Researchers have identified a significant risk factor that affects the prognosis of people with chronic thromboembolic pulmonary hypertension (CTEPH) in a large 26-year study.
They found that elevated left ventricular filling pressure (LVFP), a measure of left heart function, was common in patients and predicted worse outcomes. Pulmonary hypertension (PH), or high blood pressure in the pulmonary arteries — those that supply the lungs — is typically associated with right heart malfunction.
This study demonstrated that left heart involvement also plays a significant role in the outcomes of CTEPH patients. Irregular heartbeat, calcium deposits in heart valves, and leaky heart valves were also found to be independent predictors for LVFP.
“The authors [of the study] have explored the presence and preliminary significance of coexisting LVFP elevation in a relatively large CTEPH cohort [group],” Paul Forfia, MD, a PH specialist at Temple University Hospital in Philadelphia, wrote in an editorial comment published alongside the study.
“In doing so, bringing to light a concept that highly experienced CTEPH providers are all too familiar with,” Forfia said. “Competing conditions must be considered at the outset of CTEPH diagnosis and on follow-up, including [post-surgery].”
First-line treatment is surgery to remove blood clots from pulmonary arteries
The large-scale study, “Left Ventricular Filling Pressure in Chronic Thromboembolic Pulmonary Hypertension,” was published in the Journal of the American College of Cardiology.
CTEPH is a subtype of PH whereby the formation of blood clots in the pulmonary arteries causes high blood pressure. Alterations in the structures of blood vessels, called vascular remodeling, have also been observed in CTEPH patients.
First-line CTEPH treatment is the surgical removal of blood clots from the pulmonary arteries, a procedure called pulmonary thromboendarterectomy. In those unable to undergo surgery, balloon pulmonary angioplasty to widen blocked pulmonary arteries is a treatment option.
The right side of the heart, which pumps blood through the lung via the pulmonary arteries, is known to be affected by PH. However, CTEPH is frequently complicated by elevated LVFP — the blood pressure that fills the left ventricle (from the lungs) between heartbeats and determines the volume of blood pumped to the body.
In the study, researchers based at the Medical University of Vienna, in Austria, and their collaborators sought to investigate the prevalence and predictive implications of elevated LVFP in CTEPH.
The researchers investigated 26-year data of 593 patients with CTEPH, all of whom had undergone right and left heart catheterization — a procedure to measure blood pressure within the heart chambers by inserting a thin, flexible tube (catheter) through a blood vessel.
Among the participants, 332 underwent pulmonary thromboendarterectomy, and of the 257 inoperable patients, 118 received balloon pulmonary angioplasty, and 139 were given medication therapy before balloon pulmonary angioplasty became available.
Our data demonstrate that at least 11% of patients with CTEPH have elevated LVFP at the time of diagnosis, representing an additional disease component in CTEPH that independently impacts prognosis.
Elevated LVFP was defined by an increase in the mean pulmonary artery wedge pressure, a measure of blood pressure in the upper left heart chamber (left atrium), and/or left ventricular end-diastolic pressure, which is a measure of left ventricle performance.
Values above 15 mmHg were considered abnormally high, based on PH guidelines. A secondary measure of more than 11 mmHg, the upper limit of the normal range, was also included. At diagnosis, LVFP was over 15 mmHg in 63 patients (10.6%) and over 11 mmHg in 222 patients (37.4%).
Elevated LVFP was significantly associated with older age, systemic (body-wide) high blood pressure, diabetes, irregular heartbeat (atrial fibrillation), calcium deposits in heart valves (calcific valve stenosis), and leaky heart valves (mitral regurgitation).
Chronic kidney disease, left atrial volume, and higher NT-proBNP levels (a biomarker for heart damage) were also significantly linked to LVFP.
Overall, LVFP increased from initial measurements during the six- to 12-month follow-up (mean 10.6 vs. 11.2 mmHg) in 378 patients with available data. At follow-up, LVFP was higher than 15 mmHg in 65 patients (17.2%) and above 11 mmHg in 164 patients (43.4%).
Elevated LVFP significantly linked to worse outcomes
Notably, LVFP was unchanged at follow-up in those who had not undergone surgery (mean 11.2 vs. 10.9 mmHg), whereas a significant increase was seen in patients who had undergone pulmonary thromboendarterectomy (mean 10.1 vs. 11.5 mmHg). Similar data were obtained when LVFP was defined as over 11 mmHg.
After adjustments, statistical analysis found that irregular heartbeat, calcium deposits in heart valves, and leaky heart valves were independent risk factors for LVFP. Adding left arterial volume improved diagnostic accuracy.
During a median follow-up of 5.9 years, 204 of the 590 patients with available data died. After adjusting for all blood flow factors, elevated LVFP, above both 15 and 11 mmHg, was significantly associated with worse long-term survival.
“Our data demonstrate that at least 11% of patients with CTEPH have elevated LVFP at the time of diagnosis, representing an additional disease component in CTEPH that independently impacts prognosis [outcomes],” the researchers concluded. “Features of the metabolic syndrome [diabetes/high blood pressure], atrial fibrillation, mitral regurgitation, and LA [left atrial] enlargement are associated with elevated LVFP in CTEPH.”
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