Abstract Body (Do not enter title and authors here): Background: Invasive hemodynamics are the gold standard for heart failure (HF) evaluation, with cardiac output (CO) representing a key indicator of HF severity. Among outpatients with HF, the prognostic significance of CO measured by different methods and in different physiologic states remains incompletely defined. We hypothesized that direct Fick CO and thermodilution (TD) CO would similarly predict event-free survival in HF, and that peak exercise Fick CO would provide the strongest prognostic value.
Methods: From a referral cohort undergoing supine right heart catheterization and upright invasive cardiopulmonary exercise testing (iCPET) for evaluation of exertional dyspnea, we included patients with characteristic symptoms of HF and (HFpEF: LVEF ≥50% plus ≥1 of the following: supine pulmonary capillary wedge pressure ≥15 mmHg, NT-proBNP ≥125 pg/mL, or BNP ≥35 pg/mL; HFmrEF (LVEF 41–49%); and HFrEF (LVEF ≤40%). Three CO measurements were evaluated: supine resting TD CO, upright resting direct Fick CO, and upright peak exercise direct Fick CO. Multivariable Cox proportional hazards models and natural spline curves adjusted for age, sex, and BMI were used to assess the association between CO and cardiovascular (CV) events or all-cause mortality. CO values were log-transformed, and hazard ratios (HR) reported per one standard deviation (SD) increase.
Results: Among 649 HF patients (age 63.4 ± 13.4 years, 44.4% female, BMI 29.7 ± 6.4 kg/m²), 477 had HFpEF, 57 HFmrEF, and 115 HFrEF. The mean CO values were: supine TD CO 5.1 ± 1.4 L/min, resting Fick CO 4.7 ± 1.4 L/min, and peak exercise Fick CO 10.1 ± 3.5 L/min. All three CO measures were independently associated with CV events or mortality (all p-value < 0.01) (Figure). Resting CO measured by TD in the supine position (HR 0.81, 95% CI 0.72–0.91, p<0.001), or upright by the direct Fick method (HR 0.83, 95% CI 0.75–0.93, p=0.0013) yielded similar protection from the combined outcome of CV events or mortality. Peak exercise Fick CO exhibited the lowest HR per 1 SD increase in CO (HR 0.66, 95% CI 0.59–0.74, p<0.001). Natural cubic spline curves demonstrate the close relationship between ascending exercise CO and protection from CV events or mortality.
Conclusion: Resting CO ascertained by direct Fick or thermodilution confers similar, modest prediction of CV outcomes in ambulatory patients with HF whereas exercise Fick CO enhances risk stratification.