Marker of left heart function better predicts outcomes in PAH: Study
Left ventricular underfilling linked to more severe disease, higher risk of death
Routine heart ultrasound measurements of left ventricular (LV) underfilling may significantly improve the prediction of poorer outcomes in people with pulmonary arterial hypertension (PAH) beyond currently used prognostic tools, a study has found.
LV underfilling refers to the extent to which the left ventricle, the heart chamber that pumps oxygen-rich blood throughout the body, fills with blood.
According to the study conducted in China, LV underfilling was linked to more severe disease and a higher risk of death or hospitalization due to heart failure. It also added meaningful prognostic value when combined with existing tools used to predict outcomes in PAH.
“Incorporating LV markers into prognostic frameworks offers a promising approach for personalized PAH management and improved patient outcomes,” researchers wrote, emphasizing that LV underfilling is a noninvasive measure “easily obtained via routine echocardiography” that can significantly enhance “risk stratification accuracy in severe PAH.”
The study, “Transthoracic echocardiography of left ventricular underfilling improves risk stratification in pulmonary arterial hypertension,” was published in Scientific Reports.
Right-sided heart failure leading cause of serious illness, death in PAH
PAH occurs when the blood vessels that carry blood from the heart to the lungs become narrowed and stiff. This raises blood pressure in the lungs and forces the right ventricle — the heart’s chamber that pushes blood into the lungs — to work harder.
Over time, the right ventricle may enlarge and weaken, eventually leading to right-sided heart failure, which is the main cause of serious illness and death in PAH. For this reason, doctors have traditionally focused on imaging tests that assess the size and function of the right side of the heart when estimating a patient’s prognosis.
As the disease progresses, enlargement of the right ventricle can limit the amount of blood the left ventricle can hold between heartbeats, leading to LV underfilling. This may reduce the heart’s ability to increase oxygen-rich blood delivery when needed, worsening PAH symptoms.
“Although LV underfilling has been noted in PAH, the prognostic significance of this phenomenon … remains unexplored,” the researchers wrote.
To investigate this further, researchers in China enrolled 270 people with PAH at the First Affiliated Hospital of Xi’an Jiaotong University between June 2014 and December 2024. All underwent transthoracic echocardiography (TTE), a standard heart ultrasound scan, along with invasive pressure measurements.
Using TTE, the researchers assessed LV filling by calculating a ratio comparing the size of the left ventricle with the thickness of its muscle. Values lower than 0.8 milliliters per gram (mL/g) indicated LV underfilling.
Signs of more advanced disease seen in LV underfilling group
Among the 200 participants included in the final analysis, 107 (53.5%) showed evidence of LV underfilling, while 93 (46.5%) did not. The mean age was 38 years, with no significant differences in general characteristics between the two groups.
At the start of the study, individuals with LV underfilling showed signs of more advanced disease. They had higher lung blood pressure, poorer right heart function, and higher levels of NT-proBNP, a blood marker linked to heart strain, compared with those whose left ventricles filled normally.
Heart imaging also showed that individuals with LV underfilling had a larger right ventricle relative to the left and a smaller left ventricular volume, suggesting that compression from the enlarged right ventricle may limit the amount of blood the left ventricle fills with.
Symptoms were also more severe in this group: 42.9% of individuals with LV underfilling experienced symptoms at rest, compared with 26.8% of those without LV underfilling.
Over a median follow-up of 29.8 months, or nearly 2.5 years, 114 patients experienced a major clinical event. This included 11 deaths (4.9%) and 98 cases (51.3%) requiring hospitalization for heart failure or escalation of heart failure-related treatment.
Overall, individuals without LV underfilling showed better event-free survival throughout the follow-up period.
Patients with LV underfilling more than 5 times as likely to experience serious events
In adjusted analyses, LV underfilling emerged as one of the strongest predictors of poor outcomes. Individuals with LV underfilling were more than five times as likely to experience serious events, such as death or hospitalization, compared with those without LV underfilling.
Measures reflecting an enlarged right ventricle relative to the left and reduced left ventricular size were also significantly linked to a higher risk.
When compared with standard tools used to predict outcomes in PAH, LV underfilling provided additional prognostic value. A prediction model incorporating LV underfilling showed better accuracy at identifying patients at high risk of serious outcomes than commonly used tools such as REVEAL-Lite 2.0. This tool predicts survival in PAH based on factors including functional class, exercise capacity, and blood markers.
When LV underfilling was combined with imaging measures of right heart function, as assessed by REVEAL-ECHO,it resulted in the highest overall predictive accuracy.
“TTE-assessed LV underfilling is a novel, valuable prognostic marker in PAH,” the researchers wrote. “The current LV model, in addition to REVEAL-ECHO, offers enhanced prognostic capabilities for PAH management and may serve as a key tool in optimizing PAH patient care. Future research should validate these results in larger, multicenter cohorts and investigate LV underfilling as a therapeutic target in PAH,” the team added.
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