Novel techniques for quantifying oxygen pulse curve characteristics during cardiopulmonary exercise testing in tetralogy of fallot

Abstract

Background: Cardiopulmonary exercise testing (CPET) is used in evaluation of repaired tetralogy of Fallot (rTOF), particularly for pulmonary valve replacement need. Oxygen pulse (O₂P) is the CPET surrogate for stroke volume and peripheral oxygen extraction.

Objectives: This study assessed O₂P curve properties against non-invasive cardiac output monitoring (NICOM) and clinical testing.

Methods: This cross-sectional study included 44 rTOF patients and 10 controls. Three new evaluations for O₂P curve analysis during CPET were developed. Best fit early and late regression slopes of the O₂P curve were used to calculate: 1) the early to late ratio, or "O₂ pulse response ratio" (O₂PRR); 2) the portion of exercise until slope inflection, or "flattening fraction" (FF); 3) the area under the O₂P response curve, or "O₂P curve area".

Results: rTOF patients (median age 35.2 (27.6-39.4); 61% female) had a lower VO₂ max (23.4 vs 45.6 ml/kg/min; p < 0.001) and O₂P max (11.5 vs 19.1 ml/beat; p < 0.001) compared to controls. Those with a FF occurring <50% through exercise had a lower peak cardiac index and stroke volume, but not VO₂ max, compared to those >50%. FF and O₂P curve area significantly correlated with peak cardiac index, stroke volume, left and right ventricular ejection fraction, and right ventricular systolic pressure.

Conclusion: CPET remains an integral part in the evaluation of rTOF. We introduce three non-invasive methods to assess exercise hemodynamics using the O₂P curve data. These evaluations demonstrated significant correlations with stroke volume, cardiac output, and right ventricular pressure.

Keywords: Cardiopulmonary exercise testing; Exercise physiology; Non-invasive cardiac output monitoring; Oxygen pulse; Stroke volume; Structural heart disease.

Fig. 1

Oxygen Pulse Curve Characteristics. An example of two cardiopulmonary exercise test results. A is a subject from the control group whereas B is from the repaired tetralogy of Fallot group and demonstrated early flattening. The early slope (x), late slope (y), and transition point (δ) are determined by the algorithm for the best fit. Oxygen pulse response ratio (O₂PRR) is calculated as x/y. The fattening fraction (FF) is the point where δ occurs. It also can be characterized as α/(α+β) or the amount of time during exercise until the slope changes. The area under the curve (entire shaded area) was used to quantify the oxygen pulse curve area (O₂P curve area).

Fig. 2

Correlogram of Oxygen Pulse Curve Characteristics and Clinical Measurements. Boxes are colored based on r valve for Pearson correlation. LV = left ventricle, MRI = magnetic resonance imaging, PV = pulmonary valve, RV = right ventricle, RVEDV = right ventricular end diastolic volume, RVSP = right ventricular systolic pressures * = p < 0.05, ** = p < 0.01, *** = p < 0.001.

Fig. 3

Correlation Plots of Selected Comparisons. Shaded areas show 95% confidence intervals. LV = left ventricle, METS = metabolic equivalents, NICOM = non-invasive cardiac output monitor, PV = pulmonary valve, RER = respiratory exchange ratio, RV = right ventricle, RVEDV = right ventricular end diastolic volume, RVSP = right ventricular systolic pressures.

Fig. 4

3 Novel Oxygen Pulse Measurements During Cardiopulmonary Exercise Testing. Oxygen pulse curve area and flattening fraction, derived during cardiopulmonary exercise testing correlated with stroke volume, cardiac output, and right ventricular pressure. RVSP = right ventricular systolic pressure. The arrow shows “flattening” of the oxygen pulse curve compared to a normal response.