Ryanodine receptor 2 mutations in catecholaminergic polymorphic ventricular tachycardia: From molecular mechanisms to precision medicine

Figure 1 Integrated catecholaminergic polymorphic ventricular tachycardia risk assessment algorithm. Comprehensive risk assessment algorithm incorporating clinical presentation, genetic information, functional investigations, and emerging biomarkers for personalized catecholaminergic polymorphic ventricular tachycardia management. The algorithm integrates multiple parameters, including mutation location, family history, exercise testing results, and biomarker profiles, to stratify patients into high, moderate, and low-risk categories. CPVT: Catecholaminergic polymorphic ventricular tachycardia; SCD: Sudden cardiac death; ECG: Electrocardiogram; RyR2: Ryanodine receptor 2; CASQ2: Calcium-sensing machinery, such as calsequestrin; CALM1-3: Calmodulin 1-3; VT: Ventricular tachycardia.

Figure 2 Precision medicine approach to catecholaminergic polymorphic ventricular tachycardia management. Comprehensive precision medicine framework for catecholaminergic polymorphic ventricular tachycardia management incorporating genomic analysis, functional validation using patient-specific models, biomarker assessment, and personalized therapeutic selection. The approach enables mutation-specific risk stratification and targeted therapy selection based on individual patient characteristics. hiPSC: Human induced pluripotent stem cell; ICD: Implantable cardioverter defibrillator; SCD: Sudden cardiac death.

Figure 3 Catecholaminergic polymorphic ventricular tachycardia treatment algorithm. Systematic treatment algorithm for catecholaminergic polymorphic ventricular tachycardia management incorporating risk stratification, first-line β-blocker therapy, adjunctive pharmacological interventions, and advanced therapeutic options, including left cardiac sympathetic denervation and implantable cardioverter defibrillator implantation for refractory cases. CPVT: Catecholaminergic polymorphic ventricular tachycardia; ECG: Electrocardiogram; RyR2: Ryanodine receptor 2; CASQ2: Calcium-sensing machinery, such as calsequestrin; CALM1-3: Calmodulin 1-3; TRDN: Triadin; LSCD: Left cardiac sympathetic denervation; ICD: Implantable cardioverter defibrillator; QoL: Quality of life.