Progression of the Ascending Aortic Diameter After Transcatheter Aortic Valve Implantation: Based on Computed Tomography Images

Abstract: Objectives. The natural history of ascending aortic diameter after transcatheter aortic valve implantation (TAVI) has not been investigated. Our aim was to determine the progression of ascending aortic diameter in patients undergoing TAVI. Methods. We retrospectively included 134 patients undergoing TAVI for aortic stenosis at our institution from June 2012 to November 2016, including 79 patients with bicuspid aortic valve (BAV) and 55 patients with tricuspid aortic valve (TAV). Preoperative measurements of the ascending aorta were compared with aortic measurements at 1-year follow-up based on computed tomography images. Results. A very slight decrease in median aortic diameter was identified in overall patients: 4.07 cm (interquartile range [IQR], 3.76-4.54 cm) vs 4.06 cm (IQR, 3.74-4.51 cm); P=.04. Further subgroup analysis found that the decrease remained statistically significant in the subgroup of TAV and mild aortic dilation. In addition, no aortic events occurred during long-term follow-up (median, 27 months; IQR, 20-42 months). Conclusions. TAVI could prevent a further progression of aortic diameter for both BAV or TAV patients by correcting hemodynamic derangements, especially for patients with TAV, mild aortic dilation, and small annulus angles. Aortic events appeared rarely during long-term follow-up after TAVI. However, our results need further confirmation with future investigations in a larger population with longer-term follow-up.

J INVASIVE CARDIOL 2019;31(8):E234-E241.

Key words: aortic dilation, bicuspid, transcatheter aortic valve implantation

Aortic stenosis (AS) is frequently associated with a dilated ascending aorta.¹ The dimension of the aortic dilation determines whether ascending aorta replacement is needed at the time of surgical aortic valve replacement (SAVR). Patients with bicuspid aortic valve (BAV) are considered predisposed to aortic aneurysm formation due to an inherent weakness of the aortic wall. Thus, a more aggressive prophylactic surgical aortic repair is recommended to BAV patients with aortic dilation.²

Previous investigations have suggested that aortic dilation associated with AS may be an integrated consequence of both the hemodynamic abnormality caused by valve dysfunction and intrinsic aortic wall fragility of BAV patients.³ For example, eccentric systolic jets accompanying right-handed helical ascending aorta flow have been identified that do not present in the general population but exist in normally functioning BAV patients.⁴ Moreover, a linear relationship between the diameter of tubular ascending aorta and AS severity was also discovered, which supported the hemodynamic theory.⁵ On the other hand, in cases of ascending aortic aneurysm in BAV patients, the presence of abnormal extracellular matrix deposition was identified that was similar to the histology of Marfan’s syndrome, a genetic disease related to FBN1 gene mutation.⁶ Thus, an underlying genetic defect was suspected to play a role in aneurysm formation in BAV patients.

Up to now, there have been a few studies addressing the natural history of poststenotic aortic dilation after SAVR. However, the results were controversial. Some studies reported a similar annual progression rate of aortic dilation after SAVR between BAV and tricuspid aortic valve (TAV), proving that hemodynamics play an important role in dilation rate of the ascending aorta.⁷ In contrast, some studies showed a faster dilation rate in BAV patients after SAVR than preoperatively, implying genetics theory.⁸

Transcatheter aortic valve implantation (TAVI) has become an alternative to SAVR as a treatment for severe symptomatic AS patients.⁹ However, the aortic diameter progression after TAVI has not been investigated. In this study, we test the hypothesis that the dilation of the ascending aorta in AS patients is mainly caused by hemodynamic disturbance and TAVI could prevent a further dilation of the ascending aorta.

Methods

Patient populations and study design. This study was a single-center analysis conducted on a cohort of consecutive patients undergoing TAVI for AS at our institution from June 2012 to November 2016. Data were prospectively collected into a TAVI database and retrospectively analyzed. All patients were qualified for TAVI by a multidisciplinary heart team. Informed consent was obtained from all patients and the study was approved by the local ethics committee of Sichuan University West China Hospital. Patients with multidetector computed tomography (CT) images available at both baseline and 1-year follow-up were included in this study. To minimize the influence of aortic diameter progression before TAVI, patients were excluded if baseline CT was performed >2 weeks prior to TAVI. Patients were also excluded if CT images were not clear enough for ascending aorta diameter measurements.

Follow-up and outcomes. Patients were followed at 1, 3, 6, and 12 months after the TAVI procedure and each year thereafter by outpatient visit and telephone interview. The outcomes were classified according to the Valve Academic Research Consortium (VARC)-2 definitions.¹⁰ The median follow-up duration was 27 months (interquartile range [IQR], 20-42 months). The follow-up was 100% complete.

Technical aspects and procedure. Transfemoral access was the first choice; alternative transvascular access was obtained if the femoral artery was not feasible due to severe calcification or tortuosity. Four types of prosthesis were used in this study: CoreValve (Medtronic); Venus-A valve (Venus Medtech); Lotus valve (Boston Scientific); and MicroPort valve (MicroPort Medical). The prosthesis type and size were determined according to the anatomic structure of the patient’s aortic root.

CT imaging protocol and measurement. First, all patients underwent CT scans for preoperative assessment. The native aortic valve morphology was identified through evaluation of CT images. Then, CT images were obtained postoperatively (before discharge) and 1 year after the procedure to visualize the cardiac structure and assess the function of the implanted valve. All multidetector CT scans for analysis in this study were performed with a second-generation dual-source CT system (Somatom Definition Flash; Siemens Healthineers). A retrospectively electrocardiographically gated CT angiographic examination of the heart was performed during a single 15-second breath-hold prior to and following TAVI.

End-systolic ascending aortic diameter was measured for each CT image by using the coaxial double-oblique measurement with OsiriX Dicom Viewer software (OsiriX Foundation). To make sure that the measurement of the aortic lumen was comparable at the same slice for each patient, the left coronary ostia was identified as a mark for CT images at baseline, post TAVI, and at 1-year follow-up. The maximal diameter of the proximal ascending aorta lumen and the distance above the annular plane for the maximal measurement were measured for each patient. In addition, standard measurement slices included 1, 2, 3, 4, and 5 cm above the left coronary ostia along the central axis of the ascending aorta (Figure 1). Two independent physicians performed the aortic diameter measurements. To improve the precision of our results, measurements from two physicians were averaged if the difference was <0.5 mm; otherwise, the measurement was performed by consulting a more experienced radiologist.   

Statistical analysis. Continuous variables are presented as mean ± standard deviation or median (IQR) as suitable. Categorical variables are presented as number of patients (percentage). Student’s t-test or Mann-Whitney U-test were performed to compare continuous variables between different populations depending on the distribution normality of the data. Similarly, Student’s t-test for paired samples and Wilcoxon signed-rank test were used to compare the baseline data and follow-up data depending on the distribution normality. Nominal variables were compared by Chi-square test. The statistical analyses were performed with SPSS, version 22.0 (IBM).

We primarily compared the baseline aortic diameter with 1-year follow-up aortic diameter to identify the changes of aortic size 1 year post TAVI procedure. We also compared postoperative measurements with the baseline measurements to show the short-term changes of the ascending aorta. In addition, patients were divided into subgroups according to the aortic anatomy features, including native aortic valve morphology, angle between aortic annulus to the horizontal plane (annulus angle), and the preoperative maximal aortic lumen diameter to identify whether these factors could influence the aortic dilation progression 1 year post TAVI. Finally, for some patients with an ascending aorta larger than the outflow dimension of the deployed prosthesis, we compared the implantation depth on the procedural angiography with 1-year CT images to determine whether the prosthesis moved in these patients.

Results

Patient population. Among 196 consecutive patients who underwent TAVI in our institution, a total of 17 patients died before 1-year follow-up (none of them died of aortic aneurysm rupture or dissection) and 34 patients refused to undergo a 1-year CT scan. Six patients were excluded due to poor image quality and 5 patients were excluded because their baseline CTs were performed >2 weeks prior to TAVI. Baseline and 1-year follow-up CTs were thus available in 134 patients; among these, a total of 117 patients also underwent postoperative CT scan, and therefore had CT images at all three timepoints (Figure 2).

Baseline patient characteristics are listed in Table 1. The cohort consisted of 72 males (53.7%) and 62 females (46.3%) with a mean age of 73.19 ± 6.20 years. Most patients (88.8%) were New York Heart Association class III or IV and only a few patients had a poor left ventricular ejection fraction (LVEF <30%). Thirty-seven patients were accompanied by a moderate or severe aortic regurgitation (AR) at baseline. Chronic obstructive pulmonary disease (COPD), peripheral vascular disease, and hypertension were the most common comorbidities. A Venus-A valve was used in one-half of the patients, and a CoreValve, MicroPort valve, or Lotus valve was implanted in the rest of the patients.

Moderate or severe AR and COPD were more common in the TAV group. In contrast, a large annulus angle was more common in the BAV group. Mean diameter of the ascending aorta was significantly larger in the BAV group vs the TAV group. However, there was no significant difference in aorta aneurysm (diameter >4.0 cm) distribution between the BAV and TAV groups, nor was a significant difference in the distance above the annular plane for the maximal measurement observed (6.16 ± 0.97 cm in BAV patients vs 6.00 ± 0.81 cm in TAV patients; P=.31).

Progression of the ascending aortic diameter between TAVI and 1-year follow-up. In the entire cohort (n = 134 patients), the maximal diameter of the ascending aorta showed a slight decrease at 1-year follow-up (4.07 cm [IQR, 3.76-4.54 cm] vs 4.06 cm [IQR, 3.74-4.51 cm]; P=.04). The frequency distribution of absolute change of the maximal aortic diameter is shown in Figure 3. Moreover, a slight decrease in diameter at levels 3, 4, and 5 (P=.04, P=.02, and P=.04, respectively) was found at 1-year follow-up (Table 2). No progressive aortic dilation (>0.3 cm) was observed in either BAV or TAV patients.

Subgroup analysis showed that ascending aorta diameter decreased in terms of the maximal diameter (4.03 cm [IQR, 3.61-4.32 cm] vs 3.93 cm [IQR, 3.62-4.29 cm]; P<.01) and at levels 3, 4, and 5 (P<.01 for all three levels) at 1-year follow-up in TAV patients. However, in the BAV group, no statistically significant change in aortic diameter was observed regardless of the measurement level (P=.82). Figure 4 details the changes of maximal aortic diameter during the follow-up in BAV and TAV patients.

We also examined the aortic diameter progression in subgroups classified by different BAV phenotypes, as defined by the Sievers classification system.¹¹ Only three phenotypes (type 0 lat, type 0 ap, and type 1 LR) had enough patients for statistical analysis. No statistically significant change in aortic diameter was identified regardless of BAV phenotype and measurement level (Figure 5).

When the patients were divided into different subgroups according to the annulus angle, none of the subgroups showed statistically significant changes in maximal diameter of the ascending aorta (P=.06 for small angles [<50°], P=.16 for medium angles [50°-60°], and P=.71 for large angles [>60°]). However, the small-angle group showed a decrease in aortic diameter at levels 3, 4, and 5 (P<.01, P<.01, and P=.02, respectively). The medium-angle group showed a decrease in aortic diameter at level 5 (P=.03). However, the large-angle group showed no statistically significant change of aortic diameter regardless of measurement level (Table 2).

When the patients were stratified according to the preoperative dimension of aortic dilation, only the group with mild aortic dilation (4.0-4.5 cm) showed a decrease in maximal aortic diameter (P=.03). There was also a decrease in aortic diameter at levels 3, 4, and 5 for patients with mild aortic dilation (P=.04, P=.03, and P=.03, respectively) and at level 5 for patients with no aortic dilation (P=.02). No other statistically significant decrease in aortic diameter was observed in the serial measurement slices in patients with moderate or severe aortic dilation. Besides, the aortic diameter showed a slight increase at level 1 for patients with no dilation (P=.04) (Table 2).

Postoperative diameter change. A total of 117 patients with available postoperative CT images were analyzed to compare the preoperative aortic size with the postoperative aortic size. The mean aortic diameter change trend for each measurement level is presented in Figure 6. A slight increase of aortic diameter at level 1 was observed postoperatively (P<.01). However, this result became statistically insignificant 1 year after TAVI in these patients (P=.10). Besides, no statistically significant change in postoperative aortic lumen diameter was found for other measurement slices. Nevertheless, a decrease in diameter at levels 3, 4, and 5 and maximal diameter was identified at 1-year follow-up for these 117 patients, which was consistent with the result from the entire study cohort (n = 134).

Adverse aortic events. Clinical follow-up after TAVI was obtained in all 134 patients (100%). The median follow-up was 27 months (IQR, 20-42 months). There were 2 late deaths during the late follow-up; 1 patient died of cerebral infarction (preoperative aortic diameter, 4.07 cm) and 1 patient died of cancer (preoperative aortic diameter, 3.30 cm). During the follow-up, no aortic events or sudden cardiac deaths were documented, and no patients underwent surgery for treatment of the ascending aorta dilation.

Prosthesis movement during the follow-up. Twenty-five of the 115 patients implanted with self-expanding long-frame valves in this study had an ascending aorta larger than the outflow dimension of the deployed prosthesis on the procedural angiography. The implantation depth on the procedural angiography was compared with the 1-year follow-up CT, and no significant change of prosthesis implantation depth was observed (6.40 mm [IQR, 4.57-13.14 mm] vs 6.80 mm [IQR, 4.55-12.91 mm]; P=.44), suggesting that the inflow was adequate to anchor the prosthesis.

Discussion

Patients with AS frequently have ascending aortic dilation, which can progressively expand at a rate ranging from 0.12 to 0.42 cm/year if the valve dysfunction is left untreated.^12,13 However, whether to do an additional surgery on the ascending aorta at the time of SAVR is hard to decide because the natural history of the dilated ascending aorta after SAVR has not been clarified. As TAVI becomes a safe and efficient alternative to SAVR for intermediate-to-high risk patients with symptomatic severe AS, the progression rate of aortic dilation post TAVI is concerning to cardiologists.

To date, this is the first study to investigate the ascending aortic lumen diameter progression after TAVI. In the present study, we found that the ascending aortic diameter showed a very slight reduction at 1-year follow-up post TAVI in the entire cohort, and this result was consistent in the TAV and mild aortic dilation subgroups. This implies that hemodynamic abnormality caused by valve dysfunction plays an important role in aortic dilation and TAVI can prevent further progression of ascending aortic diameter by correcting the hemodynamic derangements.

When BAV and TAV were analyzed separately, we found that TAV patients showed a slight reduction in aortic diameter at a rate of -0.3 mm/year. This result was supported by Andrus et al,¹⁴ who reported a mean expansion rate of -0.3 mm/year in the ascending aortic diameter after SAVR in 185 TAV patients. Similarly, Yasuda et al⁸ reported a mean annual progression rate of -0.08 mm/mm²/year after SAVR in 14 TAV patients. These results indicated that after the removal of hemodynamic disturbance caused by valve dysfunction, the aortic diameter presented a slight reduction in TAV patients.

We also found that the mean aortic dilation rate (-0.02 mm/year) after TAVI in BAV patients showed a tendency to decrease, although the difference was not statistically significant. This implies that the ascending aortic size remains stable after TAVI for BAV patients. Similarly, Evaldas et al¹⁵ reported an annual dilation rate of 0.09 mm/year, revealing no significant aortic dilation after SAVR, and concluded that BAV-associated aortic dilation was predominantly a flow-triggered phenomenon, and thus showed a benign result after the correction of the flow abnormality. This was in agreement with Kim et al,⁵ who reported a significantly lower dilation progression rate for BAV patients after SAVR compared with BAV patients without SAVR, thus indicating that hemodynamic abnormality was a major factor in the development of aortic dilation.

When BAV patients were further stratified according to BAV phenotypes, no significant change in the aortic diameter was identified in either subgroup regardless of measurement levels. Few studies focus on the correlation between BAV phenotype and aortic dilation progression after SAVR. In contrast, an association between BAV phenotype and aortopathy in terms of aortic size, aortic dilation rate, and histological properties has been reported in non-surgical BAV patients.^16,17 However, the mechanism behind these phenomena remains controversial. On the one hand, Fernández et al¹⁸ have reported that R-N fusion type derives from a morphogenetic defection before the outflow tract septation, whereas L-R fusion type is a production of abnormal outflow tract septation, indicating that different BAV phenotypes should be considered as different etiological entities. Thus, it is speculated that different behaviors in aortic dilation among BAV phenotypes represent an inherent difference of the aorta’s development. On the other hand, some studies reported a significant impact of BAV phenotype on the flow pattern and wall shear stress on the ascending aorta, thus indicating that particular hemodynamic changes in each BAV morphology influenced the aortic dilation process.^19,20 In this study, we found similar changes among different BAV phenotype subgroups, which further support the hemodynamic pathogenesis theory of aortic dilation. However, this result requires further confirmation in studies with larger sample sizes.

In this study, we found the reduction in aortic diameter seemed to be more significant for TAV patients than BAV patients. We speculate that this result may partially derive from distinct aortic wall types for the different valve types. For example, previous studies have reported an inherent weakness in the aortic wall of BAV, which is characterized by cystic medial necrosis and extensive loss of elastic elements.²¹ Thus, we speculate that after eliminating the hemodynamic derangements, TAV patients show a more significant decrease in aortic diameter because it has better elastic recovery. Importantly, in spite of the speculation on the histological characteristic of the BAV aortic wall, TAVI could prevent a further progression of the aortic dilation. Again, our results need to be confirmed by studies with larger samples and longer follow-up.

In subgroups based on the baseline aortic dimensions, we found that only patients with mild aortic dilation showed a statistically significant decrease in the aortic diameter. However, no statistically significant decrease was found in patient subgroups with no dilation, moderate dilation, or severe dilation. In addition, a slight increase in aortic diameter was identified at level 1 for patients with no dilation. We speculate that these phenomena could be explained by the following reasons. First, for patients with no baseline aortic dilation, the stent of the prosthesis may have a stronger radial force compared to subgroups with a larger aorta. Therefore, the aortic diameter demonstrates an increase at level 1 where the stent contacts the ascending aorta. For the same reason, the regression of the aortic diameter was impeded until level 5. Second, according to Laplace’s law, the tangential stress on the aneurysm is proportional to pressure and radius and inversely proportional to wall thickness.¹² Thus, larger aneurysms experience stronger wall stress and that may explain why patients with moderate and severe dilation did not show a decrease in aortic diameter.

In subgroups based on the annulus angle, we found a statistically significant decrease in aortic diameter at three slices in the small annulus angle subgroup, only one slice in the moderate annulus angle subgroup, and no slice in the large annulus angle subgroup. We speculate this is because the larger annulus angle is frequently accompanied by greater curvature of the ascending aorta, which makes the helical turbulence easier to form, thus facilitating aneurysm formation. The fact that the annulus angle is related to the baseline aortic diameter (r=0.4; P<.001) may prove this speculation. Therefore, we think the aortic dilation formation and progression may be associated with a larger annulus in two ways. First, the large annulus angle facilitates the helical turbulence formation which leads to the aortic dilation. Then, the aortic dilation is further aggravated due to the large radius of the aorta.

The fact that no aortic events occurred in this study indicates that TAVI is safe in terms of aortic accidents during the long-term follow-up and suggests that the potentially vulnerable ascending aorta could be left untreated.²² However, a well-designed prospective study with a larger population and longer follow-up is required to confirm our findings.

Study limitations. There are several major limitations to the present study. First, the radiological follow-up was not long enough, because only 1-year CT was available for the patients. Thus the aortic diameter change could not be identified during the long-term follow-up. Second, the aortic dilation rate for the BAV subgroup was heterogeneous in this study. However, we could not identify any factors associated with a rapid progression rate. Third, the sample size of subgroup analysis based on the BAV phenotype was small; thus, further investigation with a larger sample size are necessary to confirm the influence of the BAV phenotype on the aortic dilation progression after TAVI.

Conclusion

The present study demonstrates that TAVI could prevent further progression of aortic dilation in both BAV or TAV patients by correcting the hemodynamic derangement, especially for patients with TAV, mild aortic dilation, and small annulus angles. Our results suggest that aortic events appear rarely in patients undergoing TAVI. However, our results need further confirmation by future studies with larger populations and longer follow-up periods.

Acknowledgments. Special thanks to the English language polishing contributions from Mrs. Hong Xie, from the Institution of Medical English, West China Medical School of Sichuan University, Chengdu, China.

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^*Joint first authors.

From ¹the Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China; and ²the Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Chen and Dr Feng are consultants and proctors for Venus MedTech and MicroPort. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted August 10, 2018, provisional acceptance given December 3, 2018, final version accepted February 25, 2019.

Address for correspondence: Mao Chen, MD, PhD, Department of Cardiology, West China Hospital, Sichuan University, #37 Guo Xue Alley, Chengdu, 610041, China. Email: hxmaochen@foxmail.com