Heart Failure Risk Stratification Using Cardiopulmonary Exercise Testing

Cardiopulmonary exercise testing (CPET) in heart failure (HF), both for clinical and research purposes, is becoming an increasingly valid tool to measure HF severity.

In a recent study published by JACC: Heart Failure, researchers outlined practical aspects of using CPET as well as interpretation of gas exchange patterns from pre-clinical to advanced HF. As they explained, “CPET provides breath-by-breath gas exchange measures of 3 variables: O₂ uptake (VO₂), carbon dioxide output (VCO₂), and ventilation (V_E).”

“These 3 measures are used to derive various other gas exchange patterns that reflect organ-specific maladaptive responses to exercise, particularly when CPET is coupled with standard exercise variables (heart rate, blood pressure, ECG), cardiac imaging, and invasive hemodynamic measurements during exercise.”

In terms of VO₂ the researchers reported that it is an important predictor of prognosis. In a landmark study involving patients with HF and reduced ejection fraction (HFrEF), a peak VO₂ cutoff of ≤14 mL/kg/min was established as a criterion, for which the 1-year survival was significantly lower than what was achieved via transplantation. However, patients with a peak VO₂ >14 mL/kg/min had 6% 1-year mortality, which suggested that transplantation could be deferred in this particular subgroup.

Meanwhile, in the HF-ACTION trial, peak VO₂, percent predicted peak VO₂, and exercise duration were the strongest factors in predicting HFrEF mortality. Peak VO₂ continues to be a significant prognostic tool even in HFrEF patients on beta-blockers, and is an important predictor of mortality in HF patients with preserved left ventricular ejection fraction (LVEF; HFpEF).

However, researchers noted that submaximal exercise gas exchange variables now rival or even exceed the prognostic utility of peak VO₂. “We recently reported that O₂ uptake kinetics, as measured by mean response time (MRT), were only modestly related to peak VO₂ and more accurately reflected the ability to augment cardiac output during low-level exercise, indicating its complementary role to peak VO₂ in signaling different aspects of cardiac reserve capacity,” they wrote.

A MRT >60 sec was related to reduced exercise right ventricular ejection fraction (RVEF) and increased transpulmonary gradient-cardiac output slope. This supports the concept that MRT reflects RV-pulmonary vascular function during exercise. In a multivariate analysis of predictors of outcome in 243 HFrEF patients, researchers found that the O₂ uptake efficiency slope (the relationship between VO₂ and log V_E throughout exercise) outperformed peak VO₂ which conferred in an approximately 2-fold increase in mortality at values <1.47 L/min. It is also very reproducible and differs by <2% if derived from 75%, 90%, or 100% of exercise duration.

“Ventilatory efficiency and stability reflect HF severity, with V_E/VCO₂ slope in excess of 34-36 and the presence of EOV [exercise oscillatory ventiliation] both consistently indicating 1-year mortality rates ≥20%. Conversely, efficient ventilation without EOV, particularly with relatively preserved peak VO₂, signals excellent event-free survival,” researchers concluded. “An approach that integrates O₂ uptake parameters, hemodynamic responses to exercises, and ventilatory efficiency and stability is what we recommend to risk stratify HF patients, particularly those with intermediate values of peak VO₂.”

In addition, pulmonary artery pressure (PAP) measurements and pulmonary artery wedge pressure (PAWP) patterns during exercise also independently predict HFpEF and HFrEF outcomes. Therefore, the authors recommend at least 4 measurements of PAP and PAWP, plus cardiac output during incremental ramp testing to determine accurate pressure-flow relationships during exercise.

In the future, researchers believe CPET’s role in evaluating patients with early stages of HF and predisposed conditions to HF will be expanded. “Recent studies have begun to combine CPET responses with assessment of circulating metabolites and microRNAs that are rapidly modulated by exercise,” they noted.

These types of investigations may provide molecular signatures of acute adaptations to exercise that complement CPET and alert clinicians to early forms of HF and other cardiovascular diseases.

Reference

Malhotra R, Bakken K, D’Elia E, Lewis GD. Cardiopulmonary exercise testing in heart failure. JACC Heart Fail. doi:10.1016/j.jchf.2016.03.022.