Primary tricuspid regurgitation (TR) is an underrecognized valve disease characterized by structural abnormalities of the tricuspid valve (TV) apparatus, including leaflet prolapse, flail, rheumatic degeneration, carcinoid involvement and congenital malformations such as Ebstein’s anomaly. Historically neglected and often misclassified as functional, primary TR has recently gained attention due to advances in multimodality imaging and increased awareness of its pathophysiological complexity and adverse outcomes. A major challenge that remains is the accurate diagnosis of primary TR, as well as the optimal timing for intervention, particularly in asymptomatic patients. While surgical repair or replacement has been the traditional approach, recent developments in transcatheter therapies, such as tricuspid edge-to-edge repair, have broadened the therapeutic landscape for patients considered at high surgical risk. In this context, personalized medicine has emerged as a central paradigm in the management of this valvular disease. Tailored therapeutic decisions should include anatomical, functional, and clinical parameters, as well as patient-specific risk factors such as age and comorbidities. Advanced imaging modalities, including 3D echocardiography and cardiac magnetic resonance, are essential for guiding this individualized approach. This review summarizes the current understanding of the etiology, pathophysiology, diagnostic tools, and treatment strategies for primary TR, highlighting the critical role of personalized treatment pathways in optimizing clinical outcomes.

• Sustained TAVR benefits in low-risk and intermediate-risk patients. • TAVR effective for bicuspid aortic valve, cancer patients. • TAVR Trans-axillary, trans-carotid and trans-caval alternative access are safe and effective in TAVR, although data are limited. • Persistent at least moderate MR and worsening TR after TAVR associated with worse outcomes. • Transcatheter edge-to-edge repair (TEER) is now supported by ACC/AHA and ESC/EACTS guidelines for primary and functional MR. • Sustained outcomes with MitraClip, PASCAL, TENDYNE device for severe MR. • TEER in post-MI MR may be an alternative to surgery. • Sustained 2-year outcomes with the TENDYNE device. • Promising transcatheter tricuspid technologies with the TriClip, PASCAL, Cardioband and EVOQUE TTVR are evolving. • LAAO is non-inferior to NOACs in patients with AF and history of cardioembolism. • Combined LAAO and AF ablation is safe and effective. • LAAO may carry higher risk in women. • Gore and Amplatzer devices yield comparable results in patients with PFO and ASA. • PFO closure is safe in patients with hypercoagulable disorders. • PFO closure may decrease the frequency and duration of migraines. • PFO closure significantly lowers the incidence of decompression sickness in divers but with increased adverse events.