Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post-Coronavirus Disease

Abstract

Objectives: The authors used cardiopulmonary exercise testing (CPET) to define unexplained dyspnea in patients with post-acute sequelae of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (PASC). We assessed participants for criteria to diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Background: Approximately 20% of patients who recover from coronavirus disease (COVID) remain symptomatic. This syndrome is named PASC. Its etiology is unclear. Dyspnea is a frequent symptom.

Methods: The authors performed CPET and symptom assessment for ME/CFS in 41 patients with PASC 8.9 ± 3.3 months after COVID. All patients had normal pulmonary function tests, chest X-ray, and chest computed tomography scans. Peak oxygen consumption (peak VO₂), slope of minute ventilation to CO₂ production (VE/VCO₂ slope), and end tidal pressure of CO₂ (PetCO₂) were measured. Ventilatory patterns were reviewed with dysfunctional breathing defined as rapid erratic breathing.

Results: Eighteen men and 23 women (average age: 45 ± 13 years) were studied. Left ventricular ejection fraction was 59% ± 9%. Peak VO₂ averaged 20.3 ± 7 mL/kg/min (77% ± 21% predicted VO₂). VE/VCO₂ slope was 30 ± 7. PetCO₂ at rest was 33.5 ± 4.5 mm Hg. Twenty-four patients (58.5%) had a peak VO₂ <80% predicted. All patients with peak VO₂ <80% had a circulatory limitation to exercise. Fifteen of 17 patients with normal peak VO₂ had ventilatory abnormalities including peak respiratory rate >55 (n = 3) or dysfunctional breathing (n = 12). For the whole cohort, 88% of patients (n = 36) had ventilatory abnormalities with dysfunctional breathing (n = 26), increased VE/VCO₂ (n = 17), and/or hypocapnia PetCO₂ <35 (n = 25). Nineteen patients (46%) met criteria for ME/CFS.

Conclusions: Circulatory impairment, abnormal ventilatory pattern, and ME/CFS are common in patients with PASC. The dysfunctional breathing, resting hypocapnia, and ME/CFS may contribute to symptoms. CPET is a valuable tool to assess these patients.

Keywords: cardiopulmonary exercise testing; dyspnea; post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection.

Graphical abstract

Figure 1

Patient #1 Shows Normal Ventilatory Pattern in 3 Graphs (Top) VE increases smoothly over time. (Middle) Tight linear correlation of VE and VCO₂. (Bottom) RR (orange, left y axis) and TV (blue, right y axis) is plotted vs minute ventilation (x axis). A slow increase in RR and an early large increase in TV at the start of exercise is observed. Patients #2 and #3 show examples of the dysfunctional breathing. (Top) VE vs time in patient #2 and #3 show numerous erratic spikes. (Middle) A thicker line correlating VE with VCO₂. (Lower) Dissociation between RR and TV vs VE is observed. Total overlap of RR and TV is seen in patient #2 and an overlap of RR and TV early and late in exercise occurs in patient #3. RR = respiratory rate; VE = minute ventilation; VT = tidal volume.

Figure 2

Dysfunctional Breathing in 4 Additional Patients (Patients #4-#7) The graph of RR and TV vs VE for each patient shows overlap of the RR and TV throughout exercise with loss of the normal pattern as seen in the graph in Figure 1 patient #1. Abbreviations as in Figure 1.

Figure 3

Dysfunctional Breathing in 4 Patients (Patients #8-#11) In these individual patient graphs of RR and TV vs ventilation, the reverse of normal exercise ventilatory pattern is observed. In these patients, the RR rapidly increases on exercise rather than the TV. Abbreviations as in Figure 1.

Figure 4

Stroke Volume During Rest and Exercise in the 7 Patients With Invasive Cardiopulmonary Exercise Testing

Central Illustration

Development of PASC With Possible Causes and How These can Be Classified Using CPET Schematic showing the evolution of acute COVID to PASC and ME/CFS with possible underlying mechanisms and how CPET parameters may help to differentiate these mechanisms. COVID = coronavirus disease; CP = chest pain; CPET = cardiopulmonary exercise testing; ME/CFS = myalgic encephalomyelitis/chronic fatigue syndrome; OUES = oxygen uptake efficiency slope; PASC = post-acute sequelae of SARS-CoV-2 infection; PHT = pulmonary hypertension; VD/VT = dead space to tidal volume ratio; VE/VCO₂ = ventilatory equivalent for CO₂ production; VO₂AT = oxygen consumption at anaerobic threshold.