Impact of Targeted Therapies on Hemodynamic Parameters and Outcomes in Adults with Congenital Heart Disease and Pulmonary Arterial Hypertension – An International Multicenter Analysis

C. Hohmann (Köln)¹, R. Luna-Lopez (Barcelona)², J. Bayne (San Francisco)³, A. Vergara (Napoli)⁴, G. Kopec (Krakau)⁵, I. Blanco (Barcelona)⁶, S. Orwat (Münster)⁷, S. Freilinger (München)⁸, A. Constantine (London)⁹, M. Khalil (Köln)¹⁰, A. Arvanitaki (Thessaloniki)¹¹, D. Lovric (Zagreb)¹², D. Dumitrescu (Bad Oeynhausen)¹³, D. Momcilovic (Bonn)¹⁴, M. Brida (London)⁹, G. Giannakoulas (Thessaloniki)¹¹, K. Dimopoulos (London)⁹, H. Kaemmerer (München)⁸, G. P. Diller (Münster)¹⁵, P. Escribano-Subías (Madrid)¹⁶, M. Simon (San Francisco)³, M. D'Alto (Napoli)¹⁷, S. Rosenkranz (Köln)¹, P. von Stein (Köln)^1
1Herzzentrum der Universität zu Köln Klinik III für Innere Medizin Köln, Deutschland; ²University of Barcelona Department of Cardiology Barcelona, Spanien; ³University of California San Francisco Division of Cardiology San Francisco, USA; ⁴University of Campania 'L. Vanvitelli' Department of Cardiology Napoli, Italien; ⁵Pulmonary Circulation Centre Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College Krakau, Polen; ⁶Hospital Clínic, University of Barcelona Department of Pulmonary Medicine Barcelona, Spanien; ⁷Universitätsklinikum Münster Klinik für Kardiologie III: Angeborene Herzfehler (EMAH) und Klappenerkrankungen Münster, Deutschland; ⁸Deutsches Herzzentrum München Klinik für angeborene Herzfehler und Kinderkardiologie München, Deutschland; ⁹Royal Brompton Hospital London, Großbritannien; ¹⁰Herzzentrum der Universität zu Köln Klinik für Kinderkardiologie Köln, Deutschland; ¹¹Aristotle University of Thessaloniki First Department of Cardiology Thessaloniki, Griechenland; ¹²University Hospital Centre Zagreb Department of Cardiology Zagreb, Kroatien; ¹³Herz- und Diabeteszentrum NRW Allgemeine und Interventionelle Kardiologie/Angiologie Bad Oeynhausen, Deutschland; ¹⁴University of Bonn Department of Cardiology Bonn, Deutschland; ¹⁵Universitätsklinikum Münster Klinik und Poliklinik für angeborene (EMAH) & erworbene Herzfehler Münster, Deutschland; ¹⁶Hospital Universitario Doce de Octubre Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII) Madrid, Spanien; ¹⁷University of Campania 'L. Vanvitelli', A.O.R.N. dei Colli, Monaldi Hospital Department of Cardiology Napoli, Italien

Background: Pulmonary arterial hypertension (PAH) complicates the clinical course of adults with congenital heart disease (ACHD) in 10% of patients, and is associated with worse outcome. Data on the impact of disease targeting therapies (DTT) on invasive hemodynamics in PAH-ACHD and the relevance for outcomes are scarce.

Aims: Monitor the effects of DTT on hemodynamics, ESC/ERS risk status, and outcomes in patients with PAH-ACHD in real-world clinical practice.

Methods: Data from consecutive patients with ACHD-PAH who underwent assessment of cardiopulmonary hemodynamics by right heart catheterization (RHC) prior to initiation of DTT in adulthood (therapy-naïve) and at least one subsequent RHC on DTT between 2000 and 2022 in 14 expert centres in Europe and the U.S. were analyzed. Comprehensive analyses of RHC parameters was performed, and key non-invasive measures as well as ESC/ERS risk status were recorded. The correlation between hemodynamic parameters and the combined outcome of all-cause mortality or hospitalization for heart failure was assessed.

Results: 141 patients (77% female, median age 38 [27-52] years) were included. Underlying CHD was a pre- or post-tricuspid shunt in 35% and 59%, respectively. 17% had complex CHD, 7% had innate left heart disease, and 19% presented with Eisenmenger´s syndrome. Upon diagnostic RHC, DTT was started and maintained in all patients (38% upfront combination therapy; 62% monotherapy). The median time to follow-up RHC was 16 [8–27] months. DDT was associated with significant reductions in mean pulmonary artery pressure and pulmonary vascular resistance (both p<0.001), and improvement of stroke volume index, pulmonary arterial compliance, and cardiac index (all p<0.01). Clinical measures such as WHO-FC and NT-proBNP, and ESC/ERS risk status also improved. PVR and NT-proBNP at baseline, and the extent of PVR reduction during follow-up were associated with outcome (composite of all-cause mortality or hospitalization for heart failure). Repeat RHC resulted in treatment escalation in 48% of patients.

Conclusions: In PAH-ACHD, DTT led to a moderate but sustained hemodynamic and functional improvement, and the degree of PVR reduction was associated with outcomes. Repeat RHC resulted in subsequent treatment escalation in many patients, indicating that invasive follow-up is warranted.