Sriharsha Talapaneni, Danial Ahmad, Meena Khandelwal, Monica Mesiha, Pooya Jalali, Nafiye Busra Celik, Sair Ahmad Tabraiz, Sedem Dankwa, Irbaz Hameed, Rita C. Milewski, Prashanth Vallabhajosyula
Objective: Prosthesis–patient mismatch (PPM) occurs after aortic valve replacement (AVR) when the effective orifice area of the implanted prosthetic valve is small relative to the patient’s body surface area. Beyond simply elevating transvalvular gradient, PPM profoundly affects cardiac remodeling, coronary physiology, and ultimately patient survival. This comprehensive review synthesizes current evidence regarding PPM pathophysiology, clinical consequences, and therapeutic strategies. Methods: We conducted a narrative review of PPM in surgical (SAVR) and transcatheter (TAVR) aortic valve replacement. PubMed and Embase were systematically searched using terms related to AVR and PPM and reference lists of key studies and reviews were screened. Studies addressing PPM prevalence, hemodynamic impact, clinical outcomes, and mitigation strategies were included. Results: PPM, defined as an iEOA ≤ 0.85 cm2/m2 (moderate) or ≤0.65 cm2/m2 (severe), demonstrates variable prevalence across studies, typically ranging from 5 to 30% after SAVR and 2–35% after TAVR. It is associated with increased transvalvular gradients, reduced left ventricular mass regression, persistent coronary flow abnormalities, higher rates of heart failure, and both early and late mortality. Supra-annular self-expanding transcatheter aortic valve replacement (TAVR) devices and newer generation stentless or bovine pericardial surgical valves exhibit lower PPM rates than older stented or porcine valves. Valve-in-valve (ViV) TAVR and bioprosthetic valve fracture (BVF) can improve outcomes in failed surgical valves but are less effective in small annuli. TAVR-in-TAVR procedures are limited by anatomic and technical constraints, especially in maintaining coronary access and minimizing residual gradients. Conclusions: PPM remains a common and clinically consequential complication of AVR that compromises long-term outcomes. It is largely preventable through accurate preoperative imaging, valve sizing, and consideration of annular enlargement. Optimal outcomes require matching valve characteristics to individual patient anatomy and physiology. In an era of expanding TAVR use, preventing PPM during the index procedure is critical to optimizing survival and preserving future reintervention options.