CPET test may help ID PAH patients at risk of worse outcomes: Study

Noninvasive testing determines how heart responds to exercise

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A heart-shaped image is superimposed over the human heart in this illustration of the heart and lungs.

The noninvasive CPET test — known in full as cardiopulmonary exercise testing, which determines how the heart responds to exercise — may help to identify pulmonary arterial hypertension (PAH) patients at higher risk of clinical worsening, according to a new study in the U.S.

The presence of heart rhythm abnormalities as seen in the CPET test was as good of a predictor of worse outcomes as elevated mean pulmonary arterial pressure, called mPAP. This is important, researchers say, because mPAP is assessed with an invasive procedure called right heart catheterization, or RHC.

“Our findings demonstrate that the [CPET] results may assist with identifying patients who may need escalated medical surveillance,” the researchers wrote, adding that “routine CPET may provide added value to the patient’s medical surveillance and therapy.”

The study “Exercise-Induced Electrocardiography Changes in Pulmonary Arterial Hypertension,” was published in The American Journal of Cardiology.

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Researchers examine CPET test records from 155 PAH patients

PAH is caused by the narrowing of pulmonary arteries, which carry blood from the heart through the lungs, raising blood pressure in those arteries and weakening the heart’s right ventricle — its pumping chamber.

The gold standard test to diagnose PAH is RHC, which involves inserting a catheter into a vein in the neck, arm, or groin to measure mPAP, or the pressure in the arteries supplying blood to the lungs.

CPET is a noninvasive test that uses electrocardiography (ECG), a blood pressure cuff, and a pulse oximeter to assess heart and lung performance at rest or during exercise. The ECG during CPET can detect exercise-induced heart rhythm problems, including ST-T-wave abnormalities.

The ST segment is the flat line in an ECG that occurs between the end of the S-wave, the final step of ventricle contraction, and the start of the T-wave, when the ventricles relax.

Whether CPET and exercise-induced ECG changes such as ST-T wave abnormalities could be used to predict outcomes in PAH patients remains unknown.

To fill this knowledge gap, a team of researchers in the U.S. looked back at clinical records of 155 children and adults with PAH who underwent CPET at a single pulmonary hypertension center between 2012 and 2019.

The patients’ median age was 19, with a range from 7 to 40 years. Among them, 69% were female individuals; all were followed for a median of five years.

At the researchers’ center, PAH patients older than 7  generally undergo a CPET test every six to 12 months. Given that, “most patients had multiple CPETs done within our time frame,” the team noted.

CPETs were performed while patients were on either a stationary bicycle or a treadmill.

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Results may be noninvasive predictor of deterioration in PAH

For outcomes, clinical worsening was defined as severe when patients died or required a lung transplant. It was deemed mild to moderate if they needed PAH medication escalation, hospitalization, shunt creation, or were listed for a lung transplant. Shunt creation is a surgical procedure of the heart that aims to reduce blood pressure. All these events were considered adverse outcomes.

The results showed that 63 patients (41%) had signs of clinical worsening, from mild to severe, during follow-up.

Significant ST-segment abnormalities during exercise were registered in 39 patients (25%), while 4% had T-wave inversions during exercise. A total of 13% of patients registered extra or skipped heartbeats, known as ectopy, during exercise.

A significantly greater proportion of patients with ST-T-wave abnormalities experienced adverse outcomes during follow-up relative to those without ECG changes on exercise (56% vs. 36%).

Among patients with ST-T wave changes, 44% showed no worsening, 28% had mild to moderate worsening, and the other 28% demonstrated severe clinical worsening. Conversely, 7% of those without ECG changes showed signs of severe worsening, and 30% experienced mild to moderate worsening.

Statistical analyses showed that ST-T wave changes during exercise were significantly associated with a 20% higher risk of death or the need for lung transplant when compared with patients with no ECG changes.

Patients with ST-T wave changes also were significantly younger — with a median age of 19 versus 22 years — than those without such changes. They also had significantly higher mPAP (median of 65.9 vs. 42.7 mmHg) and pulmonary vascular resistance index (PVRi, 17.3 vs. 10.6 m2), in comparison to those without changes. PVRi measures the resistance to blood flow in arteries that supply blood to the lungs.

The group with ST-T wave changes also showed significantly higher heart rate, and other breathing and respiratory abnormalities.

Among patients who had a recent RHC, statistical analysis adjusted for age and sex showed those with higher mPAP were significantly more likely to have ST-T-wave changes during exercise. An mPAP of 55 mmHg was found to be the optimal cutoff value that better predicted ST-T-wave changes with exercise.

The team then used a statistical tool called the area-under-the curve, or AUC, to determine how an mPAP value of 55 mmH or higher, or the presence of ST-T-wave changes with exercise, could predict death or lung transplant in PAH patients.

[Changes seen in test] may be a noninvasive predictor of clinical deterioration and signify the need for closer monitoring and/or referral for more invasive testing.

Essentially, AUC values, ranging from 0-1, reveal how well a test performs, with higher values indicating a better ability to correctly identify people with a given condition.

The two parameters resulted in nearly identical predictive abilities, according to the team, with an AUC value of 0.664 for the cut-off mPAP value and 0.659 for the CPET-assessed ST-T-wave changes.

Overall, these findings highlighted that “exercise-induced ST-T-wave changes in pediatric and young adult patients with PAH are associated with worsening pulmonary vascular disease and an increased risk of adverse outcomes, including death,” the team wrote.

These changes “may be a noninvasive predictor of clinical deterioration and signify the need for closer monitoring and/or referral for more invasive testing,” the researchers added.

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