The subcutaneous implantable cardioverter-defibrillator and extravascular implantable cardioverter-defibrillator do not require intravascular, intracardiac, or epicardial leads, making them attractive alternatives to transvenous implantable cardioverter defibrillators in patients without bradycardia pacing or cardiac resynchronization therapy indications. These systems are especially useful for patients with venous access challenges and those at risk for endovascular infections, including patients with renal failure or those who are immunocompromised. Women with prior or anticipated breast surgery, such as mastectomy or breast reconstruction surgery, or those who are lactating present unique anatomic, procedural, and post-operative quality-of-life considerations. This commentary provides a practical, scenario-based framework for managing this unique patient group. Key considerations include individualized incision and pulse generator planning, proactive multidisciplinary coordination, procedure-specific management, and shared decision-making in patients with prior or anticipated breast augmentation or reduction, pregnancy, lactation, mastectomy, radiation therapy, and breast imaging.

Brugada syndrome is usually interpreted through SCN5A genetics, yet many patients with a Brugada phenotype carry no clearly pathogenic SCN5A variant and penetrance among carriers is incomplete. Cardiac sodium-channel function is therefore not a direct readout of coding sequence but an integrated property shaped by the channelosome, transcriptional and epigenetic control, post-translational modification, metabolic state, and inflammatory signaling. Through these routes, oxidative stress, altered glycosylation, and Nedd4-2-dependent ubiquitination can reduce peak sodium current in experimental systems, potentially lowering conduction reserve; inflammatory mediators may additionally modify the regional substrate through other ionic pathways without altering the SCN5A coding sequence in the experimental system, converging on the loss-of-function phenotype that characterizes Brugada syndrome, in contrast to the late-current gain of function of long QT syndrome type 3. Epicardial adipose tissue may provide a regional context for such signals at the right ventricular outflow tract, where conduction reserve is low and the substrate preferentially localizes, and anti-Nav1.5 autoantibodies provide a humoral route to reduced channel availability. We examine sequence-independent modifiers that may dynamically reduce Nav1.5 function and define the experimental framework needed to establish their clinical weight.