Subscribe to RSS
Visit-to-Visit Heart Rate Variability in the Prediction of Clinical Outcomes of Patients with Atrial FibrillationFunding This study was funded by the Health Systems Research Institute (HSRI) (grant no. 59–053), and grants from the Heart Association of Thailand under the Royal Patronage of H.M. the King. None of the aforementioned funding sources influenced any aspect of this study or the decision of the authors to submit this manuscript for publication.
Background Visit-to-visit heart rate variability (VVV-HR) has been associated with adverse cardiovascular outcomes. We aimed to determine the predictive value of VVV-HR for adverse clinical outcomes in patients with nonvalvular atrial fibrillation (AF).
Methods We used data from a prospective multicenter AF registry of 27 hospitals in Thailand during 2014 to 2017. After the baseline visit, patients were followed up every 6 months until 3 years. VVV-HR was calculated from the standard deviation of heart rate data from baseline visit and every follow-up visit. VVV-HR was categorized into four groups according to the quartiles. Clinical outcomes were all-cause death, ischemic stroke/systemic embolism (SE), and heart failure. Cox proportional hazard models were used for multivariable analysis.
Results There were a total of 3,174 patients (mean age: 67.7 years; 41.8% female). The incidence rates of all-cause death, ischemic stroke/SE, and heart failure were 3.10 (2.74–3.49), 1.42 (1.18–1.69), and 2.09 (1.80–2.42) per 100 person-years respectively. The average heart rate was 77.8 ± 11.0 bpm and the average of standard deviation of heart rate was 11.0 ± 5.9 bpm. VVV-HR Q4 was an independent predictor of all-cause death, ischemic stroke/SE, and heart failure with adjusted hazard ratios of 1.45 (95% confidence interval: 1.07–1.98), 2.02 (1.24–3.29), and 2.63 (1.75–3.96), respectively. VVV-HR still remained a significant predictor of clinical outcomes when analyzed based on coefficient of variation and variability independent of mean.
Conclusion VVV-HR is an independent predictor for adverse clinical outcomes in patients with AF. A J-curve appearance was demonstrated for the effect of VVV-HR on all-cause death.
Keywordsvisit-to-visit heart rate variability - heart rate - atrial fibrillation - clinical outcomes
Data Availability Statement
The dataset that was used to support the results and conclusion of this study is included within the manuscript. Additional data are available upon contacting the corresponding author with reasonable request.
All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.
The review process for this paper was fully handled by Christian Weber, Editor in Chief.
Received: 31 December 2022
Accepted: 31 March 2023
Article published online:
28 April 2023
© 2023. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
- 1 Lippi G, Sanchis-Gomar F, Cervellin G. Global epidemiology of atrial fibrillation: an increasing epidemic and public health challenge. Int J Stroke 2021; 16 (02) 217-221
- 2 Burdett P, Lip GYH. Atrial fibrillation in the United Kingdom: predicting costs of an emerging epidemic recognising and forecasting the cost drivers of atrial fibrillation-related costs. Eur Heart J Qual Care Clin Outcomes 2022; 8 (02) 187-194
- 3 Ding WY, Rivera-Caravaca JM, Marin F, Torp-Pedersen C, Roldán V, Lip GYH. Prediction of residual stroke risk in anticoagulated patients with atrial fibrillation: mCARS. J Clin Med 2021; 10 (15) 3357
- 4 Potpara TS, Lip GYH, Blomstrom-Lundqvist C. et al. The 4S-AF Scheme (Stroke Risk; Symptoms; Severity of Burden; Substrate): a novel approach to in-depth characterization (rather than classification) of atrial fibrillation. Thromb Haemost 2021; 121 (03) 270-278
- 5 Lip GYH. The ABC pathway: an integrated approach to improve AF management. Nat Rev Cardiol 2017; 14 (11) 627-628
- 6 Hindricks G, Potpara T, Dagres N. et al; ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42 (05) 373-498
- 7 Lip GYH, Banerjee A, Boriani G. et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest 2018; 154 (05) 1121-1201
- 8 Chao TF, Joung B, Takahashi Y. et al. 2021 Focused update consensus guidelines of the Asia Pacific Heart Rhythm Society on stroke prevention in atrial fibrillation: executive summary. Thromb Haemost 2022; 122 (01) 20-47
- 9 Romiti GF, Pastori D, Rivera-Caravaca JM. et al. Adherence to the ‘Atrial Fibrillation Better Care’ pathway in patients with atrial fibrillation: impact on clinical outcomes-a systematic review and meta-analysis of 285,000 patients. Thromb Haemost 2021; 122 (03) 406-414
- 10 Schnabel RB, Marinelli EA, Arbelo E. et al. Early diagnosis and better rhythm management to improve outcomes in patients with atrial fibrillation: the 8th AFNET/EHRA consensus conference. Europace 2023; 25 (01) 6-27
- 11 Piccini JP, Fauchier L. Rhythm control in atrial fibrillation. Lancet 2016; 388 (10046): 829-840
- 12 Van Gelder IC, Groenveld HF, Crijns HJ. et al; RACE II Investigators. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med 2010; 362 (15) 1363-1373
- 13 Benetos A, Thomas F, Bean K, Albaladejo P, Palatini P, Guize L. Resting heart rate in older people: a predictor of survival to age 85. J Am Geriatr Soc 2003; 51 (02) 284-285
- 14 Hutcheon JA, Chiolero A, Hanley JA. Random measurement error and regression dilution bias. BMJ 2010; 340: c2289
- 15 Zeng R, Wang Z, Cheng W, Yang K. Visit-to-visit heart rate variability is positively associated with the risk of adverse cardiovascular outcomes. Front Cardiovasc Med 2022; 9: 850223
- 16 Lang CC, Gupta S, Kalra P. et al. Elevated heart rate and cardiovascular outcomes in patients with coronary artery disease: clinical evidence and pathophysiological mechanisms. Atherosclerosis 2010; 212 (01) 1-8
- 17 Zhang S, Zhao M, Sun Y. et al. Frequency of visit-to-visit variability of resting heart rate and the risk of new-onset atrial fibrillation in the general population. Am J Cardiol 2021; 155: 45-51
- 18 Pagonas N, Schmidt S, Eysel J. et al. Impact of atrial fibrillation on the accuracy of oscillometric blood pressure monitoring. Hypertension 2013; 62 (03) 579-584
- 19 Hicks KA, Tcheng JE, Bozkurt B. et al. 2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards). J Am Coll Cardiol 2015; 66 (04) 403-469
- 20 Austin PC, Lee DS, Fine JP. Introduction to the analysis of survival data in the presence of competing risks. Circulation 2016; 133 (06) 601-609
- 21 Gauthier J, Wu QV, Gooley TA. Cubic splines to model relationships between continuous variables and outcomes: a guide for clinicians. Bone Marrow Transplant 2020; 55 (04) 675-680
- 22 Bassand JP, Accetta G, Camm AJ. et al; GARFIELD-AF Investigators. Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF. Eur Heart J 2016; 37 (38) 2882-2889
- 23 Ogawa H, Hamatani Y, Doi K. et al; Fushimi AF Registry Investigators. Sex-related differences in the clinical events of patients with atrial fibrillation - the Fushimi AF Registry. Circ J 2017; 81 (10) 1403-1410
- 24 Proietti M, Lip GYH, Laroche C. et al; ESC-EORP Atrial Fibrillation General Long-Term Registry Investigators Group. Relation of outcomes to ABC (Atrial Fibrillation Better Care) pathway adherent care in European patients with atrial fibrillation: an analysis from the ESC-EHRA EORP Atrial Fibrillation General Long-Term (AFGen LT) Registry. Europace 2021; 23 (02) 174-183
- 25 Guo Y, Lane DA, Wang L. et al; mAF-App II Trial Investigators. Mobile health technology to improve care for patients with atrial fibrillation. J Am Coll Cardiol 2020; 75 (13) 1523-1534
- 26 Rouch L, Cestac P, Sallerin B. et al; S.AGES investigators, AGES Cohort. Visit-to-visit blood pressure variability is associated with cognitive decline and incident dementia: the S.AGES cohort. Hypertension 2020; 76 (04) 1280-1288
- 27 January CT, Wann LS, Calkins H. et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74 (01) 104-132
- 28 Chao TF, Liu CJ, Tuan TC. et al. Rate-control treatment and mortality in atrial fibrillation. Circulation 2015; 132 (17) 1604-1612
- 29 Vamos M, Erath JW, Hohnloser SH. Digoxin-associated mortality: a systematic review and meta-analysis of the literature. Eur Heart J 2015; 36 (28) 1831-1838
- 30 Holmqvist F, Kim S, Steinberg BA. et al; ORBIT-AF Investigators. Heart rate is associated with progression of atrial fibrillation, independent of rhythm. Heart 2015; 101 (11) 894-899
- 31 Khan AA, Junejo RT, Thomas GN, Fisher JP, Lip GYH. Heart rate variability in patients with atrial fibrillation and hypertension. Eur J Clin Invest 2021; 51 (01) e13361
- 32 Vazir A, Claggett B, Jhund P. et al. Prognostic importance of temporal changes in resting heart rate in heart failure patients: an analysis of the CHARM program. Eur Heart J 2015; 36 (11) 669-675
- 33 Böhm M, Robertson M, Borer J. et al. Effect of visit-to-visit variation of heart rate and systolic blood pressure on outcomes in chronic systolic heart failure: results from the Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial (SHIFT) trial. J Am Heart Assoc 2016; 5 (02) e002160
- 34 Khan AA, Lip GYH, Shantsila A. Heart rate variability in atrial fibrillation: the balance between sympathetic and parasympathetic nervous system. Eur J Clin Invest 2019; 49 (11) e13174
- 35 Kronish IM, Lynch AI, Oparil S. et al. The association between antihypertensive medication nonadherence and visit-to-visit variability of blood pressure: findings from the antihypertensive and lipid-lowering treatment to prevent heart attack trial. Hypertension 2016; 68 (01) 39-45
- 36 Proietti M, Romiti GF, Olshansky B, Lip GYH. Systolic blood pressure visit-to-visit variability and major adverse outcomes in atrial fibrillation: the AFFIRM study (Atrial Fibrillation Follow-Up Investigation of Rhythm Management). Hypertension 2017; 70 (05) 949-958