Reliability and Physiological Interpretation of Pulmonary Gas Exchange by “Circulatory Equivalents” in Chronic Heart Failure

Abstract

BackgroundPeak ratios of pulmonary gas‐exchange to ventilation during exercise (normalV˙normalO2/trueV˙normalE and normalV˙CO2/trueV˙normalE, termed “circulatory equivalents”) are sensitive to heart failure (HF) severity, likely reflecting low and/or poorly distributed pulmonary perfusion. We tested whether peak normalV˙normalO2/trueV˙normalE and normalV˙CO2/trueV˙normalE would: (1) distinguish HF patients from controls; (2) be independent of incremental exercise protocol; and (3) correlate with lactate threshold (LT) and ventilatory compensation point (VCP), respectively.Methods and ResultsTwenty‐four HF patients (61±11 years) with reduced ejection fraction (31±8%) and 11 controls (63±7 years) performed ramp‐incremental cycle ergometry. Eighteen HF patients also performed slow (5±1 W/min), medium (9±4 W/min), and fast (19±6 W/min) ramps. Peak normalV˙normalO2/trueV˙normalE and normalV˙CO2/trueV˙normalE from X‐Y plot, and LT and VCP from 9‐panel plot, were determined by 2 independent, blinded, assessors. Peak normalV˙normalO2/trueV˙normalE (31.2±4.4 versus 41.8±4.8 mL/L; P<0.0001) and normalV˙CO2/trueV˙normalE (29.3±3.0 versus 36.9±4.0 mL/L; P<0.0001) were lower in HF than controls. Within individuals, there was no difference across 3 ramp rates in peak normalV˙normalO2/trueV˙normalE (P=0.62) or normalV˙CO2/trueV˙normalE (P=0.97). Coefficient of variation (CV) in peak normalV˙normalO2/trueV˙normalE was lower than for LT (5.1±2.1% versus 8.2±3.7%; P=0.014), and coefficient of variation in peak normalV˙CO2/trueV˙normalE was lower than for VCP (3.3±1.8% versus 8.7±4.2%; P<0.001). In all participants, peak normalV˙normalO2/trueV˙normalE was correlated with, but occurred earlier than, LT (r 2=0.94; mean bias, −0.11 L/min), and peak normalV˙CO2/trueV˙normalE was correlated with, but occurred earlier than, VCP (r 2=0.98; mean bias −0.08 L/min).ConclusionsPeak circulatory equivalents during exercise are strongly associated with (but not identical to) LT and VCP. Peak circulatory equivalents are reliable, objective, effort‐independent indices of gas‐exchange abnormality in HF.

Application of stepper in cardiopulmonary exercise test for patients with hemiplegia

“…ventilatory equivalent for O 2nadir and ventilatory equivalent for CO 2 ( EqCO 2)nadir were the lowest values of V E /VO 2 ratio and V E /VCO 2 ratio during exercise. [ 9 ] V E –VCO 2 slope was obtained as the slope of the regression line between V E and VCO 2 during the exercise test. [ 10 ] Oxygen uptake efficiency slope (OUES) represents the rate of increase in VO 2 in response to a change in V E and was computed as the slope of the regression line derived from VO 2 and the logarithm of V E based on the equation: VO 2 = OUES × ln V E + b. OUES is an estimation of the oxygen uptake efficiency, with steeper slopes indicating better oxygen uptake efficiency.…”

Quantifying the relationship and contribution of mitochondrial respiration to systemic exercise limitation in heart failure

“…Exercise tolerance depends on the succession of several steps in the oxygen delivery-utilization cascade from lungs, heart, and vasculature to skeletal muscle mitochondria, 44 which is most commonly quantified using CPET 42 where key exercise variables that include V O 2peak , V O 2LT , and V E /V CO 2LT strongly predict mortality. 4 Mitochondrial abnormalities in peripheral skeletal muscle are a major mechanism limiting whole-body V O 2peak in patients with HFrEF. [17][18][19][20][21] Surprisingly few studies have provided a comprehensive assessment of the relationship between mitochondrial function and prognostic CPET variables to delineate mitochondrial-specific impairments vs. CPET indices beyond V O 2peak .…”

“…CPET is considered the gold‐standard assessment of exercise intolerance in patients with HFrEF, 1–3 providing an integrated multi‐organ assessment. This facilitates refined non‐invasive assessment of key indices of exercise limitation that independently predict prognosis, which include peak oxygen uptake (V̇O 2peak ), oxygen uptake at the lactate threshold (V̇O 2LT ), and the ventilatory equivalent for carbon dioxide at the lactate threshold (V̇ E /V̇CO 2LT ) 4–11 …”

“…This facilitates refined non-invasive assessment of key indices of exercise limitation that independently predict prognosis, which include peak oxygen uptake (V O 2peak ), oxygen uptake at the lactate threshold (V O 2LT ), and the ventilatory equivalent for carbon dioxide at the lactate threshold (V E /V CO 2LT ). [4][5][6][7][8][9][10][11] Although a defining feature of the HFrEF phenotype, the degree of left ventricular (LV) systolic dysfunction assessed by LV ejection fraction (LVEF) poorly correlates with the degree of exercise intolerance. [12][13][14] In addition, pharmacological and device interventions that improve both LVEF and prognosis in HFrEF do not consistently improve exercise tolerance.…”

Anaerobic Threshold and Respiratory Compensation Point Identification During Cardiopulmonary Exercise Tests in Chronic Heart Failure

“…Notably, even the absence of an identifiable AT, despite the achievement of exercise-induced anaerobiosis, has a strong prognostic power 4 . Only few reports evaluated the prognostic power of RCP identification and of VO 2 value at RCP in HF patients, although RCP VO 2 is related to the buffering capability of H + produced by exercise-induced acidosis and, consequently, its value may carry important physiological and prognostic information 8,9 . However, the precise definitions of VO 2 at AT or RCP have been questioned, and even skilled readers from highly experienced laboratories may provide different values 10,11 .…”