January 09, 2020
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Exercise pulmonary hypertension predicts CV, all-cause death

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Jennifer E. Ho
Gregory Lewis

Pulmonary hypertension that occurs during exercise was found to be associated with poor CV event-free survival for patients with chronic dyspnea who show no signs of pulmonary hypertension at rest

Using minute-by-minute pulmonary arterial pressure and cardiac output measurements, or PAP/CO, among patients with chronic exertional dyspnea, researchers found that those with abnormal PAP/CO slope had a two times greater risk for CV or death events (adjusted HR = 2.03; 95% CI, 1.48-2.78), according to findings published in the Journal of the American College of Cardiology.

This association between abnormal PAP/CO slope and CV event-free survival remained significant after excluding pulmonary hypertension at rest (HR = 1.75; 95% CI, 1.21-2.54), according to the study.

“Pulmonary hypertension at rest is a well-known disease entity that carries with it substantial morbidity and mortality,” Jennifer E. Ho, MD, associate professor at Harvard Medical School and faculty member of the advanced heart failure and cardiac transplantation section and the Cardiovascular Research Center at Massachusetts General Hospital, told Healio. “Whether pulmonary hypertension uncovered with exercise provocation is clinically relevant was unclear and prognostic implications of how exercise pulmonary hypertension is defined were also unclear. Our study now shows that exercise pulmonary hypertension is associated with worse clinical outcomes, even in the absence of rest pulmonary hypertension.”

In other findings, researchers found both pre- and postcapillary contributions to exercise pulmonary hypertension independently predicted adverse events (P < .001 for both).

Validating current definitions

“In 2008, at a consensus conference, the use of exercise pulmonary arterial pressure in excess of 30 mm Hg to define pulmonary hypertension was appropriately abandoned due to concern that high pulmonary arterial pressures in isolation may not be pathological and uncertainty about their clinical and prognostic relevance,” Gregory Lewis, MD, section head of heart failure; director of the cardiopulmonary exercise testing laboratory; and medical director of cardiology ICU and mechanical circulatory support at Massachusetts General Hospital, told Healio. “We now confirm that the previous definition of exercise pulmonary hypertension lacks prognostic significance. However, defining exercise pulmonary hypertension by appropriately accounting for changes in blood flow during exercise led us to determine that exercise pulmonary hypertension, as defined by a steep PAP flow relationship, is highly prognostic.”

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Researchers assessed individuals with chronic exertional dyspnea (n = 714; mean age, 57 years; 59% women; 41% with abnormal PAP/CO slopes) who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring. According to the study, exercise pulmonary hypertension was defined as a PAP/CO slope of less than 3 mm Hg/L per minute. The primary outcome was CV hospitalization or all-cause mortality.

“This work will help to catalyze several future investigations to understand the pathobiology of this clinically important entity of exercise pulmonary hypertension, whether its detection facilitates earlier implementation of appropriate therapeutic interventions and provides further diagnostic resolution and whether we can use noninvasive imaging or biomarkers to create easily measured signatures of this condition,” Lewis said in an interview.

“Future studies are certainly needed to see whether identification of this at-risk population may lead to future targeted therapeutic or preventive interventions,” Ho said in an interview. “We also recognize that cardiopulmonary exercise testing with careful invasive hemodynamic testing may not be widely available, and the identification of noninvasive correlates or predictors of pulmonary vascular exercise responses is of great interest.”

Related editorial
“Diagnosing exercise pulmonary hypertension will occasionally help physicians and patients to better understand exertional dyspnea and to detect early pulmonary vascular disease in patients at risk,” Marius M. Hoeper, MD, from the department of respiratory medicine at the Hannover Medical School and German Center of Lung Research (DZL), wrote in a related editorial. “In addition, a globally accepted definition of exercise pulmonary hypertension will form the basis for developing targeted management strategies.” – by Scott Buzby

Disclosures: The authors report no relevant financial disclosures. Hoeper reports he received consultant and/or lecture fees from Actelion, Bayer, Merck Sharpe & Dohme and Pfizer.