{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T21:37:25Z","timestamp":1770413845094,"version":"3.49.0"},"reference-count":25,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Manfred-Roth-Stiftung F\u00fcrth"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Progress in diagnostic and therapeutic strategies has resulted in an increasing prevalence of adults with congenital heart disease (ACHD), including those involving genetically determined syndromes. This study aimed to characterize prevalence, congenital phenotypes, heart failure (HF) stages, comorbidity burden, and current medical management of ACHD and concomitant genetically determined syndromes enrolled in a prospective HF-focused registry. Methods: The PATHFINDER-CHD Registry is a German-based (est. 2022) multicenter observational registry. This web-based platform consecutively tracks ACHD patients across the heart failure spectrum, including those with current or prior HF, as well as those at high structural or functional risk. HF stage was classified using a modified ACC\/AHA scheme adapted for CHD; functional capacity was graded according to the Perloff classification. Baseline demographics, CHD anatomy, prior surgical\/interventional treatment, cardiac and extracardiac comorbidities, and medication were collected from medical records. Results: Among 1987 enrolled ACHD, 107 (5.4%) had a genetic syndrome (n = 65, 60.7% women; mean age 33.5 \u00b1 9.4 years; range 18\u201368). Most common syndromes were trisomy 21 (n = 49; 45.8%) and 22q11.2 deletion (n = 27; 25.2%); 31 patients (30.0) had rarer syndromes. Predominant CHD diagnoses were atrioventricular septal defect (n = 42, 39.3%), tetralogy of Fallot (n = 19, 17.8%), and pulmonary atresia with ventricular septal defect (n = 7, 6.5%). A systemic left ventricle was present in 102 (95.3%); 40 (37.4%) had primarily cyanotic CHD, and 7 (6.5%) an Eisenmenger physiology. Most patients (n = 71; 66.4%) had undergone definite surgical repair; 25 patients (23.3%) had at least one catheter intervention, including transcatheter valve implantation in 17 cases (15.9%). HF stage was mainly B (n = 30, 28.0%) or C (n = 75, 70.1%). Perloff functional class I\/II was present in 97 (90.7%). Leading cardiac comorbidities included intrinsic aortopathy (n = 49, 45.8%), pulmonary arterial hypertension (n = 12, 11.2%), and arrhythmias (n = 10, 9.3%). Frequent extracardiac comorbidities were thyroid dysfunction (n = 34, 31.8%), kidney disease (n = 16, 15.0%), hyperuricemia (n = 13, 12.1%), and depression (n = 15, 14.0%). Pharmacotherapy was used in 66 patients (61.7%). Beta-blockers (n = 25, 23.4%) were common, while ACEi\/ARB (n = 9, 8.4%), diuretics (n = 10, 9.3%), MRAs (n = 8, 7.5%), and SGLT2 inhibitors (n = 3; 2.8%) were infrequently prescribed; no patient received ARNI or digitalis. For targeted treatment of pulmonary arterial hypertension, phosphodiesterase-5 inhibitors (n = 7, 6.5%), endothelin receptor antagonists (n = 6, 5.6%), or prostacyclin analogues (n = 1, 0.9%) were used. As oral anticoagulants, vitamin K antagonists or direct oral anticoagulants (DOACs) were prescribed in 17 cases (15.9%). Forty-one patients (38.3%) received thyroid hormone replacement. Conclusions: Syndromic ACHD constitute a small but clinically high-risk subgroup within an HF-oriented registry, marked by complex CHD, substantial cardio\u2013extracardiac multimorbidity (notably aortopathy, PAH, thyroid disease, renal dysfunction, depression), and low utilization of contemporary HF therapies. These data support specialized, interdisciplinary, longitudinal care pathways and prospective studies addressing outcomes and evidence-based HF management in syndromic ACHD.<\/jats:p>","DOI":"10.3390\/jcm15031290","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T10:05:47Z","timestamp":1770372347000},"page":"1290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Syndromes and Multimorbidity in Adults with Congenital Heart Disease and Heart Failure: Insights from the PATHFINDER-CHD Registry"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6385-7632","authenticated-orcid":false,"given":"Ann-Sophie","family":"Kaemmerer-Suleiman","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fritz","family":"Mellert","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Achenbach","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pinar","family":"Bambul-Heck","sequence":"additional","affiliation":[{"name":"International Center for Adults with Congenital Heart Disease, Department of Congenital Heart Disease and Paediatric Cardiology, TUM University Hospital, German Heart Center Munich, 80636 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Cesnjevar","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5216-7978","authenticated-orcid":false,"given":"Oliver","family":"Dewald","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Herz-und Gef\u00e4\u00dfchirurgie am Klinikum Karlsburg, Herz-und Diabeteszentrum MV, 17495 Karlsburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Dreher","sequence":"additional","affiliation":[{"name":"International Center for Adults with Congenital Heart Disease, Department of Congenital Heart Disease and Paediatric Cardiology, TUM University Hospital, German Heart Center Munich, 80636 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Eicken","sequence":"additional","affiliation":[{"name":"International Center for Adults with Congenital Heart Disease, Department of Congenital Heart Disease and Paediatric Cardiology, TUM University Hospital, German Heart Center Munich, 80636 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Engel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0253-1190","authenticated-orcid":false,"given":"Peter","family":"Ewert","sequence":"additional","affiliation":[{"name":"International Center for Adults with Congenital Heart Disease, Department of Congenital Heart Disease and Paediatric Cardiology, TUM University Hospital, German Heart Center Munich, 80636 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika","family":"Freiberger","sequence":"additional","affiliation":[{"name":"International Center for Adults with Congenital Heart Disease, Department of Congenital Heart Disease and Paediatric Cardiology, TUM University Hospital, German Heart Center Munich, 80636 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2716-1424","authenticated-orcid":false,"given":"J\u00fcrgen","family":"H\u00f6rer","sequence":"additional","affiliation":[{"name":"Department of Congenital and Paediatric Heart Surgery, German Heart Center Munich, University Hospital of the Technical University, 80636 Munich, Germany"},{"name":"Division of Congenital and Pediatric Heart Surgery, European Kids Heart Center, University Hospital Gro\u00dfhadern, Ludwig-Maximilians-University Munich (LMU), 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Hohmann","sequence":"additional","affiliation":[{"name":"Clinic III for Internal Medicine, Heart Center, Faculty of Medicine, University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9210-7064","authenticated-orcid":false,"given":"Stefan","family":"Holdenrieder","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, German Heart Centre Munich, Technical University of Munich, 80636 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Huntgeburth","sequence":"additional","affiliation":[{"name":"International Center for Adults with Congenital Heart Disease, Department of Congenital Heart Disease and Paediatric Cardiology, TUM University Hospital, German Heart Center Munich, 80636 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0789-2684","authenticated-orcid":false,"given":"Harald","family":"Kaemmerer","sequence":"additional","affiliation":[{"name":"International Center for Adults with Congenital Heart Disease, Department of Congenital Heart Disease and Paediatric Cardiology, TUM University Hospital, German Heart Center Munich, 80636 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renate","family":"Kaulitz","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Universit\u00e4tsklinikum T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9613-182X","authenticated-orcid":false,"given":"Frank","family":"Klawonn","sequence":"additional","affiliation":[{"name":"Helmholtz Centre for Infection Research, Biostatistics, Technical University Braunschweig, 38124 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1367-3410","authenticated-orcid":false,"given":"Christian","family":"Meierhofer","sequence":"additional","affiliation":[{"name":"International Center for Adults with Congenital Heart Disease, Department of Congenital Heart Disease and Paediatric Cardiology, TUM University Hospital, German Heart Center Munich, 80636 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Montenbruck","sequence":"additional","affiliation":[{"name":"International Center for Adults with Congenital Heart Disease, Department of Congenital Heart Disease and Paediatric Cardiology, TUM University Hospital, German Heart Center Munich, 80636 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Nagdyman","sequence":"additional","affiliation":[{"name":"International Center for Adults with Congenital Heart Disease, Department of Congenital Heart Disease and Paediatric Cardiology, TUM University Hospital, German Heart Center Munich, 80636 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhoia C.","family":"Neidenbach","sequence":"additional","affiliation":[{"name":"Department of Sport and Human Movement Science, University of Vienna, 1010 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2673-4772","authenticated-orcid":false,"given":"Robert D.","family":"Pittrow","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7331-8840","authenticated-orcid":false,"given":"Christoph R.","family":"Sinning","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart and Vascular Centre Hamburg, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3431-0862","authenticated-orcid":false,"given":"Fabian","family":"von Scheidt","sequence":"additional","affiliation":[{"name":"International Center for Adults with Congenital Heart Disease, Department of Congenital Heart Disease and Paediatric Cardiology, TUM University Hospital, German Heart Center Munich, 80636 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pelagija","family":"Zlatic","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1817-4207","authenticated-orcid":false,"given":"Frank","family":"Harig","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9541-9888","authenticated-orcid":false,"given":"Mathieu N.","family":"Suleiman","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1161\/01.CIR.103.21.2637","article-title":"Challenges posed by adults with repaired congenital heart 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Drugs"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/3\/1290\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T10:29:41Z","timestamp":1770373781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/3\/1290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":25,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jcm15031290"],"URL":"https:\/\/doi.org\/10.3390\/jcm15031290","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]}}}