Natriuretic Peptides, Body Mass Index, and Clinical Outcomes in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.

Background: Natriuretic peptides are the primary biomarkers recommended in heart failure (HF) guidelines to risk stratify patients in clinical practice and serve as key eligibility criteria in contemporary clinical trials. However, threshold levels typically do not account for measures of adiposity, such as body mass index (BMI).

Objective: To evaluate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) with clinical outcomes in individuals with HF and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), stratified according to BMI.

Adiposity-Related Anthropometrics and Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Participant-Level Pooled Analysis of Randomized Clinical Trials.

Background: Obesity is highly prevalent among individuals with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) and is associated with increased risk of disability and death.

Objectives: The purpose of this study is to explore the association between different adiposity-related anthropometrics and clinical outcomes in this population.

Methods: In this participant-level pooled analysis of 5 international randomized trials that enrolled adults with HFmrEF/HFpEF, the association between adiposity-related anthropometrics (body mass index [BMI], waist circumference [WC], and waist-to-height ratio [WHtR]) and heart failure (HF) and mortality outcomes was evaluated, overall and by age and sex.

Differences in Characteristics and Clinical Outcomes According to Age in Patients Following High-Risk Myocardial Infarction: Insights from PARADISE-MI.

The prevalence of coronary heart disease is increasing in an aging population. A better understanding of how risk profiles and outcomes differ by age may allow for targeted treatment and prevention strategies. PARADISE-MI randomized 5661 adults without prior heart failure (HF) to sacubitril/valsartan versus ramipril within 0.

Long-term outcomes of recurrent myocardial infarction: a nationwide Danish study.

Background: During the past decades outcomes of first-time myocardial infarction (MI) have improved substantially. However, it is unknown if the prognosis following a recurrent MI has also improved similarly.

Methods: We conducted a nationwide registry-based study including all patients with first-time recurrent MI in Denmark during 2003 to 2022.

Obesity and Risk of Kidney Outcomes in Heart Failure With Preserved Ejection Fraction: A Participant-Level Pooled Analysis of 4 Contemporary Trials.

Background: Obesity is prevalent among patients with heart failure with preserved ejection fraction (HFpEF).

Objectives: This study aims to evaluate whether anthropometrics including body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) are associated with kidney outcomes in patients with HFpEF.

Methods: In this participant-level pooled analysis of DELIVER, PARAGON-HF, TOPCAT Americas, and I-PRESERVE, we evaluated the impact of adiposity-related anthropometrics on risk of kidney outcomes (sustained eGFR reduction of ≥50%, end-stage kidney disease, or kidney-related death).

Application of a transthyretin amyloid cardiomyopathy score to heart failure with mildly reduced or preserved ejection fraction.

Aims: The safety and efficacy of heart failure (HF)-directed medical therapy among patients who might be considered for further diagnostic evaluation to rule out transthyretin amyloid cardiomyopathy (ATTR-CM) is largely unknown.

Methods And Results: We applied a previously validated ATTR-CM screening score in patients with HF and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and assessed treatment effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i), angiotensin receptor-neprilysin inhibitor (ARNI) and mineralocorticoid receptor antagonists (MRAs) based on their score-based ATTR-CM risk, from the DELIVER, PARAGON-HF and TOPCAT Americas trials. We applied a re-derived five-variable modified ATTR-CM score (range -1 to 9) which included age, male sex, hypertension, left ventricular ejection fraction <60%, posterior wall thickness ≥12 mm.

NT-proBNP in the Early Convalescent Phase after High-Risk Myocardial Infarction Is Associated with Adverse Cardiovascular Outcomes: the PARADISE-MI Trial.

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with heart failure (HF) hospitalizations and death when measured during a myocardial infarction (MI). However, NT-proBNP concentrations change following the initial ischemic insult and less is known about the prognostic importance of NT-proBNP in the early convalescent phase.

Methods: PARADISE-MI randomized 5661 patients with MI complicated by LVEF ≤40% and/or pulmonary congestion to sacubitril/valsartan or ramipril.

Aspirin in primary prevention: Undue reliance on an uninformative trial led to misinformed clinical guidelines.

Best practices for design, conduct, analysis, and interpretation of randomized controlled trials should adhere to rigorous statistical principles. The reliable detection of small effects of treatment should be based on results reported from the primary pre-specified endpoints of large-scale randomized trials designed a priori to test relevant hypotheses. Inference about treatment should not be based on undue reliance on individual small trials, meta-analyses of small trials, subgroups, or post hoc analyses.

Multiparametric Assessment of Right Ventricular Dysfunction in Heart Failure: An Analysis From PARAGON-HF.

Background: This study aims to characterize right ventricular dysfunction (RVD) in heart failure (HF) with preserved ejection fraction and understand the cumulative prognostic value of abnormal RV echocardiographic parameters in HF with preserved ejection fraction.

Methods And Results: Data from 809 patients in the PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in HF With Preserved Ejection Fraction) echocardiographic substudy (55% women, mean age 74±8 years) were analyzed. Correlates of RVD (defined as tricuspid annular plane systolic excursion <1.

Mortality after high-risk myocardial infarction over the last 20 years: Insights from the VALIANT and PARADISE-MI trials.

Aims: The temporal changes in clinical profiles and outcomes of high-risk myocardial infarction survivors enrolled in clinical trials are poorly described. This study compares mortality rates, baseline characteristics, and the prognostic impact of therapies among participants of the VALIANT and PARADISE-MI trials.

Methods And Results: Exclusively VALIANT participants who matched the inclusion criteria of the PARADISE-MI trial were included in the analysis.

Association between body mass index and clinical outcomes in patients with acute myocardial infarction and reduced systolic function: Analysis of PARADISE-MI trial data.

Aims: The relationship between body mass index (BMI) and clinical outcomes in patients with cardiovascular disease, including acute heart failure (AHF) and acute myocardial infarction (AMI), remains debated. This study investigates the association between BMI and clinical outcomes within the PARADISE-MI cohort, while also evaluating the impact of angiotensin receptor-neprilysin inhibitor (ARNI) versus angiotensin-converting enzyme inhibitor (ACE-I) treatment on this relationship.

Methods And Results: The analysis included 5589 patients from the PARADISE-MI study with available baseline BMI data.

Effect of sacubitril/valsartan in heart failure with preserved ejection fraction across the age spectrum in PARAGON-HF.

Aims: To evaluate clinical outcomes, echocardiographic features, and the efficacy and safety of sacubitril/valsartan compared to valsartan across age groups in the PARAGON-HF trial.

Methods And Results: A total of 4796 participants ≥50 years of age with chronic heart failure (HF) and left ventricular ejection fraction (LVEF) ≥45% were divided into three age groups: <65 years (n = 825), 65-74 years (n = 1772), and ≥75 years (n = 2199). Echocardiograms of 1097 patients were analysed in a standardized fashion at a core imaging laboratory.

Visit-to-visit changes in heart rate in heart failure: A pooled participant-level analysis of the PARADIGM-HF and PARAGON-HF trials.

Aims: Resting heart rate (HR) is a strong risk marker in patients with heart failure (HF), but the clinical implications of visit-to-visit changes in HR (ΔHR) are less well established. We aimed to explore the association between ΔHR and subsequent outcomes in a pooled dataset of two well-characterized cohorts of patients with HF across the full range of left ventricular ejection fraction (LVEF).

Methods And Results: PARADIGM-HF and PARAGON-HF were randomized trials testing sacubitril/valsartan versus enalapril or valsartan, respectively, in patients with HF and LVEF ≤40% (PARADIGM-HF) or LVEF ≥45% (PARAGON-HF).

Sacubitril/valsartan reduces incident anaemia and iron therapy utilization in heart failure: The PARAGON-HF trial.

Aims: Renin-angiotensin system inhibitors (RASi) have been shown to lower haemoglobin levels, potentially related to reductions in erythropoietin levels and haematopoiesis. We examined whether sacubitril/valsartan might attenuate this effect of RASi alone on incident anaemia in patients with heart failure (HF) with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF).

Methods And Results: PARAGON-HF was a global, multicentre randomized clinical trial of sacubitril/valsartan versus the RASi valsartan in patients with HF and left ventricular ejection fraction ≥45%.

Therapeutic Effects of Heart Failure Medical Therapies on Standardized Kidney Outcomes: Comprehensive Individual Participant-Level Analysis of 6 Randomized Clinical Trials.

Background: Kidney outcomes have been variably defined using nonstandardized composite end points in key heart failure trials, thus introducing complexity in their interpretation and cross-trial comparability. We examined the effects of steroidal mineralocorticoid receptor antagonists, the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan, and SGLT2 (sodium-glucose cotransporter-2) inhibitors on composite kidney end points using uniform definitions in 6 contemporary heart failure trials.

Methods: Individual participant-level data from trials of steroidal mineralocorticoid receptor antagonists (EMPHASIS-HF [Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure], TOPCAT [Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist] Americas), angiotensin receptor-neprilysin inhibitor (PARADIGM-HF [Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure], PARAGON-HF [Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blockers Global Outcomes in HF With Preserved Ejection Fraction]), and SGLT2 inhibitors (DAPA-HF [Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure], DELIVER [Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure]) were included.