Right Heart Reverse Remodeling Correlates with NT-proBNP Outcomes Among Pulmonary Arterial Hypertension Patients on Combination Therapy

Abstract

<h3>Purpose</h3> Combination therapy is the current standard for severe pulmonary arterial hypertension (PAH). Few studies have characterized reverse remodeling achievable with therapy, and in particular, how it correlates with prognostic trends in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. We evaluated the longitudinal impact of PAH combination therapy on echocardiographic right heart parameters and observed how reverse remodeling correlates with a prognostic indicator of treatment response. <h3>Methods</h3> Thirty-two adults (age, 32±9years) with newly diagnosed PAH were initiated on combination therapy and had transthoracic echocardiograms performed prior to, and at least 3 months after, starting therapy. Pre- and follow-up NT-proBNP values were collected and speckle-tracking strain analysis was applied to echocardiogram images. Paired samples t-test was used to evaluate the statistical difference between baseline and follow-up measurements. <h3>Results</h3> After a mean 2.7 years, there was a significant decrease in mean RV basal diameter from 4.6cm to 4.2cm (p=0.03) and mean right atrial area from 23.6cm² to 19.8cm² (p<0.01). RV fractional area change (RVFAC) increased from 21% to 31% (p<0.01) and mean RV free wall strain (RVFWS) improved from -11.4% to -15.8% (p<0.01). Prior to therapy, 63% of patients had elevated NT-proBNP levels (>900pg/mL). By follow-up, there was a greater improvement in RVFAC among patients who maintained or achieved a normal NT-proBNP level with therapy compared to those whose biomarker level increased or remained elevated (+0.10% vs +0.003%, p=0.03). RVFWS improved to a greater extent in the former group compared to the latter, though this did not reach statistical significance (-5.32% vs. -0.86%, p=0.07). Five out of the 6 patients who died during follow-up maintained elevated NT-proBNP levels despite therapy. Half were on aggressive regimens including intravenous prostacyclin therapy. <h3>Conclusion</h3> While combination PAH therapy was associated with improved RV structure and function parameters among our cohort; patients with persistently elevated or deteriorated NT-proBNP levels demonstrated less reverse remodeling and had increased mortality. These findings highlight a need for novel future therapies that target right heart-specific remodeling pathways in high-risk PAH patients.