Results of the one-time assessment were correlated with the study’s primary outcome – cardiovascular hospitalization or all-cause death – over a mean follow up of 3.7 years. Subjects were 57 years old, on average, and 59% were women; just 2% had a previous diagnosis of pulmonary hypertension. Overall, 41% of the subjects had abnormal PAP/CO slopes, 26% had abnormal slopes without resting pulmonary hypertension, and 208 subjects (29%) met the primary outcome.
After adjustments for age, sex, and cardiopulmonary comorbidities, abnormal slopes more than doubled the risk of the primary outcome (hazard ratio [HR] 2.03; 95% confidence interval [CI]: 1.48-2.78; P less than .001). The risk remained elevated even in the absence of resting pulmonary hypertension (HR 1.75, 95% CI 1.21-2.54, P = .003), and in people with only mildly elevated resting PAPs of 21-29 mm Hg.
Older people were more likely to have abnormally elevated slopes, as well as were those with cardiopulmonary comorbidities, lower exercise tolerance, lower peak oxygen uptake, and more severely impaired right ventricular function. Diabetes, prior heart failure, chronic obstructive pulmonary disease, and interstitial lung disease were more prevalent in the elevated slope group, and their median N-terminal pro–B type natriuretic peptide level was 154 pg/mL, versus 52 pg/mL among people with normal slopes.
A simpler test is needed
In his editorial, Dr. Hoeper noted that diagnosing exercise PH by elevated slope “will occasionally help physicians and patients to better understand exertional dyspnea and to detect early pulmonary vascular disease in patients at risk,” but for the most part, the new definition “will have little immediate [effect] on clinical practice, as evidence-based treatments for this condition are not yet available.”
Even so, “having a globally accepted gold standard” for exercise PH based on the PAP/CO slope might well spur development of “simpler, noninvasive” ways to measure it so it can be used outside of specialty settings.
Dr. Ho and her team agreed. “These findings should prompt additional work using less invasive measurement modalities such as exercise echocardiography to evaluate” exercise PAP/CO slopes, they said.
The work was funded by the National Institutes of Health, Gilead Sciences, the American Heart Association, and the Massachusetts General Hospital Heart Failure Research Innovation Fund. The investigators had no relevant disclosures. Dr. Hoeper reported lecture and consultation fees from Actelion, Bayer, Merck Sharp and Dohme, and Pfizer.
SOURCE: Ho JE et al., J Am Coll Cardiol. 2020 Jan 7;75(1):17-26. doi: 10.1016/j.jacc.2019.10.048.