Utility of E/e′ Ratio During Low-Level Exercise to Diagnose HFpEF

Quick Takes

  • Obtaining an E/e’ ratio during low-level (20-W) exercise is more feasible than at peak exercise and, if normal, has high predictive accuracy for normal E/e’peak (<15).
  • E/e’20W has moderate predictive accuracy for normal PCWP during exercise right heart catheterization (<25 mm Hg).
  • E/e’20W may have some value in ruling out HFpEF in patients with exertional dyspnea.

Study Questions:

Can the E/e’ ratio during low-level (20-W) exercise predict noninvasive and invasive parameters of elevated filling pressures during exercise? And, can it be used to exclude a diagnosis of heart failure with preserved ejection fraction (HFpEF)?


This was a retrospective study looking at 528 consecutive patients with exertional dyspnea referred for supine bicycle stress echocardiography. Exclusion criteria included: ages <20 years, ejection fraction <50%, significant left-sided valvular disease (> moderate regurgitation and > mild stenosis), hypertrophic cardiomyopathy, and inability to reach the 40-W exercise stage, resting E/e’ ratio >15, elevated B-type natriuretic peptide (BNP) (>80 pg/mL in sinus rhythm or >240 pg/mL in atrial fibrillation), or no BNP data available.

Protocol 1 investigated the diagnostic ability of E/e’20W to predict a normal E/e’ ratio during peak exercise, defined as E/e’peak ≤15. Supine bicycle stress echocardiography was performed according to usual guidelines, with a 5-minute first stage at 20-W followed by graded 20-W increments up to patient-reported exhaustion. Mitral inflow velocity € and tissue Doppler at the septal annulus (e’) were acquired 30 seconds after the initiation of each stage. Protocol 2 investigated the diagnostic performance of E/e’20W in predicting PCWP <25 mm Hg in the subset of patients who had been brought back within several weeks for exercise right heart catheterization after bicycle stress echocardiography. The probability of HFpEF was determined using the HFA-PEFF diagnostic algorithm from the European Society of Cardiology.


Of the 528 dyspneic patients referred for exercise echocardiography, 215 patients were included in Protocol 1. Average age was 68 ± 12 years, 52% were female, body mass index (BMI) was 24 kg/m2 ± 6, 69% had hypertension, and 24% had atrial fibrillation. The feasibility of obtaining the E/e’ ratio decreased from 100% at rest to 96.3% during 20-W exercise and 74.9% during peak exercise, due to E-A wave fusion. E/e’ 20W had excellent predictive accuracy for E/e’peak ≤15, with an area under the curve (AUC) of 0.91 and an optimal cutoff value of ≤12.4, demonstrating both high specificity (94%) and sensitivity (77%).

The protocol 2 subset included 45 patients, with an average age of 71 ± 10 years, 76% were female, BMI was 23 kg/m2 ± 4, 82% had hypertension, and 7% had atrial fibrillation. At a cutoff of 12.4, E/e’20W had high specificity (83%) and moderate sensitivity (75%) in predicting normal pulmonary capillary wedge pressure (PCWP) during exercise (<25 mm Hg) with an AUC of 0.77. While E/e’peak had a higher AUC (0.81), its feasibility was only 66.7% vs. 86.7% for E/e’20W.


Obtaining an E/e’ ratio during low-level exercise (20-W) is more feasible than at peak exercise due to the frequency of E-A fusion at high heart rate. E/e’20W has excellent predictive accuracy for E/e’peak (AUC 0.91), with an optimal cutoff of 12.4 in this study. E/e’20W has less overall predictive accuracy for normal PCWP during exercise, but has high specificity at the same cutoff of 12.4. The predictive accuracy of E/e’20W for the diagnosis of HFpEF was not directly evaluated in this study.


In the 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines on evaluation of diastolic function, diastolic stress testing is recommended for patients with stage 1 diastolic dysfunction (i.e., delayed myocardial relaxation, but normal left atrial pressure) who have symptomatic and unexplained dyspnea with exertion. This test is considered normal when E/e’ ratio is <10 and tricuspid regurgitation velocity is <2.8 m/s with peak exercise. However, obtaining these values at peak exercise can be challenging due to E-A wave fusion at high heart rate.

This retrospective study evaluates the feasibility of using the E/e’ ratio at a lower level of exercise (20-W) and its ability to predict normal E/e’ ratio during peak exercise and normal PCWP on exercise right heart catheterization. Unfortunately, the study seems to overstate its findings, extrapolating the predictive accuracy of E/e’20W to the diagnosis of HFpEF, which is never directly evaluated. Moreover, the relatively low BMIs, lack of obstructive sleep apnea, and exclusion of patients unable to exercise to a level of 40-W are all likely to skew the study population away from a typical cohort of HFpEF patients in North America.

Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Valvular Heart Disease, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound, Exercise, Hypertension

Keywords: Atrial Fibrillation, Body Mass Index, Diagnostic Imaging, Dyspnea, Echocardiography, Exercise, Exercise Test, Geriatrics, Heart Failure, Heart Valve Diseases, Hypertension, Natriuretic Peptide, Brain, Pulmonary Wedge Pressure, Stroke Volume

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