Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation.

Patients with heart failure (HF) and atrial fibrillation (AF) have higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) than HF patients without AF. There is uncertainty about the prognostic importance of a given concentration of NT-proBNP in HF patients with and without AF. We investigated this question in a large cohort of patients with HF and reduced ejection fraction. We studied 14 737 patients with HF and reduced ejection fraction and a measurement of NT-proBNP at time of screening, enrolled in either the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG. Median (Q1, Q3) levels of NT-proBNP were 1817 pg/mL (1095-3266 pg/mL) in those with AF and 1271 pg/mL (703-2569 pg/mL) in those without (P<0.0001). Patients with AF were older (67 versus 62 years), had worse New York Heart Association class (III/IV; 36% versus 24%), and experienced fewer previous HF hospitalizations (52% versus 61%) or myocardial infarction (30% versus 46%); all P<0.001. We categorized patients with and without AF into 5 NT-proBNP bands: <400, 400 to 999 (reference), 1000 to 1999, 2000 to 2999, and ≥3000 pg/mL. For the primary composite outcome of cardiovascular death or HF hospitalization, event rates differed for patients with and without AF in the lowest band (<400 pg/mL; 8.2 versus 5.0 per 100 patient-years), but not for the higher bands (400-999 pg/mL, 7.4 versus 7.7 per 100 patient-years; 1000-1999 pg/mL, 9.8 versus 11.4 per 100 patient-year; 2000-2999 pg/mL, 13.5 versus 13.4 per 100 patient-years; ≥3000 pg/mL, 22.7 versus 23.0 per 100 patient-years). These findings were consistent whether NT-proBNP was examined as a categorical or continuous variable and before and after adjustment for other prognostic variables. We found similar results for the components of the composite outcome and all-cause mortality. HF and reduced ejection fraction patients with AF had higher NT-proBNP than those without AF. However, above a concentration of 400 pg/mL (representing most patients in each group), NT-proBNP had similar predictive value for adverse cardiovascular outcomes, irrespective of AF status. URL: https://www.clinicaltrials.gov. Unique identifier NCT00853658 (ATMOSPHERE) and NCT01035255 (PARADIGM-HF).

Kristensen SL ，Jhund PS ，Mogensen UM ，Rørth R ，Abraham WT ，Desai A ，Dickstein K ，Rouleau JL ，Zile MR ，Swedberg K ，Packer M ，Solomon SD ，Køber L ，McMurray JJV ，PARADIGM-HF and ATMOSPHERE Committees and Investigators ... -  《-》

N-Terminal Pro-B-Type Natriuretic Peptide Levels for Risk Prediction in Patients With Heart Failure and Preserved Ejection Fraction According to Atrial Fibrillation Status.

Kristensen SL ，Mogensen UM ，Jhund PS ，Rørth R ，Anand IS ，Carson PE ，Desai AS ，Pitt B ，Pfeffer MA ，Solomon SD ，Zile MR ，Køber L ，McMurray JJV ... -  《-》

Comparison of BNP and NT-proBNP in Patients With Heart Failure and Reduced Ejection Fraction.

Rørth R ，Jhund PS ，Yilmaz MB ，Kristensen SL ，Welsh P ，Desai AS ，Køber L ，Prescott MF ，Rouleau JL ，Solomon SD ，Swedberg K ，Zile MR ，Packer M ，McMurray JJV ... -  《-》

Clinical Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction and Chronic Obstructive Pulmonary Disease: Insights From PARADIGM-HF.

Ehteshami-Afshar S ，Mooney L ，Dewan P ，Desai AS ，Lang NN ，Lefkowitz MP ，Petrie MC ，Rizkala AR ，Rouleau JL ，Solomon SD ，Swedberg K ，Shi VC ，Zile MR ，Packer M ，McMurray JJV ，Jhund PS ，Hawkins NM ... -  《Journal of the American Heart Association》

Effects of Sacubitril/Valsartan on N-Terminal Pro-B-Type Natriuretic Peptide in Heart Failure With Preserved Ejection Fraction.

The authors sought to evaluate the prognostic significance of baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP), whether NT-proBNP modified the treatment response to sacubitril/valsartan, and the treatment effect of sacubitril/valsartan on NT-proBNP overall and in key subgroups. Sacubitril/valsartan reduces NT-proBNP in heart failure (HF) with both reduced and preserved ejection fraction (EF), but did not significantly reduce total HF hospitalizations and cardiovascular death compared with valsartan in patients with HF with preserved EF (HFpEF). In the PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) trial, 4,796 patients with HFpEF and elevated NT-proBNP were randomized to sacubitril/valsartan or valsartan. NT-proBNP was measured at screening in all patients and at 5 subsequent times in >2,700 patients: before, between, and after sequential valsartan and sacubitril/valsartan run-in periods, and 16 and 48 weeks post-randomization. Median NT-proBNP was 911 pg/ml (interquartile range: 464 to 1,613 pg/ml) at screening. Screening NT-proBNP was strongly associated with the primary endpoint, total HF hospitalizations and cardiovascular death (rate ratio [RR]: 1.68 per log increase in NT-proBNP, 95% confidence interval [CI]: 1.53 to 1.85; p < 0.001). This relationship was stronger in patients with atrial fibrillation (adjusted RR: 2.33 [95% CI: 1.89 to 2.87] vs. 1.58 [95% CI: 1.42 to 1.75] in patients without atrial fibrillation; p interaction <0.001) and weaker in obese patients (adjusted RR: 1.50 [95% CI: 1.31 to 1.71] vs. 1.92 [95% CI: 1.70 to 2.17] in nonobese patients; p interaction <0.001). Screening NT-proBNP did not modify the treatment effect of sacubitril/valsartan compared with valsartan (p interaction = 0.96). Sacubitril/valsartan reduced NT-proBNP by 19% (95% CI: 14% to 23%; p < 0.001) compared with valsartan 16 weeks post-randomization, with similar reductions in men (20%) and women (18%), and in patients with left ventricular EF ≤57% (20%) and >57% (18%). Decreases in NT-proBNP predicted lower subsequent risk of the primary endpoint. Baseline NT-proBNP predicted HF events but did not modify the sacubitril/valsartan treatment effect in patients with HFpEF. Sacubitril/valsartan reduced NT-proBNP consistently in men and women, and in patients with lower or higher EF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

Cunningham JW ，Vaduganathan M ，Claggett BL ，Zile MR ，Anand IS ，Packer M ，Zannad F ，Lam CSP ，Janssens S ，Jhund PS ，Kober L ，Rouleau J ，Shah SJ ，Chopra VK ，Shi VC ，Lefkowitz MP ，Prescott MF ，Pfeffer MA ，McMurray JJV ，Solomon SD ... -  《-》