⚡ DCM: arrhythmic risk varies by sex and genotype

A systematic review and meta-analysis of dilated cardiomyopathy (DCM) found arrhythmic risk clusters differently by sex and genotype: in men, PLN/DSP/LMNA variants had higher arrhythmic event rates than TTNtv and BAG3, while in women, RBM20/DSP/PLN carried the highest arrhythmic risk and TTNtv the lowest. PLN and LMNA variants were linked to the highest heart failure (CHF) risk in both sexes, and BAG3/RBM20/TTN variants showed lower heart failure rates in female vs male carriers.

Why It Matters To Your Practice

• DCM is common (≈1 in 250) and a leading cause of heart failure and transplant; genotype- and sex-specific risk patterns can change who you monitor more closely for ventricular arrhythmias and progression.

• Sex-neutral thresholds in current risk tools (e.g., ICD decision pathways) may undertreat women if their risk is not captured by traditional cutoffs.

Clinical Benefits

• Use genetic results to refine counseling: TTNtv tends toward lower arrhythmic risk (especially in women), while PLN/DSP/LMNA (men) and RBM20/DSP/PLN (women) signal higher arrhythmic risk.

• Prioritize earlier electrophysiology referral and rhythm surveillance (e.g., ambulatory monitoring) when high-risk genotypes are present—particularly when symptoms or family history suggest malignant arrhythmias.

Managing Risks

• Don’t assume “milder phenotype” in women equals lower long-term risk; women may present with less fibrosis and better LV function yet still have genotype-driven arrhythmic vulnerability.

• Screen for sex-specific modifiers that can shift risk and management (pregnancy history/complications, peripartum timing, menopause), and coordinate cardio-obstetrics when relevant.

The Bottom Line

• In DCM, arrhythmic and heart failure (CHF) risks are not one-size-fits-all—sex and genotype meaningfully stratify outcomes and should inform monitoring, referral urgency, and shared decision-making about ICDs.