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Cardiology Research

Original Article

Volume 13, Number 4, August 2022, pages 228-235

Atrial Fibrillation as a Prognostic Indicator in Patients With Orthostatic Hypotension: Nationwide Inpatient Sample Analysis

Orthostatic hypotension (OH), a common manifestation of autonomic dysfunction, and atrial fibrillation (AF), the most common sustained arrhythmia, have shared risk factors such as advancing age, hypertension, and diabetes and are highly prevalent conditions. The prevalence of OH, defined as a drop in systolic blood pressure of at least 20 mm Hg or of at least 10 mm Hg in diastolic blood pressure within 3 min of standing up [1], is estimated to be around 5-6% among those aged 55 years or older [2, 3] although the prevalence of asymptomatic OH may be as high as 16% among those aged 65 years and older [4]. In 2004, OH caused 36 hospitalizations per 100,000 US adults with an in-hospital mortality rate of 0.9% [5]. On the other hand, AF currently affects about 6 million patients in the USA alone and accounts for more than 454,000 hospitalizations each year [6, 7].

Although OH [2, 3, 8-14] and AF [15] are both well-recognized risk factors for morbidity and mortality and have a bidirectional relationship with several cardiovascular conditions such as coronary heart disease, heart failure, myocardial infarction, venous thromboembolism (VTE), and stroke, the current literature largely considers AF and OH independently of each other. Nevertheless, the intricate link between OH and AF has been emerging over the past decade. For instance, the Malmo Preventive Project demonstrated that OH is an independent risk factor of incident AF in middle-aged adults [13], while similar observations were reported from the Framingham Heart Study in older adults [16]. Moreover, several recent meta-analyses confirm the association between OH and increased risk of incident AF [12, 17], which might be partly due to the structural and hemodynamic heart remodeling seen with OH [18].

Similarly, the Irish Longitudinal Study on Ageing (TILDA) and a Chinese cohort study reported a higher OH occurrence among AF patients [19, 20]. In older adults, AF independently increases the risk of syncope and nonaccidental falls [21-23] and is likely to exacerbate the symptoms of OH and the need for hospitalization.

Despite the higher prevalence of OH [24] and AF [25] among hospitalized patients than in the general population, there is a paucity of studies reporting in-hospital outcomes of patients with concomitant OH and AF. In this retrospective cohort study, we aim to assess whether the presence of AF is an independent predictor of cardiac arrest and mortality in patients with OH using hospitalization records from the National Inpatient Sample (NIS) database.

Patient hospitalization records for 2019 were retrieved from the NIS, the largest in-patient healthcare database in the USA, developed and maintained by the Healthcare Cost and Utilization Project (HCUP) under the sponsorship of the Agency for Healthcare Research and Quality. The details of the NIS database have been described previously [26].

In this study, patients aged 18 years or older hospitalized in 2019 with OH as the primary diagnosis were identified from the NIS database using the International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code I95.1. The study sample was then categorized into OH patients with AF (ICD-10 = codes I48.20 and I48.91 corresponding to chronic AF and unspecified AF, respectively) and OH patients without AF. ICD10 code Z95.5 was used to identify patients with a history of coronary angioplasty or graft. We then compared in-hospital clinical outcomes between OH patients with AF and those without AF. Patient baseline characteristics included age, sex, race/ethnicity, household income, insurance type, and comorbidities. Hospital characteristics included hospital teaching status.

The primary outcomes of interest were in-patient mortality and in-hospital cardiac arrest. Secondary outcomes of interest were the length of stay and total hospital charges.

We expressed continuous variables as median ± interquartile range (IQR) and used t-tests or regression to compare differences between exposure and non-exposure group. Similarly, categorical variables were presented as percentages, and a Chi-squared test was used to compare the differences between the variables. All statistical tests were two-sided, and tests with P values of < 0.05 were considered significant. Multivariate logistic regression was used to adjust for comorbidities, hospital characteristics, and Charlson comorbidity index (CCI) [27]. Data were analyzed with Software for Statistics and Data Science (STATA V.14.2, Stata Corp 4905 Lakeway Drive, College Station, TX 77845, USA).

Howard University Hospital IRB exempted this study from full review because it was determined to be a non-human study. We have utilized anonymized data available from a public data repository. The study was conducted in compliance with the ethical standards of the responsible institution on human subjects as well as with the Helsinki Declaration.

We identified 10,630 hospitalizations with the primary diagnosis of OH in 2019, 2,987 (28%) of whom had a concomitant diagnosis of AF (Table 1). OH patients with AF were older (78.5 (IQR: 68.5 - 88.5) vs. 71.6 (IQR: 57.6 - 85.6) years, P < 0.001) and predominantly male (1,790 (59.9%) vs. 4,019 (52.6%), P < 0.001) than patients without AF. While most of the patients in the two groups were White, the proportion was significantly higher (2,474 (87.5%) vs. 5,247 (76.5%), P < 0.001) in the AF group (Table 1). Similarly, Medicare was the primary insurer in both groups but with significantly more coverage among OH patients with AF than those without AF (2,632 (89.5%) vs. 5,745 (77.0%), P < 0.001) (Table 1). Nearly three-fourths of the patients were treated at a teaching hospital with no intergroup differences (Table 1). Also, patients’ location was similar in the two groups (Table 1).

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Table 1. Baseline Demographics, Comorbidities of Patients, Admitted for Orthostatic Hypotension (OH) With or Without Concomitant Atrial Fibrillation (AF)

The prevalence of several comorbidities including congestive heart failure (1,263 (42.3%) vs. 1,367 (17.9%); P < 0.001), history of percutaneous coronary intervention (PCI) or graft (443 (14.8%) vs. 860 (11.3%); P < 0.001), coronary artery disease (1,432 (47.9%) vs. 2,481 (32.5%)), chronic obstructive pulmonary disease (COPD) (644 (21.6%) vs. 1,131 (14.8%); P < 0.001), chronic kidney disease (1,182 (39.6%) vs. 2,216 (29.0%); P < 0.001), and hyperlipidemia (1,828 (61.2%) vs. 4,087 (53.5%); P < 0.001) were significantly higher in OH patients with AF (Table 1). Furthermore, patients with OH and concomitant AF had higher mean CCI (3.1 (standard deviation (SD): 2.1) vs. 2.5 (SD: 2.1), P < 0.001). However, the prevalence of hypertension (905 (30.3%) vs. 3,299 (43.2%), P < 0.001), alcohol use (103 (3.5%) vs. 380 (5.0%); P < 0.001), and nicotine use (229 (7.7%) vs. 951 (12.4%); P < 0.001) were significantly lower in OH patients with AF (Table 1). The prevalence of diabetes mellitus, obesity, end-stage renal disease, and previous history of cardiac arrest was similar in the two groups (Table 1).

In the univariate analysis, the risk of in-hospital mortality (odds ratio (OR) = 3.2 (95% confidence interval (CI): 1.5 - 6.9), P = 0.003) and cardiac arrest (OR = 7.7 (95% CI: 2.5 - 23.9), P < 0.001) were significantly higher in OH patients with AF with longer length of stay (0.4 days, P < 0.001) and higher total charges ($1,877, P = 0.016) (Table 2). Although the risk of cardiac arrest remained significantly higher in OH patients with concomitant AF (adjusted odds ratio (aOR): 5.0 (95% CI: 1.4 - 18.2), P = 0.014) in the multivariate logistic regression analysis (Table 2), similar rates of in-hospital mortality (aOR: 2.1 (95% CI: 0.9 - 5.0), P = 0.090), length of stay (0.2 days, P = 0.054), and total charges ($1,536, P = 0.074) were observed between the two groups.

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Table 2. Univariate and Multivariate Logistic Regression Analysis of Primary Outcomes of Patients With Orthostatic Hypotension and Concomitant Atrial Fibrillation

Earlier studies have reported an elevated risk of incident coronary events, stroke, AF, heart failure, and all-cause mortality among patients hospitalized for OH compared to non-OH hospitalizations [28, 29], although OH patients were examined independently of AF. However, not all studies support the notion that OH is predictive of adverse cardiovascular outcomes. The Last Evidences of Genetic Risk factors in the Aged (LEOGRA) Study, for instance, reported null associations between OH and cardiovascular events, including coronary events, heart failure, and arrhythmias after adjusting for confounders [30]. Comparably, Veronese et al showed that OH was only associated with higher non-cardiovascular disease (CVD) mortality but not with CVD mortality in older adults [31].

To our knowledge, this is the first study to examine the in-hospital outcomes of OH patients with pre-existing AF. We noted a disproportionately higher prevalence of several cardiovascular comorbidities such as congestive heart failure, history of coronary angioplasty or graft, COPD, chronic kidney disease, and hyperlipidemia in patients with concomitant diagnoses of OH and AF. Hence, we observed a higher mean comorbidity index in OH patients with AF. The higher prevalence of these comorbidities in patients hospitalized for OH is consistent with earlier observations in middle-aged [28] or older adults [32]. However, it is noteworthy that patients with contaminant diagnoses of OH and AF in our study cohort had a significantly lower prevalence of hypertension, nicotine use, and alcohol use. Prior studies suggest that pre-arrest comorbidity score may be a key determinant of survival after an in-hospital cardiac arrest [33-35]. A study by Mankoo et al noted that while higher blood pressure is generally considered detrimental to cardiovascular or cerebrovascular outcomes, chronic hypertension necessitates higher pressure for the cerebral autoregulation of blood pressure, thereby increasing the risk of ischemia at lower blood pressure [36]. As a result, they observed an inverse relationship between blood pressure and mortality outcomes with increased mortality risks among patients with pre-existing OH and AF presenting with a transient ischemic attack [36].

It is, therefore, plausible that the lower prevalence of hypertension in our cohort of OH patients with AF prevents further exacerbation of mortality outcomes.

An earlier analysis of the NIS database demonstrated that the in-hospital mortality in patients hospitalized with AF-related complications consistently declined between 2000 and 2010 but with increased inflation-adjusted hospitalization costs [37]. While our analysis only included NIS data from 2019, the length and cost of hospitalization in OH patients with AF remained comparable to OH patients without AF.

Although the presence of AF in OH patients did not further exacerbate the length and cost of in-hospital care or mortality risk, we observed an increased risk of cardiac arrest among patients with concomitant OH and AF. To the best of our knowledge, the association between OH and cardiac arrest in either hospital or out-of-hospital settings has not been reported yet. However, consistent with our findings, a Swedish retrospective cohort study reported a positive association between AF and the occurrence of in-hospital cardiac arrest, albeit they did not explicitly recruit patients with concomitant OH diagnosis [38].

Several mechanisms have been proposed which may explain the increased risk of cardiac arrest among patients with concomitant OH and AF. Autonomic nervous system dysregulation is thought to be central in the pathogenesis of OH [39], AF [40], and cardiac arrest [41]. Additionally, autonomic nervous system dysregulation may lead to arterial stiffness [42], a common pathophysiological change attributed to hypertension and aging. While arterial stiffness has been independently associated with OH [43] and AF [44], it may also potentially increase the risk of cardiac arrest [45]. It has been proposed that the development of OH is secondary to autonomic nervous system dysregulation [17], and the development of AF occurs further downstream in the CVD continuum [17, 46]. Therefore, it is very likely that the presence of AF in OH patients indicates the severity of autonomic nervous system dysregulation to increase the risk of cardiac arrest.

Furthermore, studies suggest that although OH and AF may have shared etiology, they may have an additive detrimental effect on the cardiovascular remodeling and risk of cardiac arrest. For instance, echocardiographic assessments in OH patients show greater left atrial volume and left ventricular (LV) mass [47], while left atrial size progressively increases in AF patients independent of changes in LV size or function [48]. Patients with OH may also experience an orthostatic surge in catecholamine levels leading to ectopic ventricular tachycardia, premature ventricular contractions, and episodes of non-sustained ventricular tachycardia [49, 50], which in turn may precipitate into sustained ventricular tachycardia, ventricular fibrillation, primary cardiomyopathy, tachycardia-induced cardiomyopathy, and sudden cardiac death [51]. The concomitant presence of AF in OH patients further exacerbates the risk of ventricular tachycardia and sudden cardiac death as normal atrioventricular (AV) node conduction during AF is known to cause ventricular tachycardia and impaired LV function [52-54]. Similarly, pooled data from the prospective Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) Study show a moderately increased risk of VTE in older adults with OH [55], while thromboembolic complications in AF patients have been extensively reported by Rubart et al [56]. A recent meta-analysis by Noumegni et al shows that over 35% of deaths among VTE patients were attributable to cardiovascular deaths [57].

At least two previous meta-analyses show that AF is associated with a two-fold increased risk of sudden cardiac death and exacerbated risks of all-cause and cardiovascular mortality [58, 59]. However, several large prospective studies, including the Rotterdam Study [60], the Malmo Preventive Project [3], and the ARIC study [61], and a meta-analysis [9], show that OH increases the risk of all-cause mortality but not sudden cardiac death. Hence it is plausible that AF may introduce the additional risk of sudden cardiac death in patients with OH, which may have contributed to the increased risk of cardiac arrest observed in our study cohort.

Our study has limitations. First, since many patients with OH are treated in an out-patient setting or do not seek medical treatment, our study population may have a selection bias. Moreover, there is a potential risk of selection bias by the non-random allocation of interventions, the risk of coding errors, and missing data that are inherent to any large database study. However, the NIS auditing process is well established, minimizing data inaccuracy issues. While unmeasured confounders may exist, they are expected to be evenly distributed among all groups. Second, the findings of this retrospective observational study are hypothesis-generating and need to be confirmed in future randomized control trials. Third, our findings are limited to in-hospital setting, and long-term cardiovascular and mortality outcomes of patients with OH and AF remain unclear. Finally, the pharmacological treatment history of OH patients, especially anti-hypertensive medication, may affect hospital outcomes [62], and we were unable to account for this due to database limitations.

The findings of this study showed that AF is an independent predictor for cardiac arrest but not in-hospital mortality in patients with OH. Given that the survival to discharge after an in-hospital cardiac arrest is typically around 20% [35], our findings on an increased risk of cardiac arrest but not mortality in OH patients with AF suggest the involvement of additional factors which warrant further investigation.

Acknowledgments

The authors would like to acknowledge the contributions of Dr. Daniel Larbi of Howard University Hospital, Washington, DC, USA, for his critical review of this manuscript.

Financial Disclosure

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of Interest

None to declare.

Informed Consent

Patient consent was waived because the study utilized de-identified publicly available data.

Author Contributions

Ahmed Brgdar: conceptualization, methodology, writing - original draft preparation, and investigation. John Gharbin: data curation, formal analysis, and software. Ahmad Awan: conceptualization and visualization. Richard Ogunti: formal analysis. Qasim Khurshid: investigation. Mayar Hamad: formal analysis and supervision. Prafulla Mehrotra: supervision. All authors have read and agreed to the published version of the manuscript

Data Availability

The data utilized in this study can be found online at www.hcups-us.ahrq.gov (accessed on February 2, 2022).

1. Freeman R, Abuzinadah AR, Gibbons C, Jones P, Miglis MG, Sinn DI. Orthostatic hypotension: JACC State-of-the-Art review. J Am Coll Cardiol. 2018;72(11):1294-1309.
   doi pubmed
2. Rose KM, Eigenbrodt ML, Biga RL, Couper DJ, Light KC, Sharrett AR, Heiss G. Orthostatic hypotension predicts mortality in middle-aged adults: the Atherosclerosis Risk In Communities (ARIC) Study. Circulation. 2006;114(7):630-636.
   doi pubmed
3. Fedorowski A, Stavenow L, Hedblad B, Berglund G, Nilsson PM, Melander O. Orthostatic hypotension predicts all-cause mortality and coronary events in middle-aged individuals (The Malmo Preventive Project). Eur Heart J. 2010;31(1):85-91.
   doi pubmed
4. Rutan GH, Hermanson B, Bild DE, Kittner SJ, LaBaw F, Tell GS. Orthostatic hypotension in older adults. the cardiovascular health study. CHS Collaborative Research Group. Hypertension. 1992;19(6 Pt 1):508-519.
   doi pubmed
5. Shibao C, Grijalva CG, Raj SR, Biaggioni I, Griffin MR. Orthostatic hypotension-related hospitalizations in the United States. Am J Med. 2007;120(11):975-980.
   doi pubmed
6. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, et al. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56-e528.
7. Colilla S, Crow A, Petkun W, Singer DE, Simon T, Liu X. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. Am J Cardiol. 2013;112(8):1142-1147.
   doi pubmed
8. Luukinen H, Koski K, Laippala P, Airaksinen KE. Orthostatic hypotension and the risk of myocardial infarction in the home-dwelling elderly. J Intern Med. 2004;255(4):486-493.
   doi pubmed
9. Ricci F, Fedorowski A, Radico F, Romanello M, Tatasciore A, Di Nicola M, Zimarino M, et al. Cardiovascular morbidity and mortality related to orthostatic hypotension: a meta-analysis of prospective observational studies. Eur Heart J. 2015;36(25):1609-1617.
   doi pubmed
10. Gaspar L, Kruzliak P, Komornikova A, Celecova Z, Krahulec B, Balaz D, Sabaka P, et al. Orthostatic hypotension in diabetic patients-10-year follow-up study. J Diabetes Complications. 2016;30(1):67-71.
    doi pubmed
11. Ricci F, De Caterina R, Fedorowski A. Orthostatic hypotension: epidemiology, prognosis, and treatment. J Am Coll Cardiol. 2015;66(7):848-860.
    doi pubmed
12. Min M, Shi T, Sun C, Liang M, Zhang Y, Bo G, Sun Y. Orthostatic hypotension and the risk of atrial fibrillation and other cardiovascular diseases: An updated meta-analysis of prospective cohort studies. J Clin Hypertens (Greenwich). 2019;21(8):1221-1227.
    doi pubmed
13. Fedorowski A, Hedblad B, Engstrom G, Gustav Smith J, Melander O. Orthostatic hypotension and long-term incidence of atrial fibrillation: the Malmo Preventive Project. J Intern Med. 2010;268(4):383-389.
    doi pubmed
14. Fagard RH, De Cort P. Orthostatic hypotension is a more robust predictor of cardiovascular events than nighttime reverse dipping in elderly. Hypertension. 2010;56(1):56-61.
    doi pubmed
15. Kornej J, Borschel CS, Benjamin EJ, Schnabel RB. Epidemiology of atrial fibrillation in the 21st century: novel methods and new insights. Circ Res. 2020;127(1):4-20.
    doi pubmed
16. Ko D, Preis SR, Lubitz SA, McManus DD, Vasan RS, Hamburg NM, Benjamin EJ, et al. Relation of orthostatic hypotension with new-onset atrial fibrillation (From the Framingham Heart Study). Am J Cardiol. 2018;121(5):596-601.
    doi pubmed
17. Prasitlumkum N, Kewcharoen J, Angsubhakorn N, Chongsathidkiet P, Rattanawong P. Orthostatic hypotension is associated with new-onset atrial fibrillation: Systemic review and meta-analysis. Indian Heart J. 2019;71(4):320-327.
    doi pubmed
18. Magnusson M, Holm H, Bachus E, Nilsson P, Leosdottir M, Melander O, Jujic A, et al. Orthostatic Hypotension and Cardiac Changes After Long-Term Follow-Up. Am J Hypertens. 2016;29(7):847-852.
    doi pubmed
19. McNicholas T, Tobin K, O'Callaghan S, Kenny RA. Is orthostatic hypotension more common in individuals with atrial fibrillation?-Findings from The Irish Longitudinal Study on Ageing (TILDA). Age Ageing. 2017;46(6):1006-1010.
    doi pubmed
20. Chen X, Kang Y, Xie D. Associated factors of orthostatic hypotension in the elderly essential hypertension patients and relationship between orthostatic hypotension and early renal damage. Ann Palliat Med. 2021;10(1):302-311.
    doi pubmed
21. Sanders NA, Ganguly JA, Jetter TL, Daccarett M, Wasmund SL, Brignole M, Hamdan MH. Atrial fibrillation: an independent risk factor for nonaccidental falls in older patients. Pacing Clin Electrophysiol. 2012;35(8):973-979.
    doi pubmed
22. Hung CY, Wu TJ, Wang KY, Huang JL, Loh el W, Chen YM, Lin CS, et al. Falls and atrial fibrillation in elderly patients. Acta Cardiol Sin. 2013;29(5):436-443.
23. Malik V, Gallagher C, Linz D, Elliott AD, Emami M, Kadhim K, Mishima R, et al. Atrial fibrillation is associated with syncope and falls in older adults: a systematic review and meta-analysis. Mayo Clin Proc. 2020;95(4):676-687.
    doi pubmed
24. Feldstein C, Weder AB. Orthostatic hypotension: a common, serious and underrecognized problem in hospitalized patients. J Am Soc Hypertens. 2012;6(1):27-39.
    doi pubmed
25. Otite FO, Khandelwal P, Chaturvedi S, Romano JG, Sacco RL, Malik AM. Increasing atrial fibrillation prevalence in acute ischemic stroke and TIA. Neurology. 2016;87(19):2034-2042.
    doi pubmed
26. Brgdar A, Yi J, Awan A, Taha M, Ogunti R, Gharbin J, Prafulla M, et al. Impact of obstructive sleep apnea on in-hospital outcomes in patients with atrial fibrillation: a retrospective analysis of the national inpatient sample. Cureus. 2021;13(12):e20770.
    doi pubmed
27. Austin SR, Wong YN, Uzzo RG, Beck JR, Egleston BL. Why summary comorbidity measures such as the charlson comorbidity index and elixhauser score work. Med Care. 2015;53(9):e65-72.
    doi pubmed
28. Yasa E, Ricci F, Magnusson M, Sutton R, Gallina S, Caterina R, Melander O, et al. Cardiovascular risk after hospitalisation for unexplained syncope and orthostatic hypotension. Heart. 2018;104(6):487-493.
    doi pubmed
29. Chou RH, Liu CJ, Chao TF, Chen SJ, Tuan TC, Chen TJ, Chen SA. Association between orthostatic hypotension, mortality, and cardiovascular disease in Asians. Int J Cardiol. 2015;195:40-44.
    doi pubmed
30. Casiglia E, Tikhonoff V, Caffi S, Boschetti G, Giordano N, Guidotti F, Segato F, et al. Orthostatic hypotension does not increase cardiovascular risk in the elderly at a population level. Am J Hypertens. 2014;27(1):81-88.
    doi pubmed
31. Veronese N, De Rui M, Bolzetta F, Zambon S, Corti MC, Baggio G, Toffanello ED, et al. Orthostatic Changes in Blood Pressure and Mortality in the Elderly: The Pro.V.A Study. Am J Hypertens. 2015;28(10):1248-1256.
    doi pubmed
32. Maule S, Milazzo V, Maule MM, Di Stefano C, Milan A, Veglio F. Mortality and prognosis in patients with neurogenic orthostatic hypotension. Funct Neurol. 2012;27(2):101-106.
33. Schluep M, Hoeks SE, Blans M, van den Bogaard B, Koopman-van Gemert A, Kuijs C, Hukshorn C, et al. Long-term survival and health-related quality of life after in-hospital cardiac arrest. Resuscitation. 2021;167:297-306.
    doi pubmed
34. Yakar MN, Yakar ND, Akkilic M, Karaoglu RO, Mingir T, Turgut N. Clinical outcomes of in-hospital cardiac arrest in a tertiary hospital and factors related to 28-day survival: A retrospective cohort study. Turk J Emerg Med. 2022;22(1):29-35.
    doi pubmed
35. Sandroni C, Nolan J, Cavallaro F, Antonelli M. In-hospital cardiac arrest: incidence, prognosis and possible measures to improve survival. Intensive Care Med. 2007;33(2):237-245.
    doi pubmed
36. Mankoo AS, Minhas JS, Coles B, Hussain ST, Khunti K, Robinson TG, Mistri AK, et al. Clinical relevance of orthostatic hypotension in patients with atrial fibrillation and suspected transient ischemic attack. High Blood Press Cardiovasc Prev. 2020;27(1):93-101.
    doi pubmed
37. Patel NJ, Deshmukh A, Pant S, Singh V, Patel N, Arora S, Shah N, et al. Contemporary trends of hospitalization for atrial fibrillation in the United States, 2000 through 2010: implications for healthcare planning. Circulation. 2014;129(23):2371-2379.
    doi pubmed
38. Ryden A, Engdahl J, Claesson A, Nordberg P, Ringh M, Hollenberg J, Djarv T. Is atrial fibrillation a risk factor for in-hospital cardiac arrest?: a Swedish retrospective cohort study. BMJ Open. 2018;8(6):e022092.
    doi pubmed
39. Mansoor GA. Orthostatic hypotension due to autonomic disorders in the hypertension clinic. Am J Hypertens. 2006;19(3):319-326.
    doi pubmed
40. Shen MJ, Zipes DP. Role of the autonomic nervous system in modulating cardiac arrhythmias. Circ Res. 2014;114(6):1004-1021.
    doi pubmed
41. Kim SW, Park CJ, Kim K, Kim YC. Cardiac arrest attributable to dysfunction of the autonomic nervous system after traumatic cervical spinal cord injury. Chin J Traumatol. 2017;20(2):118-121.
    doi pubmed
42. Milazzo V, Maule S, Di Stefano C, Tosello F, Totaro S, Veglio F, Milan A. Cardiac organ damage and arterial stiffness in autonomic failure: comparison with essential hypertension. Hypertension. 2015;66(6):1168-1175.
    doi pubmed
43. Mattace-Raso FU, van der Cammen TJ, Knetsch AM, van den Meiracker AH, Schalekamp MA, Hofman A, Witteman JC. Arterial stiffness as the candidate underlying mechanism for postural blood pressure changes and orthostatic hypotension in older adults: the Rotterdam Study. J Hypertens. 2006;24(2):339-344.
    doi pubmed
44. Lage JGB, Bortolotto AL, Scanavacca MI, Bortolotto LA, Darrieux F. Arterial stiffness and atrial fibrillation: A review. Clinics (Sao Paulo). 2022;77:100014.
    doi pubmed
45. Kim K, Kang MG, Koh JS, Park JR, Hwang SJ, Hwang JY, et al. Impact of arterial stiffness on diastolic function and outcomes of heart failure in patients presenting with acute myocardial infarction. Eur Heart J. 2020;41(Supplement_2):900.
    doi
46. Fedorowski A, Ricci F, Hamrefors V, Sandau KE, Hwan Chung T, Muldowney JAS, Gopinathannair R, et al. Orthostatic hypotension: management of a complex, but common, medical problem. Circ Arrhythm Electrophysiol. 2022;15(3):e010573.
    doi pubmed
47. Ali A, Holm H, Molvin J, Bachus E, Tasevska-Dinevska G, Fedorowski A, Jujic A, et al. Autonomic dysfunction is associated with cardiac remodelling in heart failure patients. ESC Heart Fail. 2018;5(1):46-52.
    doi pubmed
48. Suarez GS, Lampert S, Ravid S, Lown B. Changes in left atrial size in patients with lone atrial fibrillation. Clin Cardiol. 1991;14(8):652-656.
    doi pubmed
49. Kanjwal K, Jamal SM, McComb DW, Mughal M, Kichloo A. Paroxysmal orthostatic ventricular tachycardia in a patient with supine hypertension and orthostatic hypotension. J Investig Med High Impact Case Rep. 2020;8:2324709620958303.
    doi pubmed
50. Kanjwal K, George A, Figueredo VM, Grubb BP. Orthostatic hypotension: definition, diagnosis and management. J Cardiovasc Med (Hagerstown). 2015;16(2):75-81.
    doi pubmed
51. Sheldon SH, Gard JJ, Asirvatham SJ. Premature ventricular contractions and non-sustained ventricular tachycardia: association with sudden cardiac death, risk stratification, and management strategies. Indian Pacing Electrophysiol J. 2010;10(8):357-371.
52. Schmidt C, Kisselbach J, Schweizer PA, Katus HA, Thomas D. The pathology and treatment of cardiac arrhythmias: focus on atrial fibrillation. Vasc Health Risk Manag. 2011;7:193-202.
    doi pubmed
53. Friberg L. Ventricular arrhythmia and death among atrial fibrillation patients using anti-arrhythmic drugs. Am Heart J. 2018;205:118-127.
    doi pubmed
54. Gillis AM. Atrial fibrillation and ventricular arrhythmias: sex differences in electrophysiology, epidemiology, clinical presentation, and clinical outcomes. Circulation. 2017;135(6):593-608.
    doi pubmed
55. Bell EJ, Agarwal SK, Cushman M, Heckbert SR, Lutsey PL, Folsom AR. Orthostatic hypotension and risk of venous thromboembolism in 2 cohort studies. Am J Hypertens. 2016;29(5):634-640.
    doi pubmed
56. Rubart M, Zipes DP. NO hope for patients with atrial fibrillation. Circulation. 2002;106(22):2764-2766.
    doi pubmed
57. Noumegni SR, Grangereau T, Demir A, Bressollette L, Couturaud F, Hoffmann C. Cardiovascular mortality after venous thromboembolism: a meta-analysis of prospective cohort studies. Semin Thromb Hemost. 2022;48(4):481-489.
    doi pubmed
58. Odutayo A, Wong CX, Hsiao AJ, Hopewell S, Altman DG, Emdin CA. Atrial fibrillation and risks of cardiovascular disease, renal disease, and death: systematic review and meta-analysis. BMJ. 2016;354:i4482.
    doi pubmed
59. Rattanawong P, Upala S, Riangwiwat T, Jaruvongvanich V, Sanguankeo A, Vutthikraivit W, Chung EH. Atrial fibrillation is associated with sudden cardiac death: a systematic review and meta-analysis. J Interv Card Electrophysiol. 2018;51(2):91-104.
    doi pubmed
60. Verwoert GC, Mattace-Raso FU, Hofman A, Heeringa J, Stricker BH, Breteler MM, Witteman JC. Orthostatic hypotension and risk of cardiovascular disease in elderly people: the Rotterdam study. J Am Geriatr Soc. 2008;56(10):1816-1820.
    doi pubmed
61. Juraschek SP, Daya N, Appel LJ, Miller ER, 3rd, McEvoy JW, Matsushita K, Ballantyne CM, et al. Orthostatic hypotension and risk of clinical and subclinical cardiovascular disease in middle-aged adults. J Am Heart Assoc. 2018;7(10):e008884.
    doi pubmed
62. Benvenuto LJ, Krakoff LR. Morbidity and mortality of orthostatic hypotension: implications for management of cardiovascular disease. Am J Hypertens. 2011;24(2):135-144.
    doi pubmed

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