Pulmonary Hypertension in Adults with Congenital Heart Disease: Real-World Data from the International COMPERA-CHD Registry

Kaemmerer H, Gorenflo M, Huscher D, Pittrow D, Apitz C, Baumgartner H, Berger F, Bruch L, Brunnemer E, Budts W, Claussen M, Coghlan G, Dähnert I, D’Alto M, Delcroix M, Distler O, Dittrich S, Dumitrescu D, Ewert R, Faehling M, Germund I, Ghofrani HA, Grohé C, Grossekreymborg K, Halank M, Hansmann G, Harzheim D, Nemes A, Havasi K, Held M, Hoeper MM, Hofbeck M, Hohenfrost-Schmidt W, Jurevičienė E, Gumbienè L, Kabitz HJ, Klose H, Köhler T, Konstantinides S, Köestenberger M, Kozlik-Feldmann R, Kramer HH, Kropf-Sanchen C, Lammers A, Lange T, Meyn P, Miera O, Milger-Kneidinger K, Neidenbach R, Neurohr C, Opitz C, Perings C, Remppis BA, Riemekasten G, Scelsi L, Scholtz W, Simkova I, Skowasch D, Skride A, Stähler G, Stiller B, Tsangaris I, Vizza CD, Vonk Noordegraaf A, Wilkens H, Wirtz H, Diller GP, Grünig E, Rosenkranz S.J Clin Med. 2020 May 13;9(5):E1456. doi: 10.3390/jcm9051456.PMID: 32414075 Free article.



Introduction: Pulmonary hypertension (PH) is a common complication in patients with congenital heart disease (CHD), aggravating the natural, post-operative, or post-interventional course of the underlying anomaly. The various CHDs differ substantially in characteristics, functionality, and clinical outcomes among each other and compared with other diseases with pulmonary hypertension.

Objective: To describe current management strategies and outcomes for adults with PH in relation to different types of CHD based on real-world data.

Methods and results: COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) is a prospective, international PH registry comprising, at the time of data analysis, >8200 patients with various forms of PH. Here, we analyzed a subgroup of 680 patients with PH due to CHD, who were included between 2007 and 2018 in 49 specialized centers for PH and/or CHD located in 11 European countries. At enrollment, the patients´ median age was 44 years (67% female), and patients had either pre-tricuspid shunts, post-tricuspid shunts, complex CHD, congenital left heart or aortic disease, or miscellaneous other types of CHD. Upon inclusion, targeted therapies for pulmonary arterial hypertension (PAH) included endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, and soluble guanylate cyclase stimulators. Eighty patients with Eisenmenger syndrome were treatment-naïve. While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%. The use of oral anticoagulants or antiplatelets was dependent on the underlying diagnosis or comorbidities. In the entire COMPERA-CHD cohort, after follow-up and receiving targeted PAH therapy (n = 511), 91 patients died over the course of a 5-year follow up. The 5-year Kaplan-Meier survival estimate for CHD associated PH was significantly better than that for idiopathic PAH (76% vs. 54%; p < 0.001). Within the CHD associated PH group, survival estimates differed particularly depending on the underlying diagnosis and treatment status.

Conclusions: In COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH. Nevertheless, overall survival of patients with PAH due to CHD was still markedly reduced compared with survival of patients with other types of CHD, despite an increasing number of patients on PAH-targeted combination therapy.


Figure 1 Age distribution of the population with CHD-associated pulmonary arterial hypertension (PAH). Data represent the percentage of patients from each subgroup in the respective age groups. CHD, congenital heart disease.


Figure 2 Drug classes for targeted PAH therapy in the patients with CHD-associated PAH at inclusion and at last observation (mean/median observation time of 50.5/45.3 months respectively; for 512 patients with at least one follow-up). “Other therapy” includes soluble guanylate cyclase (sGC) stimulator, tyrosine kinase inhibitor, calcium channel blockers, and other PAH-specific trial therapies. Abbreviations: PCA, prostanoids.


Figure 3 Targeted mono- or combination therapy in 512 CHD patients with PAH, with at least one follow-up using different drug classes at inclusion and at last observation (mean/median observation time of 50.5/45.3 months respectively). CHD, congenital heart disease; PAH, pulmonary arterial hypertension


Figure 4 Anticoagulation/platelet inhibition regime in patients with CHD-associated PAH at inclusion and at last observation. Abbreviations: CHD, congenital heart disease; NOAC, non-vitamin K antagonists; vit, vitamin; PAH, pulmonary arterial hypertension

Figure 5 Kaplan–Meier 5-year survival estimates. (A) Comparison of all patients who underwent targeted PAH treatment for either congenital heart disease-associated pulmonary hypertension (CHD treated, total) or incident idiopathic PAH. The 5-year Kaplan–Meier survival estimate was 76% for PAH due to CHD and 54% for idiopathic PAH (p < 0.001). (B) Comparison of subgroups of patients with CHD and PAH under targeted PAH medication: (1) CHD-treated, total (green); (2) Eisenmenger-patients-treated (EM treated; purple); (3) non-Eisenmenger-PAH-patients (Non-EM treated; blue). The overall 5-year survival estimate was 76%, compared with 78% for the Eisenmenger patients, and 77% for the non-Eisenmenger-PAH-patients (p = 0.384). (C) Comparison of subgroups of patients with Eisenmenger syndrome due to complex or simple CHD. The 5-year Kaplan–Meier survival estimate was 81% for Eisenmenger syndrome caused by simple CHD and 64% for Eisenmenger syndrome due to complex CHD (p = 0.063). Kaplan–Meier survival estimates (top) and number of cases still under observation (bottom) are shown in tabular form. Abbreviations: CHD, congenital heart disease; non-EM, non-Eisenmenger-PAH-patients; PAH, pulmonary arterial hypertension.