Baseline characteristics of patients with heart failure and preserved ejection fraction in the PARAGON-HF trial

Background: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. Methods and Results: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464–1610), and structural heart disease. Conclusions: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

P5265Magnetic resonance multilayer assessment of strain in patients with heart failure

Abstract Introduction Muscular architecture of the heart is three dimensionally complex and contractility parameters vary widely. Cardiac magnetic resonance (CMR) feature tracking is a largely available and facile method to assess myocardial strain at different layers of the myocardium. Purpose Assessing and compare the myocardial longitudinal (GLS) and circumferential strain (GCS) at three distinct layers of the myocardium in patients with heart failure (HF). Methods 59 patients with a clinical diagnosis of HF who were post-hoc subdivided according to the measured EF and echo assessment of diastolic impairment into 3 groups, following ESC guidelines, were included: (1) patients with HF with preserved ejection fraction (HFpEF) where EF &gt;50% and diastolic dysfunction (E/e' ratio) is present and plasma levels of natriuretic peptides are elevated, (2) patients with HF with mid-range ejection fraction (HFmrEF), where EF = 40–49% and similar additional criterias are present, (3) patients with HF with reduced ejection fraction (HFrEF) where EF &lt;40%. Exclusion criteria: valvulopathy, arrhythmias, insufficient acquisition and artefacts. Results Strain values are the highest in the Endo− and progressively lower in the Myo− and Epi− layers with a gradient present in all groups but decreasing in HFmEF and further in HFrEF. GLS decrease with the severity of the disease in all 3 layers Normal &gt; HFpEF &gt; HFmrEF &gt; HFrEF (Endo−: −23.0±3.5 vs −20.0±3.3 vs −16.4±2.2 vs −11.0±3.2, p&lt;0.001, Myo−: −20.7±2.4 vs −17.5.0±2.6 vs −14.5±2.1 vs −9.6±2.7, p&lt;0.001, Epi−: −15.7±1.9 vs −12.2±2.1 vs −10.6±2.3 vs −7.7±2.3, p&lt;0.001) (Figure A), GCS is not different between the Normal and HFpEF (Endo−: −34.5±6.2 vs −33.9±5.7, p=0.51; Myo−: −21.9±3.8 vs −21.3±2.2, p=0.39; Epi−: −11.4±2.0 vs −10.9±2.3, p=0.54) but markedly lower in systolic HF groups Normal &gt; HFmrEF &gt; HFrEF (Endo−: −34.5±6.2 vs −20.0±4.2 vs −12.3±4.2, p&lt;0.001; Myo−: −21.9±3.8 vs −13.0±3.4 vs −8.0±2.7, p&lt;0.001; Epi−: −11.4±2.0 vs −7.9±2.3 vs −4.5±1.9) (Figure B). ROC analysis renders Endo− GCS (AUC=0.89) and respectively Endo− GLS (AUC=0.74) as optimal to detect contractile impairment in HF with Youden's thresholds of −20.2 for Endo− GLS and, respectively, −28.1 for Endo− GCS. Endo− GCS is not different between control and HFpEF and GLS impairment is present only inconstantly in HFpEF. Conclusions Feature tracking CMR successfully assess layer-specific myocardial strain and emerges as a powerful tool in functional stratification of patients with HF. Strain amplitude varies consistently throughout the myocardium and its quantification warrants careful standardization. Sub-endocardial strain values of strain are comparatively the highest and show most predictive power to detect contractile impairment. Underlying systolic impairment is present only in a subgroup of patients with HFpEF and only GLS and not the GCS is for this purpose a useful diagnostic tool. </jats:sec