. 2025 May;18(5):e012602.

doi: 10.1161/CIRCHEARTFAILURE.124.012602. Epub 2025 Apr 14.

Antecedent Flu-Like Illness and Onset of Idiopathic Dilated Cardiomyopathy: The DCM Precision Medicine Study

Hanyu Ni^{1

2}, Jinwen Cao^{1

2}, Daniel D Kinnamon^{1

2}, Elizabeth Jordan^{1

3}, Garrie J Haas^{2

3}, Mark Hofmeyer^{2

4}, Evan P Kransdorf⁵, Jamie Diamond⁶, Anjali Owens^{3

4

7}, Brian Lowes^{4

8}, Douglas Stoller⁸, W H Wilson Tang^{5

6

9}, Mark H Drazner¹⁰, Palak Shah¹¹, Jane E Wilcox¹², Stuart D Katz¹³, Javier Jimenez^{7

8

14}, Supriya Shore¹⁵, Daniel P Judge^{9

10

16}, Jonathan O Mead^{1

2}, Jason Cowan^{1

2}, Patricia K Parker^{1

2}, Gordon S Huggins¹⁷, Ray E Hershberger^{1

2

3}

Affiliations

¹ Division of Human Genetics, Department of Internal Medicine (H.N., J. Cao, D.D.K., E.J., J.O.M., J. Cowan, P.K.P., R.E.H.), The Ohio State University, Columbus.
² Davis Heart and Lung Research Institute (H.N., J. Cao, D.D.K., E.J., G.J.H., J.M., J. Cowan, P.P., R.E.H.), The Ohio State University, Columbus.
³ Division of Cardiovascular Medicine, Department of Internal Medicine (G.J.H., R.E.H.), The Ohio State University, Columbus.
⁴ MedStar Health Research Institute, MedStar Washington Hospital Center, Washington, DC (M.H.).
⁵ Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA (E.P.K.).
⁶ Department of Medicine, Emory University School of Medicine, Atlanta, GA (J.D.).
⁷ Division of Cardiology, Center for Inherited Cardiovascular Disease, Perelman School of Medicine, University of Pennsylvania, Philadelphia (A.O.).
⁸ Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha (B.L., D.S.).
⁹ Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Columbus, OH (W.H.W.T.).
¹⁰ Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (M.H.D.).
¹¹ Inova Heart and Vascular Institute, Falls Church, VA (P.S.).
¹² Cardiology Division, Northwestern University Feinberg School of Medicine, Chicago, IL (J.E.W.).
¹³ Department of Medicine, New York University Langone Medical Center. (S.D.K.).
¹⁴ Miami Cardiac & Vascular Institute, Baptist Health South, FL (J.J.).
¹⁵ University of Michigan Medical Center, Ann Arbor (S.S.).
¹⁶ Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston (D.P.J.).
¹⁷ Cardiology Division, Tufts Medical Center and Tufts University School of Medicine, Boston, MA (G.S.H).

PMID: 40392911
PMCID: PMC12094084 (available on 2026-05-01)
DOI: 10.1161/CIRCHEARTFAILURE.124.012602

Antecedent Flu-Like Illness and Onset of Idiopathic Dilated Cardiomyopathy: The DCM Precision Medicine Study

Hanyu Ni et al. Circ Heart Fail. 2025 May.

. 2025 May;18(5):e012602.

doi: 10.1161/CIRCHEARTFAILURE.124.012602. Epub 2025 Apr 14.

Authors

Affiliations

¹ Division of Human Genetics, Department of Internal Medicine (H.N., J. Cao, D.D.K., E.J., J.O.M., J. Cowan, P.K.P., R.E.H.), The Ohio State University, Columbus.
² Davis Heart and Lung Research Institute (H.N., J. Cao, D.D.K., E.J., G.J.H., J.M., J. Cowan, P.P., R.E.H.), The Ohio State University, Columbus.
³ Division of Cardiovascular Medicine, Department of Internal Medicine (G.J.H., R.E.H.), The Ohio State University, Columbus.
⁴ MedStar Health Research Institute, MedStar Washington Hospital Center, Washington, DC (M.H.).
⁵ Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA (E.P.K.).
⁶ Department of Medicine, Emory University School of Medicine, Atlanta, GA (J.D.).
⁷ Division of Cardiology, Center for Inherited Cardiovascular Disease, Perelman School of Medicine, University of Pennsylvania, Philadelphia (A.O.).
⁸ Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha (B.L., D.S.).
⁹ Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Columbus, OH (W.H.W.T.).
¹⁰ Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (M.H.D.).
¹¹ Inova Heart and Vascular Institute, Falls Church, VA (P.S.).
¹² Cardiology Division, Northwestern University Feinberg School of Medicine, Chicago, IL (J.E.W.).
¹³ Department of Medicine, New York University Langone Medical Center. (S.D.K.).
¹⁴ Miami Cardiac & Vascular Institute, Baptist Health South, FL (J.J.).
¹⁵ University of Michigan Medical Center, Ann Arbor (S.S.).
¹⁶ Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston (D.P.J.).
¹⁷ Cardiology Division, Tufts Medical Center and Tufts University School of Medicine, Boston, MA (G.S.H).

PMID: 40392911
PMCID: PMC12094084 (available on 2026-05-01)
DOI: 10.1161/CIRCHEARTFAILURE.124.012602

Abstract

Background: Previous studies have speculated that a viral infection may act as a trigger in the development of idiopathic dilated cardiomyopathy (DCM) among individuals genetically at risk. This study aims to describe the frequency of patients with DCM who reported experiencing symptoms of flu-like illness before their DCM diagnosis and to examine if this experience modified the association between genetics and DCM.

Methods: We analyzed data from the family-based cross-sectional DCM Study conducted between 2016 and 2021. Self-reported symptoms of flu-like illness proximal to DCM diagnosis were obtained from patient interviews. Exome sequencing identified rare variants (pathogenic, likely pathogenic, or variant of uncertain significance) in DCM genes. In a case-only design, logistic mixed models were used to examine if flu-like illness modified the effect of these rare variants on DCM risk. Firth logistic regression was used to examine if flu-like illness modified the effect of each of 13 400 141 common autosomal variants (minor allele frequency ≥1%) on DCM risk.

Results: Of 1164 patients with DCM, 30.2% reported symptoms of flu-like illness proximal to DCM diagnosis. The percentage of patients with antecedent flu-like illness by variant classification was 30.0% for pathogenic/likely pathogenic, 29.6% for variant of uncertain significance only, and 30.0% for no pathogenic/likely pathogenic/variant of uncertain significance. Antecedent flu-like illness was not found to modify the effect of carrying any pathogenic, likely pathogenic, or variant of uncertain significance variants on DCM risk (interaction relative risk, 0.9 [95% CI, 0.7-1.3]). However, significant modification of the effect of rs2102158 (3q24) by antecedent flu-like illness (P=2.74×10^-8) was identified by case-only genome-wide association study.

Conclusions: Approximately one-third of patients with DCM experienced flu-like illness symptoms before DCM diagnosis. We did not find evidence that a flu-like illness modified the effect of rare variants on DCM risk; however, our genome-wide association study analysis suggested that flu-like illness may modify the effect of a common variant on DCM risk.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037632.

Keywords: cardiomyopathy, dilated; gene-environmental interaction; odds ratio; precision medicine; viral diseases.

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Conflict of interest statement

None.

References

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Antecedent Flu-Like Illness and Onset of Idiopathic Dilated Cardiomyopathy: The DCM Precision Medicine Study

Affiliations

Antecedent Flu-Like Illness and Onset of Idiopathic Dilated Cardiomyopathy: The DCM Precision Medicine Study

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

Supplementary concepts

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical