TAVI has become the first line of treatment for the elderly population with severe symptomatic aortic stenosis, especially those with high or moderate operative risk. In the current era, the choice of percutaneous intervention has gained a higher level of evidence, even in low-risk individuals [2].

One of the main complications that can still affect the clinical outcomes of the procedure is para-valvular leakage (PVL), even if it is present in mild grades as it is associated with higher all-cause mortality and re-hospitalization [5, 6, 20].

The major predictors of the PVL can be classified into procedural factors and anatomical characteristics [20]. Anatomical factors include the degree of device landing zone calcium, and LVOT eccentricity [20, 24].

The procedural factors are related to the choice of the type of device, whether self-expandable (SE) or balloon-expandable (BE), with more radial force related to the balloon-expandable valve [25], Accordingly in cases of mild to moderate calcification, both types can perform equally, unlike cases of higher grades of calcification, BE valves can be preferred to decrease the expected PVL, especially if the calcification does not reach out to the annulus. The other device-related factor is the use of early versus newer generations that have leak-proof functions (covered by outer sealing skirts). Those devices include, but are not limited to, Evolut R PRO and SAPIEN 3 [26].

Furthermore, the incidence of PVL is related to the positioning of the valve and the oversizing index (OI), which is beneficial mainly to valves without leak proof function like Evolut R valves. Most of the recent studies recommend an OI of 14 to 17% and around 15% for valves with leak proof function as the upper limit [11, 20]. There is scarce data available about oversizing of 20% or more and its impact when using valves without leak-proof functions [10].

Based on the previous data,PVL can be reduced by pre-procedurally identifying the anatomical features and choosing the most suitable available device as well as performing the best degree of over sizing index (OI) according to the type of the device and the anatomical characteristic.

In developing countries with limited resources the luxury of choosing a certain valve type to suit a specific patient may not be present. The available valve during the study period in our cardiac catheterization -labs was Evolut R, so we had to devise techniques for its use in order to limit complications.

The main interest of our study focused on detecting the most accurate oversizing index with the best results and the least risk of PVL and annular rupture.

To the best of our knowledge, the data provided by the manufacturer that regarding the degree of oversizing for every millimeter of the depth of implantation has not been studied before.

This study is the first to integrate new data for calculating the oversizing index (OI) in the case of Evolut R devices based on the depth of implantation. Our study aimed not only to identify the effect of oversizing based on the depth of implantation as a modifier of PVL risk, but also to propose a predictive model which might help modify of the implantation technique aiming at reducing the incidence of Paravalvular leakage without inducing conduction disturbance complicating TAVI.

The Evolut R valve is a bulky valve with a 45 mm length that needs a large area of implantation. Moreover, being a SE valve, it has less radial force than (BE) valves. Both features have advantages and disadvantages [27].However, the lower radial force of Evolut R devices in comparison with (BE) valves makes it safer in the setting of annular calcification [27, 28]. Its efficacy to prevent PVL in the absence of the optimum degree of oversizing and in the presence of high grades of calcium is less than that of (BE) valves [29]. The large device size allows easy implantation, but it can affect the conduction system, or the device can be affected by the LVOT calcification.

In our study, patients with severe LVOT calcification were excluded due to possible contribution to significant PVL even with performing the optimum degree of oversizing [24, 30] Patients with preexisting conduction disturbance were excluded as well in order to detect the isolated effect of the oversizing on the conduction system.

In our study, group B (oversizing of 20% or more) had a mild to moderate aortic valve calcification prevalence of 73.9% versus 51.5% in group A, while severe calcification was more prevalent in group A (48.5% vs. 26.1% in group B), as we tend to avoid oversizing in cases of severe aortic valve calcification (AVC). This goes in line with Barbanti et al., who recommended avoiding oversizing in severe AVC to avoid annular rupture [27].

The main findings of the study were consistent with our study interests. We found that oversizing by 20% or more had no hazardous effect on the coronary blood flow or the annular integrity and better outcomes concerning the degree of the post-procedural PVL. We found new predictors of new onset conduction disturbances (NOCD) other than the preexisting conduction abnormalities. The depth of implantation-derived oversizing index (DIDO) was inversely related to the incidence of new-onset conduction disturbance (NOCD), indicating that DIDO is not a predisposing factor for NOCD.

Only two cases required permanent pacemaker (PPM) implantation. Both cases had been implanted with devices of size 34 with an oversizing index of 8%. In the first case [patient no. 35], NOCD could be attributed to deep implantation (8 mm), while in the second case [patient no. 127], grade 4 aortic valve calcification and ischemic heart disease were the major contributors. The previous data confirm once again that oversizing is not an independent predictor of NOCD.

According to the study results, oversizing by at least 17% can reduce significant PVL in absence of severe LVOT calcification. In this study, two cases ended up with grade 3 (moderate) PVL. One of those cases had zero percent oversizing [patient no. 7], and the other case had a 17% oversizing index but grade 4 aortic calcification [patient no. 119]. This boosts the fact that oversizing cannot always overcome anatomical factors, Therefore avoiding extreme oversizing is a sound practice in cases of severe annular calcification in terms of safety and without missing a lot of added benefits.

Drakopoulou et al. [11] have proposed oversizing by 14% as a cutoff point to reduce significant PVL with the least incidence of PPM using ROC analysis in a retrospective pattern (AUC, 0.806; 95% confidence interval [CI], 0.706–0.905; P < 0.01). The reported incidence of significant PVL was 19% in group 1 (oversizing by less than 14%) vs. 3% in the other group P < 0.01.In our study, less than 17% of oversizing was predictive of significant PVL by similar analysis (AUC, 0.69; 95% CI, 0,608–0,765; P = 0.04).Similarly, our study reported a higher incidence of significant PVL in group A (oversizing by less than 20%) than in group B (14.4% vs. 0%, respectively, and a P value of 0.007). The differences in the reported rates of PVL may be attributed to different study populations and different degrees of oversizing.

Our study conform with Ki et al. [20] who have set 17.3% or more as the optimum OI for predicting no or trace PVL in valves without leak-proof function (AUC, 0.639, P = 0.018) and an upper limit of OI of 30%. Moreover there was no significant difference in OI regarding PPM insertion (PPM insertion vs. no insertion, OI, 14.2 ± 10.8% vs. 13.7 ± 7.0%, P = 0.893). There was no difference in the volume of calcium regarding PPM insertion (PPM insertion vs. no insertion, 351 mm3 vs. 551 mm3, P = 0.776). The relatively similar Cov of OI predicting non-significant PVL can be explained by close population size since their study included 37 CoreValves 56 Evolut R valves,and 19 Evolut PRO valves.Similarly in our study, new-onset conduction disturbance (NOCD) was not related to the grade of aortic valve calcification, That's to say, there was no significant difference between the population without NOCD and the population with NOCD as regards grade 4 aortic valve calcification (38% vs. 46.7%, P = 0.45). Furthermore, NOCD was not related to the degree of OI. There was no significant difference between group A and group B in our study as regards NOCD (23.7% vs. 15.2%, respectively, P value 0.244) which apparently nullifies the effect of oversizing on NOCD.

Likewise, our study results were in accordance with the study by Ammar, et al. [10] which detected that the incidence rate of significant PVL decreased from 7.4 to 2.8% when comparing OI by less than 20% vs. more than 20% (P value = 0.02). Over and above, there was no significant difference as regards the rates of PPM implantation in the population with OI less than 20% vs. the population with OI more than 20% (13 vs. 12%, p value more than 0.05). Similarly, our study noted that the rates of significant PVL decreased from 14.4 to 0% when comparing the population with OI less than 20% vs. those with OI more than 20% (P value = 0.007). In our study, there was no significant difference as regards the rates of PPM implantation among both groups (2.1% vs. 0%, P value = 0.327), and the cases that required PPM were belonged to group A. The difference in the incidence rates as regards the PVL or PPM between both studies might be explained by different population size.

Our study opposed Mauri V. et al.’s study [29] (n = 212 Accurate Neo), which concluded that there was no association between significant PVL and the oversizing index (P = 0.259) or eccentricity of the aortic annulus (P = 0.062), and that aortic valve calcification (AVC) more than 410.6 mm3 (OR 6.9, CI 3.0–15.8; P 0.001) was solely the independent predictor of significant PVL after multivariate regression analysis. On the contrary, our study found that only OI less than 17% is the independent predictor of significant PVL after multivariate analysis with OR 8.7 and P value = 0.04. However, the wide range of CI in the multivariate analysis can be explained by the Presence of only single case with significant PVL in population with OI more than 17%. The different conclusions may be due to different (SE) valve types.

In contrast to Hagar, et al.’s study [31] (n = 270,different types of valves) suggesting that AVC and the larger annular perimeters and areas were significantly associated with significant PVL, our study found that there was no significant association between the annulus area or perimeter even when indexed to BSA and significant PVL (P values 0.44, 0.60, respectively). However, meaningful comparisons cannot be warranted due to different methodologies and different population sizes.

Our study could also prove that, apart from the size of the valve, the oversizing index is affected by the depth of implantation. Deeper implantation was observed in group A (oversizing less than 20%) than in group B (oversizing equal to or more than 20%), with a P value of 0.001. To the best of our knowledge, such a parameter was not studied before and further studies are needed for verification.

Other than the preexisting conduction disturbances, new predictors for NOCD were depicted using uni-variate logistic regression. These predictors are RHD, Euro score II more than 5.58, STS score more than 3.28, septal Calcification, IHD, CVS, DI more than 3.4 mm, DI i more than 2.02 mm/m2, and DIMS more than 52.63%. By performing multivariate logistic regression analysis, IHD and RHD were found to be significant predictors, a hypothesis that needs further confirmation in larger studies.

According to Choi, et al. and Putra et al. [32, 33], cardiac magnetic resonance imaging (CMRI) in patients with RHD detected myocardial fibrosis surrounding the involved valve annulus and even in other parts of the myocardium. This evidence of myocardial fibrosis may be the predisposing factor for NOCD in our study, especially with cardiac interventions that may affect the conduction system. In our research, all cases with RHD who developed NOCD had new-onset LBBB.

The previous data can be explained in the setting of selecting patients with absent preexisting conduction disturbances,targeting the least depth of implantation, and avoiding extreme oversizing in the setting of severe aortic valve calcification and short membranous septum.

Boonyakiatwattana et al. [34] found that there was no correlation between perimeter-based oversizing and NOCD (P value = 0.338), a finding that is similar to our study. In our study,oversizing more than 20% was safe in the context of the NOCD,coronary encroachment even in smaller annular perimeters, as evidenced by our results, which revealed that group B had smaller annular perimeters (75.67 ± 5.31 mm versus 79.06 ± 4.62 in group A). However, we did not find that membranous septum(MS) is an independent predictor factor, as in their study. The last finding in our study may be attributed to avoiding deep implantation in case of short MS and non randomization of study population.

In contrast to Dallan et al. [35] who found that the safe and effective cut-off point for oversizing in those with annulus diameters less than 30 mm is 12% or more, our study found that the least effective cut-off point for oversizing effectively reducing significant PVL with no other hazards is 17%.This can be attributed to different study populations with larger aortic areas and perimeters in their study.

Our study goes in line with Majeed et al. [36] who found that there was no statistically significant difference between the rate of permanent pacemaker implantation in the minimally oversizing group (8% versus 13% in the severe or moderately oversizing group) (P value = 0.4).

Finally we concluded that oversizing by at least 20% is a safe and effective method of reducing significant PVL in our cohort of patients and any other similar populations. The upper limit in our study was 30% but it needs further verification to be considered as a safe upper limit value.

The concept of the-depth-of-implantation-derived oversizing is a more accurate method of calculating the oversizing index (OI).

The prosthesis oversizing was not a predictor of new onset conduction disturbance (NOCD) in our study. New predictors of new onset conduction disturbance in our study have been suggested but these predictors need more verification in larger trials.