Using a noninvasive test may help better diagnose PH-ILD, study says

Such tests may reduce the need for invasive procedures like RHC

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Using a noninvasive test in conjunction with other assessments may reduce the need to undergo right heart catheterization — a reliable but invasive procedure known as RHC — for diagnosing pulmonary hypertension (PH) in people with interstitial lung disease (ILD), according to a new study.

Cardiopulmonary exercise testing (CPET), combined with either a echocardiogram measure or a lung function assessment, allowed identification “with high probability” of those with PH-ILD, the investigators wrote.

“We are excited to have this helpful adjunct to our routine assessment,” Danielle Antin-Ozerkis, MD, associate professor of medicine at the Yale School of Medicine, in Connecticut, said in a university press release. Antin-Ozerkis was not one of the study’s authors, but serves as medical director of the Yale Interstitial Lung Disease Center of Excellence.

“If we can only perform catheterization on those who need it and avoid invasive testing in those who don’t, that is a win for our patients,” Antin-Ozerkis said.

The study, “Noninvasive determinants of pulmonary hypertension in interstitial lung disease,” was published in the journal Pulmonary Circulation.

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Investigating the noninvasive test CPET for diagnosing PH-ILD

ILDs are a group of lung diseases characterized by fibrosis (scarring) within the lungs. Often, ILD is complicated by PH, in which abnormally high pressure in the lung’s blood vessels makes the heart’s right ventricle work harder to pump blood into the lungs.

The gold standard test to diagnose PH is right heart catheterization, or RHC, which involves inserting a catheter into a vein in the neck, arm, or groin to measure the pressure in the pulmonary arteries.

Noninvasive approaches — such as measuring blood biomarkers, echocardiography, and the six-minute walking distance (6MWD) — also are commonly used, but these measures lack the specificity needed for a definite PH diagnosis.

Now, a team led by Phillip Joseph, MD, associate director of the Yale Pulmonary Vascular Disease (PVD) program, investigated whether several parameters from noninvasive tests could prove useful to diagnose and distinguish PH-ILD patients from those with interstitial lung disease alone.

The researchers analyzed test results from 66 ILD patients referred to the Yale PVD program. Noninvasive parameters included pulmonary function assessments, namely the predicted diffusing capacity for carbon monoxide, known as DLCO, and the ratio between forced vital capacity (FVC) and DLCO. FVC is a measure of the amount of air forcibly exhaled after a deep breath. DLCO assesses the ability of the lungs to transfer oxygen from air sacs into the blood.

Right ventricle systolic pressure (RVSP), assessed through echocardiogram, also was measured, along with oxygen consumption, gas exchange, and 6MWD — a test of exercise capacity and endurance that examines a person’s walking ability over a six-minute period.

In total, 44 patients with PH-ILD and 22 with ILD but not PH were included in the study. The mean age of PH-ILD patients was 66 verus 62 for those with ILD alone.

PH was defined as a mean pulmonary artery pressure above 20 mmHg and pulmonary vascular resistance above 2 wood units along with a pulmonary artery wedge pressure of 15 mmHg or lower. Whereas pulmonary vascular resistance refers to the internal resistance to blood flow within the lung arteries, PAWP provides an estimate of pressure in the heart’s top left chamber.

No differences between the two groups were seen regarding age, sex, body mass index (a ratio of weight to height), hemoglobin levels — the protein responsible for transporting oxygen in red blood cells — and NT-proBNP levels, a heart failure biomarker.

Results showed that the PH-ILD group had significantly lower predicted DLCO (mean of 33% vs. 55%) and greater FVC/DLCO ratio (2.31 vs. 1.74) compared with the only ILD group.

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Noninvasive test results together may help in diagnosis

On echocardiogram, the PH-ILD group also had significantly elevated RVSP (58 vs. 37 mmHg), and a reduced tricuspid annular systolic plane excursion to RVSP ratio (0.44 vs. 0.76) — a measure of the relationship between the right ventricle’s ability to contract and the amount of pressure it needs to exert to eject blood.

In the 6MWD, the PH-ILD group walked a shorter distance — 223 versus 331 meters, or about 732 versus about 1,086 feet — and had less oxygen saturation (85% vs. 94%) compared with the ILD only participants. Oxygen saturation is a measure of how much oxygen is circulating in the blood.

On CPET, PH-ILD patients showed worse ventilatory efficiency compared with the ILD group. They also had lower gas exchange-derived pulmonary vascular capacitance (GXCAP) measured during exercise tests, and lower delta end-tidal carbon dioxide (delta ETCO2), which measures cardiac output. A higher capacitance in GXCAP means improved pulmonary vasodilation, or widening of blood vessels.

The researchers found that GXCAP and delta ETCO2 were the strongest predictors of PH in people with ILD. Using a statistical analysis, they found that the combination of GXCAP, estimated RVSP, and an elevated FVC/DLCO ratio could predict PH with high sensitivity (86%) and specificity (93%). A test’s sensitivity is its ability to correctly identify those with a given disease, while specificity refers to correctly identifying those without it.

A probability of 100% of PH-ILD in this study was linked with a GXCAP equal or below 416 mLxmmHg, and an estimated RVSP above 43 mmHg.

This combination can give us a good pre-procedure probability that someone has pulmonary hypertension, and with more studies, potentially reduce the need for right heart catheterization.

In the future, these parameters could help clinicians to determine which ILD patients would need to undergo RHC and benefit from PH-directed therapy.

“Using our study and combinations of variables, we were able to predict the presence of pulmonary hypertension within interstitial lung disease,” Joseph said.

“This combination can give us a good pre-procedure probability that someone has pulmonary hypertension, and with more studies, potentially reduce the need for right heart catheterization,” he added.

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