Dysfunction of Heart Left Ventricle Linked to Worse Prognosis in IPAH
High scores on a measure known as H2FPEF — which reflect an increased probability of dysfunction of the left ventricle (LV) of the heart — were associated with signs of LV impairment and a worse prognosis in patients with idiopathic pulmonary arterial hypertension (IPAH), a study found.
Patients with high scores also tended to be older, obese, and male, and have worse functional abilities.
Notably, however, responses to treatment were equally positive among these patients compared with those who did not show signs of LV dysfunction, according to researchers.
“In contrast to our hypotheses, we observed favourable responses to PAH-treatment irrespective of H2FPEF-score,” the team wrote, noting that the so-called typical IPAH patient “is changing from a predominantly young female patient to an older, frequently obese patient of either sex.”
The study, “Idiopathic pulmonary arterial hypertension patients with a high H2FPEF-score: insights from the Amsterdam UMC PAH-cohort,” was published in The Journal of Heart and Lung Transplantation.Â
In IPAH, increased pressure in the arteries supplying blood to the lungs causes excessive strain to the heart’s right ventricle, often leading to heart failure.
Now, however, the IPAH patient demographic is shifting from one with mostly young, otherwise healthy females to one with older patients who have more co-existing conditions. With that shift, clinicians are seeing an increase in the number of people with IPAH who show signs of LV diastolic dysfunction. This condition — affecting the left ventricle of the heart — is characterized by the LV’s inability to relax properly between heartbeats, making it unable to fill up with enough blood.
The presence of heart failure with preserved ejection fraction (HFpEF) in IPAH patients — when the heart’s ability to pump blood out to the body is impaired — may mean that these individuals will require different disease management.
However, more research is needed to determine the relationship between potential LV dysfunction, disease outcomes, and treatment responses.
The H2FPEF scoring system, which considers parameters including body weight, age, signs of high blood pressure, and heart function, is one way to screen for the likelihood of HFpEF in patients with unexplained shortness of breath. Yet, it had not been tested to date in IPAH patients.
In this study, a research team from the Netherlands evaluated the correlation between H2FPEF scores, clinical characteristics, and treatment responses among 253 people with IPAH and 33 with PH-HFpEF.
Results showed that the presence of high H2FPEF scores among newly diagnosed IPAH patients rose by 30% over a 30-year period, reflecting a significant increase in IPAH patients with potentially co-existing dysfunction of the left ventricle of the heart.
At the study’s start, or baseline, a number of clinical features differed between IPAH patients with an intermediate or high H2FPEF score and those who had a low score. Overall, the clinical characteristics of IPAH patients with higher scores were similar to PH-HFpEF patients.
Specifically, those with higher scores tended to be older, were more often obese and male, and had more co-existing health conditions, called comorbidities, than individuals with low scores.
Functional capacity also was influenced by H2FPEF scores, with higher scores associated with signs of worse lung function and significantly lower exercise capacity. Higher scores also were linked to increased levels of NT-proBNP — a biomarker of heart damage.
Survival was lower among those with higher scores, although that finding likely was influenced by the generally older age of these patients. Researchers noted that the mean age at diagnosis was 70 in the high H2FPEF score group, versus 41 in those with low scores.
Blood flow measurements, called hemodynamics, revealed that participants with IPAH and high H2FPEF scores had hemodynamic function in between that observed in the low score IPAH group and those with PH-HFpEF.
But the cardiac index, a measure of heart performance, was significantly lower in the high score IPAH group compared with either of the other two groups. Such lower scores suggest worse heart function.
“In contrast to the clinical characteristics, the hemodynamic profile of iPAH with a high H2FPEF-score did not resemble PH-HFpEF,” the researchers wrote.
While the function of the heart’s right ventricle was equally impaired regardless of H2FPEF score, the team saw signs of concealed LV diastolic dysfunction among those with higher scores.
Patients with intermediate or high scores were more likely to be prescribed phosphodiesterase-5 inhibitors (PDEi5), which include medications such as Adcirca (taladafil) and Revatio (sildenafil). Those with intermediate or lower scores, meanwhile, tended to be treated with prostacylin analogs — therapies that mimic the action of a naturally produced blood vessel widener.
Discontinuation of endothelin receptor antagonists, which include Opsumit (macitentan), occurred significantly more often in patients with higher H2FPEF scores compared with those with low or intermediate scores.
With treatment, hemodynamic changes and cardiac function were improved across all IPAH groups. Exercise capacity significantly improved in those with low and intermediate H2FPEF scores, and tended to improve in the high score group.
Overall, the findings highlight that high H2FPEF scores are increasingly common in people with IPAH, reflecting a subset of patients with signs of LV dysfunction and a worse prognosis, but favorable treatment responses.
The findings suggest that for IPAH patients with high H2FPEF scores, “there are no compelling reasons to withhold PAH-targeted treatment,” the team concluded.
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