Atrial Fibrillation and the Risk of Ventricular Arrhythmias and Cardiac Arrest: A Nationwide Population-Based Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Population
2.2. Follow-Up and Outcomes
2.3. Statistical Analysis
3. Results
3.1. Incidence of VT/VF/CA
3.2. Predictors of VT/VF/CA in the Hospitalised Population
3.3. Risk of VT/VF/CA
3.4. PSM Analysis
3.5. Mediation Analysis
4. Discussion
Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Benjamin, E.J.; Wolf, P.A.; D’Agostino, R.B.; Silbershatz, H.; Kannel, W.B.; Levy, D. Impact of Atrial Fibrillation on the Risk of Death. Circulation 1998, 98, 946–952. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, E.; Choi, E.-K.; Han, K.-D.; Lee, H.; Choe, W.-S.; Lee, S.-R.; Cha, M.-J.; Lim, W.-H.; Kim, Y.-J.; Oh, S. Mortality and causes of death in patients with atrial fibrillation: A nationwide population-based study. PLoS ONE 2018, 13, e0209687. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Odutayo, A.; Wong, C.X.; Hsiao, A.J.; Hopewell, S.; Altman, D.G.; Emdin, C.A. Atrial fibrillation and risks of cardiovascular disease, renal disease, and death: Systematic review and meta-analysis. BMJ 2016, 354, i4482. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fauchier, L.; Villejoubert, O.; Clementy, N.; Bernard, A.; Pierre, B.; Angoulvant, D.; Ivanes, F.; Babuty, D.; Lip, G.Y. Causes of Death and Influencing Factors in Patients with Atrial Fibrillation. Am. J. Med. 2016, 129, 1278–1287. [Google Scholar] [CrossRef]
- Rattanawong, P.; Upala, S.; Riangwiwat, T.; Jaruvongvanich, V.; Sanguankeo, A.; Vutthikraivit, W.; Chung, E.H. Atrial fibrillation is associated with sudden cardiac death: A systematic review and meta-analysis. J. Interv. Card. Electrophysiol. 2018, 51, 91–104. [Google Scholar] [CrossRef] [PubMed]
- Chen, L.Y.; Sotoodehnia, N.; Bůžková, P.; Lopez, F.L.; Yee, L.M.; Heckbert, S.R.; Prineas, R.; Soliman, E.Z.; Adabag, S.; Konety, S.; et al. Atrial Fibrillation and the Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities Study and Cardiovascular Health Study. JAMA Intern. Med. 2013, 173, 29–35. [Google Scholar] [CrossRef] [PubMed]
- Eisen, A.; Ruff, C.T.; Braunwald, E.; Nordio, F.; Corbalán, R.; Dalby, A.; Dorobantu, M.; Mercuri, M.; Lanz, H.; Rutman, H.; et al. Sudden Cardiac Death in Patients with Atrial Fibrillation: Insights from the ENGAGE AF-TIMI 48 Trial. J. Am. Heart Assoc. 2016, 5, e003735. [Google Scholar] [CrossRef]
- Marijon, E.; Le Heuzey, J.-Y.; Connolly, S.; Yang, S.; Pogue, J.; Brueckmann, M.; Eikelboom, J.; Themeles, E.; Ezekowitz, M.; Wallentin, L.; et al. Causes of death and influencing factors in patients with Atrial fibrillation: A competing-risk analysis from the randomized evaluation of long-term anticoagulant therapy study. Circulation 2013, 128, 2192–2201. [Google Scholar] [CrossRef] [Green Version]
- Baron, R.M.; Kenny, D.A. The moderator-mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. J. Pers. Soc. Psychol. 1986, 51, 1173–1182. [Google Scholar] [CrossRef]
- Pearl, J. An Introduction to Causal Inference. Int. J. Biostat. 2010, 6. [Google Scholar] [CrossRef]
- Bardai, A.; Blom, M.T.; van Hoeijen, D.A.; van Deutekom, H.W.M.; Brouwer, H.J.; Tan, H.L. Atrial fibrillation is an independent risk factor for ventricular fibrillation: A large-scale population-based case-control study. Circ. Arrhythmia Electrophysiol. 2014, 7, 1033–1039. [Google Scholar] [CrossRef]
- Kim, Y.G.; Choi, Y.Y.; Han, K.-D.; Min, K.; Choi, H.Y.; Shim, J.; Choi, J.-I.; Kim, Y.-H. Atrial fibrillation is associated with increased risk of lethal ventricular arrhythmias. Sci. Rep. 2021, 11, 18111. [Google Scholar] [CrossRef] [PubMed]
- Conen, D.; Chae, C.U.; Glynn, R.J.; Tedrow, U.B.; Everett, B.M.; Buring, J.E.; Albert, C.M. Risk of Death and Cardiovascular Events in Initially Healthy Women With New-Onset Atrial Fibrillation. JAMA 2011, 305, 2080–2087. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chao, T.-F.; Liu, C.-J.; Tuan, T.-C.; Chen, S.-J.; Chen, T.-J.; Lip, G.Y.H.; Chen, S.-A. Risk and Prediction of Sudden Cardiac Death and Ventricular Arrhythmias for Patients with Atrial Fibrillation—A Nationwide Cohort Study. Sci. Rep. 2017, 7, srep46445. [Google Scholar] [CrossRef] [Green Version]
- Nattel, S. Experimental evidence for proarrhythmic mechanisms of antiarrhythmic drugs. Cardiovasc. Res. 1998, 37, 567–577. [Google Scholar] [CrossRef] [Green Version]
- Shantsila, E.; Watson, T.; Lip, G.Y.H. Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias. EP Eur. 2007, 9 (Suppl. S4), iv37–iv44. [Google Scholar] [CrossRef]
- Gillis, A.M. Atrial Fibrillation and Ventricular Arrhythmias: Sex Differences in Electrophysiology, Epidemiology, Clinical Presentation, and Clinical Outcomes. Circulation 2017, 135, 593–608. [Google Scholar] [CrossRef] [PubMed]
- Feng, J.-L.; Nedkoff, L.; Knuiman, M.; Semsarian, C.; Ingles, J.; Briffa, T.; Hickling, S. Temporal Trends in Sudden Cardiac Death From 1997 to 2010: A Data Linkage Study. Heart Lung Circ. 2017, 26, 808–816. [Google Scholar] [CrossRef] [PubMed]
- Linde, C.; Bongiorni, M.G.; Birgersdotter-Green, U.; Curtis, A.B.; Deisenhofer, I.; Furokawa, T.; Gillis, A.M.; Haugaa, K.H.; Lip, G.Y.H.; Van Gelder, I.; et al. Sex differences in cardiac arrhythmia: A consensus document of the European Heart Rhythm Association, endorsed by the Heart Rhythm Society and Asia Pacific Heart Rhythm Society. EP Eur. 2018, 20, 1565-1565ao. [Google Scholar] [CrossRef]
- Krisai, P.; Cheniti, G.; Takagi, T.; Kamakura, T.; Surget, E.; André, C.; Duchateau, J.; Pambrun, T.; Derval, N.; Sacher, F.; et al. Sex differences in ventricular arrhythmia: Epidemiology, pathophysiology and catheter ablation. Rev. Cardiovasc. Med. 2022, 23, 14. [Google Scholar] [CrossRef]
- Kostapanos, M.S.; Liberopoulos, E.N.; Goudevenos, J.A.; Mikhailidis, D.P.; Elisaf, M.S. Do statins have an antiarrhythmic activity? Cardiovasc. Res. 2007, 75, 10–20. [Google Scholar] [CrossRef] [Green Version]
- Wanahita, N.; Chen, J.; Bangalore, S.; Shah, K.; Rachko, M.; Coleman, C.; Schweitzer, P. The effect of statin therapy on ventricular tachyarrhythmias: A meta-analysis. Am. J. Ther. 2012, 19, 16–23. [Google Scholar] [CrossRef] [PubMed]
- Sharma, Y.P.; Batta, A.; Makkar, K.; Hatwal, J.; A Gawalkar, A.; Kaur, N.; Malhi, T.S.; Kasinadhuni, G.; Gupta, H.; Panda, P.; et al. Angiographic profile and outcomes in persistent non-valvular atrial fibrillation: A study from tertiary care center in North India. Indian Heart J. 2022, 74, 7–12. [Google Scholar] [CrossRef] [PubMed]
- Nucifora, G.; Schuijf, J.; Tops, L.F.; van Werkhoven, J.M.; Kajander, S.; Jukema, J.W.; Schreur, J.H.; Heijenbrok, M.W.; Trines, S.A.; Gaemperli, O.; et al. Prevalence of coronary artery disease assessed by multislice computed tomography coronary angiography in patients with paroxysmal or persistent atrial fibrillation. Circ. Cardiovasc. Imaging 2009, 2, 100–106. [Google Scholar] [CrossRef] [Green Version]
- Tucker, N.R.; Ellinor, P.T. Emerging directions in the genetics of atrial fibrillation. Circ. Res. 2014, 114, 1469–1482. [Google Scholar] [CrossRef] [Green Version]
- Chambers, J.C.; Zhao, J.; Terracciano, C.M.N.; Bezzina, C.R.; Zhang, W.; Kaba, R.; Navaratnarajah, M.; Lotlikar, A.; Sehmi, J.S.; Kooner, M.K.; et al. Genetic variation in SCN10A influences cardiac conduction. Nat. Genet. 2010, 42, 149–152. [Google Scholar] [CrossRef] [PubMed]
- Gunasekaran, T.; Sanders, R.A. Sudden cardiac death in a dog during Holter recording—R on T phenomenon. J. Vet. Cardiol. 2017, 19, 455–461. [Google Scholar] [CrossRef]
- Denes, P.; Wu, D.; Dhingra, R.; Pietras, R.J.; Rosen, K.M. The effects of cycle length on cardiac refractory periods in man. Circulation 1974, 49, 32–41. [Google Scholar] [CrossRef] [Green Version]
- Denker, S.; Lehmann, M.; Mahmud, R.; Gilbert, C.; Akhtar, M. Facilitation of ventricular tachycardia induction with abrupt changes in ventricular cycle length. Am. J. Cardiol. 1984, 53, 508–515. [Google Scholar] [CrossRef]
- Shen, M.J.; Zipes, D.P. Role of the autonomic nervous system in modulating cardiac arrhythmias. Circ. Res. 2014, 114, 1004–1021. [Google Scholar] [CrossRef]
- Saliba, W.; Wazni, O.M. Sinus Rhythm Restoration and Treatment Success: Insight From Recent Clinical Trials. Clin. Cardiol. 2011, 34, 12. [Google Scholar] [CrossRef] [PubMed]
- Camm, A.J.; Naccarelli, G.V.; Mittal, S.; Crijns, H.J.; Hohnloser, S.H.; Ma, C.-S.; Natale, A.; Turakhia, M.P.; Kirchhof, P. The Increasing Role of Rhythm Control in Patients With Atrial Fibrillation: JACC State-of-the-Art Review. J. Am. Coll. Cardiol. 2022, 79, 1932–1948. [Google Scholar] [CrossRef] [PubMed]
Baseline Characteristics | Total | Before Matching | After Matching | ||||
---|---|---|---|---|---|---|---|
No AF | AF | SDi * | No AF | AF | SDi | ||
(n = 3,345,638) | (n = 3,033,412) | (n = 312,226) | (%) | (n = 289,332) | (n = 289,332) | (%) | |
Age (years), mean ± SD | 59.1 ± 21.5 | 57.2 ± 21.4 | 78.1 ± 10.6 | 124.0 | 77.7 ± 10.8 | 77.6 ± 10.6 | −0.7 |
Sex (male), n (%) | 1,562,002 (46.7) | 1,387,154 (45.7) | 174,848 (56.0) | 20.7 | 164,634 (56.9) | 161,616 (55.9) | −2.1 |
Hypertension, n (%) | 1,014,316 (30.3) | 799,376 (26.4) | 214,940 (68.8) | 94.0 | 203,184 (70.2) | 193,786 (67.0) | −7.2 |
Diabetes mellitus, n (%) | 460,626 (13.8) | 378,657 (12.5) | 81,969 (26.3) | 35.4 | 78,225 (27.0) | 74,766 (25.8) | −3.1 |
Heart failure, n (%) | 335,808 (10.0) | 188,903 (6.2) | 146,905 (47.1) | 104.1 | 120,800 (41.8) | 124,229 (42.9) | 3.0 |
History of pulmonary oedema, n (%) | 20,929 (0.6) | 11,523 (0.4) | 9406 (3.0) | 20.5 | 6942 (2.4) | 7460 (2.6) | 1.4 |
Valve disease, n (%) | 116,586 (3.5) | 63,329 (2.1) | 53,257 (17.1) | 52.6 | 37,679 (13.0) | 39,514 (13.7) | 2.2 |
Dilated cardiomyopathy, n (%) | 72,025 (2.2) | 38,617 (1.3) | 33,408 (10.7) | 40.5 | 24,757 (8.6) | 26,204 (9.1) | 2.2 |
Coronary artery disease, n (%) | 345,007 (10.3) | 251,195 (8.3) | 93,812 (30.0) | 57.5 | 87,299 (30.2) | 82,429 (28.5) | −4.5 |
Previous MI, n (%) | 51,624 (1.5) | 38,985 (1.3) | 12,639 (4.0) | 17.2 | 12,328 (4.3) | 11,354 (3.9) | −2.1 |
Previous PCI, n (%) | 83,454 (2.5) | 67,151 (2.2) | 16,303 (5.2) | 15.9 | 16,720 (5.8) | 15,153 (5.2) | −2.9 |
Vascular disease, n (%) | 279,140 (8.3) | 211,598 (7.0) | 67,542 (21.6) | 42.8 | 62,815 (21.7) | 59,747 (20.6) | −3.1 |
Ischemic stroke, n (%) | 62,335 (1.9) | 41,508 (1.4) | 20,827 (6.7) | 27.2 | 17,669 (6.1) | 17,244 (6.0) | −0.8 |
Intracranial bleeding, n (%) | 34,054 (1.0) | 26,095 (0.9) | 7959 (2.5) | 13.1 | 7074 (2.4) | 6888 (2.4) | −0.5 |
Smoker, n (%) | 227,270 (6.8) | 205,249 (6.8) | 22,021 (7.1) | 1.1 | 22,176 (7.7) | 20,406 (7.1) | −2.4 |
Dyslipidaemia, n (%) | 435,784 (13.0) | 353,455 (11.7) | 82,329 (26.4) | 38.2 | 78,569 (27.2) | 74,344 (25.7) | −3.8 |
Obesity, n (%) | 352,408 (10.5) | 296,549 (9.8) | 55,859 (17.9) | 23.7 | 51,002 (17.6) | 49,801 (17.2) | −1.2 |
Alcohol-related diagnoses, n (%) | 184,632 (5.5) | 165,522 (5.5) | 19,110 (6.1) | 2.8 | 18,056 (6.2) | 17,652 (6.1) | −0.6 |
Chronic kidney disease, n (%) | 116,110 (3.5) | 82,155 (2.7) | 33,955 (10.9) | 32.9 | 27,889 (9.6) | 28,302 (9.8) | 0.6 |
Lung disease, n (%) | 334,127 (10.0) | 261,744 (8.6) | 72,383 (23.2) | 40.6 | 63,688 (22.0) | 62,630 (21.6) | −1.0 |
Sleep apnoea syndrome, n (%) | 132,626 (4.0) | 107,336 (3.5) | 25,290 (8.1) | 19.6 | 22,366 (7.7) | 22,248 (7.7) | −0.2 |
COPD, n (%) | 182,824 (5.5) | 137,856 (4.5) | 44,968 (14.4) | 34.1 | 39,484 (13.6) | 38,622 (13.3) | −1.0 |
Liver disease, n (%) | 112,721 (3.4) | 97,796 (3.2) | 14,925 (4.8) | 7.9 | 13,259 (4.6) | 13,413 (4.6) | 0.3 |
Thyroid diseases, n (%) | 180,643 (5.4) | 138,648 (4.6) | 41,995 (13.5) | 31.4 | 32,728 (11.3) | 34,529 (11.9) | 2.2 |
Inflammatory disease, n (%) | 176,135 (5.3) | 152,159 (5.0) | 23,976 (7.7) | 10.9 | 20,727 (7.2) | 20,988 (7.3) | 0.4 |
Anaemia, n (%) | 274,384 (8.2) | 214,629 (7.1) | 59,755 (19.1) | 36.3 | 51,294 (17.7) | 51,111 (17.7) | −0.2 |
Previous cancer, n (%) | 500,053 (14.9) | 441,098 (14.5) | 58,955 (18.9) | 11.7 | 56,123 (19.4) | 55,044 (19.0) | −1.0 |
Poor nutrition, n (%) | 127,089 (3.8) | 97,179 (3.2) | 29,910 (9.6) | 26.3 | 25,354 (8.8) | 25,439 (8.8) | 0.1 |
Cognitive impairment, n (%) | 112,846 (3.4) | 83,072 (2.7) | 29,774 (9.5) | 28.6 | 27,068 (9.4) | 26,189 (9.1) | −1.3 |
Frailty index, mean ± SD | 6.3 ± 8.1 | 5.7 ± 7.7 | 12.2 ± 9.8 | 74.0 | 12.1 ± 10.1 | 11.9 ± 9.6 | −2.4 |
Cohort | Events, (n) | Person-Time (Patient Years) | Incidence, (Events per 1000 Person-Years) | Incidence, %/Year (95% CI) | p-Value |
---|---|---|---|---|---|
No AF | 23,252 | 14,587,126 | 1.59 | 0.56 (0.56–0.57) | <0.0001 |
AF | 81,899 | 1,041,506 | 78.6 | 2.23 (2.20–2.26) |
Predictor | Univariable Analysis | p Value | Multivariable Analysis | p Value |
---|---|---|---|---|
HR, 95% CI | HR, 95% CI | |||
Age (years) | 1.038 (1.037–1.038) | <0.0001 | 1.023 (1.023–1.023) | <0.0001 |
Sex (male) | 2.011 (1.986–2.036) | <0.0001 | 1.607 (1.586–1.628) | <0.0001 |
Hypertension | 2.687 (2.655–2.720) | <0.0001 | 1.079 (1.063–1.095) | <0.0001 |
Diabetes mellitus | 2.354 (2.321–2.386) | <0.0001 | 1.241 (1.222–1.261) | <0.0001 |
Heart failure | 4.743 (4.679–4.808) | <0.0001 | 1.594 (1.563–1.625) | <0.0001 |
History of pulmonary oedema | 5.007 (4.789–5.236) | <0.0001 | 1.269 (1.212–1.329) | <0.0001 |
Valve disease | 3.568 (3.494–3.643) | <0.0001 | 1.268 (1.239–1.296) | <0.0001 |
Dilated cardiomyopathy | 4.470 (4.369–4.574) | <0.0001 | 1.337 (1.303–1.373) | <0.0001 |
Coronary artery disease | 3.392 (3.345–3.440) | <0.0001 | 1.221 (1.198–1.245) | <0.0001 |
Previous MI | 3.017 (2.924–3.112) | <0.0001 | 1.013 (0.976–1.051) | 0.50 |
Previous PCI | 2.552 (2.489–2.617) | <0.0001 | 0.982 (0.953–1.011) | 0.22 |
Vascular disease | 3.230 (3.182–3.279) | <0.0001 | 1.232 (1.209–1.255) | <0.0001 |
Atrial fibrillation | 3.657 (3.604–3.711) | <0.0001 | 1.349 (1.327–1.372) | <0.0001 |
Ischaemic stroke | 2.064 (1.993–2.138) | <0.0001 | 0.966 (0.932–1.001) | 0.06 |
Intracranial bleeding | 1.821 (1.724–1.924) | <0.0001 | 1.006 (0.952–1.063) | 0.83 |
Smoker | 1.771 (1.737–1.805) | <0.0001 | 1.222 (1.196–1.248) | <0.0001 |
Dyslipidaemia | 1.968 (1.940–1.997) | <0.0001 | 0.876 (0.862–0.891) | <0.0001 |
Obesity | 1.566 (1.540–1.592) | <0.0001 | 1.025 (1.006–1.044) | 0.009 |
Alcohol-related diagnoses | 2.022 (1.982–2.064) | <0.0001 | 1.432 (1.399–1.466) | <0.0001 |
Chronic kidney disease | 3.290 (3.222–3.360) | <0.0001 | 1.368 (1.337–1.399) | <0.0001 |
Lung disease | 2.505 (2.467–2.544) | <0.0001 | 1.286 (1.254–1.318) | <0.0001 |
Sleep apnoea syndrome | 1.808 (1.766–1.851) | <0.0001 | 1.004 (0.979–1.030) | 0.74 |
COPD | 2.912 (2.858–2.966) | <0.0001 | 1.015 (0.985–1.045) | 0.33 |
Liver disease | 1.996 (1.944–2.049) | <0.0001 | 1.171 (1.137–1.205) | <0.0001 |
Thyroid diseases | 1.458 (1.424–1.492) | <0.0001 | 0.998 (0.974–1.022) | 0.87 |
Inflammatory disease | 1.177 (1.148–1.207) | <0.0001 | 0.910 (0.887–0.934) | <0.0001 |
Anaemia | 2.301 (2.261–2.341) | <0.0001 | 1.144 (1.122–1.166) | <0.0001 |
Previous cancer | 1.634 (1.608–1.660) | <0.0001 | 1.190 (1.171–1.209) | <0.0001 |
Poor nutrition | 2.457 (2.396–2.520) | <0.0001 | 1.170 (1.139–1.201) | <0.0001 |
Cognitive impairment | 2.335 (2.270–2.403) | <0.0001 | 0.975 (0.946–1.004) | 0.09 |
Frailty index | 1.056 (1.055–1.056) | <0.0001 | 1.027 (1.027–1.028) | <0.0001 |
Risk | Model A | Model B | Model C | Model D |
---|---|---|---|---|
HR, (95% CI) | HR 3.657 (3.604–3.711) | HR 2.166 (2.133–2.199) | HR 1.349 (1.327–1.372) | HR 1.339 (1.313–1.366) |
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Fawzy, A.M.; Bisson, A.; Bodin, A.; Herbert, J.; Lip, G.Y.H.; Fauchier, L. Atrial Fibrillation and the Risk of Ventricular Arrhythmias and Cardiac Arrest: A Nationwide Population-Based Study. J. Clin. Med. 2023, 12, 1075. https://doi.org/10.3390/jcm12031075
Fawzy AM, Bisson A, Bodin A, Herbert J, Lip GYH, Fauchier L. Atrial Fibrillation and the Risk of Ventricular Arrhythmias and Cardiac Arrest: A Nationwide Population-Based Study. Journal of Clinical Medicine. 2023; 12(3):1075. https://doi.org/10.3390/jcm12031075
Chicago/Turabian StyleFawzy, Ameenathul M., Arnaud Bisson, Alexandre Bodin, Julien Herbert, Gregory Y. H. Lip, and Laurent Fauchier. 2023. "Atrial Fibrillation and the Risk of Ventricular Arrhythmias and Cardiac Arrest: A Nationwide Population-Based Study" Journal of Clinical Medicine 12, no. 3: 1075. https://doi.org/10.3390/jcm12031075
APA StyleFawzy, A. M., Bisson, A., Bodin, A., Herbert, J., Lip, G. Y. H., & Fauchier, L. (2023). Atrial Fibrillation and the Risk of Ventricular Arrhythmias and Cardiac Arrest: A Nationwide Population-Based Study. Journal of Clinical Medicine, 12(3), 1075. https://doi.org/10.3390/jcm12031075