TOPCAT

Background Although high resting heart rates are associated with adverse outcomes in heart failure with reduced ejection, the reports for heart failure with preserved ejection fraction (HFpEF) are conflicting. Design A secondary analysis was conducted in order to examine the relationship between resting heart rate and adverse outcomes in 2705 patients (mean age = 68 ± 10 years; 47% men; 88% white) with HFpEF who were in sinus rhythm from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT)...

No abstract text is available yet for this article.

BACKGROUND: Peripheral artery disease (PAD) in heart failure with preserved ejection fraction (HFpEF) is associated with an increased mortality risk, but the risk of individual outcomes associated with PAD in this patient group is less clear. HYPOTHESIS: PAD is associated with adverse outcomes in HFpEF, including hospitalization and specific cardiovascular outcomes. METHODS: We examined the association between PAD and adverse outcomes in 3385 patients with HFpEF (mean age, 69 ± 9...

AIMS: To investigate the effect of the different eligibility criteria used by phase III clinical studies in heart failure with preserved ejection fraction (HFpEF) on patient selection, phenotype, and survival. METHODS AND RESULTS: We applied the key eligibility criteria of 7 phase III HFpEF studies (Digitalis Investigation Group Ancillary, Candesartan in Patients With Chronic Heart Failure and Preserved Left-Ventricular Ejection Fraction, Perindopril in Elderly People With Chronic Heart Failure, Irbesartan in Heart Failure With Preserved Systolic Function, Japanese Diastolic Heart Failure, Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist, and Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF; ongoing]) to a typical and well-characterized HFpEF population (n = 557) seen in modern European cardiological practice...

Aims: To determine if markers of diastolic dysfunction are associated with atrial fibrillation (AF) development among patients with heart failure with preserved ejection fraction (HFpEF). Methods and results: We examined the association of several echocardiographic measures of diastolic dysfunction with incident AF in 573 patients (mean age = 68 ± 9.5 years; 48% men; 79% white) with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT) who were free of baseline AF...

OBJECTIVES: The aims of this study were to explore the relationship of baseline levels of natriuretic peptides (NPs) with outcomes and to test for an interaction between baseline levels of NPs and the effects spironolactone. BACKGROUND: Plasma NPs are considered to be helpful in the diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF), and elevated levels are associated with adverse outcomes. Levels of NPs higher than certain cutoffs are often used as inclusion criteria in clinical trials of HFpEF to increase the likelihood that patients have HF and to select patients at higher risk for events...

AIMS: Left ventricular mechanical dyssynchrony has been described in heart failure with preserved ejection fraction (HFpEF), but its prognostic significance is not known. METHODS AND RESULTS: Of 3445 patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, dyssynchrony analysis was performed on 424 patients (12%) by multiple speckle tracking echocardiography strain-based criteria. The primary dyssynchrony analysis was the standard deviation of the time to peak longitudinal strain (SD T2P LS)...

BACKGROUND: Gynaecological cancers are diagnosed in over 1000 women in Wales every year. We estimate that this is costing the National Health Service (NHS) in excess of £1 million per annum for routine follow-up appointments alone. Follow-up care is not evidence-based, and there are no definitive guidelines from The National Institute for Health and Care Excellence (NICE) for the type of follow-up that should be delivered. Standard care is to provide a regular medical review of the patient in a hospital-based outpatient clinic for a minimum of 5 years...

Clinical trial Data and Safety Monitoring Boards (DSMBs) have a primary obligation of ensuring study participant safety, while maintaining trial integrity. The role of DSMBs is expanding, and ideally should include post-hoc reporting of deliberative processes related to clinically important safety issues or factors that could impact on future trial designs. We describe how the TOPCAT DSMB detected, investigated, and adjudicated an unexpectedly large renal adverse event signal midway through the trial, and offer general guidelines for dealing with similar unanticipated occurrences in future trials...

Aldosterone's deleterious pathophysiological effects on the cardiovascular system if blocked by mineralcorticord antagonists (MRAs) logically should lead to improvement in heart function and outcomes in heart failure (HF). The first trial to test this hypothesis was tthe RALES trial in 1999 which treated patients with class III-IV HF with spironolactone. It showed significant reduction in mortality and cardiovascular hospitalzation rates. This was confirmed & extended in EMHASIS-HF RCT with classs II-III being treated with ACEIs & BB who received placebo or elperinone (a MRA) with again a statistically significant fall in mortality & hospitalization...

TOPCAT was a multinational clinical trial of 3,445 heart failure with preserved ejection fraction (HFpEF) patients that enrolled in 233 sites in six countries in North America, Eastern Europe and South America. Patients with a heart failure hospitalization in the last 12 months or an elevated B-type natriuretic peptide (BNP) were randomized to the mineralocorticoid receptor antagonist spironolactone vs. placebo. Sites in Russia and the Republic of Georgia provided the majority of early enrollment, primarily based on the hospitalization criterion since BNP levels were initially unavailable there...

Aldosterone's deleterious pathophysiological effects on the cardiovascular system if blocked by mineralcorticord antagonists (MRAs) logically should lead to improvement in heart function and outcomes in heart failure (HF). The first trial to test this hypothesis was tthe RALES trial in 1999 which treated patients with class III-IV HF with spironolactone. It showed significant reduction in mortality and cardiovascular hospitalzation rates. This was confirmed & extended in EMHASIS-HF RCT with classs II-III being treated with ACEIs & BB who received placebo or elperinone (a MRA) with again a statistically significant fall in mortality & hospitalization...

No abstract text is available yet for this article.

Although patients with heart failure and preserved ejection fraction (HF-PEF) represent nearly half of the population with chronic heart failure, few evidence-based medical therapies are available. The neutral overall results of the TOPCAT trial of spironolactone in HF-PEF leave clinicians who treat heart failure with an ongoing clinical dilemma. In this review, we outline an approach to the clinical management of the patient with HF-PEF synthesizing data from available clinical trials and expert consensus.

BACKGROUND: Left atrial (LA) size is an established marker of risk for adverse outcomes in heart failure with preserved ejection fraction (HFpEF). However, the independent prognostic importance of LA function in HFpEF is not known. METHODS AND RESULTS: We assessed LA function measured by speckle-tracking echocardiography in 357 patients with HFpEF enrolled in the Treatment Of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial who were in sinus rhythm at the time of echocardiography...

OBJECTIVES: This study examined the relationship between baseline QRS duration and clinical outcomes in subjects enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial. BACKGROUND: Heart failure with preserved ejection fraction (HFPEF) is a heterogeneous clinical syndrome. Whether QRS duration identifies HFPEF subjects at an increased risk of adverse outcomes has not been well studied. METHODS: QRS duration was analyzed as a dichotomous variable (≥120 ms or <120 ms) and as a continuous variable to determine its relation to the primary outcome (composite of cardiovascular death, aborted cardiac arrest, or HF hospitalization [HFH]) and to each component of the primary outcome...

BACKGROUND: Heart failure (HF) with preserved ejection fraction patients have equally impaired health-related quality of life (HRQL) compared with those with HF with reduced ejection fraction, but limited studies have evaluated the impact of therapies on changes in HRQL. METHODS AND RESULTS: Patients ≥50 years of age, with symptomatic HF and left ventricular ejection fraction ≥45%, were enrolled in Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) and randomized to spironolactone or placebo...

BACKGROUND: Limited data exist regarding the impact of aldosterone antagonist therapy on cardiac structure and function in heart failure with preserved ejection fraction and on the prognostic relevance of changes in cardiac structure and function in heart failure with preserved ejection fraction. METHODS AND RESULTS: Cardiac structure and function were assessed by quantitative echocardiography at baseline and at 12- to 18-month follow-up in 239 patients with heart failure with preserved ejection fraction (left ventricular [LV] ejection fraction [LVEF] ≥45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial...

Mineralocorticoid receptor antagonists (MRAs) represent an attractive class of drugs for the treatment of heart failure with preserved ejection fraction (HFpEF) because of the deleterious cardiovascular effects of aldosterone and because MRAs combat myocardial fibrosis and improve cardiac structure/function and vascular health. Recently, the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study, a randomized, double-blind clinical trial of spironolactone versus placebo, was conducted in 3445 patients with symptomatic HFpEF...

AIMS: While mineralocorticoid receptor antagonists (MRAs) have been shown to benefit patients with reduced left ventricular ejection fraction (LVEF), spironolactone did not reduce the primary endpoint of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest in patients with heart failure with preserved ejection fraction (HFpEF) in the TOPCAT trial, which enrolled patients with LVEF of 45% or greater. We utilized data from TOPCAT to assess the relationship between LVEF as well as outcomes and efficacy of spironolactone...