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OBJECTIVES This study sought to determine the frequency and magnitude of impaired systolic deformation in heart failure with preserved ejection fraction (HFpEF). BACKGROUND Although diastolic dysfunction is widely considered a key pathophysiologic mediator of HFpEF, the prevalence of concomitant systolic dysfunction has not been clearly defined. METHODS(More)
BACKGROUND Heart failure with preserved ejection fraction is associated with substantial morbidity and mortality, but effective treatments are lacking. We assessed the efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), in patients with this disorder. METHODS PARAMOUNT was a phase 2, randomised,(More)
IMPORTANCE Diastolic heart failure (ie, heart failure with preserved ejection fraction) is a common condition without established therapy, and aldosterone stimulation may contribute to its progression. OBJECTIVE To assess the efficacy and safety of long-term aldosterone receptor blockade in heart failure with preserved ejection fraction. The primary(More)
BACKGROUND Heart failure (HF) is a clinical syndrome characterized by signs and symptoms involving multiple organ systems. Longitudinal data demonstrating that asymptomatic cardiac dysfunction precedes overt HF are scarce, and the contribution of noncardiac dysfunction to HF progression is unclear. We hypothesized that subclinical cardiac and noncardiac(More)
IMPORTANCE Worsening chronic heart failure (HF) is a major public health problem. OBJECTIVE To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF). DESIGN, SETTING, AND PARTICIPANTS Dose-finding phase 2 study that(More)
BACKGROUND Low levels of the amino acid homoarginine and parathyroid hormone (PTH) excess are both independently related to an increased risk of cardiovascular morbidity and mortality. Accumulating evidence points to a mutual interplay between homoarginine and PTH. The authors therefore aimed to investigate circulating homoarginine levels in patients with(More)
AIMS Reduced physical activity is associated with increased risk of heart failure (HF) in middle-aged individuals. We hypothesized that physical inactivity is also associated with greater HF risk in older individuals, and examined if the association was consistent for HF with preserved ejection fraction (HFPEF) vs. HF with a reduced ejection fraction(More)
AIM Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. METHODS We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and(More)
AIMS Mechanical dyssynchrony has been postulated to play a pathophysiologic role in heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS We quantified left ventricular (LV) systolic dyssynchrony in 130 HFpEF patients with NYHA class II-IV symptoms, ejection fraction (EF) ≥45%, and NT-proBNP levels >400 pg/mL enrolled in the(More)
AIMS The clinical outcomes for patients with worsening chronic heart failure (WCHF) remain exceedingly poor despite contemporary evidence-based therapies, and effective therapies are urgently needed. Accumulating evidence supports augmentation of cyclic guanosine monophosphate (cGMP) signalling as a potential therapeutic strategy for HF with reduced or(More)