A Comparison of Hemodynamic and Clinical Outcomes After Transcatheter Versus Surgical Therapy in Adults in Coarctation of Aorta

Abstract: Background. Transcatheter stent therapy provides similar acute reduction in coarctation of aorta (COA) gradient and systolic blood pressure (SBP) as compared with surgery. However, there are limited data comparing mid-term outcomes after transcatheter vs surgical therapy for COA. The purpose of this study was to compare temporal changes in Doppler COA gradient and SBP after transcatheter stent therapy versus surgical therapy for COA. Methods. A retrospective study of COA patients (≥18 years old) undergoing transcatheter stent therapy or surgical therapy at Mayo Clinic in Rochester, Minnesota from 2000-2018 was performed. Linear regression analyses were used to compare temporal changes in Doppler gradient and SBP between the 2 groups. Propensity matching was used to adjust for between-group differences in clinical and anatomic characteristics. Results. A total of 44 and 128 patients underwent transcatheter and surgical therapy, respectively; there were no significant between-group differences in the anatomy of the thoracic aorta. Both groups had similar acute reduction in Doppler peak gradient (P=.66), mean gradient (P=.41), SBP (P=.22), and upper-to-lower extremity SBP (ULE-SBP) gradient (P=.69). The median follow-up was 46 months (interquartile range, 27-81 months) and 63 months (interquartile range, 41-94 months) in the transcatheter and surgical groups, respectively. There were no significant between-group differences in the temporal change in Doppler peak gradient (P_interaction=.06), mean gradient (P_interaction=.15), SBP (P_interaction=.20), and ULE-SBP gradient (P_interaction=.51). Conclusions. These favorable short- and mid-term outcome data support the use of transcatheter therapy as an alternative to surgery in adults with COA. Further studies are required to determine if these favorable outcomes are maintained on long-term follow-up.

J INVASIVE CARDIOL 2021;33(3):E191-E199. Epub 2021 February 11. 

Key words: coarctation of aorta, surgical repair, transcatheter stent therapy, Doppler gradient

Coarctation of the aorta (COA) results in left ventricular pressure overload, which ultimately leads to left ventricular dysfunction, heart failure, and cardiovascular mortality.^1-3 It is also associated with an increased risk of coronary artery disease, which can further accelerate the progression of left ventricular dysfunction.^4,5 Surgical COA repair is an effective palliation for hemodynamically significant COA.^2,3 Transcatheter stent therapy is a less-invasive treatment option for native and recurrent COA, and has been shown to be as effective as surgical therapy for acute reduction in COA gradient and upper-to-lower extremity systolic blood pressure (ULE-SBP) gradient, as well as a decreased need for ongoing antihypertensive therapy.^6,7

Although several studies have demonstrated acute procedural success after transcatheter stent therapy, there are limited data about how well these hemodynamic results are maintained during mid-term follow-up.^6,7 Additionally, most of the previous studies were conducted in a combined cohort of pediatric and adult patients, which creates a translational challenge since age is an important determinant of long-term outcomes in this population.^6,7 Since there are robust long-term outcome data for surgical COA repair,^2,8 a direct comparison of the clinical and hemodynamic results of transcatheter stent therapy during mid- to long-term follow-up will provide a good foundation for evidence-based clinical decision making.

The purpose of this study was to compare the temporal changes in Doppler COA gradient and SBP after transcatheter stent therapy and surgical therapy for COA. Based on the limited but favorable outcome data for transcatheter stent therapy in adults with COA,^6,7 we hypothesized that COA patients undergoing transcatheter stent therapy would have a similar temporal change in Doppler COA gradient and SBP as compared with those who had surgical therapy.

Methods

Study population. The MACHD (Mayo Adult Congenital Heart Disease) registry was queried for patients (age ≥18 years) who underwent COA repair at Mayo Clinic in Rochester, Minnesota from January 1, 2000 through December 31, 2018. A previous study has been published on this cohort.⁹ The Mayo Clinic institutional review board approved this study and waived informed consent for patients who provided research authorization. We excluded the following patients: (1) patients who had extra-anatomic repair (ascending-to-descending aorta bypass graft), because it was not feasible to reliably assess residual COA gradient post repair; and (2) patients who underwent transcatheter or surgical therapy for the management of aortic aneurysm/pseudoaneurysm. In order to account for between-group differences in clinical and demographic characteristics of the transcatheter and surgical groups, we performed 1:1 matching using propensity-score method based on age, sex, history of hypertension, SBP at the time of echocardiogram, and procedure era (before vs after January 1, 2010).

Outcomes. The preprocedure Doppler peak and mean gradients were obtained from the last echocardiogram performed <1 month prior to the procedure, and the immediate postprocedure Doppler peak and mean gradients were obtained from the echocardiogram performed at the time of hospital discharge. The last echocardiograms during follow-up or prior to reintervention were reviewed to ascertain Doppler peak and mean gradients. Temporal change in Doppler gradient was calculated as Doppler gradient at last follow-up minus Doppler gradient at hospital discharge. 

SBP was measured in the right arm, and ULE-SBP gradient was calculated as SBP from the right arm minus SBP from the leg. Preprocedure SBP and ULE-SBP gradients were ascertained by review of the last clinic note prior to COA intervention, and the immediate postprocedure SBP was measured at the time of hospital discharge. The SBP during follow-up was ascertained from the last outpatient clinic visit during follow-up or prior to reintervention. Temporal change in SBP was calculated as SBP at last follow-up minus SBP at hospital discharge. Because ULE-SBP gradients were not measured at the time of hospital dismissal, the ULE-SBP gradient obtained at the time of first outpatient visit was used as the baseline for calculating temporal change in ULE-SBP gradient.

Echocardiography. Two-dimensional (2D) and Doppler echocardiography were performed according to contemporary guidelines.^10,11 Pulsed-wave Doppler was obtained about 2-5 mm proximal to the aortic isthmus (site of COA), and continuous-wave Doppler was obtained across the aortic isthmus. Only Doppler signals with optimal alignment (defined as angle of insonation <20°) were analyzed for this study. Doppler peak velocity and time velocity integral were used to calculate peak gradient (maximum instantaneous gradient) and mean gradient, respectively.^10,11 All digital images were reviewed and offline measurements were performed by 2 very experienced sonographers (JW and KT). 

Transcatheter therapy. Transcatheter stent implantation was performed via femoral artery access under general anesthesia. Pressure measurements were obtained proximal and distal to the site of COA. Contrast angiography was performed for measurements of the aortic arch, including the minimum dimension at the COA site and diameter of the descending aorta at the level of the diaphragm. The procedural details for transcatheter COA therapy have been previously described.^6,12,13 Procedural complication was defined as aortic wall injury (dissection, intimal tear, aneurysm), femoral/access site hematoma, and death prior to hospital discharge.^6,12,13 Reintervention was defined as subsequent surgical COA repair or repeat cardiac catheterization for stent redilation or further stent therapy. Reintervention was classified as “anticipated” if it was performed as part of a staged approach or “unanticipated” if it was performed because of recurrent COA.^6,12,13

Cross-sectional imaging. Chest computed tomographic angiogram and magnetic resonance angiogram performed within 12 months prior to procedure were reviewed. Similar to previous studies,^6,12 hypoplastic transverse aortic arch was defined as a ratio of the distal transverse arch dimension divided by descending aorta measured at the level of the diaphragm ≤0.5. Discrete and long segment COA were defined as COA segments measuring ≤5 mm and >5 mm in length, respectively. Aneurysm was defined as a diameter greater than that of the descending aorta at the level of the diaphragm by >20%, or an abnormal localized enlargement of the aortic segment. 

Statistical analysis. Data are presented as mean ± standard deviation, median (interquartile range [IQR]), count (%), or statistic (95% confidence interval [CI]). Between-group differences were assessed with unpaired t-test, Wilcoxon ranked sum test, and Fisher’s exact test, as appropriate. Linear regression was used to assess temporal change in COA gradient and SBP, and the between-group differences were assessed by comparison of the beta coefficients. Propensity-score matching was used to balance the between-group differences in baseline characteristics. A propensity score (which is the probability of undergoing transcatheter therapy) was estimated using logistic regression based on age, sex, history of hypertension, SBP at the time of echocardiogram, and procedure era. One-to-one nearest-neighbor caliper matching was used to match patients based on the logit of the propensity score using a caliper equal to 0.2 of the standard deviation of the logit of the propensity score.¹⁴ A P-value <.05 was considered statistically significant. All statistical analyses were performed with JMP software, version 14.1.0 (SAS Institute).

Results

Baseline characteristics. A total of 44 patients underwent transcatheter stent therapy; of these, 9 (19%) had native COA while 35 (81%) had recurrent COA. The surgical group comprised 128 patients, of which 26 (20%) had native COA while 102 (80%) had recurrent COA. Compared with the surgical group, the transcatheter group was younger, had higher COA peak gradient and lower left ventricular mass index, and had a lower prevalence of long-segment COA (Table 1). In a propensity-matched cohort of 39 surgical and 39 transcatheter therapy patients, these between-group differences were no longer statistically significant (Table 2).

Interventions. The types of stents and surgical repair techniques used in this cohort are shown in Table 3. Among the patients who received transcatheter stent therapy, there was a significant reduction in COA peak-to-peak gradient from 22 mm Hg (IQR, 12-29 mm Hg) to 3 mm Hg (IQR, 0-6 mm Hg; P<.001) with corresponding increase in aortic isthmus dimension from 9 ± 3 mm to 17 ± 2 mm (P<.01) after stent implantation (Table 4). The median hospital stay was 1 day (IQR, 1-2 days) and there were no procedural complications or in-hospital mortality. 

In the surgical group, the median hospital stay was 5 days (IQR, 4-7 days) and there was no in-hospital mortality. As expected, the patients who received transcatheter stent therapy had a shorter hospital stay compared with the surgical group (P<.001). 

Outcomes. Table 5 shows a comparison of postprocedure Doppler gradient and SBP. Compared with the surgical group, the patients who received transcatheter stent therapy had similar acute reduction in Doppler peak gradient (28 mm Hg [95% CI, 20-35] vs 27 mm Hg [95% CI, 23-31]; P=.66), Doppler mean gradient (18 mm Hg [95% CI, 12-23] vs 17 mm Hg [95% CI, 13-21]; P=.41), and SBP (12 mm Hg [95% CI, 9-15] vs 15 mm Hg [95% CI, 10-19]; P=.22). At the time of the first outpatient clinic visit, the ULE-SBP gradient decreased from 36 ± 11 mm Hg to 9 ± 4 mm Hg in the transcatheter group and from 31 ± 9 mm Hg to 4 ± 3 mm Hg in the surgical group. There was no significant difference in reduction of ULE-SBP gradient between the transcatheter group vs the surgical group (26 mm Hg [95% CI, 17-38] vs 29 mm Hg [95% CI, 10-37], respectively; P=.69).

The median follow-up was 46 months (IQR, 27-81 months) and 63 months (IQR, 41-94 months) in the transcatheter and surgical groups, respectively (P<.001). There was no significant difference in the temporal change in Doppler peak gradient (P_interaction=.06) and Doppler mean gradient (P_interaction=.15) (Figure 1). Similarly, there was no significant difference in the temporal change in SBP (P_interaction=.20) and ULE-SBP gradient (P_interaction=.51) (Figure 2).

Propensity-matched subgroup analysis. Consistent with the results observed in the entire cohort, the subgroup analysis using the propensity-matched data did not show any significant between-group differences in acute reduction of Doppler peak gradient, Doppler mean gradient, and SBP (Table 5). Similarly, there was no significant difference in the temporal change in Doppler peak gradient (P_interaction= .10), Doppler mean gradient (P_interaction=.22), SBP (P_interaction=.38), and ULE-SBP gradient (P_interaction=.40).

Of the 39 patient pairs, 19 (49%) had echocardiographic and clinical evaluations at 5 years without any interval reinterventions. There were no significant between-group differences in the temporal change in Doppler peak gradient (6 ± 2 mm Hg vs 5 ± 2 mm Hg; P=.08), Doppler mean gradient (5 ± 2 mm Hg vs 4 ± 2 mm Hg; P=.16), SBP (6 ± 2 mm Hg vs 5 ± 2 mm Hg; P=.10), and ULE-SBP (4 ± 2 mm Hg vs 3 ± 2 mm Hg; P=.63) at 5 years post procedure (Figure 3). 

Reintervention and aortic wall complications. There were no reinterventions in the surgical group. On the other hand, 3 of the 44 patients (7%) in the transcatheter stent therapy group had reinterventions (2 anticipated reinterventions and 1 unanticipated reintervention). The unanticipated reintervention occurred in a 24-year-old female who initially received Palmaz Genesis XD stent (Cardinal Health), but subsequently developed stenosis proximal to the site of the initial stent for which she underwent implantation of a 36 mm IntraStent Max LD stent (Medtronic) 91 months after the initial intervention. The anticipated reinterventions were redilation of a Palmaz Genesis XD stent 9 months post implantation in a 46-year old-female, and redilation of a 36 mm IntraStent Max LD stent 12 months post implantation in a 47-year-old male.

Postprocedural cross-sectional imaging was performed in all 44 patients in the transcatheter group and 103 patients in the surgical group; the interval between COA intervention and imaging was 1.2 ± 0.6 years for the transcatheter group and 2.6 ± 0.8 years for the surgical group. There were no cases of aortic aneurysm/pseudoaneurysm.

Discussion

In this study, we demonstrated that in comparison with surgical therapy, transcatheter stent therapy was associated with similar acute clinical and hemodynamic results, as shown by acute reduction in Doppler gradient and SBP at the time of hospital discharge. More importantly, the clinical and hemodynamic results were maintained in both treatment arms, as demonstrated by similar temporal change in Doppler gradient, SBP, and ULE-SBP gradient during mid-term follow-up. These data suggest that transcatheter stent therapy had similar mid-term outcomes compared with surgical therapy in adults with COA.

A diagnosis of COA is associated with a higher risk of cardiovascular mortality compared with the general population, and the excess cardiovascular mortality is attributed to left ventricular dysfunction resulting from chronic pressure overload and premature coronary artery disease.^1-5,8 Surgical therapy provides an acute relief of left ventricular pressure overload, but some patients will require reintervention because of recurrent COA.^2,8,15,16 Transcatheter stent therapy is a less-invasive alternative to surgery for the treatment of native and recurrent COA.^6,7,12,17 In a multicenter study of a combined cohort of pediatric and adult COA patients, Forbes et al⁶ showed that in comparison with surgical therapy, transcatheter stent therapy was associated with a similar acute reduction in ULE-SBP gradient and lower risk of procedural complications. Similar acute clinical and hemodynamic improvement after transcatheter stent therapy has been reported in studies conducted in pediatric and adult COA patients,^15,18 and studies conducted exclusively in adults.^17,19 The result of the current study is consistent with these previous studies.

Although there are robust data showing immediate hemodynamic improvement after transcatheter stent therapy,^6,7,12,17 how well these hemodynamic results are maintained during mid-term follow-up has not been well studied. In the multicenter study by Forbes et al,⁶ transcatheter stent therapy and surgical therapy had similar SBP and ULE-SBP during intermediate follow-up, defined as 18-60 months post intervention. The median age at the time of intervention in that study was 10 years, and there was no subgroup analysis comparing outcomes in patients older than 18 years at the time of intervention. This creates a problem translating these data to clinical practice, since age is a known prognostic indictor of procedural success, complications, and reintervention.^2,3,8 While the mid-term outcome results in our study were similar to those of Forbes et al,⁶ our results were based exclusively on data from adults. The mid-term outcomes in the current study were based on comparative analyses of both clinical (SBP) and hemodynamic (Doppler gradient) indices, which increases the robustness of our data.

A major concern of transcatheter stent therapy for COA is the potential need for intervention, which results in an increased cumulative procedural risk.⁶ Of 217 patients who underwent transcatheter stent therapy in the study by Forbes et al,⁶ a total of 35 (16%) had planned reintervention while 9 (4%) had unplanned reintervention. In the current study, the rate of planned reintervention was 4% and the rate of unplanned reintervention was 2%, which is lower than reported by Forbes et al.⁶ We speculate that the lower rate of reintervention in our study might be related to older age, since pediatric patients were excluded from the study.

In clinical practice, the anatomy of the thoracic aorta plays a significant role in deciding between surgical vs transcatheter therapy for patients with recurrent COA.^20-22 Patients with long-segment COA and hypoplastic aortic arch are often referred for surgical therapy, because these anatomic features are considered unfavorable for transcatheter stent therapy.^20-22 Both the transcatheter and surgical groups had similar thoracic aortic anatomy after propensity matching, suggesting comparable outcomes after transcatheter vs surgical therapy regardless of the anatomy of the thoracic aorta.

Study limitations. This is a non-randomized, retrospective, single-center study conducted in a tertiary center, and it is therefore prone to selection and referral bias. In the absence of randomization, it is impossible to completely eliminate selection bias even with propensity matching. Procedural volume and expertise are known predictors of outcomes; hence, it is unknown how well these results would be replicated at other centers. Finally, the study was limited by small sample size (especially in the transcatheter stent therapy arm), which increases the risk of type II error. 

Conclusion

Transcatheter stent therapy was associated with similar acute reduction in Doppler gradient and SBP as compared with surgical therapy. The temporal changes in Doppler gradient and SBP were similar between the transcatheter and surgical therapy groups. While previous studies have demonstrated that transcatheter therapy provides similar acute hemodynamic results compared with surgical therapy, the current study shows that both therapies had similar clinical and hemodynamic outcomes at mid-term follow-up. Since transcatheter therapy is less invasive and requires a shorter hospital stay, these results support the use of transcatheter therapy as alternative to surgery based on favorable results during short-term and mid-term follow-up. Further studies are required to determine whether these favorable outcomes are also maintained during long-term follow-up.

Acknowledgment. The authors wish to thank James Welper and Katrina Tollefsrud for performing offline measurements of the echocardiographic indices used in this study.

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From the ¹Department of Cardiovascular Medicine, ²Division of Pediatric Cardiology, and ³Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota. 

Funding: Dr Egbe is supported by National Heart, Lung, and Blood Institute (NHLBI) grant K23 HL141448. 

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Final version accepted July 17, 2020.

Address for correspondence: Alexander Egbe, MD, MPH, FACC, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905. Email: egbe.alexander@mayo.edu