Caring for Families After a Dilated Cardiomyopathy Diagnosis: Practical Guidance from the 2025 Clinical Consensus

Introduction and Context

Dilated cardiomyopathy (DCM) is a common cause of heart failure and sudden cardiac death characterized by left ventricular (LV) dilatation and reduced systolic function (LV ejection fraction <50%) not explained by abnormal loading conditions or coronary artery disease. Family clustering is frequent: genetic causes are identified in a substantial minority of patients, and early identification of disease or risk in relatives can change management and outcomes.

The 2025 clinical consensus “Clinical care of family members of patients with dilated cardiomyopathy” (Verdonschot et al., Eur Heart J. 2025) synthesizes contemporary evidence and expert opinion to provide a practical framework for assessing and managing family members after a proband with DCM is identified. This short guide summarizes the consensus core recommendations, explains why the statement was issued, highlights practical actions for clinicians, and offers an illustrative patient vignette.

Why this consensus matters now
– Genetic testing technology, gene curation efforts, and variant interpretation frameworks have matured (ClinGen, Gene Curation Coalition, ACMG/AMP standards), enabling more reliable identification of pathogenic variants that truly cause DCM.
– Greater recognition that many relatives are phenotype-negative yet genotype-positive—and may benefit from targeted surveillance—has outpaced consistent clinical pathways.
– Emerging early-intervention data and expanding options for family planning make accurate risk stratification more clinically relevant.

This consensus aims to (1) standardize how clinicians estimate a family member’s a priori risk, (2) clarify when and how to offer genetic testing and cardiac screening, and (3) propose practical follow-up strategies that integrate genotype and phenotype.

New Guideline Highlights

Major themes and takeaways
– Genetic testing of every patient who meets DCM diagnostic criteria is recommended (facilitates cascade testing and clarifies risk for relatives).
– A three-phase approach simplifies a priori risk assessment for relatives: (1) determine proband genetic status; (2) determine the relative’s genetic status; (3) determine whether disease appears familial when genetic data are absent or inconclusive.
– Targeted (cascade) genetic testing of first-degree relatives is recommended when a pathogenic or likely pathogenic (P/LP) variant is identified in the proband; pre- and post-test genetic counseling is essential.
– Variants of uncertain significance (VUS) should not trigger routine predictive testing of asymptomatic relatives; segregation studies can be valuable but often limited by family size and must be coordinated with the diagnostic laboratory.
– Cardiac screening (history, ECG, echocardiography; consider CMR and ambulatory rhythm monitoring) is recommended for all first-degree relatives, but the intensity and frequency should be individualized based on combined genetic and clinical information.

Key clinical tools emphasized
– Confirm that any P/LP variant reported in the proband sits in a gene with robust gene–disease evidence (use ClinGen / Gene Curation Coalition resources).
– Use the presence/absence of a familial P/LP variant plus phenotype status to classify relatives into categories that guide surveillance frequency and additional testing.
– Recognize and monitor minor, non-diagnostic abnormalities (e.g., new conduction disease, non-ischaemic late gadolinium enhancement, mild LV dilation or borderline EF), which may represent early disease.

Fig 1. Characterizing the genetic status of a family with dilated cardiomyopathy. The dashed line at the variant of unknown significance indicates that after cardiac screening and segregation, the variant of unknown significance could be reclassified towards (likely) pathogenic. The dashed line at refrain indicates that family members that refrain from genetic testing for the familial variant should be considered as genotype-positive family members until they are tested for the familial variant. The box with the solid line contains family members with a (mild) phenotype whose follow-up will deviate from unaffected family members, as they will be followed based on their phenotype. The box with the dashed line indicates risk categories of family member without phenotype; see Figure 2 for the follow-up of these individuals. *If the proband has a variant of unknown significance or the genotype is unknown, cardiac screening of the first-degree family members is advised before potential genetic testing. When a (minor) phenotype is detected (Table 1), genetic testing of the affected family member can be considered. **Definition of familial disease: two or more individuals (first- or second-degree family members) in a single family who are diagnosed with dilated cardiomyopathy, or a proband with dilated cardiomyopathy and a first-degree family member with autopsy-proven dilated cardiomyopathy or sudden death below the age of 50 years

Updated Recommendations and Key Changes

What is new or reinforced compared with prior guidance
– Stronger emphasis on gene curation: not all genes previously linked to DCM have equivalent evidence. The consensus explicitly recommends verifying gene–disease validity (ClinGen/Gene Curation Coalition) before acting on a variant.
– Clearer operational approach to VUS: routine predictive testing of asymptomatic relatives for VUS is discouraged; instead, focus on phenotype-driven testing and coordinated segregation analysis where useful.
– Formal three-phase risk assessment structure (proband genotype → relative genotype → familial phenotype) to drive downstream decisions and personalize surveillance.
– Integration of cardiac imaging (including CMR) and ECG findings with genotype to refine risk and personalize screening intensity.

Evidence driving these updates
– Molecular diagnostic yield in DCM has been heterogeneous across panels and time; better-curated gene lists and consistent variant interpretation have reduced false-positive attribution of causality.
– Data showing that many genotype-positive relatives remain phenotype-negative for years but still carry elevated lifetime risk, supporting targeted surveillance rather than a one-size-fits-all approach.

Fig 2. Screening and long-term follow-up of family members based on their a priori risk to develop dilated cardiomyopathy. Clinical screening is indicated for every first-degree family member of a patient with dilated cardiomyopathy according to the 2023 European Society of Cardiology guidelines on the management of cardiomyopathies¹. ^Consider termination of periodic screening at the age of 50 years based on clinical information of the proband (e.g. presence of other non-ischaemic aetiologies of dilated cardiomyopathy and age of diagnosis in proband) in an individual with normal cardiac investigations.

Topic-by-Topic Recommendations

Diagnostic criteria (consensus definition)
– DCM: LV dilatation (dimensions or volumes > 2 z-scores above population mean corrected for body size/sex/age) plus systolic dysfunction (LVEF < 50%), unexplained by abnormal loading conditions or coronary disease (Verdonschot et al., 2025).

Genetic testing of the proband
– Offer comprehensive genetic testing to all patients meeting DCM criteria (this enables cascade testing and family risk stratification).
– When a P/LP variant is found, verify that the gene has acceptable clinical validity for DCM using curated resources (ClinGen; thegencc.org).
– If testing is not performed or returns negative, document this and proceed to thorough family phenotyping; absence of identified variant does not exclude familial disease.

Family (cascade) testing strategy
– If the proband harbors a P/LP variant in a gene with established disease association: offer targeted predictive testing to first-degree relatives after pre-test genetic counseling. Discuss implications for surveillance, reproductive risk, and cascade testing to children.
– If the proband’s result is genotype-negative or a VUS was identified: do not offer predictive testing to asymptomatic relatives based solely on a VUS. If a family member is affected with DCM, consider full panel testing (including genes with strong evidence) in that affected relative to identify an actionable variant.
– Use segregation studies of VUS only as part of a systematic effort with the diagnostic lab; realize that meaningful reclassification often needs multiple informative meioses.

Cardiac screening of relatives
– Baseline screening for first-degree relatives (regardless of genetic status): focused history, physical exam, 12-lead ECG, and transthoracic echocardiography. Consider ambulatory rhythm monitoring (e.g., 24–48h Holter) and CMR where available and clinically indicated.
– Tailor surveillance frequency according to a priori risk:
– Genotype-positive, phenotype-negative relatives: more intensive surveillance (typically clinical review, ECG, and echocardiogram at regular intervals — for many centers every 1–3 years; consider earlier or more frequent follow-up if minor abnormalities or arrhythmias develop). CMR should be considered for baseline assessment or if echocardiography/ECG are abnormal.
– Genotype-negative relatives in a family with a known familial P/LP variant: if testing proves negative for the family variant, routine cardiac surveillance beyond population screening is usually unnecessary, but clinicians should remain vigilant for new symptoms.
– Probands without an identified P/LP variant: if family history fulfills criteria for familial disease (two or more relatives with DCM, or DCM in proband plus sudden cardiac death 200 ms), unexplained high burden of ventricular ectopy (>100 PVCs/h), non-sustained VT, atrial fibrillation/flutter, low limb-lead voltages, T-wave inversion in ≥2 contiguous leads.
– Imaging: segmental LV wall-motion abnormalities (not explained by conduction), LV dilatation (>2 SD for BSA/sex), mildly reduced EF, non-ischaemic late gadolinium enhancement on CMR.

Genetic counseling
– Pre- and post-test genetic counseling by trained personnel is recommended for all relatives considering predictive testing. Counseling should cover potential outcomes, implications for insurance and employment where applicable, reproductive options (e.g., prenatal or preimplantation genetic testing), and psychosocial impact.

Special populations and considerations
– Children and adolescents: the consensus highlights the need for pediatric cardiology/genetics collaboration. If a familial P/LP variant is known, discuss timing of testing and surveillance individually (age of onset in family, penetrance, and psychological considerations). When testing is deferred, clinical surveillance remains important.
– Deceased proband: counsel close relatives (including second-degree relatives) and consider genetic testing of stored tissue if available; when not possible, evaluate relatives clinically and consider wider panel testing in any affected relative.

Follow-up, re-evaluation, and data stewardship
– VUS reclassification: encourage care in centers with processes for regular reinterpretation of VUS and communication to families when reclassification occurs.
– Maintain curated familial records and pedigrees; recontact families when new genotype–phenotype data or reclassifications arise.

Expert Commentary and Insights

Committee perspective
– The expert panel emphasizes pragmatism: genetic data are powerful but must be interpreted in a clinical-genetic context. The stepwise three-phase assessment provides a structured way to integrate heterogeneous information.
– The group stressed gene curation: misattributing pathogenicity to poorly validated genes can lead to unnecessary anxiety and inappropriate interventions.

Controversies and areas of active research
– Optimal surveillance intervals and the role of routine CMR in asymptomatic genotype-positive relatives remain debated; the consensus endorses individualized approaches while noting that research is ongoing.
– The clinical value of early therapeutics for genotype-positive, phenotype-negative relatives is an emerging field. Trials testing whether early heart failure therapies can delay or prevent phenotypic emergence are needed.

Future trends
– Better polygenic and environmental risk models may further refine which relatives need closer follow-up.
– Expanded population-level sequencing and improved variant databases will reduce the fraction of VUS and refine penetrance estimates.

Practical Implications

How clinicians can apply the consensus today
– Ensure genetic testing is offered to all probands meeting DCM criteria and document results clearly in the medical record and a pedigree.
– If a P/LP variant is found, arrange pre-test genetic counseling and offer targeted predictive testing to first-degree relatives, with coordinated cardiac screening.
– If a VUS is reported, avoid cascade testing of asymptomatic relatives on that variant alone and seek laboratory guidance on the potential value of family segregation testing.
– Implement a structured follow-up plan that integrates genotype and phenotype: more frequent visits and imaging for genotype-positive relatives; reassurance and discharge from intensive surveillance when a relative tests negative for a familial P/LP variant.
– Develop local pathways to re-evaluate VUS and re-contact families when variant classifications change.

Practical case vignette
John is a 42-year-old man recently hospitalized and diagnosed with non-ischaemic DCM (LVEF 35%). Genetic testing identified a likely pathogenic truncating TTN variant in a well-curated DCM-associated region. He is referred to genetic counseling and agrees to have his three adult children offered targeted testing. Two children test negative for the familial variant and are reassured; routine population healthcare continues. The third daughter (age 18) is genotype-positive but asymptomatic. She undergoes baseline ECG, echocardiogram and 24-h Holter: all normal. The multidisciplinary team recommends surveillance with annual clinical review, ECG and echocardiogram, plus consideration of CMR if any abnormalities appear. She receives counseling about reproductive implications and the option to notify her future partners/children. This approach follows the consensus: targeted cascade testing, phenotype-driven screening, and individualized follow-up.

References

1. Verdonschot JAJ, Kaski JP, Asselbergs FW, Behr ER, Charron P, Dawson D, Haugaa KH, Kuchynka P, Lopes LR, Mazzanti A, et al. Clinical care of family members of patients with dilated cardiomyopathy. Eur Heart J. 2025 Nov 14;46(43):4569-4582. doi:10.1093/eurheartj/ehaf571 IF: 35.6 Q1 B1. PMID: 40902100 IF: 35.6 Q1 B1; PMCID: PMC12614981 IF: 35.6 Q1 B1.2. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-24. doi:10.1038/gim.2015.30 IF: 6.2 Q1 B1.3. Clinical Genome Resource (ClinGen). Clinical validity curation framework. https://clinicalgenome.org (accessed 2025).4. Gene Curation Coalition (GenCC). https://thegencc.org (accessed 2025).5. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015 Mar;16(3):233-71. doi:10.1093/ehjci/jev014 IF: 6.6 Q1 B1.

(Additional guideline sources referenced in the consensus include the 2023 ESC Guidelines for the Management of Cardiomyopathies; clinicians should consult the ESC guidance and local recommendations for detailed, jurisdiction-specific directives.)