspnea relative to valsartan. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
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JACC. Heart failure · Jan 2021
Multicenter Study Observational StudyCOVID-19 in Heart Transplant Recipients: A Multicenter Analysis of the Northern Italian Outbreak.
The aim of this study was to assess the clinical course and outcomes of all heart transplant recipients affected by coronavirus disease-2019 (COVID-19) who were followed at the leading heart transplant centers of Northern Italy. ⋯ The prevalence and mortality of SARS-CoV-2 should spur clinicians to immediately refer heart transplant recipients suspected as having SARS-CoV2 infection to centers specializing in the care of this vulnerable population.