Unexplained Exertional Dyspnea Caused by Low Ventricular Filling Pressures: Results from Clinical Invasive Cardiopulmonary Exercise Testing

Abstract

To determine whether low ventricular filling pressures are a clinically relevant etiology of unexplained dyspnea on exertion, a database of 619 consecutive, clinically indicated invasive cardiopulmonary exercise tests (iCPETs) was reviewed to identify patients with low maximum aerobic capacity (V O 2 max) due to inadequate peak cardiac output (Qtmax) with normal biventricular ejection fractions and without pulmonary hypertension (impaired: n = 49, V O 2 max = 53% predicted [interquartile range (IQR): 47%-64%], Qtmax = 72% predicted [62%-76%]). These were compared to patients with a normal exercise response (normal: n = 28, V O 2 max = 86% predicted [84%-97%], Qtmax = 108% predicted [97%-115%]). Before exercise, all patients received up to 2 L of intravenous normal saline to target an upright pulmonary capillary wedge pressure (PCWP) of ≥5 mmHg. Despite this treatment, biventricular filling pressures at peak exercise were lower in the impaired group than in the normal group Dyspnea on exertion is a common presenting symptom with a broad differential diagnosis. Often the etiology remains unclear despite a thorough clinical and laboratory investigation. 1,2 Cardiopulmonary exercise testing (CPET) may assist in the diagnostic evaluation by defining the degree of impairment in maximum aerobic capacity (V O 2 max), identifying the limiting organ system (e.g., heart vs. lung), and providing clues as to more specific pathophysiology. When CPET is coupled with invasive hemodynamic monitoring using radial and pulmonary arterial catheters (i.e., invasive CPET [iCPET]), the presence of peripheral and central cardiovascular abnormalities can be better characterized through direct measurements of systemic and pulmonary vascular pressures and systemic and mixed venous oxygen content as well as precise estimation of cardiac output (Qt). 3 For example, these measurements have been used to characterize the exercise-induced increases in ventricular filling pressure and pulmonary arterial pressure in patients with heart failure 4-8 and pulmonary arterial hypertension, 9 respectively. Despite a detailed hemodynamic and metabolic evaluation, nearly 10% of symptomatic patients studied with iCPET in our laboratory had low V O 2 max and low maximum Qt (Qtmax) without a clearly identified cause.During the normal exercise response, sympathetic stimulation and vagal withdrawal increase heart rate (HR), contractility, and mean systemic pressure. Increased respiratory efforts and vigorous limb skeletal muscle contractions also enhance venous return to the heart. Together, these responses increase stroke volume (SV) through the Frank-Starling mechanism. In this study, we tested the hypothesis that failure of these mechanisms to increase cardiac preload during exercise, as evidenced by persistently low ventricular filling pressures, may be the primary limitation of Qtmax in an undiagnosed population of patients with unexplained exercise intolerance. METHODS PatientsFor the single-test cohort, results from 619 consecutive, clinically ...

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