Assessing the impact of transcatheter aortic valve replacement on myocardial work indices and left ventricular diastolic function in aortic valve stenosis patients

Aortic valve stenosis (AS) is the most common valvular heart disease worldwide. When timely intervention is performed, aortic valve replacement can improve patients' quality and duration of life. Load‐independent left ventricular (LV) functional assessments, such as myocardial work indices (MWIs) and LV diastolic function parameters, could help clinicians decide on the optimal timing of intervention.


INTRODUCTION
Measuring left ventricular (LV) function in the presence of increased load is challenging. Conventional and newer measures of LV systolic function, such as left ventricle ejection function and global longitudinal strain, are load-dependent. 1 Aortic valve stenosis (AS) is the most common valvular heart disease, characterized by fibrosis, thickening, and calcification of the aortic valve, leading to a reduction in valve leaflet motion and valve area. The increased afterload in patients with AS leads to changes in LV geometry, such as concentric LV hypertrophy, and tissue architecture, initially resulting in LV adaptation and subsequently maladaptation leading to LV systolic and diastolic dysfunction (DD). [2][3][4] However, the LV does not always respond uniformly and proportionally to the degree of strain and individual differences in the LV response to increased afterload in AS may explain the heterogeneity of its clinical presentation. 4 In fact, patients with severe aortic stenosis may have few symptoms or be completely asymptomatic, whereas the degree of symptoms may not be directly associated with the prognosis in patients with moderate AS. Furthermore, DD has been associated with symptom status and clinical outcomes after valve replacement, 5 but it has not been mentioned in the last American society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI). 6 Therefore, an accurate load-independent measurement of LV systolic function and DD could be essential to identify a point of no return and help identify the optimal timing for intervention. Myocardial Work Index (MWI) is an improved myocardial deformation-based measure of LV systolic function. 7 Essentially, it is LV longitudinal strain normalized by intraventricular LV pressure making it virtually loadindependent. 8,9 MWI is a noninvasive surrogate for LV myocardial contractility, measured by the gold standard P-V, and has been validated against invasively obtained P-V loops in the catheterization laboratory under various loading conditions, showing potential to identify CRT responders 10 and detect subtle changes in segmental kinetics in patients with CAD. 11 However, its application in patients with AS has yet to be fully investigated. The aim of this study was to evaluate the reliability of MWI in AS patients and to analyze the changes in MWI indices and LV DD indices after TAVR.  12 where AS was con-sidered severe when mean gradient was ≥40 mm Hg, peak aortic velocity was ≥4 m/sand aortic valve area (AVA) was ≤1 cm 2 (or indexed AVA ≤ .6 cm 2 /m 2 ).

Exclusion criteria
Exclusion criteria were more than mild aortic regurgitation, more than mild mitral regurgitation, significant coronary artery disease requiring revascularization, previous myocardial infarction (MI), and left bundle branch block (LBBB) on ECG. Echocardiographic images had to be of sufficient quality to perform speckle-tracking echocardiography. This study was approved by the local ethics committee, and all patients provided written informed consent. History, clinical examination, and a 12-lead ECG were performed at baseline. All echocardiography examinations were performed by the same operator (DF) and reviewed by an expert sonographer (AS).

Blood pressure assessment
Three simultaneous blood pressure measurements were taken in each patient during TAVR hospitalization: the noninvasive cuff pressure on the left arm, the LV pressure measured by a 5-Fr pigtail catheter and the aortic pressure measured through the femoral sheath during the catheterization procedure.

Echocardiographic examination
Echocardiograms were performed in all patients using the Vivid

Myocardial work analysis
The mean gradient of the AV from the continuous-wave Doppler signal was incorporated into the arterial blood cuff, aortic and LV 1-year all cause mortality (%) 3 (5.60%) Abbreviations: CAD, coronary artery disease; PAD, periphery artery disease.
systolic pressures as previously described. 13,14 The resulting adjusted pressures were used to compute the MWI indices: Global work index (GWI mm Hg%) indicates the non-invasive equivalent of LV stroke work, as it represents the area under the curve.
It is calculated from mitral valve closure to opening and provides an assessment of LV diastolic and systolic work.
Global constructive work (GCW mm Hg%) represents the myocardial work that contributes to LV performance. It measures the work required by the LV to contract during systole and relax during diastole.
Global wasted work (GWW mm Hg%) is the work that does not contribute to myocardial performance.
Global work efficiency (GWE %) is the percentage of total work that is constructive (GCW/[GCW + GWW]). It offers a comprehensive estimation of LV performance.
Before discharge, all patients underwent an echocardiographic examination to assess MWIs.

DATA ANALYSIS AND STATISTICS
All analyses were performed using Prism GraphPad 9.0 (GraphPad

RESULTS
Fifty-three consecutive patients were enrolled in the study and their clinical characteristics are summarized in Table 1. Baseline echocardiographic data are reported in Table 2. All patients underwent TAVR successfully via a transfemoral approach using current generation valves. All cases were performed under light sedation, and no major complications were observed. Correlations between invasive and noninvasive pressures are shown in ( Figure S1). There was a strong correlation between cuff systolic blood pressure and aortic pressure 15.96 ± 2.52% for GCW, and 18.38 ± 5.70% for GWW (Table 4).
However, prior-TAVR MWIs values were inversely correlated with the degree of post-TAVI MWIs improvement, expressed as delta MWIs ( Figure 1).
The optimal cut-off value for noninvasive GWI predicting an improvement equal to the mean improvement observed for our population (AUC .84; 95% CI = .75-.92; p < .001; Youden index .6) was 1974 mm Hg%, yielding a sensitivity of 72% and specificity of 85% ( Figure 2). Similarly, most of the echocardiographic parameters of LV diastolic function improved (Table 5). In particular, the E/e' ratio, used as a benchmark to assess LV filling pressures and as a reliable marker of DD, showed an average improvement of 36.02% ± 20.07% (Table 4), with pre-TAVR E/e′ detected as a strong predictor of its delta change ( Figure 3).

Prior-TAVR E/e′ also represents a good predictor of noninvasive
MWIs delta change, except for GWE ( Figure 4). In addition, multiple logistic regression analysis suggest that only the non invasive GWI was an independent predictor of 1-year mortality [OR = .99; 95% C.I. = .95-1.01; p = .042]. The other variables, including E/e′ septal, LVEF (%), and AVAi (cm 2 /m 2 ), were not found to be significant predictors of 1-year mortality ( Table 6). also observed a good correlation between cuff systolic pressure, aortic pressure, and LV systolic pressure. Additionally, the MWIs obtained using AV mean gradient from the continuous-wave Doppler signal were strongly correlated with those obtained with invasive pressures, with a slight overestimation that did not negatively affect the reliability of prior and post-TAVR assessment.

DISCUSSION
After TAVR, all MWIs were significantly decreased and the degree of improvement was greater in patients with lower pre-TAVR values.
Our results confirm and extend previous findings by De Rosa

CONCLUSION
The Myocardial Work Index (MWI) and its associated indices might provide valuable insights into the decision-making process regarding the timing of performing TAVR in patients with AS trough: In summary, MWI and its associated indices offer valuable information regarding LV systolic function and diastolic performance. By incorporating these measurements into the decision-making process for TAVR in patients with AS, clinicians can assess baseline LV function, monitor disease progression, predict treatment response, and evaluate DD. This comprehensive evaluation helps determine the optimal timing for TAVR, ensuring that intervention is performed when it can provide the maximum benefit to the patient.