Abstract
The objective of the study was to find the prevalence of metabolic syndrome along with identifying the atrial arrhythmias, QTC interval, and coronary artery disease among these patients during follow-ups. Among 171 subjects who were implanted with permanent pacemakers, metabolic syndrome was present in 90 (52.6 %). Prevalence of Arrhythmias was 49 (28.7 %), atrial tachycardia (AT)/atrial fibrillation (AF) was seen in 29 (17 %) patients. Our study showed that there is a strong association between metabolic syndrome and atrial arrhythmias. Metabolic syndrome, age, coronary artery disease and Systolic blood pressure were good independent predictors of atrial arrhythmias among patients with pacemaker implantation.
Keywords: Metabolic syndrome, Permanent pacemaker implants, Atrial arrhythmia
1. Introduction
Metabolic syndrome, a constellation of conditions including abdominal obesity, dyslipidemia, hypertension, and insulin resistance, is a prothrombotic and proinflammatory state which has increased to epidemic proportions.1 Metabolic syndrome is known to alter the electrical remodeling of the sinus node and produce arrhythmia.2 The most noted arrhythmias include sinus arrhythmia, premature atrial and ventricular contractions, atrial fibrillation (AF), ventricular and supraventricular tachycardia.3,4 Various components of metabolic syndrome have been known to have a role in the pathogenesis of atrial fibrillation.5 The incidence of AF following dual-chamber pacemaker implantation was relatively high in a Chinese cohort.6 AF was detected in 24 % of patients without history of AF, in patients with sinus node dysfunction, > or = 50 % cumulative right ventricular pacing is associated with a 2-fold increase in risk of developing AF.7 This study aimed to find the prevalence of metabolic syndrome and the association between metabolic syndrome and various types of cardiac conduction abnormalities in patients who have undergone permanent pacemaker implantation.
2. Methods
This is a retrospective observational study that included consecutive patients who underwent permanent pacemaker implantation between January 2018 to December 2019. Baseline characteristics including demographic variables were noted. The primary objective was to study the prevalence of metabolic syndrome in patients among patients with permanent pacemaker implantation. Secondary objectives were to identify the association between metabolic syndrome and arrhythmias, QTC interval and coronary artery disease among these patients. Patients with a history of chronic kidney disease, hepatic, psychiatric, malignant, infectious disorders, patients with valvar heart disease, or those patients taking drugs that affect the QT interval were excluded from the study.
In our study, Metabolic syndrome was diagnosed using AHA/NHLBI,8 guidelines. We considered SSS to be present if the medical record included a diagnosis of SSS and symptoms or signs consistent with SSS (e.g., syncope, dizziness, bradycardia, sinus pauses), without a secondary cause.9 Atrial arrhythmias including atrial fibrillation were identified based on non-pacing, intrinsic activity capture. Likewise, the QTC interval was assessed from the non-pacing ECG. Coronary angiogram data wherever done was taken. The patients were recruited from the medical records, and the study was cleared by the institutional ethical committee.
3. Results
The study included 171 subjects who were implanted with permanent pacemaker, among which 92 (53.8 %) were males and 79 (46.2 %) were females. Table 1 demonstrates the baseline parameters of these patients. Dual chamber pacemaker was the commonest type of pacemaker implanted (66.1 %) with commonest indications being Sick Sinus Syndrome (51.5 %) and complete heart block (48.5 %). Arrhythmias were present in 49 (28.7 %) patients with atrial tachycardia (AT)/atrial fibrillation (AF)/Atrial flutter seen in 29 (17 %) patients; ventricular ectopic in 5 (2.9 %) patients; functional escape rhythm, RBBB, premature atrial complex and pacemaker mediated tachycardia was found in 1 (0.6 %) patient each. Pacemaker interrogation revealed high ventricular rates in 4 (2.3 %) patients, high atrial rates, and high ventricular rates in 7 (4.1 %) patients and pacemaker mediated tachycardia in 1 (0.6 %) patient. Among 171 PPI patients, atrial fibrillation was found in 10 (5.8 %) patients. Coronary artery disease (CAD) was present in 33 (19.3 %) patients. Among CAD, single vessel disease was reported among 20 (11.7 %), double vessel disease among 5 (2.9 %) patients and triple vessel disease was seen in 8 (4.7 %) patients. Among 171 PPI patients, metabolic syndrome was present in 90 (52.6 %) patients including 43 (47.8 %) males and 47 (52.2 %) females (p value 0.124). Arrhythmias were more common in those with metabolic syndrome than those without 35 (38.9 %) vs 14 (17.3 %) respectively, p = 0.002) (Table 2). In our study 22 (24.4 %) patients with metabolic syndrome developed atrial arrhythmias (atrial tachycardia or atrial flutter or atrial fibrillation) and 7 (8.6 %) patients without metabolic syndrome developed atrial arrhythmias (P value 0.007). The incidence of AF was not significantly different between the two groups (6 (6.7 %) vs 4 (4.9 %) respectively, p = 0.75). Similarly, atrial flutter was found in only 2 subjects in patients with metabolic syndrome group and was not evident in patients with no metabolic syndrome. Interestingly, sick sinus syndrome was commoner (51 (63 %)) in patients without metabolic syndrome while complete heart block constituted the main indication (53 (58.9 %)) among metabolic syndrome (p = 0.006). There was significant mean difference was noted in age and QTc between those with and without metabolic syndrome. A multivariate analysis showed Metabolic syndrome, coronary artery disease (p = 0.04), age and systolic blood pressure to be independent predictors of atrial arrhythmias (Table 3). Univariate analysis using binary logistic regression showed that metabolic syndrome could predict CHB with an unadjusted Odds ratio of 2.963 (P5% CI: 1.403–6.256; p-value of 0.004).
Table 1.
Baseline parameters of patients.
| PARAMETERS | Mean ± SD |
|---|---|
| Age (years) | 63.1 ± 13.7 |
| Height (cm) | 160.5 ± 7.5 |
| Weight (kg) | 61.1 ± 11.0 |
| BMI(kg/m2) | 24.8 ± 14.9 |
| QTC Interval (ms) | 466.9 ± 53.9 |
| Diastolic BP(mmHg) | 82.2 ± 11.8 |
| Fasting blood glucose (mg/dL) | 115.5 ± 32.2 |
| Glyco Hb (%) | 6.2 ± 1.8 |
| HDL (mg/dL) | 45.4 ± 12.0 |
| Hip circumference (cm) | 94.1 ± 15.2 |
| LDL (mg/dL) | 95.2 ± 36.5 |
| Postprandial blood glucose (mg/dL) | 171.1 ± 67.7 |
| Random blood glucose (mg/dL) | 138.9 ± 52.9 |
| Systolic BP(mmHg) | 134.6 ± 24.2 |
| T3 (ng/dL) | 1.12 ± 0.93 |
| T4 (μg/dL) | 7.4 ± 2.1 |
| Total Cholesterol (mg/dL) | 168.7 ± 44.5 |
| Triglycerides (mg/dL) | 135 ± 73.7 |
| TSH(μIU/mL) | 2.6 ± 2.1 |
| Waist circumference (cm) | 85.7 ± 11 |
BMI: body mass index, BP: blood pressure, Hb: haemoglobin, HDL: high density cholesterol, LDL: low density cholesterol, TSH: thyroid stimulating hormone.
Table 2.
Comparison of demographic and clinical parameters between patients with and without metabolic syndrome.
| Variables | Metabolic Syndrome N (%) or Mean SD |
p - value | ||
|---|---|---|---|---|
| Present (n = 90) | Absent (n = 81) | |||
| Gender | Male | 43 (47.8 %) | 49 (60.5 %) | 0.124 |
| Female | 47 (52.2 %) | 32 (39.5 %) | ||
| Pacemaker type | Single chamber | 29 (32.2 %) | 29 (35.8 %) | 0.632 |
| Dual Chamber | 61 (67.8 %) | 52 (64.2 %) | ||
| Implant Indication | SSS | 37 (41.1 %) | 51 (63.1 %) | 0.006 |
| CHB | 53 (58.9 %) | 30 (37.0 %) | ||
| Arrhythmias | 35 (38.9 %) | 14 (17.3 %) | 0.002 | |
| Atrial arrhythmias (Atrial tachycardia/atrial flutter) | 22 (24.4 %) | 07 (8.6 %) | 0.007 | |
| Atrial fibrillation | 6 (6.7 %) | 4 (4.9 %) | 0.75 | |
| Coronary artery Diseases | 19 (21.1 %) | 14 (17.3 %) | 0.562 | |
| Age_years | 65.4 ± 11.8 | 60.5 ± 15.2 | 0.02 | |
| QTc Interval_msec | 475.5 ± 53.0 | 457.5 ± 53.3 | 0.03 | |
SSS: Sick sinus syndrome; CHB: Complete Heart block.
Table 3.
Multivariable analysis using Binary logistic regression in the prediction of Atrial arrhythmias.
| Parameters | Odds Ratio | Class Interval |
P-value | |
|---|---|---|---|---|
| Lower limit | Upper limit | |||
| Metabolic syndrome | 5.35 | 1.72 | 16.66 | 0.004* |
| Gender | 1.45 | 0.52 | 4.03 | 0.47 |
| Age | 1.0 | 1.0 | 1.10 | 0.02* |
| CAD | 5.59 | 1.0 | 30.24 | 0.04* |
| BMI | 1.02 | 0.97 | 1.08 | 0.31 |
| Systolic BP | 0.96 | 0.94 | 0.99 | 0.017* |
| TSH | 1.13 | 0.90 | 1.42 | 0.26 |
CAD: coronary artery disease, BMI: body mass index, BP: blood pressure, TSH: thyroid stimulating hormone, * statistically significant.
4. Discussion
In the present study a total number of 171 subjects were enrolled to look for the prevalence and role of metabolic syndrome in patients presenting with cardiac conduction abnormality with implanted permanent pacemaker. Out of 171 patients, 90 patients had metabolic syndrome, according to AHA/NHLBI definition of metabolic syndrome in which≥3 criteria was fulfilled.
In our study, Metabolic syndrome was present in 52.6 % patients who underwent permanent pacemaker implantation. In a study conducted by Chang He Kwon et al10 in patients with atrial fibrillation, the prevalence of metabolic syndrome significantly increased with increasing age groups. In a study conducted by Hiroshi et al,11 metabolic syndrome was found in 13 % of the subjects as per the NCEP ATP III criteria and in 16 % of the subjects as per the AHA/NHLBI definition of metabolic syndrome.
In a study by Ken Umetani et al12 among 592 patients, paroxysmal atrial fibrillation (PAF)/paroxysmal atrial flutter (PAFL) developed in 32 (5 %) subjects and metabolic syndrome was present in 127 (21 %) subjects. PAF/PAFL developed in 12 (9 %) patients with metabolic syndrome. Metabolic syndrome was a significant risk factor for the development of paroxysmal AF/paroxysmal atrial flutter. Hiroshi et al9 conducted a study in which metabolic syndrome was present in 3716 and 4544 out of 28,449 subjects as per the NCEP ATPIII and AHA/NHLBI criteria respectively.
In our study 22 (24.4 %) patients with metabolic syndrome developed atrial arrhythmias and 7 (8.6 %) patients without metabolic syndrome developed atrial arrhythmias suggesting a significant association between metabolic syndrome and atrial arrhythmias. However, Proportion of atrial fibrillation was comparable between the two groups. Also, atrial flutter was found in only two patients and both were in the metabolic syndrome group. A study by V. Ferreira et al showed that the prevalence of new-onset atrial arrhythmia was 51.6 % in patients with dual chamber pacemaker implantation.13 Another study by Mario Augusto Cray da Costa documented that the prevalence of AF post-PPI was 25 %.14 Multivariable logistic regression analysis showed that metabolic syndrome, age, coronary artery disease and systolic BP were good independent predictors of atrial arrhythmias among patients who underwent permanent pacemaker implantation. Metabolic syndrome is an important key factor in the final common pathway of the atrial fibrillation pathogenesis which includes atrial structural/electrical remodeling, inflammatory processes, along with cardiac autonomic changes.11 In the present study, coronary artery disease (CAD) was present in 33 (19.3 %). Among the patients with metabolic syndrome, CAD was found in 19 (21.1 %) whereas in patients without metabolic syndrome, CAD was present in 14 (17.3 %), suggesting no significant association between metabolic syndrome and CAD. High fasting glucose, high HbA1C and high Systolic BP were the most prevalent risk factors in CAD patients with metabolic syndrome. Farzaneh Montazerifar et al15 included 200 coronary artery diseases. Of these, 49.5 % had metabolic syndrome. Low LDL, high fasting glucose, high waist circumference and increasing age were the most prevalent risk factors in CAD patients with metabolic syndrome.
In our study complete heart block was found in 53 (58.9 %) subjects with metabolic syndrome and 30 (37 %) subjects without metabolic syndrome suggesting there was a statistically significant association of metabolic syndrome with the indication for permanent pacemaker implantation. Univariate analysis using binary logistic regression also suggested statistically a significant association between CAD and metabolic syndrome (p = 0.005). In a study by Milovancev Aleksandra et al16 which included 50 patients with metabolic syndrome and 30 healthy individuals, Qtc interval was significantly longer in metabolic syndrome patients than in the control group. Our study depicted similar results where QTc was significantly different between patients with and without metabolic syndrome. Metabolic syndrome does have an association with various forms of conduction abnormalities either related to degenerative/arrhythmic changes that were evident after PPI implantation. In this facet Evaluation of metabolic syndrome and timely screening for the new onset of atrial conduction abnormality/arrhythmias becomes an imperative step during the follow-up of these patients.
5. Limitations
This study included the follow-up data of 2–3 years after the implantation. Hence, we could not demonstrate any long-term effect of PPI such as CHF and Left ventricular dysfunction. Also, this study did not include the atrial dimension as this could be one of the important predictors of atrial arrhythmias.
6. Conclusion
In the present study, the prevalence of metabolic syndrome in patients who underwent permanent pacemaker implantation was 52.6 %. Our study showed that there is a strong association between metabolic syndrome and overall atrial arrhythmias. However, the proportion of Atrial fibrillation was similar among the two groups. Metabolic syndrome, age, coronary artery disease and Systolic blood pressure were good independent predictors of atrial arrhythmias among patients who underwent permanent pacemaker implantation.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.ihj.2023.10.006.
Contributor Information
Umesh M. Pai, Email: umesh.pai@manipal.edu.
Mukund A. Prabhu, Email: mukund.prabhu@manipal.edu, mukundaprabhu@gmail.com.
Dr Tom Devasia, Email: tom.devasia@manipal.edu.
Dr Sudhakar Rao, Email: msudhakar88@gmail.com.
Rekha V, Email: rekha.v@manipal.edu.
Jyothi Samanth, Email: jyothisamanth@ymail.com, samanth.jyothi@manipal.edu.
Sridevi Prabhu, Email: sridevi.santhosh@manipal.edu.
Hazel Lolita Mathias, Email: mathiashazel31@gmail.com.
Chaithra V, Email: chaithrav402@gmail.com.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
References
- 1.Grundy S.M., Brewer H.B., Jr., Cleeman J.I., Smith S.C., Jr., Lenfant C. American heart association; national heart, lung, and blood institute. Definition of metabolic syndrome: report of the national heart, lung, and blood institute/American heart association conference on scientific issues related to definition. Circulation. 2004;109(3):433–438. doi: 10.1161/01.CIR.0000111245.75752.C6.PMID.14744958. Jan 27. [DOI] [PubMed] [Google Scholar]
- 2.Albarado-Ibañez A., Avelino-Cruz J.E., Velasco M., Torres-Jácome J., Hiriart M. Metabolic syndrome remodels electrical activity of the sinoatrial node and produces arrhythmias in rats. PLoS One. 2013;8(11) doi: 10.1371/journal.pone.0076534. Nov 8. PMID: 24250786; PMCID: PMC3826723. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Mozos I. Arrhythmia Risk and Obesity. J Mol Genet Med. 2014 doi: 10.4172/1747-0862.S1-006. S1: 006. [DOI] [Google Scholar]
- 4.Wilborn C., Beckham J., Campbell B., et al. Obesity: prevalence, theories, medical consequences, management, and research directions. J Int Soc Sports Nutr. 2005;2(2):4–31. doi: 10.1186/1550-2783-2-2-4. Dec 9. PMID: 18500955; PMCID: PMC2129146. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Kumar P., Gehi A.K. Atrial fibrillation and metabolic syndrome: understanding the connection. J Atr Fibrillation. 2012;5(3):647. doi: 10.4022/jafib.647. Oct 6. PMID: 28496775; PMCID: PMC5153215. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Kwon C.H, Kim H., Kim S.H., et al. The Impact of Metabolic Syndrome on the Incidence of Atrial Fibrillation: A Nationwide Longitudinal Cohort Study in South Korea. J Clin Med. 2019 Jul 24;8(8):1095. doi: 10.3390/jcm8081095. PMID: 31344944; PMCID: PMC6723247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Cheung J.W., Keating R.J., Stein K.M., et al. Newly detected atrial fibrillation following dual chamber pacemaker implantation. J Cardiovasc Electrophysiol. 2006;17(12):1323–1328. doi: 10.1111/j.1540-8167.2006.00648.x. Dec. Epub 2006 Nov 1. PMID: 17081212. [DOI] [PubMed] [Google Scholar]
- 8.Grundy S.M., Hansen B., Smith S.C., Jr., Cleeman J.I., Kahn R.A. Conference participants. Clinical management of metabolic syndrome: report of the American heart association/national heart, lung, and blood institute/American diabetes association conference on scientific issues related to management. Circulation. 2004;109(4):551–556. doi: 10.1161/01.CIR.0000112379.88385.67. Feb 3. [DOI] [PubMed] [Google Scholar]
- 9.Jensen P.N., Gronroos N.N., Chen L.Y., et al. Incidence of and risk factors for sick sinus syndrome in the general population. J Am Coll Cardiol. 2014;64(6):531–538. doi: 10.1016/j.jacc.2014.03.056. Aug 12. PMID: 25104519; PMCID: PMC4139053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Kwon C.H., Kim H., Kim S.H., et al. The impact of metabolic syndrome on the incidence of atrial fibrillation: a nationwide longitudinal cohort study in South Korea. J Clin Med. 2019;8(8):1095. doi: 10.3390/jcm8081095. Jul 24. PMID: 31344944; PMCID: PMC6723247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Watanabe H., Tanabe N., Watanabe T., et al. Metabolic syndrome and risk of development of atrial fibrillation: the Niigata preventive medicine study. Circulation. 2008;117(10):1255–1260. doi: 10.1161/CIRCULATIONAHA.107.744466. Mar 11. Epub 2008 Feb 19. Erratum in: Circulation. 2010 Aug 17;122(7):e433. PMID: 18285562; PMCID: PMC2637133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Umetani K., Kodama Y., Nakamura T., et al. High prevalence of paroxysmal atrial fibrillation and/or atrial flutter in metabolic syndrome. Circ J. 2007;71(2):252–255. doi: 10.1253/circj.71.252. [DOI] [PubMed] [Google Scholar]
- 13.Ferreira V., Portugal G., Monteiro A Viveiros, et al. New onset atrial fibrillation after dual chamber pacemaker implantation: long term predictors. Eur Heart J. November 2020;41(2) doi: 10.1093/ehjci/ehaa946.0507. ehaa946.0507. [DOI] [Google Scholar]
- 14.Costa M.A.C., Santos J.F.L.P., Schafranski M.D. Prevalence of atrial fibrillation in pacemaker patients. Int. J. Cardiovasc. Sci. 2022;35(3):373–381. [Google Scholar]
- 15.Montazerifar F., Bolouri A., Mozaffar M.M., Karajibani M. The prevalence of metabolic syndrome in coronary artery disease patients. Cardiol Res. 2016;7(6):202. doi: 10.14740/cr507w. Dec. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Milovancev A., Stokic E., Popovic D.S., Naglic D.T., Rankov O., Ilincic B. Body weight reduction and QTc interval in obesity. Adv Weigh Loss Manag Med Dev. 2016;1(102):2. [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.