Risk of Heart Failure in Congenital Heart Disease: A Nationwide Register-Based Cohort Study

HomeCirculationVol. 147, No. 12Risk of Heart Failure in Congenital Heart Disease: A Nationwide Register-Based Cohort Study Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBRisk of Heart Failure in Congenital Heart Disease: A Nationwide Register-Based Cohort Study Niklas Bergh, Kristofer Skoglund, Maria Fedchenko, Entela Bollano, Peter Eriksson, Mikael Dellborg, Kok Wai Giang and Zacharias Mandalenakis Niklas BerghNiklas Bergh Correspondence to: Niklas Bergh, MD, PhD, Department of Cardiology, Sahlgrenska University Hospital, Blå Stråket 3, 413 45 Göteborg, Sweden. Email E-mail Address: [email protected] https://orcid.org/0000-0002-7440-2366 Department of Transplantation, Sahlgrenska University Hospital/Sahlgrenska, Gothenburg, Sweden (N.B.). Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden (N.B., K.S., M.F., E.B., P.E., M.D., K.W.G., Z.M.). Department of Cardiology, Sahlgrenska University Hospital/Sahlgrenska, Gothenburg, Sweden (N.B., K.S., E.B.). Search for more papers by this author , Kristofer SkoglundKristofer Skoglund https://orcid.org/0000-0002-9095-1218 Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden (N.B., K.S., M.F., E.B., P.E., M.D., K.W.G., Z.M.). Department of Cardiology, Sahlgrenska University Hospital/Sahlgrenska, Gothenburg, Sweden (N.B., K.S., E.B.). Search for more papers by this author , Maria FedchenkoMaria Fedchenko Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden (N.B., K.S., M.F., E.B., P.E., M.D., K.W.G., Z.M.). Department of Medicine, Geriatrics and Emergency Medicine, Region Västra Götaland, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.F., P.E., M.D., K.W.G., Z.M.). Search for more papers by this author , Entela BollanoEntela Bollano https://orcid.org/0000-0003-3341-2434 Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden (N.B., K.S., M.F., E.B., P.E., M.D., K.W.G., Z.M.). Department of Cardiology, Sahlgrenska University Hospital/Sahlgrenska, Gothenburg, Sweden (N.B., K.S., E.B.). Search for more papers by this author , Peter ErikssonPeter Eriksson Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden (N.B., K.S., M.F., E.B., P.E., M.D., K.W.G., Z.M.). Department of Medicine, Geriatrics and Emergency Medicine, Region Västra Götaland, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.F., P.E., M.D., K.W.G., Z.M.). Search for more papers by this author , Mikael DellborgMikael Dellborg https://orcid.org/0000-0001-6502-8838 Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden (N.B., K.S., M.F., E.B., P.E., M.D., K.W.G., Z.M.). Department of Medicine, Geriatrics and Emergency Medicine, Region Västra Götaland, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.F., P.E., M.D., K.W.G., Z.M.). Search for more papers by this author , Kok Wai GiangKok Wai Giang https://orcid.org/0000-0002-3452-1969 Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden (N.B., K.S., M.F., E.B., P.E., M.D., K.W.G., Z.M.). Department of Medicine, Geriatrics and Emergency Medicine, Region Västra Götaland, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.F., P.E., M.D., K.W.G., Z.M.). Search for more papers by this author and Zacharias MandalenakisZacharias Mandalenakis https://orcid.org/0000-0001-5093-9743 Department of Medicine, Geriatrics and Emergency Medicine, Region Västra Götaland, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.F., P.E., M.D., K.W.G., Z.M.). Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden (N.B., K.S., M.F., E.B., P.E., M.D., K.W.G., Z.M.). Search for more papers by this author Originally published19 Dec 2022https://doi.org/10.1161/CIRCULATIONAHA.122.061546Circulation. 2023;147:982–984This article is commented on by the following:Adult Congenital Heart Disease: A Specialty With Ever-Expanding ChallengesOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: December 19, 2022: Ahead of Print Advances in pediatric cardiology, congenital cardiac surgery, and intensive care medicine have significantly improved survival of children with congenital heart disease (CHD).1,2 Patients with CHD have a lower life expectancy than their healthy counterparts. Causes of death in the majority of adult patients with CHD are CHD related, with heart failure (HF) being the leading cause of death regardless of age.3 The present study aimed to investigate the risk for HF in patients with CHD compared with matched control subjects without CHD.Editorial, see p 939In brief, data from the Swedish National Patient Register and Cause of Death Register were used to identify patients with a CHD diagnosis who were born between 1930 and 2017. Each patient identified with CHD was matched with 10 control subjects without CHD by sex and birth year from the Total Population Register. Patients with CHD were analyzed in total, subdivided into 6 different lesions groups according to hierarchic classification of CHD or into complex (lesion groups 1 and 2) and noncomplex (lesion groups 3–6) lesion groups (for details, see the Table). The study population was followed up through the Swedish National Patient Register and Cause of Death Register from January 1, 1970, to December 31, 2017. HF was identified by the following codes: 427.00 (International Classification of Diseases, 8th Revision), 428 (International Classification of Diseases, 9th Revision), or I50 (International Classification of Diseases, 10th Revision). Incidence rates for HF were estimated as the number of events divided by total follow-up time and reported as incidence rate per 10 000 person-years with 95% CIs. Cox proportional hazard models were used to calculate the risk for developing HF for the CHD and control groups, yielding hazard ratios (HRs) with 95% CIs. For all Cox proportional hazard models, the control population was used as the reference group. The study was approved by the Regional Research Ethics Board in Gothenburg (Gbg 912-16, T619-18), and the study was conducted in accordance with the Declaration of Helsinki. The present study followed the Strengthening the Reporting of Observational Studies in Epidemiology guidelines, and data that support the findings of this study are available from the corresponding author on reasonable request.Table. Risk of HF in Patients with CHD and Control SubjectsPatients with CHDControl subjectsTotal CHD, nEvents, nPerson-time, yIR per 10 000 person-y (95% CI)HR (95 % CI)Total control subjects, nEvents, nPerson-time, yIR per 10 000 person-y (95% CI)All CHD89 53270132 218 45931.6 (30.9–32.4)8.7 (8.4–8.9)890 469968224 295 0374.0 (3.9–4.1)Sex Men455 36638061 132 07533.6 (32.6–34.7)7.7 (7.4–8.0)453 717586312 446 7034.7 (4.6–4.8) Women44 16632071 086 38529.5 (28.5–30.6)10.2 (9.7–10.7)436 752381911 848 3343.2 (3.1–3.3)CHD lesion group 1: Conotruncal defects*63261004131 06376.6 (71.9–81.5)42.3 (37.5–47.8)63 0403701 767 3372.1 (1.9–2.3) 2: Severe nonconotruncal defects †4831855105 60581.0 (75.6–86.6)21.0 (18.9–23.4)48 1995571 570 1483.6 (3.3–3.9) 3: Coarctation of the aorta4598460135 74133.9 (30.9–37.1)10.3 (9.1–11.7)45 8705731 522 7253.8 (3.5–4.1) 4: Ventricular septal defect25 1501121447 95425.0 (23.6–26.5)11.6 (10.7–12.6)249 31511884 748 3962.5 (2.4–2.7) 5: Atrial septal defect20 9291718627 82627.4 (26.1–28.7)4.8 (4.5–5.1)208 09139826 353 7636.3 (6.1–6.5) 6: Other‡27 6981855770 27024.1 (23.0–25.2)7.6 (7.2–8.0)275 95430128 332 6683.6 (3.5–3.8)CHD lesion group complexity Complex lesion group§11 1571859236 66878.6 (75.0–82.2)28.7 (26.5–31.0)111 2399273 337 4852.8 (2.6–3.0) Noncomplex lesion∥ group†78 37551541 981 79226.0 (25.3–26.7)6.9 (6.7–7.2)779 230875520 957 5524.2 (4.1–4.3)Age group, y 0–1789 53221311 144 75419 (18–19)222 (181–271)890 46910012 301 2190.08 (0.07–0.1) 18–4943 9701541861 84818 (17–19)20 (18–22)487 4068679 572 5660.9 (0.9–1.0) 50–5914 629931117 16480 (74–85)6.8 (6.2–7.3)158 17015121 281 39712 (11–12) 60–699079121666 798182 (172–193)5.1 (4.7–5.4)101 1862796771 06336 (35–38) 70–79438996324 970386 (362–411)4.0 (3.7–4.3)53 6103154320 99898 (95–102) ≥809652312926790 (691–898)3.1 (2.7–3.5)14 413125347 793262 (248–277)Birth period 1930–196917 60143091 062 25440.6 (39.4–41.8)5.6 (5.4–5.8176 010934311 139 4198.4 (8.2–8.6) 1970–201771 93127041 156 20623.4 (22.5–24.3)88.4 (78.9–98.9)714 45933913 155 6180.3 (0.2–0.3)CHD indicates congenital heart disease; HF, heart failure; HR, hazard ratio; and IR, incidence rate.* Conotruncal defects include aortopulmonary septal defect, common arterial trunk, tetralogy of Fallot, transposition of the great arteries (unrepaired lesions and surgically repaired), double-outlet right ventricle, double-outlet left ventricle, congenitally corrected transposition/discordant atrioventricular, and ventriculoatrial connection.† Severe nonconotruncal defects include endocardial cushion defect/atrioventricular septal defect, common ventricle, and hypoplastic left heart syndrome. This group also includes contains univentricular heart defects.‡ Other was defined as all other heart and circulatory system anomalies that were not included in the other groups.§ Complex lesion group: groups 1 and 2.∥ Noncomplex lesion group: groups 3 through 6.A total of 89 532 patients with CHD and 890 469 matched control subjects without CHD were included. During a mean follow-up of 25.4±22.2 years in patients with CHD and 27.3±22.0 years in control subjects, 7031 (7.8%) and 9681 (1.1%), respectively, developed HF. The mean age for an HF diagnosis was 40.3±28.8 years for patients with CHD and 66.4±13.6 years for control subjects. In the HF cohort, women accounted for 45.7% of the CHD cohort and 39.4% of the control group. The overall incidence rate for HF was 31.6 per 10 000 person-years in patients with CHD and 4.0 per 10 000 person-years in control subjects. In the complex CHD lesion group (conotruncal and severe nonconotrucal defects), the incidence rate was 79 per 10 000 person-years compared with 26 per 10 000 person-years for the noncomplex lesion group (Table). The overall risk for HF in patients with CHD was 8.7 times (95% CI, 8.4–8.9) higher than in control subjects. According to the lesion group, the highest risk for developing HF was found in patients with complex CHD lesions: HR, 42 (95% CI, 37.5–47.8) in group 1 (conotruncal defects); and HR, 21 (95% CI, 18.9–23.4) in group 2 (severe nonconotruncal defects). The risk for HF was highly age dependent, with the highest risk found within the youngest age groups: HR, 220 (95% CI, 181–271) for the group 0 to 17 years of age; and HR, 5.1 (95% CI, 4.7–5.4) for the group 60 to 69 years of age. In contrast to control subjects without CHD, women with CHD had a higher risk of HF compared with men (HR, 10.2 [95% CI, 9.7–10.7] and 7.7 [95% CI, 7.4–8.0], respectively).Several studies have clearly shown excess mortality among adult patients with CHD.4,5 The majority of patients die of cardiovascular causes, mainly chronic HF and sudden death, which has also been seen in adults with HF secondary to acquired heart disease. The definition and the treatment of HF in patients with CHD remain challenging. There is insufficient evidence-based treatment for the whole CHD population because of the heterogenicity of CHD and because the small number of observational and intervention cohort studies conducted to date have shown contradicting results. Patients with CHD have mostly been excluded from large-scale HF trials, and treatment recommendations are based mainly on small, randomized studies, as well as expert opinion. Further improvement of the therapeutic approach for HF in patients with CHD is urgently needed because HF is a common complication. Although HF is uncommon in young patients, the HR for young patients with CHD is very high. Furthermore, HF is common in people >60 years of age regardless of whether they have CHD; however, those with CHD still have a greater risk of HF than control subjects.In conclusion, 1 of 13 patients with CHD will develop HF during their lifetime, which is an important risk factor to consider when treating patients with CHD.Article InformationSources of FundingThe study was funded by grants from the Swedish state under an agreement between the Swedish government and country councils (ALF agreement grant 236611) and grants from the Swedish Research Council (grant 2019-00193 SIMSAM).Disclosures None.FootnotesFor Sources of Funding and Disclosures, see page 984.Circulation is available at www.ahajournals.org/journal/circCorrespondence to: Niklas Bergh, MD, PhD, Department of Cardiology, Sahlgrenska University Hospital, Blå Stråket 3, 413 45 Göteborg, Sweden. Email niklas.bergh@vgregion.seReferences1. Mandalenakis Z, Giang KW, Eriksson P, Liden H, Synnergren M, Wahlander H, Fedchenko M, Rosengren A, Dellborg M. Survival in children with congenital heart disease: have we reached a peak at 97%?J Am Heart Assoc. 2020; 9:e017704. doi: 10.1161/JAHA.120.017704LinkGoogle Scholar2. Moons P, Bovijn L, Budts W, Belmans A, Gewillig M. Temporal trends in survival to adulthood among patients born with congenital heart disease from 1970 to 1992 in Belgium.Circulation. 2010; 122:2264–2272. doi: 10.1161/circulationaha.110.946343LinkGoogle Scholar3. Verheugt CL, Uiterwaal CS, van der Velde ET, Meijboom FJ, Pieper PG, van Dijk AP, Vliegen HW, Grobbee DE, Mulder BJ. Mortality in adult congenital heart disease.Eur Heart J. 2010; 31:1220–1229. doi: 10.1093/eurheartj/ehq032CrossrefMedlineGoogle Scholar4. Engelings CC, Helm PC, Abdul-Khaliq H, Asfour B, Bauer UM, Baumgartner H, Kececioglu D, Korten MA, Diller GP, Tutarel O. Cause of death in adults with congenital heart disease: an analysis of the German National Register for Congenital Heart Defects.Int J Cardiol. 2016; 211:31–36. doi: 10.1016/j.ijcard.2016.02.133CrossrefMedlineGoogle Scholar5. Nieminen HP, Jokinen E, Sairanen HI. Late results of pediatric cardiac surgery in Finland: a population-based study with 96% follow-up.Circulation. 2001; 104:570–575. doi: 10.1161/hc3101.093968LinkGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited ByRosenthal E and Qureshi S (2023) Adult Congenital Heart Disease: A Specialty With Ever-Expanding Challenges, Circulation, 147:12, (939-941), Online publication date: 21-Mar-2023.Dellborg M, Giang K, Eriksson P, Liden H, Fedchenko M, Ahnfelt A, Rosengren A and Mandalenakis Z (2022) Adults With Congenital Heart Disease: Trends in Event-Free Survival Past Middle Age, Circulation, 147:12, (930-938), Online publication date: 21-Mar-2023.Related articlesAdult Congenital Heart Disease: A Specialty With Ever-Expanding ChallengesEric Rosenthal, et al. Circulation. 2023;147:939-941 March 21, 2023Vol 147, Issue 12 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.122.061546PMID: 36533451 Originally publishedDecember 19, 2022 Keywordsfailureobservational studyheartheart defects, congenitalPDF download Advertisement SubjectsCongenital Heart Disease