Angiotensin-neprilysin inhibition and renal outcomes in heart failure with preserved ejection fraction

Background: In patients with heart failure, chronic kidney disease (CKD) is common and associated with a higher risk of renal events than in patients without CKD. We assessed the renal effects of angiotensin/neprilysin inhibition in patients with heart failure and preserved ejection fraction (HFpEF) enrolled in PARAGON-HF. Methods: In this randomized, double-blind, event-driven trial, we assigned 4,822 patients with HFpEF to receive sacubitril/valsartan (n=2419) or valsartan (n=2403). Herein we present the results of the pre-specified renal composite outcome (time to first occurrence of either: ≥50% reduction in eGFR, end-stage renal disease, or death from renal causes), the individual components of this composite, and the influence of therapy on eGFR slope. Results: At randomization, eGFR was 63±19 ml/min/1.73m2. At study closure, the composite renal outcome occurred in 33 patients (1.4%) assigned to sacubitril/valsartan and 64 patients (2.7%) assigned to valsartan (hazard ratio [HR], 0.50; 95%CI, 0.33 to 0.77; P=0.001). The treatment effect on the composite renal endpoint did not differ according to the baseline eGFR (<60 vs ≥ 60 ml/min/1.73 m2 (P-interaction=0.92). The decline in eGFR was less for sacubitril/valsartan compared with valsartan (-1.8 [95%CI, -2.0 to -1.6] vs. -2.4 [95%CI, -2.6 to - 2.2] ml/min/1.73m2/year). Conclusions: In patients with HFpEF, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, compared with valsartan

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

Comorbid Heart Failure and Renal Impairment: Epidemiology and Management.

Heart failure mortality is significantly increased in patients with baseline renal impairment and those with underlying heart failure who subsequently develop renal dysfunction. This accelerated progression occurs independent of the cause or grade of renal dysfunction and baseline risk factors. Recent large prospective databases have highlighted the depth of the current problem, while longitudinal population studies support an increasing disease burden. We have extensively reviewed the epidemiological and therapeutic data among these patients. The evidence points to a progression of heart failure early in renal impairment, even in the albuminuric stage. The data also support poor prescription of prognostic therapies. As renal function is the most important prognostic factor in heart failure, it is important to establish the current understanding of the disease burden and the therapeutic implications

The relationship between renal function and cardiac structure, function, and prognosis after myocardial infarction - The VALIANT Echo study

ObjectivesThe purpose of this study was to determine whether alterations in cardiac structure or function contribute to the increased risk associated with renal impairment after myocardial infarction (MI).BackgroundRenal impairment is associated with adverse cardiovascular outcomes after MI.MethodsEchocardiography was performed on 603 patients with left ventricular (LV) dysfunction, heart failure (HF), or both after MI. Patients were grouped according to their estimated glomerular filtration rate (eGFR), and measures of cardiac structure and function were related to baseline eGFR. The relationship between eGFR and cardiac structure and function and clinical outcomes of death or HF was assessed with multivariable Cox regression.ResultsEjection fraction, infarct segment length, right ventricular function, and mitral deceleration time were not influenced by renal function. Patients with reduced eGFR had smaller LV and larger left atrial (LA) volumes and higher left ventricular mass index (LVMI) and LV mass/LV volume ratio. A greater proportion of the patients with reduced eGFR had LV hypertrophy. The relationship between eGFR and the outcome of death or HF was attenuated by including baseline differences in LVMI, and both LVMI and LA volume conferred additional prognostic information in a multivariable model.ConclusionsRenal impairment was associated with smaller LV and larger LA volumes and increased LVMI. Systolic function was similar when compared with patients with normal renal function. Thus, reduced systolic function cannot account for worse outcomes in patients with renal impairment after MI. Indirect measures of diastolic function suggest that diastolic dysfunction might be an important mediator of increased risk in this population