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Publication Date

11-20-2015

Keywords

cardiopulmonary exercise testing, oxygen pulse, dyspnea, metabolics

Abstract

Background: Only cardiopulmonary exercise (CPX) testing provides information on the ability of the cardiovascular system to meet the body’s metabolic demands in terms of oxygen consumption (VO2) and carbon dioxide production (VCO2). However, CPX testing is underutilized by cardiologists due to complex diagnostic algorithms involving up to 30 variables as well as lack of validation studies. In addition, CPX also provides oxygen (O2) pulse as a continuous measure of stroke volume, which is its superiority to other stress modalities in which systolic function is measured at peak stress and rest. In the literature, it has been recommended that a composite criterion (combining peak O2 pulse with O2 pulse curve pattern) should be used to assess the cardiac function. Furthermore, the operating test characteristics and optimal cutoff of O2 pulse for distinguishing cardiac from noncardiac causes of exercise limitation also are unknown.

Purpose: We tested whether a 6-variable algorithm would discriminate cardiac from noncardiac causes of dyspnea when compared with comprehensive CPX testing to promote its use by cardiologists. We also tested several cutoff points along with the composite criterion against the clinical standard to define the optimal O2 pulse cutoff point.

Methods: Consecutive patients (n = 54) referred for dyspnea underwent CPX test consisting of pulmonary (VO2, VCO2, 22 additional variables and invasive measurement of lactate and blood gases at peak and baseline) and cardiac (exercise ECG, heart rate and blood pressure response) components as well as medical record evaluation. Patients were categorized as normal or abnormal by an experienced pulmonologist. Abnormal patients were further categorized according to cause of dyspnea (cardiac, pulmonary, deconditioning, poor effort and miscellaneous). Subsequently, the 6-variable algorithm was applied by a cardiologist blinded to all of the information from CPX tests, and the patients were categorized similarly. The 6 variables used were peak O2 uptake, peak respiratory exchange ratio, O2 pulse, heart rate reserve, breathing reserve (1 – [peak ventilation (VE) / maximal voluntary ventilation]) and ventilatory efficiency (VE/VCO2). Seven O2 pulse reference cutoff points included nongender-based (< 15 ml/beat), gender-based (< 15 ml/beat for males and < 10 ml/beat for females) and < 80% of O2 pulse based on five different definitions of predicted VO2 max. The optimal cutoff obtained was then used to create the composite criterion. For the purpose of evaluating this composite criterion, the study population was recategorized as: noncardiac group (n = 18), normal patients according to the composite criterion; or cardiac group (n = 13), abnormal patients according to the composite criterion. Patients who were normal by only one component of the composite criterion were categorized as borderline (n = 23). Data were analyzed against the comprehensive CPX test by first excluding the borderline patients and then by including them with either the cardiac or noncardiac group.

Results: The 6-variable algorithm performed well against comprehensive CPX test in discriminating cardiac from noncardiac causes of dyspnea, with 94% sensitivity, 92% specificity, 84% positive predictive value (PPV), 97% negative predictive value (NPV) and 93% accuracy. The results remained consistent for gender and referral source. O2 pulse, as defined by Wasserman, had the highest accuracy, specificity and PPV and therefore was used to define the composite criterion. The composite criterion had an accuracy of 87%, PPV of 77%, NPV of 94%, sensitivity of 91% and specificity of 85%, when borderline patients were excluded. Including borderline patients in the cardiac group (n = 36) improved sensitivity (94%) and maintained NPV (94%) but greatly decreased specificity (46%), PPV (44%) and accuracy (61%), whereas including these patients in the noncardiac group (n = 41) improved specificity (92%) and maintained similar PPV (77%) and accuracy (81%) but decreased sensitivity (59%) and NPV (83%).

Conclusion: This is the first study to validate a diagnostic algorithm for patients undergoing CPX testing as well as demonstrate that a simplified 6-variable algorithm applied by a cardiologist without prior CPX experience is quite accurate to evaluate the optimal O2 pulse value at peak stress for discrimination of cardiac and noncardiac causes, and to provide the operating test characteristics for the common clinical practice of using composite criterion to diagnose cardiac versus noncardiac causes of dyspnea.