When Genetics Lag, Images Save: Cardiac MRI Outpaces Genetic Testing In Preventing Sudden Death In A Familial Cardiomyopathy, a case series.

Background: Cardiac MRI (CMR) is a powerful tool for early detection and risk stratification in hereditary cardiomyopathies. CMR can reveal disease before symptoms onset or genetic confirmation, allowing timely intervention. However, CMR is underutilized in screening family members with cardiomyopathy, often used if echocardiographic imaging is inadequate or equivocal. We are presenting a case series of familial LMNA cardiomyopathy as an illustrative example, showing how imaging-guided interventions often precede genetic confirmation to prevent lethal outcomes.

Methods: We reviewed the application of CMR as a screening tool in individuals at risk for hereditary cardiomyopathies. As a specific example, we analyzed a case series involving four siblings from a family identified with LMNA cardiomyopathy screened following the index case (a young adult male with incidentally discovered dilated cardiomyopathy and advanced systolic dysfunction). Cascade screening using CMR was performed on the three asymptomatic siblings. The CMR protocol included assessment of left ventricular (LV) size, systolic function (EF), and myocardial tissue characterization using T1, T2 mapping and late gadolinium enhancement (LGE) sequences. Findings were correlated with clinical outcomes and genetic testing results

Results: Index Case (Brother age 23): CMR: Severely dilated LV, EF 18%, diffuse lateral wall fibrosis and LGE. Outcome: Sudden cardiac death 3 weeks post-CMR; LMNA mutation confirmed postmortem. -Sibling 1 (Sister age 19): Similar CMR findings. Outcome: ICD placed preemptively (prior to genetic confirmation) recorded fatal ventricular tachycardia 4 weeks later. LMNA mutation confirmed 2 months post-CMR. -Siblings 2 & 3 (Ages 9 and 12): CMR: Mild LV dilation with preserved EF (55-60%) with mild lateral wall fibrosis and faint LGE. Management: Initiated on medical therapy. LMNA mutation confirmed 2 months post-CMR. -Key Imaging Findings: LGE and fibrosis identified in all siblings, including those with preserved EF. CMR abnormalities guided treatment prior to genetic confirmation by 8-12 weeks.

Conclusion: CMR provides crucial phenotypic information and risk stratification in hereditary cardiomyopathies, often identifying high-risk features like LGE before genetic results are available or in cases with genetic uncertainty. As demonstrated by the LMNA family, CMR findings directly impact clinical management, enabling timely interventions such as ICD placement or initiation of medical therapy. CMR should be considered an essential initial step of screening protocols for individuals at risk for hereditary cardiomyopathies

Index case, asymptomatic male in his twenties. Short axis and 2 chambers view demonstrate delayed transmural enhancement in the entire lateral wall.​
20 year old sister. End diastolic volume within normal limits. Ejection fraction was estimated as 45%. Short axis demonestrate delayed enhancement at the lateral wall. ICD device placed and​ two episodes of fatal arrhythmia were successfully defibrillated.
12 year old brother with preserved ejection fraction. Short axis demonstrate subtle lateral wall delayed enhancement. Medical therapy and serial exams were recommended.