Atrial Septal Defect and Heart Rhythm Disorders: Physiopathological Linkage and Clinical Perspectives
Abstract
1. Introduction
2. Pathophysiology of Atrial Septal Defect and Electrophysiological Impact
2.1. Left-to-Right Shunt and Cardiac Remodeling
2.2. Electrophysiological Basis of Arrhythmias
2.3. QT and RR Interval Variability
3. Rhythm and Conduction Abnormalities Associated with ASD
3.1. Atrial Tachyarrhythmias
3.1.1. Post-ASD Closure
3.1.2. Atrioventricular Septal Defect (AVSD) and Atrial Arrhythmias
3.2. Bradyarrhythmias and Conduction Disturbances
3.2.1. Atrioventricular Block (AVB)
3.2.2. Right Bundle Branch Block (RBBB)
3.2.3. Left Anterior Fascicular Block (LAFB)
3.2.4. Sinus Node Dysfunction
3.2.5. Pacemaker
4. Diagnosis of Arrhythmias and Conduction Disturbances in ASD
4.1. 12-Lead Electrocardiogram
4.1.1. IRBBB and Right Axis Deviation
4.1.2. Tall P Wave
4.1.3. Crochetage Sign (Notched R Wave)
4.1.4. Defective T Wave (DTW)
4.1.5. Inverted P Waves
4.1.6. Left Axis Deviation and Atrioventricular Node Delay
4.1.7. Slightly Prolonged QRS with rSr’ or rsR’ Pattern
4.2. Holter Monitoring
5. ASD Diagnosis
5.1. Echocardiography (TTE, TEE, 3DE, ICE)
5.2. Transthoracic Echocardiography (TTE)
5.3. Transesophageal Echocardiography (TEE)
5.4. Three-Dimensional Echocardiography (3DE)
5.5. Intracardiac Echocardiography (ICE)
5.6. Advanced Imaging (CMR, CT, 3D Printing, Holograms)
Cardiac Magnetic Resonance (CMR) and Computed Tomography (CT)
5.7. 3D Printing, Computational Modeling, and Holograms
5.8. Cardiac Catheterization
6. Clinical Management of Atrial Septal Defect and Associated Arrhythmias
6.1. Indications for ASD Closure
6.2. Methods of ASD Closure
6.2.1. Transcatheter Closure
6.2.2. Surgical Closure
6.3. Management of Arrhythmias
6.3.1. Transcatheter Ablation:
6.3.2. Antiarrhythmic Drugs and Cardioversion
6.3.3. Anticoagulation
6.3.4. Cardiac Remodeling After Defect Closure and Pulmonary Hypertension
7. Follow up
8. Future Perspectives in ASD Management
9. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Martin, S.S.; Shapiro, E.P.; Mukherjee, M. Atrial Septal Defects—Clinical Manifestations, Echo Assessment, and Intervention. Clin. Med. Insights Cardiol. 2014, 8s1, CMC.S15715. [Google Scholar] [CrossRef]
- Latson, L.; Briston, D. Atrial Septal Defect. JACC Cardiovasc. Interv. 2021, 14, 576–577. [Google Scholar] [CrossRef]
- Karunanithi, Z.; Nyboe, C.; Hjortdal, V.E. Long-Term Risk of Atrial Fibrillation and Stroke in Patients with Atrial Septal Defect Diagnosed in Childhood. Am. J. Cardiol. 2017, 119, 461–465. [Google Scholar] [CrossRef]
- Mauriello, A.; Correra, A.; Ascrizzi, A.; Del Vecchio, G.E.; Benfari, G.; Ilardi, F.; Lisi, M.; Malagoli, A.; Mandoli, G.E.; Pastore, M.C.; et al. Relationship Between Left Atrial Strain and Atrial Fibrillation: The Role of Stress Echocardiography. Diagnostics 2024, 15, 7. [Google Scholar] [CrossRef]
- Nyboe, C.; Karunanithi, Z.; Nielsen-Kudsk, J.E.; Hjortdal, V.E. Long-Term Mortality in Patients with Atrial Septal Defect: A Nationwide Cohort-Study. Eur. Heart J. 2018, 39, 993–998. [Google Scholar] [CrossRef]
- Pashmforoush, M.; Lu, J.T.; Chen, H.; Amand, T.S.; Kondo, R.; Pradervand, S.; Evans, S.M.; Clark, B.; Feramisco, J.R.; Giles, W.; et al. Nkx2-5 Pathways and Congenital Heart Disease. Cell 2004, 117, 373–386. [Google Scholar] [CrossRef] [PubMed]
- Ellesøe, S.G.; Johansen, M.M.; Bjerre, J.V.; Hjortdal, V.E.; Brunak, S.; Larsen, L.A. Familial Atrial Septal Defect and Sudden Cardiac Death: Identification of a Novel NKX2-5 Mutation and a Review of the Literature. Congenit. Heart Dis. 2016, 11, 283–290. [Google Scholar] [CrossRef] [PubMed]
- Geva, T.; Martins, J.D.; Wald, R.M. Atrial Septal Defects. Lancet 2014, 383, 1921–1932. [Google Scholar] [CrossRef]
- Vitarelli, A.; Mangieri, E.; Gaudio, C.; Tanzilli, G.; Miraldi, F.; Capotosto, L. Right Atrial Function by Speckle Tracking Echocardiography in Atrial Septal Defect: Prediction of Atrial Fibrillation. Clin. Cardiol. 2018, 41, 1341–1347. [Google Scholar] [CrossRef] [PubMed]
- Webb, G.; Gatzoulis, M.A. Atrial Septal Defects in the Adult: Recent Progress and Overview. Circulation 2006, 114, 1645–1653. [Google Scholar] [CrossRef]
- Brida, M.; Chessa, M.; Celermajer, D.; Li, W.; Geva, T.; Khairy, P.; Griselli, M.; Baumgartner, H.; Gatzoulis, M.A. Atrial Septal Defect in Adulthood: A New Paradigm for Congenital Heart Disease. Eur. Heart J. 2022, 43, 2660–2671. [Google Scholar] [CrossRef]
- Williams, M.R.; Perry, J.C. Arrhythmias and Conduction Disorders Associated with Atrial Septal Defects. J. Thorac. Dis. 2018, 10, S2940–S2944. [Google Scholar] [CrossRef]
- Humbert, M.; Kovacs, G.; Hoeper, M.M.; Badagliacca, R.; Berger, R.M.F.; Brida, M.; Carlsen, J.; Coats, A.J.S.; Escribano-Subias, P.; Ferrari, P.; et al. 2022 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension. Eur. Heart J. 2022, 43, 3618–3731. [Google Scholar] [CrossRef] [PubMed]
- Humenberger, M.; Rosenhek, R.; Gabriel, H.; Rader, F.; Heger, M.; Klaar, U.; Binder, T.; Probst, P.; Heinze, G.; Maurer, G.; et al. Benefit of Atrial Septal Defect Closure in Adults: Impact of Age. Eur. Heart J. 2011, 32, 553–560. [Google Scholar] [CrossRef]
- Albæk, D.H.R.; Udholm, S.; Ovesen, A.-S.L.; Karunanithi, Z.; Nyboe, C.; Hjortdal, V.E. Pacemaker and Conduction Disturbances in Patients with Atrial Septal Defect. Cardiol. Young 2020, 30, 980–985. [Google Scholar] [CrossRef]
- Mauriello, A.; Correra, A.; Molinari, R.; Del Vecchio, G.E.; Tessitore, V.; D’Andrea, A.; Russo, V. Mitochondrial Dysfunction in Atrial Fibrillation: The Need for a Strong Pharmacological Approach. Biomedicines 2024, 12, 2720. [Google Scholar] [CrossRef]
- Eryu, Y.; Hata, T.; Nagatani, A.; Funamoto, Y.; Uchida, H.; Fujino, M.; Boda, H.; Miyata, M.; Yoshikawa, T. Electrocardiographic RR and QT Interval Variability in Patients with Atrial Septal Defect and Healthy Children. Pediatr. Cardiol. 2017, 38, 582–587. [Google Scholar] [CrossRef]
- Demonceaux, M.; Benseba, J.; Ruiz, M.; Mongeon, F.-P.; Khairy, P.; Mital, S.; Dore, A.; Mondésert, B.; Gravel, M.T.; Dib, N.; et al. Right Ventricular Remodeling in Complex Congenital Heart Disease. Can. J. Cardiol. 2025, 41, 1067–1080. [Google Scholar] [CrossRef]
- Grassi, G.; Seravalle, G.; Mancia, G. Sympathetic Activation in Cardiovascular Disease: Evidence, Clinical Impact and Therapeutic Implications. Eur. J. Clin. Investig. 2015, 45, 1367–1375. [Google Scholar] [CrossRef] [PubMed]
- Himelfarb, J.D.; Shulman, H.; Olesovsky, C.J.; Rumman, R.K.; Oliva, L.; Friedland, J.; Farrell, A.; Huszti, E.; Horlick, E.; Abrahamyan, L. Atrial Fibrillation Following Transcatheter Atrial Septal Defect Closure: A Systematic Review and Meta-Analysis. Heart 2022, 108, 1216–1224. [Google Scholar] [CrossRef] [PubMed]
- Nyboe, C.; Olsen, M.S.; Nielsen-Kudsk, J.E.; Hjortdal, V.E. Atrial Fibrillation and Stroke in Adult Patients with Atrial Septal Defect and the Long-Term Effect of Closure. Heart 2015, 101, 706–711. [Google Scholar] [CrossRef] [PubMed]
- Muroke, V.; Jalanko, M.; Haukka, J.; Hartikainen, J.; Tahvanainen, A.; Ukkonen, H.; Ylitalo, K.; Pihkala, J.; Sinisalo, J. Outcome of Transcatheter Atrial Septal Defect Closure in a Nationwide Cohort. Ann. Med. 2023, 55, 615–623. [Google Scholar] [CrossRef]
- Udholm, S.; Nyboe, C.; Redington, A.; Nielsen-Kudsk, J.E.; Nielsen, J.C.; Hjortdal, V.E. Hidden Burden of Arrhythmias in Patients with Small Atrial Septal Defects: A Nationwide Study. Open Heart 2019, 6, e001056. [Google Scholar] [CrossRef]
- Hribernik, I.; Thomson, J.; Bhan, A.; Mullen, M.; Noonan, P.; Smith, B.; Walker, N.; Deri, A.; Bentham, J. A Novel Device for Atrial Septal Defect Occlusion (GORE CARDIOFORM). EuroIntervention 2023, 19, 782–788. [Google Scholar] [CrossRef]
- O’Neill, L.; Floyd, C.N.; Sim, I.; Whitaker, J.; Mukherjee, R.; O’Hare, D.; Gatzoulis, M.; Frigiola, A.; O’Neill, M.D.; Williams, S.E. Percutaneous Secundum Atrial Septal Defect Closure for the Treatment of Atrial Arrhythmia in the Adult: A Meta-Analysis. Int. J. Cardiol. 2020, 321, 104–112. [Google Scholar] [CrossRef]
- Loomba, R.S.; Chandrasekar, S.; Sanan, P.; Shah, P.H.; Arora, R.R. Association of Atrial Tachyarrhythmias with Atrial Septal Defect, Ebstein’s Anomaly and Fontan Patients. Expert. Rev. Cardiovasc. Ther. 2011, 9, 887–893. [Google Scholar] [CrossRef]
- Jacquemart, E.; Bessière, F.; Combes, N.; Ladouceur, M.; Iserin, L.; Gardey, K.; Henaine, R.; Dulac, A.; Cohen, S.; Belli, E.; et al. Incidence, Risk Factors, and Outcomes of Atrial Arrhythmias in Adult Patients With Atrioventricular Septal Defect. JACC Clin. Electrophysiol. 2022, 8, 331–340. [Google Scholar] [CrossRef] [PubMed]
- Karakayalı, M. Predictive Value of the SCORE, SCORE2, and Pooled Cohort Risk Equation Systems in Patients with Hypertension. Turk. Kardiyol. Dern. Ars. Arch. Turk. Soc. Cardiol. 2023, 51, 407–414. [Google Scholar] [CrossRef] [PubMed]
- Morton, J.B.; Sanders, P.; Vohra, J.K.; Sparks, P.B.; Morgan, J.G.; Spence, S.J.; Grigg, L.E.; Kalman, J.M. Effect of Chronic Right Atrial Stretch on Atrial Electrical Remodeling in Patients with an Atrial Septal Defect. Circulation 2003, 107, 1775–1782. [Google Scholar] [CrossRef]
- Bayar, N.; Arslan, Ş.; Köklü, E.; Cagirci, G.; Cay, S.; Erkal, Z.; Ayoglu, R.U.; Küçükseymen, S. The Importance of Electrocardiographic Findings in the Diagnosis of Atrial Septal Defect. Kardiol. Pol. 2015, 73, 331–336. [Google Scholar] [CrossRef]
- Bakalli, A.; Koçinaj, D.; Georgievska-Ismail, L.; Bekteshi, T.; Pllana, E.; Sejdiu, B. Right Bundle Branch Block as a Marker for Interatrial Septal Abnormalities. Cardiol. Young 2012, 22, 18–25. [Google Scholar] [CrossRef]
- Mehta, A.V.; O’Riordan, A.C.; Sanchez, G.R.; Black, I.F.S. Acquired Nonsurgical Complete Atrioventricular Block in a Child with Endocardial Cushion Defect. Clin. Cardiol. 1982, 5, 603–605. [Google Scholar] [CrossRef]
- Heller, J.; Hagège, A.A.; Besse, B.; Desnos, M.; Marie, F.-N.; Guerot, C. “Crochetage” (Notch) on R Wave in Inferior Limb Leads: A New Independent Electrocardiographic Sign of Atrial Septal Defect. J. Am. Coll. Cardiol. 1996, 27, 877–882. [Google Scholar] [CrossRef]
- Awa, S.; Linde, L.M.; Oshima, M.; Okuni, M.; Momma, K.; Nakamura, N. The Significance of Late-Phased Dart T Wave in the Electrocardiogram of Children. Am. Heart J. 1970, 80, 619–628. [Google Scholar] [CrossRef]
- O’Neill, L.; Sim, I.; O’Hare, D.; Whitaker, J.; Mukherjee, R.K.; Razeghi, O.; Niederer, S.; Wright, M.; Chiribiri, A.; Frigiola, A.; et al. CArdiac MagnEtic Resonance Assessment of Bi-Atrial Fibrosis in Secundum Atrial Septal Defects Patients: CAMERA-ASD Study. Eur. Heart J. Cardiovasc. Imaging 2022, 23, 1231–1239. [Google Scholar] [CrossRef] [PubMed]
- Butera, G.; Sturla, F.; Pluchinotta, F.R.; Caimi, A.; Carminati, M. Holographic Augmented Reality and 3D Printing for Advanced Planning of Sinus Venosus ASD/Partial Anomalous Pulmonary Venous Return Percutaneous Management. JACC Cardiovasc. Interv. 2019, 12, 1389–1391. [Google Scholar] [CrossRef] [PubMed]
- Kim, H.D.; Kim, M.S.; Yun, K.-J.; Bae, S.M.; Her, S.-H.; Lee, J.-H. Successful Transcatheter Closure of an Inferior Sinus Venosus Atrial Septal Defect. Korean J. Intern. Med. 2015, 31, 176–178. [Google Scholar] [CrossRef] [PubMed]
- Liava’a, M.; Kalfa, D. Surgical Closure of Atrial Septal Defects. J. Thorac. Dis. 2018, 10, S2931–S2939. [Google Scholar] [CrossRef]
- Noiri, J.; Konishi, H.; Matsuzoe, H. The Importance of Pre-ablation Atrial Septal Evaluation for a Patient with Surgical Patch Closure History. J. Arrhythm. 2023, 39, 224–226. [Google Scholar] [CrossRef]
- Nakagawa, K.; Akagi, T.; Nagase, S.; Takaya, Y.; Kijima, Y.; Toh, N.; Watanabe, A.; Nishii, N.; Nakamura, K.; Morita, H.; et al. Efficacy of Catheter Ablation for Paroxysmal Atrial Fibrillation in Patients with Atrial Septal Defect: A Comparison with Transcatheter Closure Alone. EP Eur. 2019, 21, 1663–1669. [Google Scholar] [CrossRef]
- Van Gelder, I.C.; Rienstra, M.; Bunting, K.V.; Casado-Arroyo, R.; Caso, V.; Crijns, H.J.G.M.; De Potter, T.J.R.; Dwight, J.; Guasti, L.; Hanke, T.; et al. 2024 ESC Guidelines for the Management of Atrial Fibrillation Developed in Collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur. Heart J. 2024, 45, 3314–3414. [Google Scholar] [CrossRef]
- Mauriello, A.; Maratea, A.C.; Fonderico, C.; Quagliariello, V.; Maurea, F.; Maurea, N. Factor XI and Cancer: Physiopathological Linkage and Clinical Perspectives. J. Clin. Med. 2025, 14, 6341. [Google Scholar] [CrossRef]
- Karakasis, P.; Giannakoulas, G.; Theofilis, P.; Patoulias, D.; Fragakis, N. Direct Oral Anticoagulants or Vitamin K Antagonists in Adult Patients with Congenital Heart Disease? Eur. J. Intern. Med. 2024, 129, 149–152. [Google Scholar] [CrossRef]
- Krause, U. Age Matters. JACC Clin. Electrophysiol. 2022, 8, 341–342. [Google Scholar] [CrossRef]
- Mauriello, A.; Ascrizzi, A.; Roma, A.S.; Molinari, R.; Caturano, A.; Imbalzano, E.; D’Andrea, A.; Russo, V. Effects of Heart Failure Therapies on Atrial Fibrillation: Biological and Clinical Perspectives. Antioxidants 2024, 13, 806. [Google Scholar] [CrossRef]
- Leppert, M.; Poisson, S.N.; Carroll, J.D. Atrial Septal Defects and Cardioembolic Strokes. Cardiol. Clin. 2016, 34, 225–230. [Google Scholar] [CrossRef]
- Mauriello, A.; Correra, A.; Maratea, A.C.; Caturano, A.; Liccardo, B.; Perrone, M.A.; Giordano, A.; Nigro, G.; D’Andrea, A.; Russo, V. Serum Lipids, Inflammation, and the Risk of Atrial Fibrillation: Pathophysiological Links and Clinical Evidence. J. Clin. Med. 2025, 14, 1652. [Google Scholar] [CrossRef]
Type of ASD | Prevalence | Anatomical Localization | Hemodynamic and Clinical Characteristics |
---|---|---|---|
Secundum ASD | 80% | Within the fossa ovalis, there are one or more defects in the septum primum. Generally distant from specialized conduction structures. | The most common type. Size ranges from very small to very large. Usually a left-to-right shunt. Often asymptomatic in children. Can cause dilation of the right atrium and ventricle. |
Primum ASD (partial AVSD) | 15% | Between the inferior margin of the fossa ovalis superiorly and the AV valves inferiorly. No ventricular component. Characterized by a common AV junction with two distinct valvular orifices and almost always anomalous AV valves. | Associated with AV valve abnormalities, often a mitral fissure. The defects are usually significant. Causes left axis deviation on the ECG. Higher risk of AV block. |
Sinus Venosus ASD | 5–10% | Typically located in the mouth of one of the vena cavae. The superior defect is more common (5%), due to a lack of tissue separating the right superior pulmonary vein from the superior vena cava. The inferior defect is rare (<1%). | It is often associated with anomalous pulmonary venous drainage. The proximity to the crista terminalis and the sinus node increases the risk of sinus node dysfunction. It almost always requires surgical repair. |
Coronary Sinus Defect | <1% | Result of partial or complete unroofing of the tissue separating the coronary sinus from the left atrium, allowing a shunt through the defect and the coronary sinus orifice. | Rare. Commonly associated with persistent left superior vena cava (Ragbhib syndrome). Rhythm considerations beyond the effect of the left-to-right shunt have not been widely reported. Requires surgical repair. |
Cohort/Registry | Age at Closure (or Mean Age) | Follow-up Duration/ Temporality | Endpoint and Incidence (%) |
---|---|---|---|
Muroke et al. [33] | >25 years | Overall prevalence (not specified if early or late) | AVB: 6.4% in closed defects. >60 times higher risk for AVB compared to healthy controls. |
Bergmann et al. [34] | Advanced age at closure (a factor that may influence the device group) | Prevalence (not specified, but highlights the gradient) | AV Block Prevalence: Catheter Closure: 13%; Surgical Closure: 5% |
Albæk et al. [15] | Mean age at PM implantation: 32 years | Late events | PM required: 3.4% |
Chen et al. [9] | N/A | N/A | LAFB: 5.8% in closed defects. |
Electrocardiogram Clues | Sensibility | Specificity | Likelihood Ratio Positive |
---|---|---|---|
Crochetage in at least 1 inferior lead (II, III, aVF) | 73% (0.73) | 92% (0.92) | 9.125 |
Crochetage in all 3 inferior leads (II, III, aVF) | Not directly reported | ≥95% | Extremely high |
IRBBB + Defective T Wave | ≈87% | 100% | Virtually infinite |
Risk Factor | Odds Ratio (OR) | Confidence Interval (95% CI) | p-Value |
---|---|---|---|
Age (for every 5-year increment) | 1.4 | 1.2–1.6 | <0.001 |
Number of cardiac surgeries | 4.1 | 2.5–6.9 | <0.001 |
Left atrial dilation | 3.1 | 1.4–6.8 | 0.005 |
Right atrial dilation | 4.1 | 1.7–10.3 | 0.002 |
Moderate or severe left AV valve regurgitation | 3.7 | 1.2–11.7 | 0.021 |
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Correra, A.; Mauriello, A.; Di Peppo, M.; D’Andrea, A.; Russo, V.; Esposito, G.; Brunetti, N.D. Atrial Septal Defect and Heart Rhythm Disorders: Physiopathological Linkage and Clinical Perspectives. Biomedicines 2025, 13, 2427. https://doi.org/10.3390/biomedicines13102427
Correra A, Mauriello A, Di Peppo M, D’Andrea A, Russo V, Esposito G, Brunetti ND. Atrial Septal Defect and Heart Rhythm Disorders: Physiopathological Linkage and Clinical Perspectives. Biomedicines. 2025; 13(10):2427. https://doi.org/10.3390/biomedicines13102427
Chicago/Turabian StyleCorrera, Adriana, Alfredo Mauriello, Matilde Di Peppo, Antonello D’Andrea, Vincenzo Russo, Giovanni Esposito, and Natale Daniele Brunetti. 2025. "Atrial Septal Defect and Heart Rhythm Disorders: Physiopathological Linkage and Clinical Perspectives" Biomedicines 13, no. 10: 2427. https://doi.org/10.3390/biomedicines13102427
APA StyleCorrera, A., Mauriello, A., Di Peppo, M., D’Andrea, A., Russo, V., Esposito, G., & Brunetti, N. D. (2025). Atrial Septal Defect and Heart Rhythm Disorders: Physiopathological Linkage and Clinical Perspectives. Biomedicines, 13(10), 2427. https://doi.org/10.3390/biomedicines13102427