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Clinical and genetic predictors of cardiac dysfunction assessed by echocardiography in patients with hereditary hemochromatosis

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Abstract

Purpose

Hereditary hemochromatosis (HH) may cause iron deposition in cardiac tissue. We aimed to describe the echocardiographic findings in patients with HH and identify risk factors for cardiac dysfunction.

Methods

In this retrospective study, we included patients with HH who underwent transthoracic echocardiography at our tertiary care center between August 2000 and July 2022. We defined three primary outcomes for cardiac dysfunction: 1) left ventricular ejection fraction (LVEF) < 55%, 2) ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e’) > 15, and 3) global longitudinal strain (GLS) < 18. Multivariable logistic regression was utilized to identify predictors of cardiac dysfunction.

Results

582 patients (median age 57 years, 61.2% male) were included. The frequency of LVEF < 55%, E/e’ > 15 and GLS < 18 was 9.0% (52/580), 9.6% (51/534) and 20.2% (25/124), respectively. In multivariable analysis, non-White race, age, and hypertension were associated with E/e’ > 15. No specific HFE genetic mutation was associated with LVEF < 55%. A history of myocardial infarction was strongly associated with both LVEF < 55% and E/e’ > 15. In patients with LVEF ≥ 55%, the C282Y/H63D genetic mutation was associated with reduced likelihood of E/e’ > 15, p = 0.024. Patients with C282Y/H63D had a higher frequency of myocardial infarction. Smoking and alcohol use were significantly associated with GLS < 18 in unadjusted analysis.

Conclusion

We found the traditional risk factors of male sex, and history of myocardial infarction or heart failure, were associated with a reduced LVEF, irrespective of the underlying HFE genetic mutation. Patients with a C282Y/H63D genetic mutation had a higher frequency of myocardial infarction, yet this mutation was associated with reduced odds of diastolic dysfunction compared to other genetic mutations in patients with a normal LVEF.

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Acknowledgements

The authors declare no acknowledgements.

Funding

The authors declare that funding for statistical analysis was provided by the Division of Community Internal Medicine at Mayo Clinic Florida, Jacksonville, FL 32224, USA.

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Authors and Affiliations

  1. Division of Community Internal Medicine, Mayo Clinic, Jacksonville, FL, 32224, USA

    Pedro Cortés & Fernando F. Stancampiano

  2. Clinical Research Unit, Mayo Clinic, Jacksonville, FL, 32224, USA

    Abdelhadi A. Elsayed

  3. University of Central Florida, Orlando, FL, 32816, USA

    Fernanda M. Barusco

  4. Division of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, 32224, USA

    Brian P. Shapiro

  5. Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA

    Yan Bi & William C. Palmer

  6. Division of Clinical Trials and Biostatistics, Mayo Clinic, Jacksonville, FL, 32224, USA

    Michael G. Heckman & Zhongwei Peng

  7. Division of Infectious Diseases, Mayo Clinic, Jacksonville, FL, 32224, USA

    Prakash Kempaiah

Authors
  1. Pedro Cortés
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  2. Abdelhadi A. Elsayed
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  10. William C. Palmer
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Contributions

William C. Palmer, MD, Brian P. Shapiro, MD, Yan Bi, MD, PhD, Prakash Kempaiah and Fernando F. Stancampiano, MD contributed to the study conception and design. Data collection was performed by Abdelhadi A. Elsayed and Fernando M. Barusco. Material preparation, and analysis were performed by Michael G. Heckman, MS and Zhongwei Peng, MS. The first draft of the manuscript was written by Pedro Cortés, MD and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to William C. Palmer.

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The authors declare no competing interests.

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This is an observational study. The Institutional Review Board at Mayo Clinic has confirmed that no ethical approval is required.

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A waiver of informed consent was approved by the Institutional Review Board at Mayo Clinic.

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Cortés, P., Elsayed, A.A., Stancampiano, F.F. et al. Clinical and genetic predictors of cardiac dysfunction assessed by echocardiography in patients with hereditary hemochromatosis. Int J Cardiovasc Imaging 40, 45–53 (2024). https://doi.org/10.1007/s10554-023-02973-0

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