Test based on inhaled NO likely to predict course of left-heart PH

Nitric oxide vasoreactivity test often not used for PH due to left heart disease

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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An illustration showing a heart in front of a pair of lungs.

Higher pressure in the heart’s top left chamber — a parameter called pulmonary arterial wedge pressure (PAWP) — is a likely predictor of poorer outcomes in people with pulmonary hypertension (PH) due to left heart disease, a study reports.

PAWP was measured using the inhaled nitric oxide (iNO) vasoreactivity test, commonly only given to people with pulmonary arterial hypertension (PAH), another type of PH.

“The assessment of NO-inhaled vasoreactivity can provide pivotal information, not only as a prognostic tool but also as a diagnostic tool for the application of NO-signalling treatment,” the researchers wrote in the study, “Inhaled nitric oxide testing in predicting prognosis in pulmonary hypertension due to left-sided heart diseases,” published in the journal ESC Heart Failure.

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Pulmonary hypertension is classified into five World Health Organization (WHO) groups depending on the underlying cause. Among them are PAH in WHO Group 1, and PH due to left heart disease, also known as pulmonary venous hypertension, in WHO Group 2.

Inhaled NO is a vasodilator gas that works by relaxing and widening blood vessels, which lowers blood pressure. Physicians often request a vasoreactivity test in PAH following iNO to evaluate how the pressure in the pulmonary arteries reacts to the treatment. However, “there are no reports exploring the safety and clinical usefulness of the inhaled NO vasoreactivity test for patients with Group 2 PH,” the scientists noted.

To assess the potential prognostic value of the iNO vasoreactivity test in these patients, researchers in Japan analyzed data from Group 2 PH patients followed at the Tohoku University Hospital or its satellite hospitals.

The analysis covered 69 patients (mean age of 61.5, 29% women) who underwent the iNO vasoreactivity test between January 2011 and December 2015. Patients were followed for a median of one year after undergoing the test, which included right heart catheterization, a procedure to measure pressure in the pulmonary arteries and to show the heart’s capacity to pump blood, and NO inhalation.

Several pulmonary, cardiac, and blood flow parameters were assessed before and during iNO. A response to the treatment was defined as a decrease of at least 10 mmHg in mean pulmonary arterial pressure (mPAP) to a value below 40 mmHg, with increased or unchanged cardiac output (the amount of blood pumped by the heart per minute).

At the study’s start, cardiac muscle disease, or cardiomyopathy, affected 58% of the patients and high blood pressure was found in 47.8% of them. More than 70% were treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and more than 60% were prescribed beta blockers. Mineralocorticoid receptor antagonists were administered to about 50%.

Inhaled NO test show safety, but patients did not meet responder criteria

After 10 minutes of iNO, no changes were seen regarding mean aortic pressure — that in the aorta, the body’s largest artery — heart rate, and saturation of peripheral oxygen, a measure of blood oxygen levels.

iNO safely led to a significant reduction in pulmonary vascular resistance (the internal resistance to blood flow within lung blood vessels), mPAP, and right atrial pressure — the pressure in the upper right chamber of the heart.

No patient, however, fulfilled criteria for a treatment responder.

Among these 69 people, 34 had increased PAWP. Patients in this group were significantly older (mean age of 65.5 vs 57.7) and had a normal body mass index, a measure of body fat, relative to those with a decrease in pulmonary arterial wedge pressure. They also showed left ventricle diastolic dysfunction, when the heart’s low left chamber does not relax as it should.

In patients with a higher PAWP at the iNO vasoreactivity test, blood levels of brain natriuretic peptide (BNP; a biomarker of heart failure) showed a trend toward an increase at the end of follow-up than did those with a lower PAWP.

Six patients died and 14 were hospitalized for heart failure. Instances of event-free survival, meaning neither death nor hospitalization due to heart failure, were markedly fewer in the group with elevated PAWP.

In a subsequent analysis, an increased PAWP following the iNO vasoreactivity test correlated with a 5.05 times higher risk of death and hospitalization due to heart failure. This association was maintained after adjusting for changes in BNP levels and in pulmonary vascular resistance.

At the end of follow-up, increased PAWP was the only significant factor linked to an increased risk — 4.35 times higher — of death due to any cause or hospitalization for heart failure.

Poorer outcomes seen with higher pulmonary arterial wedge pressure

Finally, the researchers conducted a subgroup analysis dividing PH patients with heart failure and preserved ejection fraction from PH patients with heart failure with reduced ejection fraction. Ejection fraction measures how much blood the heart pumps with each beat.

In both groups, all-cause death and hospitalization for heart failure were more common among patients with an increased PAWP than those with a reduced PAWP.

These findings support the prognostic value of the iNO vasoreactivity test for patients with Group 2 PH.

“In the current study, the multivariable analysis demonstrated that increased PAWP following NO inhalation was a novel and significantly correlated factor of prognosis in patients with Group 2 PH,” the researchers wrote, adding that these patients “are likely to tolerate the inhaled NO vasoreactivity test.”

Further studies, they added, “are warranted to determine whether this method is applicable to other types of PH.”

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