Hemodynamic Gain Index Is An Independent Predictor Of Adverse Clinical Outcomes In Patients With Heart Failure With Reduced Ejection Fraction Undergoing Cardiopulmonary Exercise Stress Test

Abstract

<h3>Introduction</h3> Recently, the hemodynamic gain index (HGI), a simple parameter calculated from resting and peak systolic blood pressure (SBP) and heart rate (HR) during exercise stress testing without a metabolic cart, was shown to be an independent predictor of mortality. However, the prognostic implications of the HGI in patients with heart failure with reduced ejection fraction (HFrEF) have not been well studied. <h3>Hypothesis</h3> We hypothesized that lower HGI is independently associated with adverse outcomes in the entire cohort and in subgroups of patients with HFrEF and comparable to peak VO2 in risk stratification. <h3>Method</h3> Electronic medical records of 954 HFrEF patients (LVEF ≤40%) undergoing cardiopulmonary exercise stress test from December 2012 to September 2020 were reviewed. HGI was calculated using the formula, [(SBP_peak x HR_peak)-(SBP_rest x HR_rest)]/(SBP_rest x HR_rest). We excluded patients who had a negative HGI, hypotensive, or bradycardic response. The primary outcome was the composite of all-cause mortality, LVAD implantation, or heart transplantation. Multivariable Cox proportional hazard models and the log rank test were used for statistical comparisons. Subgroups of HFrEF were stratified by respiratory exchange ratio (RER) of 1.05, median age, sex, body mass index (BMI) of 35 kg/m², and beta-blocker use. <h3>Results</h3> In our study cohort (mean age 56.3±12.0 years, 72% men, 86% with beta-blockers, mean LVEF 24.6 ±7.9%, 17% with BMI ≥35 kg/m², 73% with RER >1.05), there were 331 (34.7%) patients who met the primary outcome during a median follow up time of 946 days. After adjustment for age, sex, comorbidities, and LVEF, lower HGI was independently associated with greater risk of the primary outcome(quartile 1 vs 4, HR 2.89, 95% CI 2.00-4.20, <i>p</i><0.001, <b>Figure 1A</b>). There is no difference in the association between HGI and risk by subgroup (<b>Figure 1B</b>). The HGI was also comparable to peak VO₂ in terms of primary outcome prediction (AUC 0.69 [95%CI 0.65-0.72] vs 0.70 [95%CI 0.66-0.73], <i>p</i>=0.777). <h3>Conclusion</h3> In this well-characterized, contemporary cohort of patients with HFrEF undergoing CPET evaluation, lower HGI is independently associated with a greater risk of death, LVAD implantation and heart transplantation. The prognostic value of HGI was comparable to that of peak VO2, suggesting it may have a potential clinical utility in risk stratification when considering advanced heart failure therapies.