Adults with congenital heart disease and pulmonary arterial hypertension: Quantitative assessment of haemodynamic parameters under disease targeting therapy - A retrospective multicentre analysis
Authors: Von Stein P , D'alto M , Diller G , Orwat S , Dumitrescu D , Giannakoulas G , Arvanitaki A , Momcilovic D , Hohmann C , Rosenkranz S 
Published: November 2023

Abstract

Background
Pulmonary arterial hypertension (PAH) occurs in approximately 10% of adults with congenital heart disease (ACHD), usually develops secondary to intra- or extra-cardiac shunts resulting in pressure and/or volume overload in the pulmonary circulation, and is associated with increased morbidity and mortality. Treatment strategies for PAH-ACHD include disease targeting therapies (DTT), such as phosphodiesterase-5 inhibitors (PDE5i) and endothelin receptor antagonists (ERA). Data regarding the impact of DTT on cardiopulmonary haemodynamics in PAH-ACHD are scarce.

Purpose
Aim of this study was to quantify effects of DTT on cardiopulmonary haemodynamics (assessed by right heart catheterisation [RHC]) and on key non-invasive functional parameters contributing to ESC/ERS risk status in PAH-ACHD patients, as applied in real-world clinical practice.

Methods
We retrospectively analysed the effect of DTT in PAH-ACHD patients who had undergone RHC in adulthood at baseline (treatment-naïve) between 2000 and 2022, with at least one follow-up RHC during DTT, in six expert centres in Europe. Clinical characteristics (WHO functional class [WHO-FC], 6-minute walking distance [6MWD], N-terminal pro-brain natriuretic peptide [NTproBNP] and measures of RHC (systemic/ pulmonary cardiac output, systolic/diastolic/mean pulmonary arterial pressure [sPAP, dPAP, mPAP], and pulmonary arterial wedge pressure [PAWP]) were collected. Pulmonary vascular resistance/arterial compliance (PVR+PAC) and stroke volume index (SVI) were calculated.

Results
44 patients (70% female, mean age 45±15 years) were included. Underlying CHD was a pre- or post-tricuspid shunt in 35% and 63%, respectively. 14% had complex CHD, 7% had innate left heart disease, and 21% presented with Eisenmenger´s syndrome. At baseline 71% were in WHO-FC III/IV, 6MWD was 371±105 m, and NTproBNP was 673 [446–1021] ng/l. On RHC, mPAP was 58±15 mmHg, PVR 11 [7–17] wood units (WU), SVI 32 [27–44] ml/min/m2, CI 2.7±1.0 l/min/m2, and PAC 1.0 [0.7–1.4] ml/mmHg. DTT was started in all patients after baseline RHC. 81% received monotherapy (34% PDE5i, 66% ERA) and 19% received upfront combination therapy (PDE5i+ERA). Follow-up RHC was performed 15 [5–33] months after baseline RHC. At follow-up, WHO-FC and NTproBNP (562 [428-762] ng/l) significantly improved (p&lt;0.001 and p=0.021, respectively), as did hemodynamic measures: mPAP (53±15 mmHg, p&lt;0.001), PVR (9 [5–10] WU, p&lt;0.001), SVI (37 [30–49] ml/min/m2, p=0.010), PAC (1.3 [1.0–1.7] ml/mmHg, p&lt;0.001), and CI (3.1±1.1 l/min/m2, p=0.001). In contrast, 6MWD showed subtle change (379±111 m, p=0.164). After follow-up RHC, DTT was escalated in 78% of patients.

Conclusions
In PAH-ACHD patients, DTT was associated with a moderate but sustained haemodynamic and functional improvement after 15 months. Repeat RHC triggered treatment escalation in most patients. Therefore, ongoing vigilance for PAH-ACHD patients and subsequent treatment optimisation is warranted.