Given advancements in extracorporeal circulation and cardiac surgical techniques, surgical aortic valve replacement (SAVR) has become the predominant cardiac intervention for elderly patients with aortic valve disease (1). While transcatheter aortic valve replacement (TAVR) now offers an alternative approach for treating aortic stenosis, SAVR remains advantageous for patients experiencing aortic regurgitation, infective endocarditis, ascending aortic aneurysms, or other valvular disorders (2, 3). Optimal treatment for elderly patients, however, necessitates a thorough evaluation of benefits and risks, with accurate postoperative mortality assessment remaining a fundamental concern for clinicians.

Baseline functional status is recognized as a strong indicator of surgical risk (4). Identifying specific patient risk factors is essential in guiding clinical decisions on whether TAVR or SAVR represents the optimal approach or if aortic valve replacement (AVR) is potentially non-beneficial. Modifiable factors among these may highlight possible avenues for additional interventions accompanying valve replacement to enhance post-procedural outcomes. Sarcopenia, a condition with implications for adverse clinical results in SAVR/TAVR, is characterized by age-associated reductions in skeletal muscle mass, strength, and physical function (5). Globally, sarcopenia prevalence spans 8–36% in individuals under 60 and 10–27% in those aged 60 or older (6). Prior research has consistently linked sarcopenia with cardiovascular diseases such as coronary heart disease, heart failure, and aortic stenosis (7, 8), positioning it as a risk factor for cardiovascular disease progression and negatively influencing patient prognosis (9, 10). Notably, sarcopenia independently predicts mortality in cardiac surgery patients and is prevalent among elderly patients, where it correlates with poorer post-surgical outcomes (11). Consequently, comprehensive sarcopenia evaluation is increasingly viewed by researchers as integral to refining decision-making in SAVR/TAVR.

As the population ages, the prevalence of age-related frailty increases sharply, which increases the risk of poor health status of older adults (12). Frailty syndrome is becoming increasingly prevalent with population aging, characterized by diminished physiological reserve and impaired stress response capacity. Research indicates that this state of heightened vulnerability exerts significant adverse effects on elderly patients undergoing AVR, manifesting as worsened postoperative dependency, increased readmission rates, elevated mortality, and other negative clinical outcomes (13). Frailty holds significant importance in assessing the risks of TAVR, particularly given the advanced age of many patients (14). However, frailty assessments are often subjective and rely on indirect measurements. Sarcopenia, one of the key biological contributors to frailty (15), can be utilized to evaluate surgical risks in TAVR patients. In the pursuit of objective frailty parameters, previous studies have extensively investigated the analysis of body composition metrics, with a particular focus on muscle mass and muscle strength (16). These parameters are widely applied in cardiac risk assessment. Numerous studies have examined sarcopenia’s predictive role in outcomes post-SAVR/TAVR, yet findings remain inconsistent and, in some cases, contradictory. For instance, Brouessard et al. (17) observed no significant association between sarcopenia and one-year rehospitalization or mortality rates following TAVR. Conversely, Heidari et al. (18) identified sarcopenia as an independent predictor of mortality in TAVR patients. Additionally, Mirzai et al. (19) demonstrated that unilateral pectoralis muscle measurements from preoperative cardiac magnetic resonance imaging may serve as a supplementary metric to conventional risk scores in predicting mortality risk post-SAVR. Despite these varied findings, no meta-analysis has yet synthesized evidence on sarcopenia’s impact on clinical outcomes in SAVR/TAVR patients. This study was therefore undertaken to (i) quantify sarcopenia prevalence in SAVR/TAVR patients, and (ii) assess sarcopenia’s association with post-SAVR/TAVR mortality.

This study presents the first comprehensive systematic review and meta-analysis evaluating sarcopenia prevalence among patients with aortic stenosis (SAVR/TAVR). Sarcopenia is notably prevalent and increases with advancing age, yet it remains underdiagnosed and its clinical significance is often undervalued (54). Notably, patients selected for TAVR—representing a high-risk, elderly demographic with severe aortic stenosis ineligible for SAVR—exhibit a higher incidence of sarcopenia compared to SAVR patients. Clinicians are therefore encouraged to assess sarcopenia severity in both patient cohorts, as preoperative sarcopenia screening can enhance management planning and improve perioperative and postoperative risk assessment. Furthermore, this analysis explored the association between sarcopenia and patient outcomes across these surgical approaches, suggesting that sarcopenia may influence long-term postoperative mortality risk, potentially linked to frailty and malnutrition. Variability in diagnostic criteria likely contributed to differing sarcopenia prevalence rates across studies, but no significant disparity in sarcopenia prevalence was observed between the SAVR and TAVR groups. Additionally, race, sex, and study design were not found to impact sarcopenia prevalence.

Sarcopenia was initially defined as age-related skeletal muscle mass loss. More recently, it has been broadly characterized by both diminished muscle mass and reduced muscle strength (e.g., weak grip strength) and/or physical performance (e.g., slow gait speed) (55). In cardiovascular research, however, sarcopenia is predominantly diagnosed based on skeletal muscle mass, typically assessed by measuring muscle area at L3 vertebra using CT imaging (56). This method was employed by most studies included in the current review. A few studies, however, utilized chest CT scans at the thoracic vertebra levels T7 and T12 for muscle mass estimation. Given that CT scans in patients undergoing TAVR or SAVR are generally performed on the chest rather than the abdomen (57), the link to skeletal muscle measurements at L3 and T12 becomes particularly relevant, with stronger associations observed between these two levels (46). Further investigation is needed to establish the optimal threshold for defining sarcopenia using chest CT scans in TAVR and SAVR patients.

The prevalence of sarcopenia exhibited significant variability across studies in this meta-analysis, largely due to inconsistent cutoffs for low muscle mass. While cutoff values for sarcopenia are sex-specific, prevalence tends to be higher among male patients than female patients undergoing TAVR/SAVR, indicating a potential influence of sex on sarcopenia rates in this population. Prior research also suggests a stronger link between sarcopenia and functional decline in men compared to women (58, 59), possibly due to the higher incidence of smoking among men. Cigarette smoke, rich in free radicals, induces oxidative stress in skeletal muscle (60), and prolonged smoking contributes to neuromuscular junction degeneration (61). In this meta-analysis, smoking status likely served as a confounding factor in the sex-based differences in sarcopenia prevalence; however, subgroup analyses by smoking status were not feasible due to a lack of sex-specific smoking data in the included studies. Future research should further investigate the impact of sex differences on sarcopenia.

In noncardiac procedures, such as elective spine surgery, sarcopenia independently predicts intensive care needs and postoperative transfusion requirements (62). In cases of acute mesenteric ischemia, sarcopenic patients experience reduced postoperative complications and lower 30-day mortality rates (63). Defined by psoas muscle mass, sarcopenia also serves as an independent predictor of 2-year mortality, major complications, and complication severity following major colorectal surgery (64). As an objective indicator of frailty, sarcopenia reliably predicts early morbidity and mortality post-spine surgery (53). In the context of cardiac surgery, sarcopenia correlates with poorer prognostic outcomes (26, 65), including prolonged hospital stays among older adults (66). Consequently, sarcopenia has been increasingly recognized as a relevant predictor of adverse outcomes in cardiac procedures. This study identified sarcopenia as a significant predictor of mortality risk following TAVR/SAVR procedures. While findings suggest a limited impact of sarcopenia on short-term mortality among these patients, this may be attributed to the limited sample size across included studies. Most studies assessed sarcopenia using the SMI method, associating it with an elevated risk of postoperative mortality. In subgroup analysis, nine studies using PMAi to diagnose sarcopenia yielded a pooled HR of 1.31, also indicating the significant association between sarcopenia and post-TAVR mortality risk. In this study, we further separated participants into subgroups for ethnicity stratified analysis. In either Asian population or Caucasian population, sarcopenia was broadly and robustly associated with a higher risk of mortality. The relationship between skeletal muscle mass and post-TAVR/SAVR mortality likely involves the vital role of skeletal muscle in frailty syndromes (67), though underlying mechanisms remain poorly defined. Skeletal muscle serves as the primary amino acid reservoir, and depletion impairs several recovery-critical functions (68). TAVR/SAVR patients with diminished muscle mass exhibit reduced muscle protein synthesis and heightened vulnerability to deconditioning post-intervention, exacerbated by inadequate nutrition and limited physical activity (69). Emerging research indicating the anti-inflammatory and anti-apoptotic properties of skeletal muscle may offer insights into the observed outcomes (70). Patients with sarcopenia, however, may derive limited benefit from these protective effects (71). Post-operative muscle mass reduction extends beyond survival outcomes in TAVR/SAVR, as sarcopenic patients show an increased likelihood of requiring transfer to rehabilitation facilities (33). Consequently, CT has become a valuable tool in assessing muscle mass, facilitating early identification of sarcopenic patients who may benefit from targeted interventions—such as protein supplementation and physical rehabilitation—to improve frailty status post-TAVR/SAVR. With advances in medicine, nanoparticles may hold promise for the diagnosis and treatment of sarcopenia (72). Furthermore, several studies have shown positive impact of physical therapy and nutritional interventions on sarcopenia (73, 74), suggesting that preoperative strategies, including exercise training and dietary supplementation, may enhance outcomes for patients undergoing TAVR.

In addition, sarcopenia demonstrated a strong association with elevated long-term mortality following TAVR/SAVR, aligning with evidence from patients undergoing other cardiac procedures, including heart valve surgery (75), PCI (76), and endovascular aneurysm repair (77). Additionally, the studies analyzed indicated that sarcopenia served as an independent predictor of 1-year mortality risk, even after adjustments for STS scores and relevant covariates, reinforcing its value as a practical and accessible alternative to conventional risk scores in assessing TAVR/SAVR patients.

Analysis of studies included in this review indicated no significant link between sarcopenia and short-term (30-day) mortality in TAVR patients. This observation supports the view that short-term post-TAVR outcomes remain favorable and unaffected by sarcopenia, suggesting TAVR’s safety across a wide patient demographic with varying degrees of muscle mass decline during short-term follow-up. However, this result contrasts with findings from other cardiac surgeries. For instance, Ganapathi et al. reported the association of frailty with discharge to other than home and 30-day mortality in proximal aortic surgery patients (78), while Lee et al. (11) found sarcopenia correlated with higher 30-day mortality and extended hospital stays. Given that only six studies in this meta-analysis assessed 30-day mortality, further research is needed to clarify these findings. Accordingly, future investigations should explore the relationship between sarcopenia, short-term mortality, and other adverse outcomes post-TAVR.

However, several limitations affect this meta-analysis. First, the analysis only included English-language publications, which may exclude relevant studies in other languages. Second, the studies employed varying definitions of sarcopenia, which were adopted in this review. Although most studies rely on CT-based sarcopenia assessments, discrepancies in scan locations and cutoff values across studies may have introduced bias, potentially contributing to publication bias. Notably, sex-specific cutoff values for sarcopenia have been previously derived through optimal stratification, with thresholds of 38.9 cm²/m² (women) and 55.4 cm²/m² (men) being widely adopted; however, cutoff values in post-SAVR/TAVR studies remain inconsistent. Finally, limited reporting on postoperative complications related to sarcopenia is due to limited studies evaluating early mortality, with such interpretations vulnerable to competing risks bias. Thus, while the observed effects of sarcopenia on early outcomes merit attention, further research is needed for this domain.

In summary, the study reveals a high incidence of sarcopenia among SAVR/TAVR patients, correlating with increased long-term mortality but showing no significant association with short-term mortality. While existing guidelines advocate preoperative body composition measurement and functional assessment as screening measures (79), the findings support a stronger recommendation for pre-surgical muscle mass evaluation to enhance risk stratification and outcome prediction. Given the high prevalence and prognostic importance of sarcopenia in SAVR and TAVR patients, integrating nanoformulated therapies could offer a future-oriented, precision-based strategy to improve muscle health and reduce mortality. Future research should focus on translational applications of nanomedicine in cardiac geriatrics to bridge the gap between diagnosis and therapeutic efficacy in managing sarcopenia.