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Liver stiffness, fatty liver disease and atrial fibrillation in the Rotterdam study: Some issues

  • Wei-Chung Tsai
    Affiliations
    Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Ming-Lung Yu
    Affiliations
    Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Chia-Yen Dai
    Correspondence
    Corresponding author. Address: Department of Internal Medicine, Kaohsiung Medical University Hospital, 100, Shi-Tzyou 1st Road, Kaohsiung 807, Taiwan.
    Affiliations
    Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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      Linked Article

      • Liver stiffness not fatty liver disease is associated with atrial fibrillation: The Rotterdam study
        Journal of HepatologyVol. 77Issue 4
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          Fatty liver disease has become the most prevalent chronic liver disease globally and is linked to cardiovascular disease, including arrhythmias. However, there have been inconsistent reports on the association between fatty liver disease and atrial fibrillation, while the role of liver stiffness in this association remains unclear.
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      • Reply to: “Liver stiffness, fatty liver disease and atrial fibrillation in the Rotterdam study: Some issues”
        Journal of HepatologyVol. 77Issue 5
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          We thank Tsai et al. for their interest in our recent publication demonstrating that liver stiffness was associated with atrial fibrillation, whereas fatty liver disease was not.1,2 First, the authors mentioned in their letter the low sensitivity of a single 10-second ECG for the diagnosis of atrial fibrillation. We agree that the diagnostic accuracy of a 10-second ECG alone is generally poor. Therefore, in this study, we defined atrial fibrillation using a comprehensive approach comprising not only the 10-second 12-lead ECG at the study visit but also objective data obtained from other health care professionals by linking electronic medical records with our study database.
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      To the Editor:
      We read with great interest the recently published manuscript by van Kleef et al.
      • van Kleef L.A.
      • Lu Z.
      • Ikram M.A.
      • de Groot N.M.S.
      • Kavousi M.
      • de Knegt R.J.
      Liver stiffness, but not fattyliver disease, is associated with atrial fibrillation: the Rotterdam study.
      Based on the evaluation of atrial fibrillation (AF), hepatic steatosis and liver stiffness by 12-lead electrocardiogram (ECG), abdominal ultrasound and transient elastography, respectively, the authors concluded that liver stiffness but not non-alcoholic fatty liver disease (NAFLD) was significantly associated with atrial fibrillation. Having read the manuscript, we wanted to raise the following points:
      First, AF was diagnosed based on a 10-second 12-lead ECG performed at regular visits in the present study. Although the ECG was assessed by the modular ECG analysis system and validated by 2 research physicians, the accuracy of the prevalent rate of AF has to be reconsidered. From a recent comprehensive evaluation of AF, the sensitivity of AF diagnosis by a 10-second ECG was less than 5%.
      • Diederichsen S.Z.
      • Haugan K.J.
      • Kronborg C.
      • Graff C.
      • Højberg S.
      • Køber L.
      • et al.
      Comprehensive evaluation of rhythm monitoring strategies in screening for atrial fibrillation: snsights from aatients at risk monitored long term with an implantable loop recorder.
      Using a 7-day Holter ECG to diagnose AF might yield around 50% sensitivity for detecting AF. According to guideline recommendations,
      • Hindricks G.
      • Potpara T.
      • Dagres N.
      • Arbelo E.
      • Bax J.J.
      • Blomström-Lundqvist C.
      • et al.
      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.
      we suggest that the diagnosis of AF might be based on screening tools such as mobile/wearable devices, a single-lead ECG tracing of ≥30 seconds, long-term Holter and 1–2-week continuous ECG patches to prevent from the underestimation of AF prevalence. Furthermore, the prevalence of AF in those aged 65-69 years old was 3∼4.6% in the previous study.
      • Feinberg W.M.
      • Blackshear J.L.
      • Laupacis A.
      • Kronmal R.
      • Hart R.G.
      Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications.
      With the average age around 69.5-year-old, the prevalence of AF was reported at around 7% in this study which seems to be higher than the previous data. Not to mention that this prevalence may possibly be underestimated, as mentioned earlier. The high prevalence rate of AF in the Rotterdam Study deserves further study and clarification.
      Second, comorbidities such as obesity, thyroid disorder, valvular heart disease (mitral valve stenosis especially) and chronic obstructive pulmonary disease are well known to be the risk factors of AF,
      • Andrade J.
      • Khairy P.
      • Dobrev D.
      • Nattel S.
      The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms.
      which were not evaluated to clarify the relationship between liver disease and prevalent AF in the present study. It is a particular pity that the association between the available BMI data and AF was not studied.
      Third, the authors assessed liver stiffness by transient elastography in the present study. It would be interesting to know the results of evaluating steatosis by controlled attenuation parameter (CAP). Recently published EASL Clinical Practice Guidelines
      European Association for the Study of the Liver
      EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update.
      stated that there was insufficient evidence to recommend CAP as a first-line technique. Nevertheless, despite there being no consensual cut-offs, CAP values above 275 dB/m have high sensitivities and positive predictive value (>90%) for the identification of NAFLD. The addition of CAP data would solve several issues, enabling the: i) effective validation of the diagnosis of NAFLD by abdominal ultrasound; ii) assessment of the association between steatosis and AF; iii) assessment of the association between AF and non-alcoholic steatohepatitis (NASH) by the FAST (FibroScan-AST [aspartate aminotransferase]) score which has been reported to provide an efficient way to identify patients at risk of progressive NASH.
      • Newsome P.N.
      • Sasso M.
      • Deeks J.J.
      • Paredes A.
      • Boursier J.
      • Chan W.K.
      • et al.
      FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study.
      We believe that it will further add to the body of evidence regarding the association between AF and NAFLD/NASH.

      Financial support

      The authors received no financial support to produce this manuscript.

      Authors' contributions

      Chia-Yen Dai and Wei-Chung Tsai conceived of the presented idea. Chia-Yen Dai and Wei-Chung Tsai wrote the manuscript in consultation with Ming-Lung Yu. All authors discussed the results and contributed to the final manuscript.

      Conflicts of interest

      CY Dai: Consultant of Gilead, Abbvie; Speaker of Gilead, Abbvie and Merck. ML Yu: Research support (grant) from Gilead and Abbott; Consultant of Gilead, Abbvie and Merck; Speaker of Gilead, Abbvie and Merck.
      Please refer to the accompanying ICMJE disclosure forms for further details.

      Supplementary data

      The following are the supplementary data to this article:

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