Clinical characteristics and outcomes of HFmrEF/HFpEF patients with low NT-proBNP

In an I-PRESERVE trial analysis, 23% of the HF patients with LVEF ≥45% had NT-proBNP <125 pg/mL. Overall, they had less morbidity and a more favorable prognosis than participants with higher NT-proBNP but similarly impaired health status.

This summary is based on the publication of Kondo T, Campbell R, Jhund PS, et al. - Low Natriuretic Peptide Levels and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction. JACC Heart Fail. 2024 Aug;12(8):1442-1455. doi: 10.1016/j.jchf.2024.04.027

Introduction and methods

Background

Current clinical guidelines recommend using a NT-proBNP threshold of 125 pg/mL to rule out HF [1-3]. Yet, some patients with HFpEF or HFmrEF have NT-proBNP levels below this value, especially those with obesity or in whom diuretic therapy has been initiated [4-7]. To date, no large-scale systematic studies have been conducted on the proportion of HFmrEF/HFpEF patients with low NT-proBNP levels, nor their clinical characteristics and outcomes. Previously, the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction) trial enrolled patients based on a clinical diagnosis of HF and LVEF ≥45% but not natriuretic peptides [8,9]. In addition, patients with a high BMI were not excluded.

Aim of the study

In an analysis of the I-PRESERVE trial, the authors assessed the proportion of patients with NT-proBNP <125 pg/mL, their clinical characteristics, and outcomes.

Methods

The I-PRESERVE trial was an international, multicenter, double-blind, placebo-controlled, phase 3 RCT in which 4128 patients aged ≥60 years with LVEF ≥45%, current signs and symptoms of HF, and NYHA functional class III–IV (or NYHA class II with HF hospitalization within previous 6 months) with corroborating evidence were randomized to irbesartan 300 mg once daily or placebo. Mean follow-up duration was 49.5 months. The previously published results demonstrated irbesartan did not improve CV outcomes in this population compared with placebo [10]. Although routine measurement of natriuretic peptides was uncommon at the time of study enrollment (2002–2005), baseline NT-proBNP levels measurements were available for 3480 patients (investigators were unaware of the levels). Of these patients, 808 (23.2%) had NT-proBNP <125 pg/mL and 2672 (76.8%) had NT-proBNP ≥125 pg/mL.

Outcomes

The primary endpoint of this analysis was a composite outcome of CV death or HF hospitalization. Additional endpoints were time to CV death, HF hospitalization, and all-cause mortality.

Main results

Clinical characteristics

• Patients with NT-proBNP <125 pg/mL were younger than those with NT-proBNP ≥125 pg/mL (mean age: 68.6 vs. 72.6 years; P<0.001), were less often men (36.1% vs. 40.9%; P=0.015), and more frequently had a BMI ≥30 kg/m² (48.4% vs. 38.7%; P<0.001).

• Several signs of congestion, i.e., pulmonary congestion on chest x-ray, elevated jugular venous pressure, and rales, were less prevalent in patients with NT-proBNP <125 pg/mL compared with those with higher NT-proBNP levels (all P<0.05).

• Compared with patients with higher NT-proBNP levels, patients with lower NT-proBNP levels were less likely to have comorbidities such as AF, MI, diabetes, and COPD or asthma but more often had a history of hypertension (all P<0.05).

• Patients with lower NT-proBNP levels demonstrated a better kidney function, a lower prevalence of anemia, and less marked ECG and echocardiographic abnormalities (all P<0.05).

• With regard to health status, the median total Minnesota Living with Heart Failure Questionnaire score was similar in patients with lower and those with higher NT-proBNP levels (43 vs. 43; P=0.95).

Clinical outcomes

• The incidence rate of the primary endpoint (CV death or HF hospitalization) was lower in patients with lower NT-proBNP levels (1.9 per 100 person-years; 95%CI: 1.5–2.4) compared with those with higher NT-proBNP levels (8.7 per 100 person-years; 95%CI: 8.1–9.3; adjusted HR (aHR): 0.35; 95%CI: 0.27–0.46; P<0.001).

• Comparable results were seen for CV death (aHR: 0.43; 95%CI: 0.31–0.60; P<0.001), HF hospitalization (aHR: 0.32; 95%CI: 0.22–0.46; P<0.001), and all-cause mortality (aHR: 0.48; 95%CI: 0.36–0.62; P<0.001).

Conclusion

In this analysis of the I-PRESERVE trial, 23% of the HFmrEF/HFpEF patients had NT-proBNP <125 pg/mL at baseline. Compared with participants with higher NT-proBNP levels, these patients were younger and had less evidence of congestion, fewer comorbidities (except for hypertension), better kidney function, fewer echocardiographic abnormalities, and a lower risk of CV death or HF hospitalization. However, both groups had similarly impaired health status, which “emphasize[s] the important need for treatments that improve symptoms and quality of life in HFmrEF/HFpEF, even among patients with low NT-proBNP,” according to the authors.

Find this article online at JACC Heart Fail.

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