High pulmonary resistance indicates worse outcomes in new PH study
Findings suggest SGLT2 inhibitors may help improve prognosis
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Elevated pulmonary vascular resistance (PVR), a measure of how difficult it is for blood to move from the heart to the lungs, was associated with a higher risk of poor outcomes in people with pulmonary hypertension (PH) due to left heart disease, a real-world study in Japan shows.
The study also found that SGLT2 inhibitors, a type of medication approved to treat heart failure, were associated with a lower risk of poor outcomes, particularly among those with reduced ejection fraction.
Elevated pulmonary resistance identified as key risk factor
Overall, these findings show that “elevated PVR … is a crucial factor in determining the prognosis in patients with [PH due to left heart disease],” and better outcomes in those treated with SGLT2 inhibitors suggest “a potential therapeutic role that warrants further investigation,” the researchers wrote.
The study, “Prognostic Impact of Elevated Pulmonary Vascular Resistance in Group 2 Pulmonary Hypertension: Insights From a Japanese Multicenter Registry,” was published in the Journal of the American Heart Association.
PH due to left heart disease (group 2 PH) is a common form of PH. High PVR in these patients is associated with a higher risk of adverse clinical outcomes.
SGLT2 inhibitors, which work by blocking the sodium-glucose transport protein 2, have been reported to reduce heart filling pressures, improve blood vessel function, and ease congestion in the lungs’ blood vessels. But whether “these benefits extend to patients with Group 2 PH, especially those with an elevated PVR, remains unclear,” the scientists wrote.
In this study, researchers in Japan “aimed to evaluate the real‐world relationship between PVR and prognosis in Group 2 PH and assess the potential therapeutic role of emerging therapies in this high‐risk subgroup.”
To do this, the researchers compared two patient registries: a current registry that enrolled 563 participants between 2018 and 2024 at 15 institutions, and a previous registry including 425 participants between 2012 and 2016 at six institutions. Sex, age, body mass index (BMI, a measure of body fat based on weight and height), and heart failure severity were similar when comparing the two groups.
Patient registries reveal differences in heart failure types
Results showed a higher proportion of patients with reduced ejection fraction (HFrEF) in the current registry (about 56% vs. about 45%), and a lower proportion with preserved ejection fraction (HFpEF; about 44% vs. about 55%). HFpEF means the heart cannot properly fill with blood, whereas HFrEF means the heart is too weak to pump properly.
Combining the two registries, 61.8% of patients were free from poor outcomes after six years. These outcomes included hospitalization due to worsening heart failure, ventricular assist device implantation, heart transplant, or death from any cause. Additionally, patients with high PVR (above 3 Wood units) had a significantly higher risk of poor outcomes than those with lower PVR.
That risk was 78% higher in a statistical analysis that accounted for factors such as age, sex, BMI, heart failure severity, and chronic kidney disease.
Among participants in the current registry with HFrEF, those with elevated PVR had an 86% higher risk of poor outcomes, “suggesting that elevated PVR remains an important prognostic marker in PH-HFrEF despite current treatments,” the researchers wrote.
For those with HFpEF, a higher PVR was associated with a 70% higher risk of poor outcomes, but the difference did not reach statistical significance. “This finding suggests a modest improvement in clinical outcomes in more recent practices,” the researchers added.
SGLT2 inhibitors associated with improved outcomes
Treatment with SGLT2 inhibitors in the current registry was associated with better outcomes among patients with high PVR, with about twice as many patients remaining event-free (73.8% vs. 35.5%). SGLT2 inhibitors include empagliflozin and dapagliflozin.
In people with HFrEF and elevated PVR, SGLT2 inhibitor treatment was associated with a 78% lower risk of poor outcomes. A 66% lower risk was observed for patients with HFpEF and elevated PVR, but the effect was not statistically significant.
Among participants with high PVR, further analysis indicated that use of SGLT2 inhibitors was associated with better outcomes compared with other heart failure therapies.
“These findings suggest a potential benefit of SGLT2 inhibitors in the management of group 2 PH, particularly in the presence of elevated pulmonary vascular resistance,” the researchers wrote.
