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Exercise Testing Can Unmask Abnormal Pulmonary Vascular Responses in Patients with Chronic Dyspnea

Key findings

  • Of 714 patients who had pulmonary artery pressure (PAP) and cardiac output (CO) measured throughout exercise testing, 41% exhibited exercise-induced pulmonary hypertension (exPH), defined as a PAP/CO slope >3 mm Hg/L/min
  • Clinical determinants of exPH included older age and underlying CV and pulmonary disease
  • exPH was associated with worse functional capacity and abnormal right ventricular contractile reserve
  • The presence of exPH predicted worse CV event–free survival, even in the absence of PH at rest or known CV disease
  • Across a wide range of individuals with chronic dyspnea, exercise testing can unmask abnormal pulmonary vascular responses that could have significant clinical implications

In the past, pulmonary hypertension during exercise testing was defined as pulmonary artery pressure (PAP) >30 mm Hg. Newer data suggest that PAP should be assessed in relation to the corresponding increase in cardiac output (CO) during exercise (the PAP/CO slope).

In addition, there's increasing recognition of the clinical importance of abnormal pulmonary vascular responses to exercise. In patients with certain disease entities, such as systemic sclerosis, exercise-induced pulmonary hypertension (exPH) is now known to predate the development of pulmonary hypertension (PH) and to predict worse clinical outcomes.

Jennifer E. Ho, MD, cardiologist in the Heart Failure and Transplant Program and the Cardiovascular Research Center, and Gregory D. Lewis, MD, Heart Failure section head and medical director of Cardiac Transplantation in the Cardiology Division at Massachusetts General Hospital, and colleagues recently performed comprehensive testing for exPH in a broader population of individuals with chronic exertional dyspnea. According to their report in the Journal of the American College of Cardiology, exPH was independently associated with worse CV event-free survival even in the absence of PH at rest.

Study Details

The researchers prospectively studied 714 patients with chronic dyspnea on exertion who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring at Mass General between 2006 and 2017. The average age was 57 and 59% were women. All patients had preserved left ventricular ejection fraction (≥50%).

Patients were followed through October 29, 2018, for all-cause mortality and non-elective hospitalization for a CV-related event (heart failure, PH, arrhythmia or coronary revascularization). The primary outcome measure was CV event–free survival.

Prevalence of PH

The researchers found:

  • 296 patients (41%) had exPH, defined as a PAP/CO slope >3 mm Hg/L/min (based on an average of 10 measurements per participant)
  • 146 patients (20%) met the recently revised definition of rest PH: average PAP >20 mm Hg
  • 184 patients (26%) had exPH with normal rest PAP

Exercise Parameters Associated with exPH

Compared with patients who had normal PAP/CO slopes, those with exPH had:

  • Lower absolute and percent-predicted peak oxygen consumption
  • Higher PAP at rest and during exercise
  • Higher systemic blood pressures and intracardiac pressures, and lower CO at rest and during exercise
  • Lower right ventricular systolic function at rest and abnormal right ventricular reserve

Clinical Correlates of exPH

In multivariable analysis, independent predictors of exPH included age and a history of smoking, heart failure, interstitial lung disease or chronic obstructive pulmonary disease.

exPH Predicts Clinical Outcomes

Over an average follow-up of 3.7 years after exercise testing, 167 participants experienced a CV-related hospitalization, 80 died and 39 experienced CV hospitalization followed by death. The analysis also found:

  • exPH was independently associated with >2-fold increased risk of CV hospitalization or death (HR, 2.03; 95% CI, 1.48–2.78; P < .001)
  • Among patients with mild PH at rest (average PAP 21–29 mm Hg), exPH was similarly associated with worse prognosis (HR, 1.91; 95% CI, 1.15–3.19; P = .01)
  • exPH was a significant predictor of worse CV event–free survival even after exclusion of patients with rest PH and those with known CV disease

What Clinicians Should Know

Across a wide range of individuals with chronic dyspnea, exercise testing can be used to identify abnormal PAP that may have significant clinical implications. Exercise testing can also be used to refine the risk of individuals who have mild resting PH.

In the future, it may be possible to establish subtypes of exPH that could be used to guide preventive and therapeutic interventions.

of patients with chronic dyspnea on exertion had exercise-induced pulmonary hypertension

of patients with chronic dyspnea on exertion had exercise-induced pulmonary hypertension despite normal pulmonary artery pressure at rest

higher risk of CV-related hospitalization or all-cause mortality in patients with chronic dyspnea on exertion who had exercise-induced pulmonary hypertension

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Massachusetts General Hospital clinicians note that, to date, there is no convincing evidence that right ventricular failure in patients with COVID-19 has any novel features.