Preoperative osteosarcopenia predicts adverse outcomes in patients undergoing transcatheter aortic valve implantation

Abstract

[Purpose] Transcatheter aortic valve implantation (TAVI) has become a standard treatment for severe aortic stenosis; however, reliable predictors of post-TAVI outcomes remain unclear. Osteosarcopenia, defined as the coexistence of low muscle mass and low bone density, has been associated with poor outcomes in older adults, but its prognostic significance in TAVI patients has not yet been established. This study aimed to investigate the prognostic significance of preoperative osteosarcopenia in patients undergoing TAVI. [Participants and Methods] This retrospective study included 93 consecutive patients who underwent TAVI at Sapporo City General Hospital between 2019 and 2023. Sarcopenia and osteopenia were evaluated using computed tomography-derived psoas muscle index (PMI) and vertebral bone mineral density (BMD), respectively. Osteosarcopenia was defined as values in the lowest sex-specific tertile for both PMI and BMD. The primary outcome was a composite of all-cause mortality and unplanned hospitalization within 1 year after discharge. [Results] Among the 93 patients (mean age, 84.9 ± 5.9 year; 38.7% male), 14 (15.1%) were diagnosed with osteosarcopenia. During follow-up, 28.0% of participants experienced the composite endpoint. Patients with osteosarcopenia demonstrated significantly lower event-free survival rates. Multivariate Cox regression analysis identified osteosarcopenia as an independent predictor of adverse outcomes. [Conclusion] Preoperative osteosarcopenia independently predicts poor clinical outcomes after TAVI in ambulatory patients and may serve as a useful marker for early risk stratification.

INTRODUCTION

Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe, symptomatic aortic stenosis (AS) who are considered high-risk surgical candidates¹⁾. The global number of TAVI procedures continues to increase²⁾, and a similar trend is expected in Japan owing to the rapidly aging population³⁾. However, data from the Transcatheter Valve Therapy registry indicate that the 1-year incidence of heart failure (HF) readmission is 14.3%, with an overall mortality rate of 23.7%⁴⁾. Therefore, identifying patients at high risk of adverse outcomes following TAVI remains a critical clinical priority.

The term sarcopenia was first introduced in 1989 to describe the age-related involuntary decline in skeletal muscle mass⁵⁾. Sarcopenia is now recognized as a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, leading to an increased risk of physical disability, reduced quality of life, and mortality⁶⁾. Previous studies have shown that preoperative sarcopenia in TAVI patients is a significant risk factor for 1-year all-cause mortality and rehospitalization^{7, 8)}.

Sarcopenia and osteopenia (reduced bone mineral density [BMD]) often coexist and are closely interrelated. It has been suggested that diminished muscle mass results in decreased mechanical loading on the skeleton, thereby impairing bone formation⁹⁾. While preoperative osteopenia alone has been associated with poor prognosis in TAVI patients^{10, 11)}, the clinical significance of “osteosarcopenia”—the synchronous presence of both conditions—has recently gained attention¹²⁾. This “hazardous duet” has been shown to exert a more profound negative effect on physical function, quality of life, and survival than either condition alone, increasing the risk of falls, fractures, institutionalization, and death. However, the prognostic significance of osteosarcopenia among TAVI patients remains unclear.

Assessing osteosarcopenia typically involves the evaluation of skeletal muscle mass and BMD using dual-energy X-ray absorptiometry (DEXA)¹³⁾. However, the requirement for specialized equipment restricts its widespread use. Alternatively, recent studies have demonstrated that the psoas muscle area measured by abdominal computed tomography (CT) provides a reliable surrogate for total body skeletal muscle mass^{14, 15)}, and CT-derived BMD correlates strongly with DEXA-measured bone mineral content¹⁶⁾. Therefore, routine preoperative CT imaging, which is widely performed in TAVI candidates, offers a practical opportunity to assess osteosarcopenia in clinical practice. Furthermore, the identification of osteosarcopenia has significant clinical implications for perioperative management. Given that muscle and bone health are modifiable through targeted physical interventions, early risk stratification using CT-derived indices could guide personalized rehabilitation strategies. For instance, patients identified as having osteosarcopenia may benefit from an optimized resistance training program specifically designed to mitigate the “hazardous duet” of muscle and bone loss^{17, 18)}. Integrating this assessment into clinical practice may optimize rehabilitation outcomes and improve functional recovery following TAVI.

In this context, we hypothesized that preoperative osteosarcopenia would be a powerful independent predictor of adverse clinical outcomes after TAVI, offering more comprehensive risk stratification than the assessment of muscle or bone loss alone. This study aimed to investigate the prognostic significance of preoperative osteosarcopenia, assessed by CT imaging, in patients undergoing TAVI. In addition, we examined its association with sarcopenia, osteopenia, and other established prognostic factors to clarify its potential role in patient risk stratification.

PARTICIPANTS AND METHODS

This retrospective study included 106 consecutive patients aged ≥65 years with severe AS who underwent TAVI at Sapporo City General Hospital, Sapporo, Japan, between August 2019 and December 2023. After excluding patients who required emergency procedures (n=6), were unable to ambulate independently before TAVI (n=5), or had incomplete clinical or imaging data (n=2), 93 patients were included in the final analysis. All enrolled patients were deemed suitable candidates for TAVI following a comprehensive evaluation by a multidisciplinary heart team consisting of cardiac surgeons, interventional cardiologists, imaging specialists and physical therapists.

This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and was approved by the Ethics Review Board of Sapporo City General Hospital (Approval No. R06-064-1168). Owing to the retrospective design, informed consent was obtained using an opt-out approach, with study information publicly available on the hospital’s website. No patients declined participation.

Sarcopenia and osteopenia were evaluated using each patient’s most recent preoperative CT scan obtained within 30 days before TAVI. Sarcopenia was quantified using the psoas muscle index (PMI, cm²/m²), defined as the cross-sectional area of the psoas major muscle at the inferior border of the third lumbar vertebra, normalized to the square of the patient’s height¹⁹⁾. The PMI has been validated as an effective indicator of physical functional capacity, as it correlates significantly with functional measures such as grip strength and gait speed in elderly populations^{20, 21)}. The psoas muscle area was manually delineated on axial CT images. Osteopenia was assessed based on vertebral BMD, measured as CT attenuation at the center of the first lumbar vertebral body. A single oval region of interest was placed in the trabecular region while avoiding cortical bone, and attenuation values were recorded in Hounsfield units (HU)¹⁶⁾ (Fig. 1).

Fig. 1.

Measurement of psoas major muscle area and bone mineral density.

(A) Measurement of the psoas major muscle area at the lower border of the third lumbar vertebra. (B) Measurement of bone mineral density at the center of the first lumbar vertebra.

All CT scans were performed using a slice thickness of 5 mm and a tube voltage of 120 kVp. Measurements were conducted by a trained investigator blinded to patient outcomes, using image analysis software (SYNAPSE; Fujifilm Medical Co., Tokyo, Japan). Osteosarcopenia was defined as the coexistence of both sarcopenia and osteopenia, with cutoff values for PMI and BMD determined as the lowest sex-specific tertiles within this study cohort.

The primary outcome was a composite of all-cause mortality and unplanned hospitalization within one year after discharge. This composite endpoint has been employed in recent large-scale cohort studies of coronary artery disease as a suitable indicator of poor clinical prognosis²²⁾. Clinical events were identified through medical record review, and follow-up data were collected for all patients. For patients experiencing multiple events, only the time to the first event was used in the analysis. Follow-up information was obtained through routine clinical visits and chart reviews.

Baseline characteristics included age, sex, body mass index, New York Heart Association (NYHA) classification, Society of Thoracic Surgeons (STS) score, and comorbidities at admission. Laboratory data included hemoglobin, serum albumin, serum creatinine, estimated glomerular filtration rate, and N-terminal pro-B-type natriuretic peptide levels. The Geriatric Nutritional Risk Index (GNRI)²³⁾ was calculated as an indicator of nutritional status.

Echocardiographic parameters obtained preoperatively included left ventricular ejection fraction, aortic valve area, mean transvalvular pressure gradient (mean PG), and peak jet velocity (peak V). Perioperative data included the TAVI approach, postoperative complications, rehabilitation progress, discharge-to-home rate, and length of hospital stay.

Preoperative frailty was assessed using the Clinical Frailty Scale (CFS)²⁴⁾, the Short Physical Performance Battery²⁵⁾, and comfortable walking speed²⁶⁾. Walking speed was measured over a 4-m course, with participants instructed to walk at a normal pace. The shorter time from two trials was used for analysis.

Post-operative Rehabilitation Protocol Following TAVI, all patients participated in a standardized, progressive rehabilitation program. The protocol commenced on the first post-operative day, starting with sitting, standing, and gait training, with a gradual increase in walking distance. When necessary, low-intensity resistance training using body weight, balance exercises, and activities of daily living training were incorporated. Criteria for exercise termination and progression followed the JCS/JACR 2021 guideline on rehabilitation in patients with cardiovascular disease²⁷⁾. The rehabilitation protocol was applied consistently to all patients regardless of their osteosarcopenia status. The compliance rate with the rehabilitation program was high, at 96.8% (90 of 93 patients), with no exercise-related adverse events reported.

Continuous variables were expressed as mean ± standard deviation, and categorical variables as frequencies and percentages. Patients were stratified into two groups according to the presence or absence of osteosarcopenia at baseline. Continuous variables were compared using the unpaired t-test, and categorical variables using the χ² test or Fisher’s exact-test. To assess the clinical significance and magnitude of the differences, mean differences with 95% confidence interval (CI) and Cohen’s d were calculated for continuous variables, and odds ratio with 95% CI were calculated for categorical variables. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify predictors of the primary endpoint. In addition to the STS score, known to reflect surgical risk, clinically relevant covariates were included in the multivariate model. Survival curves were constructed using the Kaplan–Meier method, and intergroup comparisons were made with the log-rank test. All analyses were conducted using EZR version 1.68 (Saitama Medical Center, Saitama, Japan)²⁸⁾. A p-value <0.05 was considered statistically significant. A power analysis, assuming a power (1−β) of 80% and an α error of 5%, indicated that a minimum of 146 patients per group would be required to detect statistically significant differences in clinical outcomes. Because our study did not reach this required sample size.

RESULTS

The mean age of the study population was 84.9 ± 5.9 years, and 36 participants (38.7%) were male. Figure 2 shows the sex-specific distribution of PMI, with mean values of 4.9 ± 1.3 cm²/m² for men and 3.8 ± 1.0 cm²/m² for women. Similarly, Fig. 3 displays the distribution of BMD, with mean values of 135.8 ± 70.6 HU for men and 94.9 ± 53.8 HU for women. Using these cutoffs, men were classified as having osteosarcopenia if their PMI was <4.28 cm²/m² and BMD <103.06 HU; the corresponding thresholds for women were PMI <3.31 cm²/m² and BMD <76.81 HU.

Fig. 2.

Histogram of PMI among (A) men and (B) women.

PMI: psoas muscle index.

Fig. 3.

Histogram of BMD among (A) men and (B) women.

BMD: bone mineral density; HU: hounsfield units.

Table 1 summarizes baseline clinical characteristics by osteosarcopenia status. Compared with the non-osteosarcopenia group (n=79), the osteosarcopenia group (n=14) was significantly older, had a higher proportion of patients with NYHA class III/IV symptoms, a lower prevalence of hypertension, a higher mean transvalvular pressure gradient, and a lower peak jet velocity. In addition, patients with osteosarcopenia demonstrated higher CFS scores and slower comfortable walking speed, indicating greater frailty.

Table 1. Demographic and baseline clinical characteristics of participants.

		Overall (n=93)	Non-osteosarcopenia (n=79)	Osteosarcopenia (n=14)	p-value	Mean Diff./OR (95% CI)	Cohen’s d
Age, years		84.9 ± 5.9	84.2 ± 5.6	88.9 ± 6.5	**	4.70 (1.04–8.36)	0.82
Men, n (%)		36 (38.7)	30 (38.0)	6 (42.9)
Body mass index, kg/m2		22.6 ± 4.0	22.9 ± 4.0	21.1 ± 4.0
NYHA classification III/IV, n (%)		59 (63.4)	46 (58.2)	13 (92.9)	*	9.17 (1.26–407.34)
STS score, %		6.6 ± 3.6	6.3 ± 3.3	8.1 ± 4.6
Comorbidities, n (%)
	Hypertension	66 (71.0)	60 (75.9)	6 (42.9)	*	0.24 (0.06 −0.91)
	Dyslipidemia	39 (41.9)	34 (43.0)	5 (35.7)
	Diabetes mellitus	37 (39.8)	30 (38.0)	7 (50.0)
	Stroke or transient ischemic attack	17 (18.3)	15 (19.0)	2 (14.3)
	Motor system disease	30 (32.3)	24 (30.4)	6 (42.9)
	Chronic obstructive pulmonary disease	17 (18.3)	13 (16.5)	4 (28.6)
	Atrial fibrillation	22 (23.7)	17 (21.5)	5 (35.7)
	Ever smoker	34 (36.6)	30 (38.0)	4 (28.6)
Laboratory variables
	Serum hemoglobin, g/dL	11.5 ± 1.7	11.5 ± 1.8	11.4 ± 1.3
	Serum albumin, g/dL	3.7 ± 0.4	3.7 ± 0.4	3.6 ± 0.5
	Serum creatinine, mg/dL	1.2 ± 0.6	1.2 ± 0.6	1.2 ± 0.4
	estimated glomerular filtration rate, mL/min/1.73m2	47.1 ± 19.8	47.9 ± 20.5	42.5 ± 14.9
	log NT-pro BNP, pg/dL	3.0 ± 0.6	3.0 ± 0.6	3.1 ± 0.6
	Geriatric nutritional risk index, points	97.9 ± 10.6	98.7 ± 10.4	93.6 ± 11.1		5.10 (−1.28–11.48)	0.48
Echocardiographic parameters
	Left ventricular ejection fraction, %	63.5 ± 11.1	63.9 ± 10.9	61.1 ± 12.0
	Aortic valve area, cm2	0.7 ± 0.2	0.7 ± 0.2	0.7 ± 0.2
	Mean transvalvular pressure gradient, mmHg	39.2 ± 15.2	41.1 ± 14.7	28.2 ± 13.3	**	12.9 (4.57–21.23)	0.91
	Peak jet velocity, m/s	4.1 ± 0.8	4.3 ± 0.7	3.4 ± 0.7	***	0.90 (0.50–1.30)	1.29
Physical frailty
	Clinical frailty scale, points	3.8 ± 0.9	3.8 ± 0.9	4.4 ± 0.6	**	0.60 (0.11–1.09)	0.70
	Short physical performance battery score, points	7.4 ± 3.9	7.6 ± 3.9	6.1 ± 3.8
	Comfortable walking speed, m/s	0.7 ± 0.2	0.7 ± 0.2	0.6 ± 0.2	*	0.10 (−0.01–0.21)	0.50
	Approach transfemoral, n (%)	89 (95.7)	76 (96.2)	13 (92.9)
Postoperative complications, n (%)
	Delirium	14 (15.1)	11 (13.9)	3 (21.4)
	Stroke	2 (2.2)	1 (1.3)	1 (7.1)
	Pacemaker Implantation	8 (8.6)	8 (10.1)	0 (0.0)
	Postoperative walking independence day, days	2.6 ± 4.3	2.7 ± 4.6	2.3 ± 1.0
	Rate of discharge to home, n (%)	84 (90.3)	72 (91.1)	12 (85.7)
	Length of hospital stay, days	13.4 ± 11.2	13.1 ± 10.8	15.1 ± 13.3

*p<0.05, **p<0.01, ***p<0.001. Diff.: difference; OR: odds ratio; CI: confidence interval; NYHA: New York Heart Association; STS: Society of Thoracic Surgeons; NT-pro BNP: N-terminal pro B-type natriuretic peptide.

During the one-year follow-up, 26 of 93 patients (28.0%) experienced the composite endpoint. These included six cases of falls or fractures, six cases of HF, four cases of immobility due to dehydration, three cases of progressive anemia, and seven other events. Figure 4 shows the Kaplan–Meier survival curves for event-free survival according to osteosarcopenia status. Patients with osteosarcopenia had a significantly lower event-free survival rate compared with those without osteosarcopenia (log-rank test, p<0.001). Univariate Cox regression analysis showed a hazard ratio of 3.98 (95% CI: 1.72–9.25). At the 1 year mark, the absolute risk difference was 34.4%, and the number needed to harm was 2.9. The median event-free survival time was 126 days in the osteosarcopenia group, while it was not reached in the non-osteosarcopenia group.

Fig. 4.

Kaplan–Meier analysis for primary endpoints.

(A) shows the Kaplan–Meier analysis and log-rank test for the non-osteosarcopenia and osteosarcopenia groups, (B) for the sarcopenia alone and osteosarcopenia groups, and (C) for the osteopenia alone and osteosarcopenia groups. OSP: osteosarcopenia; SP: sarcopenia; OP: osteopenia; TAVI: transcatheter aortic valve implantation.

Subgroup analyses further revealed that the event-free survival rate in the osteosarcopenia group was significantly lower than that in both the sarcopenia-only and osteopenia-only groups (p=0.024 and p=0.048, respectively).

Table 2 presents the results of the univariate and multivariate Cox regression analyses for the primary endpoint. Multivariate models adjusted for NYHA class, GNRI, mean PG, peak V, CFS, and walking speed—along with the STS score—consistently identified osteosarcopenia as an independent prognostic factor associated with poorer outcomes compared with sarcopenia or osteopenia alone.

Table 2. Univariate and multivariate Cox regression analyses for the primary endpoints.

		HR	95% CI	p-value
Crude model
	Sarcopenia	2.09	0.96–4.52
	Osteopenia	3.62	1.66–7.89	**
	Osteosarcopenia	3.98	1.72–9.25	**
Model 1 (adjusted for STS score and NYHA classification)
	Sarcopenia	2.01	0.92–4.42
	Osteopenia	3.34	1.44–7.72	**
	Osteosarcopenia	3.42	1.45–8.07	**
Model 2 (adjusted for STS score and GNRI)
	Sarcopenia	1.65	0.75–3.65
	Osteopenia	3.52	1.48–8.38	**
	Osteosarcopenia	3.72	1.67–8.28	**
Model 3 (adjusted for STS score, mean PG, and peak V)
	Sarcopenia	1.97	0.86–4.50
	Osteopenia	3.38	1.54–7.41	**
	Osteosarcopenia	4.36	1.66–11.45	**
Model 4 (adjusted for STS score and CFS)
	Sarcopenia	1.92	0.88–4.17
	Osteopenia	3.14	1.40–7.03	**
	Osteosarcopenia	3.33	1.39–7.97	**
Model 5 (adjusted for STS score and comfortable walking speed)
	Sarcopenia	1.96	0.73–5.30
	Osteopenia	3.47	1.27–9.48	*
	Osteosarcopenia	4.30	1.51–12.24	**

*p<0.05, **p<0.01. HR: hazard ratio; CI: confidence interval; NYHA: New York Heart Association; STS: Society of Thoracic Surgeons; GNRI: geriatric nutritional risk index; mean PG: mean transvalvular pressure gradient; peak V: peak jet velocity; CFS: clinical frailty scale.

DISCUSSION

The principal finding of this study is that preoperative osteosarcopenia, assessed using CT imaging in patients undergoing TAVI, was independently associated with an increased risk of composite adverse events within one year after discharge. Importantly, this independent association remained significant even though the established prognostic factors included in our multivariate model demonstrated large effect sizes. This suggests that osteosarcopenia provides distinct and robust prognostic information beyond conventional risk assessments. Furthermore, osteosarcopenia was linked to a poorer prognosis than either sarcopenia or osteopenia alone. To the best of our knowledge, this is the first study to evaluate the prognostic impact of osteosarcopenia in TAVI patients in Japan—a country with one of the most rapidly aging populations worldwide.

In this cohort, the one-year composite event rate was 28.0%, which is consistent with previously reported rates ranging from 25.4% to 44.2% in similar populations^{29, 30)}. In the present study, the most frequent causes of unplanned hospitalization were falls/fractures (n=6) and HF (n=6), followed by immobility due to dehydration.

Previous studies have demonstrated that osteosarcopenia increases the risk of falls and fractures compared with sarcopenia or osteopenia alone¹²⁾. It is also closely associated with aging, malnutrition, vitamin D deficiency, and frailty^{12, 13)}. Notably, these factors have been identified as adverse prognostic indicators in patients with HF, contributing to an elevated risk of readmission^{31,32,33,34,35)}. Given that osteosarcopenia encompasses several of these high-risk features, it may be associated with a greater likelihood of heart failure-related hospitalization.

In the present study, patients with osteosarcopenia were significantly older (84.2 vs. 88.9 year, p=0.006) and had higher CFS scores (3.8 vs. 4.4, p=0.002) compared with those without osteosarcopenia. Notably, these differences were characterized by large to medium effect sizes (Cohen’s d=0.82 and 0.70, respectively), indicating substantial clinical disparities between the groups. Although the GNRI was not statistically significant (98.7 vs. 93.6, p=0.100), it demonstrated a medium effect size (Cohen’s d=0.48), suggesting a potentially meaningful nutritional deficit in the osteosarcopenia group despite the limited sample size. These results suggest that osteosarcopenia is associated with increased frailty and reduced physiological reserve, which may partly explain its relationship with adverse clinical outcomes. Skeletal muscle serves as a major reservoir of body water, and dehydration has been implicated as a contributing factor to sarcopenia in older adults³⁶⁾. Therefore, patients with osteosarcopenia, characterized by low muscle and bone mass, may be more vulnerable to physical decline associated with dehydration and related complications.

An important advantage of this study is that osteosarcopenia can be assessed using CT imaging routinely performed during preoperative evaluation for TAVI. This allows for the simultaneous assessment of muscle and bone parameters without the need for specialized equipment such as DEXA. As such, CT-based evaluation of osteosarcopenia may represent a practical and cost-effective method for risk stratification in this population.

Several randomized controlled trials (RCTs) have investigated interventions targeting osteosarcopenia in community-dwelling older adults. In one study, a 28-week high-intensity resistance training program for men aged ≥72 year with osteosarcopenia significantly improved the sarcopenia Z score (p<0.001), while the control group exhibited a significant decline (p=0.012). The skeletal muscle index (SMI) also increased significantly in the intervention group (p<0.001)¹⁷⁾. Another RCT reported that a 12-month low-volume, high-intensity dynamic resistance training program preserved lumbar BMD in the intervention group, whereas BMD declined in controls, with a significant between-group difference (p<0.001). SMI also increased in the intervention group but decreased in the control group (both p<0.001)¹⁸⁾. These findings suggest that resistance training may improve both muscle and bone health in individuals with osteosarcopenia. Unlike community-dwelling older adults, TAVI patients present with severe symptomatic aortic stenosis and multiple comorbidities, which significantly limit exercise tolerance and heighten the risk of adverse events during exertion³⁷⁾. Therefore, high-intensity training is often inappropriate for this population. Instead, a tailored, low-to-moderate intensity pre-rehabilitation program (e.g., 2–3 sessions per week) under close clinical monitoring is recommended to improve functional capacity safely before the procedure^{37, 38)}. Furthermore, nutritional support may play a crucial role alongside exercise. Evidence suggests that adequate protein intake and vitamin D supplementation are essential for mitigating the loss of muscle mass and bone mineral density in frail older adults¹³⁾. In patients with osteosarcopenia, a combined approach of targeted rehabilitation and nutritional optimization could synergistically improve musculoskeletal health and clinical resilience against the stress of the TAVI procedure. Accordingly, a multimodal intervention strategy integrating tailored physical activity and nutritional optimization should be considered for this vulnerable population. Although further studies are warranted, identifying high-risk patients through CT-based assessment and implementing targeted pre-TAVI resistance training, rehabilitation interventions, and nutritional support may help improve postoperative outcomes.

This study has several limitations. First, our study was a single-center study with a relatively small sample size, particularly in the osteosarcopenia group (n=14), which may limit the generalizability of the findings. A power analysis, assuming a power (1−β) of 80% and an α error of 5%, indicated that a minimum of 146 patients per group would be required to detect statistically significant differences in clinical outcomes. Because our study did not reach this required sample size, the statistical power was limited. Second, standardized diagnostic criteria for osteosarcopenia have not yet been established. In this study, we used sex-specific tertiles to define the cutoff values for PMI and BMD; however, these values are population-specific. Notably, our PMI cutoffs (male: 4.28 cm²/m², female: 3.31 cm²/m²) were lower than the previously proposed criteria for Asian adults (male: 6.36 cm²/m², female: 3.92 cm²/m²)¹⁹⁾. This discrepancy may be attributed to the advanced age and high prevalence of comorbidities in our TAVI cohort, and it highlights the limited generalizability of our specific cutoff criteria to other populations. Third, because of the retrospective and observational design, causal relationships between osteosarcopenia and prognosis could not be established, nor could the potential benefits of interventions targeting osteosarcopenia be confirmed. Further multicenter and interventional studies are needed to validate these findings. Fourth, we did not evaluate baseline nutritional data, such as daily protein intake or serum vitamin D levels, which are known to influence musculoskeletal health and clinical prognosis. Since we could not account for these nutritional factors, their potential impact on the association between osteosarcopenia and post-TAVI outcomes remains unclear. Fifth, the exclusion of patients unable to ambulate independently introduced a selection bias. Evidence from the TAVI-OCEAN registry has shown that non-ambulatory patients have a markedly poor prognosis³⁹⁾. By excluding these high-risk individuals, our study focused on a cohort with a relatively higher potential for functional recovery. However, this selection bias may have led to an underestimation of the overall prognostic impact of musculoskeletal frailty in the broader TAVI population. Our findings should, therefore, be interpreted as applicable to patients who maintain a baseline level of mobility.

In conclusion, preoperative osteosarcopenia assessed using CT imaging was independently associated with poorer prognosis in patients undergoing TAVI. Importantly, outcomes among patients with osteosarcopenia were worse than those observed in patients with either sarcopenia or osteopenia alone. These findings suggest that osteosarcopenia may serve as a valuable marker for risk stratification and perioperative management in this patient population.

Funding

This study received no external funding.

Conflict of interest

The authors declare no conflicts of interest.