Baseline Characteristics of Patients in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial

Abstract

Background Treatment of Preserved Cardiac Function with an Aldosterone Antagonist (TOPCAT) is an ongoing randomized controlled trial of spironolactone versus placebo for heart failure with preserved ejection fraction (HFpEF). We sought to describe the baseline clinical characteristics of subjects enrolled in TOPCAT relative to other contemporary observational studies and randomized clinical trials of HFpEF. Methods and Results Between August 2006 and January 2012, 3445 patients with symptomatic HFpEF from 270 sites in 6 countries were enrolled in TOPCAT. At the baseline study visit, all subjects provided a detailed medical history and underwent physical examination, electrocardiography, quality of life, and laboratory assessment. Key parameters were compared to other large, contemporary HFpEF studies. The mean age was 68.6±9.6 years with a slight female predominance (52%); mean body mass index was 32 kg/m2; and comorbidities were common. History of hypertension (91% prevalence in TOPCAT) exceeded all other major HFpEF clinical trials. However, baseline blood pressure was well controlled (129/76 mmHg; systolic blood pressure 7-16 mmHg lower than other similar trials). Other common comorbidities included coronary artery disease (57%), atrial fibrillation (35%), chronic kidney disease (38%) and diabetes (32%). Self-reported activity levels were low, quality of life scores were comparable to those reported for patients with end-stage renal disease, and the prevalence of moderate or greater depression was 27%. Conclusions TOPCAT subjects share many common characteristics with contemporary HFpEF cohorts. Low activity level, significantly decreased quality of life, and depression were common at baseline in TOPCAT, underscoring the continued unmet need for evidence-based treatment strategies in HFpEF. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.

Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure With Preserved Ejection Fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure])

“…Patients enrolled in REDUCE LAP-HF I were generally similar to those enrolled in HFpEF epidemiological studies 23 and contemporary HFpEF clinical trials. 22 However, unlike these prior studies, patients enrolled in the present trial had objective evidence of elevated LV filling pressure (ie, PCWP) at rest and during exercise at baseline, which confirmed the HF diagnosis. Together these findings show that patients enrolled in REDUCE LAP-HF I represent contemporary patients with HFpEF encountered in routine clinical practice.…”

“…22 Participants were elderly, 50% female, were obese, and had multiple comorbidities. Left ventricular EF was preserved (>50%) in the majority, and most of the participants were on a relatively high dose of diuretics and had a prior HF hospitalization or acute care visit within the last 12 months.…”

Impact of Spironolactone on Longitudinal Changes in Health-Related Quality of Life in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial

“…6,11,12 Briefly, TOPCAT study was a multicenter, international, randomized, double-blind, placebocontrolled trial of spironolactone versus placebo in subjects with symptomatic HF-PEF enrolled in United States, Russia, Republic of Georgia, Canada, Brazil, and Argentina. Participants were enrolled from August 2006 until January 2012.…”

Estrogens and Myocardial Chymase

“…4 In the recent trial of preserved cardiac function heart failure (HF) with the aldosterone antagonist spironolactone (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]), mean age was 68.6 years, 91% had hypertension, and 52% of the patients were women. 5 In the TOPCAT trial body mass index was 32 kg/m 2 while comorbidities were common. Patients with HF with reduced ejection fraction and HFpEF each make up approximately half of the overall HF burden.…”

“…Although concentric LV remodeling is common, it is by no means universal and many patients exhibit normal LV geometry or an eccentric pattern, which means different pathophysiologically relevant subphenotypes within this syndrome. 5 In HFpEF, it has been proposed, a systemic proinflammatory state is induced by comorbidities such as obesity or diabetes mellitus as the origin of microvascular endothelial cell inflammation and subsequent concentric cardiac remodeling and dysfunction, 8 with interactions of the endothelium with cardiac fibroblasts and cardiomyocytes and with cardiac neurohormonal status. 8 Myocardial damage, by different noxious causes, triggers an inflammatory reaction driving postinjury repair mechanisms and chronic remodeling processes that are detrimental to cardiac function.…”