High-flow nasal cannula versus noninvasive ventilation in acute heart failure–related respiratory failure: a systematic review and meta-analysis

Background Noninvasive ventilation (NIV) is the recommended first-line respiratory support for acute heart failure (AHF)–related respiratory failure. However, its tolerance is often limited. High-flow nasal cannula (HFNC) has emerged as a potential alternative, but comparative evidence remains inconsistent. This study aimed to evaluate the efficacy and safety of HFNC versus NIV in patients with AHF-related respiratory failure. Methods We conducted a systematic review and meta-analysis following PRISMA guidelines. We searched four major electronic databases from inception to April 2026. We included randomized controlled trials (RCTs) and observational studies enrolling adult patients with respiratory failure secondary to AHF or acute cardiogenic pulmonary edema, comparing HFNC and NIV. The primary outcome was composite treatment failure. Secondary outcomes included endotracheal intubation, short-term mortality, arterial blood gas (ABG) parameters, respiratory rate, dyspnea scores, and hospital length of stay. A random-effects model was used. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Ten studies ( n = 1,282 patients) were included, comprising five RCTs and five observational studies. HFNC showed no statistically significant difference compared with NIV in the composite outcome of treatment failure (RR = 1.22, 95% CI: 0.81–1.84), endotracheal intubation (RR = 0.86, 95% CI: 0.58–1.28), or short-term mortality (RR = 0.99, 95% CI: 0.69–1.42). Design-stratified estimates for treatment failure also crossed the line of no effect in both RCTs (RR = 1.00, 95% CI: 0.61–1.63) and observational studies (RR = 1.44, 95% CI: 0.77–2.69). No statistically significant differences were observed in ABG parameters, respiratory rate, dyspnea scores, or hospital length of stay. The GRADE assessment showed predominantly moderate certainty evidence for RCT comparisons, with high-certainty evidence for changes in PaCO 2 and pH. Conclusion The available evidence did not find a statistically significant difference between HFNC and NIV in terms of clinical efficacy in patients with AHF-related respiratory failure. HFNC may be considered in selected patients who do not tolerate NIV, provided that close monitoring and prompt access to NIV escalation are available. Although the certainty of evidence was generally moderate for RCTs comparisons, further adequately powered multicenter RCTs are needed to better define patient selection and clinically important differences. Systematic review registration www.crd.york.ac.uk/PROSPERO/view/CRD420261330512 , identifier CRD420261330512.