Our study demonstrates that the prognostic relevance of right heart parameters before TAVI is not uniform, but differs across clinically relevant patient subgroups. While univariate analyses suggested associations between elevated sPAP, impaired RV–PA coupling, and mortality, multivariate models showed that these parameters provided independent prognostic information primarily in patients with limited physiological reserve, most notably elderly patients and men. In contrast, TAPSE alone showed limited and inconsistent prognostic value; although reduced TAPSE was associated with higher early (30-day) mortality, this signal did not translate into a robust association with long-term all-cause mortality.

This observation likely reflects both methodological and pathophysiological factors. TAPSE is a load-dependent parameter that primarily reflects longitudinal RV shortening and may remain preserved in early or pressure-dominant stages of RV dysfunction [5, 6]. In aortic stenosis, RV impairment is frequently driven by progressive afterload increase rather than intrinsic contractile failure, particularly in the pre-procedural setting. Accordingly, integrative indices such as the TAPSE/sPAP ratio more accurately capture RV–pulmonary arterial interaction and prognosis [8, 24]. Differences compared with prior studies, including those demonstrating prognostic value of TAPSE alone, may relate to variations in timing of assessment, case-mix, and endpoints [3, 10].

In contrast to Meucci et al. [24], who reported that post-procedural RV–PA uncoupling and its longitudinal evolution predict long-term mortality, the present study focuses on the pre-procedural phase and identifies vulnerable phenotypes in whom right heart assessment is most clinically informative before intervention. Together, these findings emphasize that outcomes after TAVI are influenced not only by left ventricular function but also by right ventricular vulnerability, underscoring the need for targeted pre-procedural assessment in selected patients.

Our findings indicate that RV pressure overload is the predominant hemodynamic burden in many patients undergoing TAVI. Chronic transmission of elevated left-sided filling pressures into the pulmonary circulation increases pulmonary artery pressure and RV afterload, thereby challenging RV performance [25]. While sPAP reflects the magnitude of this load, the TAPSE/sPAP ratio provides complementary information by capturing the RV’s functional adaptation to afterload.

In our cohort, elevated sPAP and reduced TAPSE/sPAP characterized a pressure-dominant RV phenotype, but their prognostic relevance was not uniform across all patients. After multivariate adjustment, these parameters were not independently associated with mortality in patients with preserved LVEF, normal SVi, or high-gradient aortic stenosis. In contrast, their prognostic value was most evident in patients with limited physiological reserve, particularly elderly patients and men [26]. Importantly, this pressure-dominant RV dysfunction may occur even in the absence of overt clinical right heart failure and may therefore remain unrecognized during routine assessment.

RV–PA coupling, best reflected by the TAPSE/sPAP ratio, integrates RV contractile function and afterload and thus provides a more sensitive marker of maladaptive RV response than TAPSE alone [27]. In our study, impaired RV–PA coupling was consistently associated with adverse outcomes, especially in patients with preserved LV function, suggesting that afterload-related RV stress rather than intrinsic RV systolic dysfunction is the dominant mechanism in this setting [28].

Subtle abnormalities in pulmonary vascular load and compliance further contribute to RV vulnerability and are not captured by standard anatomical measures [29]. Experimental and clinical data indicate that reduced pulmonary arterial compliance and increased elastance disrupt RV–PA coupling and worsen prognosis [30], which is consistent with the vulnerability observed in our cohort.

Clinically, these findings identify a high-risk but often under-recognized group of TAVI candidates: patients with preserved LVEF and flow but elevated pulmonary pressures and impaired RV–PA coupling. In such patients, delayed intervention may permit progression toward irreversible RV maladaptation. Incorporating RV afterload and RV–PA coupling into pre-procedural assessment may help identify a vulnerable pre-procedural phenotype [4]; however, the implications for earlier referral or optimized timing of TAVI remain hypothesis-generating, as the present study was limited to single-point pre-procedural assessment without longitudinal evaluation of RV recovery or waiting-time effects.

Aging exerts a profound yet under-recognized impact on the RV. In our study, age ≥80 years significantly amplified the prognostic relevance of elevated sPAP and reduced TAPSE/sPAP. This likely reflects age-related myocardial changes, including increased fibrosis, reduced capillary density, impaired mitochondrial function, and diminished β-adrenergic responsiveness, which together limit myocardial reserve [31, 32]. As a result, the RV, which is intrinsically less tolerant of pressure overload, becomes particularly vulnerable to rising afterload [2]. Importantly, myocardial fibrosis was not directly assessed in the present study; therefore, these mechanisms are discussed as pathophysiological concepts based on prior experimental and imaging literature rather than direct tissue characterization in our cohort.

In older adults, diastolic dysfunction, atrial fibrillation, and vascular stiffening lead to chronically elevated LV filling pressures, progressive pulmonary venous hypertension, and increasing RV afterload [33]. This process disrupts RV–PA coupling and often evolves insidiously [34], while conventional markers such as TAPSE may remain preserved in early stages. Because RV–PA uncoupling in older individuals tends to occur earlier and at lower sPAP levels, reflecting reduced physiological reserve or “RV frailty,” the TAPSE/sPAP ratio emerges as a more sensitive marker of early maladaptation [27].

These observations have direct clinical implications. Current TAVI risk scores do not account for RV function or age-specific RV vulnerability. Incorporating TAPSE/sPAP into pre-procedural assessment, particularly in elderly patients, may improve detection of occult RV strain and identify individuals at higher procedural and long-term risk. Age-adapted thresholds may further refine risk stratification. Moreover, elderly patients with pre-procedural RV–PA uncoupling may benefit from closer post-TAVI surveillance, including serial echocardiographic assessment to guide follow-up intensity and medical management.

In our cohort, elevated sPAP and impaired RV–PA coupling were more strongly associated with mortality in men than in women, suggesting that adverse right heart phenotypes carry greater prognostic weight in male patients [35]. Sex-related differences in cardiovascular adaptation are increasingly recognized, but their relevance for right heart vulnerability in the setting of TAVI remains incompletely understood.

Several biological mechanisms have been proposed that may contribute to these differences. Estrogen exerts cardioprotective effects relevant to right heart physiology, including improved mitochondrial efficiency, enhanced nitric oxide bioavailability, and reduced myocardial fibrosis [36,37,38,39,40]. In contrast, testosterone has been associated with profibrotic remodeling, oxidative stress, and reduced vascular compliance, which may impair RV adaptation to chronic pressure load [36, 41,42,43]. Together, these mechanisms may partly explain why male patients appear more vulnerable to pressure-induced RV dysfunction.

These molecular differences are reflected at the clinical level. Men undergoing TAVI more frequently exhibit higher left ventricular mass and increased vascular stiffness [44, 45], both of which augment pulmonary vascular load and RV afterload. However, current risk models do not incorporate sex-specific modifiers, and identical values of RV indices may therefore carry different prognostic implications in men and women.

From a clinical perspective, male sex appears to act as a risk amplifier in the presence of elevated RV afterload and impaired RV–PA coupling. While our data do not support sex-specific treatment strategies, they highlight the need for heightened awareness and potentially closer follow-up in male patients with adverse right heart profiles.

More broadly, our findings support the concept that sex should be considered a biological variable in RV-focused risk assessment. Future studies should evaluate whether sex-stratified thresholds improve risk prediction and whether targeted interventions can preserve RV reserve in high-risk male patients undergoing TAVI.