Prognostic benefit of early diagnosis with exercise stress testing in heart failure with preserved ejection fraction
Authors: Saito Yuki , Obokata Masaru , Harada Tomonari , Kagami Kazuki , Wada Naoki , Okumura Yasuo , Ishii Hideki 
Published: April 2023

Abstract

Background
Delayed diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) can lead to poor clinical outcomes. Exercise stress testing, especially exercise stress echocardiography, plays a primary role in the early detection of HFpEF among dyspnoeic patients, but its prognostic significance is unknown, as is whether initiation of guideline-directed therapy could improve clinical outcomes in such early-stage HFpEF.

Methods and results
Ergometry exercise stress echocardiography was performed in 368 patients with exertional dyspnoea. Heart failure with preserved ejection fraction was diagnosed by a total score of HFA-PEFF algorithm Step 2 (resting assessments) and Step 3 (exercise testing) ≥ 5 or elevated pulmonary capillary wedge pressure at rest or during exercise. The primary endpoint comprised all-cause mortality and worsening HF events. Heart failure with preserved ejection fraction was diagnosed in 182 patients, while 186 had non-cardiac dyspnoea (controls). Patients diagnosed with HFpEF had a seven-fold increased risk of composite events than that of controls [hazard ratio (HR) 7.52; 95% confidential interval (CI), 2.24–25.2; P = 0.001]. Patients with an HFA-PEFF Step 2 &lt; 5 points but had an HFA-PEFF ≥ 5 after exercise stress testing (Steps 2–3) had a higher risk of composite events than controls. Guideline-recommended therapies were initiated in 90 patients diagnosed with HFpEF after index exercise testing. Patients with early treatment experienced lower rates of composite outcomes than those without (HR 0.33; 95% CI, 0.12–0.91; P = 0.03).

Conclusion
Identification of HFpEF by exercise stress testing may allow risk stratification in dyspnoeic patients. Furthermore, initiation of guideline-directed therapy may be associated with improved clinical outcomes in patients with early-stage HFpEF.

Lay Summary
Delayed diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) can lead to poor clinical outcomes. Exercise stress testing, especially exercise stress echocardiography, plays a primary role in the early identification of HFpEF among dyspnoeic patients, but its prognostic significance is unknown, as is whether initiation of guideline-directed therapy could improve clinical outcomes in such early-stage HFpEF. In the current study, ergometry exercise stress echocardiography was performed in 368 patients with exertional dyspnoea. Heart failure with preserved ejection fraction was diagnosed by the established algorithm consisting of Step 2 (resting assessments) and Step 3 (exercise echocardiography or exercise right heart catheterization). The primary endpoint comprised all-cause mortality and worsening HF events. Heart failure with preserved ejection fraction was diagnosed in 182 patients and non-cardiac dyspnoea (controls) in 186 patients. Patients newly diagnosed with HFpEF had a seven-fold increased risk of composite events than that of controls. Guideline-recommended therapies were initiated in 90 patients newly diagnosed with HFpEF after index exercise testing. Patients with early treatment experienced lower rates of composite outcomes than those without. In conclusion, identification of HFpEF by exercise stress testing may allow risk stratification in patients with chronic exertional dyspnoea. Furthermore, initiation of guideline-directed therapy may be associated with improved clinical outcomes in patients with early-stage HFpEF.