Mortality Worsens Following Borderline PH Diagnosis Among Patients With LHF

An independent association for higher 3-year mortality was found between borderline pulmonary hypertension (PH) and left heart failure (LHF) among patients with both conditions, according to a new study published in Frontiers in Cardiovascular Medicine.

With a recent revision to the diagnostic criteria for borderline PH, survival outcomes for patients who have comorbid LHF and borderline PH remain uncertain. For diagnosing borderline PH, the mean pulmonary arterial pressure (mPAP) recently dropped to above 20 mm Hg from at least 25 mm Hg, according to the study authors. For this study, the authors defined borderline PH as being between 21 and 24 mm Hg.

“Patients with LHF are often associated with the development of PH, which leads to an increased risk of death. Nonetheless, data on modestly raised mPAP (21-24 mmHg), sometimes known as borderline PH, remain scarce,” the authors wrote. “Although previous researchers have suggested that mPAP may be prognostic in patients with left heart disease, it is unknown whether borderline PH worsens mortality in people with LHF.”

Beyond borderline PH, the authors use 2 additional PH classifications for their analysis: Traditionally defined PH had an mPAP of at least 25 mm Hg and non-PH had an mPAP of 20 mm Hg or less. Their primary outcome was all-cause mortality and their secondary outcome, rehospitalization.

Among the 344 patients in this retrospective cohort study, 62.5% (n = 215) had traditionally defined PH, 26.7% (n = 92) had non-PH, and 10.8% had borderline PH (n = 37). In a multivariable Cox analysis, a 282% greater risk of death was seen among the participants who had borderline PH (HR, 3.822, 95% CI, 1.043-13.999; P = .043). Further, a univariate Cox regression analysis saw a 302% greater risk (HR, 4.023; 95% CI, 1.411-11.465; P = .009), which the authors noted was the maximum for their study.

All of the patients (mean [SD] age, 63.3 [12.0] years) underwent right heart catheterization, a procedure meant to gauge the heart’s pumping ability and heart and lung pressure, between January 2013 and November 2016. They were followed-up with every 6 months for a 3-year period via phone calls, messages, or outpatient visits. Most had New York Heart Association function class II disease: 78.3% of the non-PH group, 81.1% of the borderline PH group, and 58.6% of the traditionally defined PH group. HF with preserved ejection fraction was the most common HF subtype in 82.6%, 863.6%, and 68.8%, respectively, and was a mean 54.2% (10.6%) overall. Statins were the most common medication type in 90.2%, 83.8%, and 86.0%.

The mortality trend continued, albeit to a lesser degree, when mPAP was analyzed in the context of it being a continuous variable. For mPAP that increased from 20 to 70 mm Hg, there was an associated 6% higher mortality risk (HR, 1.006; 95% CI, 1.001-1.012). The highest risk per 1 mm Hg increase in mPAP was associated with the range of 21 to 24 mm Hg.

“This finding implies that patients with borderline PH are susceptible when exposed to the progressively increased mPAP,” the authors wrote.

For the entire study population, the median (IQR) mPAP was 27 (20-32) mm Hg, with the minimum and maxium mPAPs were 7 mm Hg and 70 mm Hg.

Three-year mortality was highest in the traditional PH group (23.1%) and lowest in the non-PH group (4.5%). Patients with borderline PH fell in the middle, at 16.7%. One- and 2-year mortality rates were similar, with the highest again in the traditionally defined PH cohort. This group, too, had the highest the 1-, 2-, and 3-year rehospitalization rates: 24.0% (vs 14.1% in the non-PH group), 43.5% (vs 22.9%), and 53.7%, respectively.

The study authors note that their findings illustrate that traditionally defined PH and borderline PH can be linked to greater 3-year all-cause mortality, with the latter having “the same clinical significance as traditionally defined PH and supporting the new PH hemodynamic criteria (mPAP > 20 mm Hg) adopted in patients with LHF.”

They concluded that their findings “suggest that the risk of mortality increases immediately and incrementally when the mPAP value exceeds 20 mm Hg.”

Future prospective studies, they suggested, need to evaluate closer monitoring of patients who have borderline PH, when treatment is intensified among these patients, and the importance of RHC among individuals suspected of having PH and LHF.

Reference

Lin Y, Pang L, Huang S, et al. Impact of borderline pulmonary hypertension due to left heart failure on mortality in a multicenter registry study: a 3-year survivorship analysis. Front Cardiovasc Med. Published online August 12, 2022. doi:10.3389/fcvm.2022.983803