EDITORIAL| VOLUME 164, ISSUE 4, P826-828, OCTOBER 2023

Breaking a Sweat to Catch Your Breath: Exercise Therapy Improves Dyspnea After Acute Pulmonary Embolism

Alexander E. Sullivan, Evan L. Brittain

Chest 2023; 164: 826-828

DOI:https://doi.org/10.1016/j.chest.2023.05.033

Acute pulmonary embolism (PE) is a sentinel event for many patients; despite guideline-directed treatment of the acute event, up to 50% of patients will experience a pattern of dyspnea and poor quality of life after the diagnosis, which are the hallmarks of post-PE syndrome.¹ These long-term sequela result in a loss of approximately 1 to 2 years of healthy life and disability that is comparable with mild COPD, angina pectoris, heart failure, and stroke.² Despite the significant prevalence and burden of post-PE syndrome, the underlying pathophysiologic mechanisms are understood poorly and are explained incompletely by PE clinical risk scores, preexisting cardiopulmonary comorbidities, and echocardiographic parameters of right ventricular dysfunction.^3,4 There are no well-studied and efficacious therapeutic interventions for post-PE syndrome, and patients struggle with dyspnea and poor quality of life for years. Exercise rehabilitation represents the only glimmer of hope for many patients.

The beneficial effects of exercise go well beyond weight control and improved exercise capacity. Aerobic training improves insulin sensitivity, macronutrient handling, and myocardial compliance; resistance training increases mitochondrial density and function while also improving skeletal muscle capillary density.5, 6, 7 Exercise training also increases nitric oxide production, induces arterial remodeling to promote improved vasodilatory capacity within conduit arteries and arterioles, and increases capillary density.⁷ In patients with pulmonary hypertension and chronic thromboembolic pulmonary hypertension, these beneficial effects are thought to increase cardiac output, reduce vascular tone and afterload, and increase metabolic efficiency. However, the precise mechanistic changes in the right ventriculoarterial relationship and the convectional and diffusion mechanisms of oxygen delivery remain elusive.⁸ What is clear, though, is that structured, hospital-based exercise rehabilitation programs improve physical functioning and quality of life and reduce subsequent events for patients with a wide variety of cardiopulmonary conditions that include heart failure, coronary artery disease, peripheral artery disease, COPD, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension.^7,8 The question is whether patients with post-PE syndrome who do not have the same hemodynamic or structural impairments as patients with other cardiopulmonary diseases will derive the same benefit.

In this issue of CHEST, Jervan et al⁹ evaluate the effects of an 8-week exercise-based rehabilitation program on exercise capacity, dyspnea, and quality of life in patients with persistent dyspnea after acute PE. They performed a two-center randomized controlled trial of patients who had been diagnosed with acute PE 6 to 72 months prior to enrollment and persistent or exacerbated subjective dyspnea corresponding to a modified Medical Research Council dyspnea scale grade ≥ 1. The patients were randomized 1:1 to an individualized, twice weekly, 8-week exercise program based on existing pulmonary rehabilitation guidelines with additional home-based exercise compared with usual care. The primary outcome was walking distance assessed by Incremental Shuttle Walk Test (ISWT); secondary outcomes included walking distance assessed by Endurance Shuttle Walk Test, quality of life assessed by the EuroQoL Group 5-Dimension 5-Level and Pulmonary Embolism Quality of Life questionnaires, and dyspnea assessed by the Shortness of Breath questionnaire. Of the 211 patients randomly assigned, those in the exercise arm tended to be younger and had slightly worse baseline ISWT walking distance. Patients in the exercise program experienced a significant improvement in their ISWT walking distance (110 m vs 30 m) and quality of life metrics. This improvement was greatest in those patients who were referred for exercise within 1 year of PE diagnosis (160 m vs 45 m) but did not vary by Pulmonary Embolism Severity Index score. Attrition was higher in those patients who were randomly assigned to exercise rehabilitation (13.0% vs 4.9%), which is an observation that is consistent with exercise interventions across many cardiopulmonary indications.¹⁰

These findings are the most robust and compelling evidence that structured exercise helps patients improve functionality and quality of life after acute PE. Although there is some benefit when exercise is initiated within 5 years after initial PE diagnosis, the real window of opportunity seems to be within the first year. Acute PE alters right ventricular and pulmonary hemodynamics; there is a long-standing concern that exercise will alter hemodynamics and precipitate cardiopulmonary collapse, especially in patients with significant pulmonary clot burden or residual lower extremity thrombus. Exercise therapy can, and likely should, be initiated safely within 4 weeks of acute PE, even in patients with massive and submassive events or evidence of right ventricular dysfunction at the time of PE.¹¹ Jervan et al⁹ saw a nearly four-fold greater improvement in walking distance in patients who were referred for structured exercise within 1 year of acute PE, which suggests that early identification of patients with dyspnea and functional limitation is paramount to mitigating long-term debility. Timing is critical because “time is functionality".

Several unanswered questions remain before exercise is ready to be a “prime time” therapy for post-PE syndrome. Most pressing are the questions of the optimal exercise regimen and where should it take place. The hospital-based intervention of Jervan et al⁹was based on preexisting pulmonary rehabilitation regimens but was tailored to each participant and included home-based exercises. Some studies have used multiphased programs, and others have used personal cardiac devices, which have also shown promise in other disease states.^11,12 Furthermore, although hospital-based exercise programs are found more consistently to be beneficial, transportation and cost remain substantial barriers for patients, even in the optimal environment of a randomized controlled trial such as this one.^13,14 Outpatient exercise programs offer promise but have had variable success both in post-PE syndrome and across the spectrum of cardiopulmonary disease.^15,16 The optimal exercise program is almost certainly one that is practical, scalable, and accessible while incorporating the patient’s social determinants of health and daily routine.

Exercise interventions offer hope for patients with post-PE syndrome where there once was just dyspnea and incomplete explanations. Wearable cardiac devices and novel technologies are likely to continue to revolutionize the field, but patients with residual dyspnea after acute PE benefit from structured exercise. Clinicians who see these patients longitudinally should regularly assess for persistent symptoms and waning quality of life and quickly initiate an exercise program to ameliorate disability before it is too late.