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Address for reprints: Puja Kachroo, MD, Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, Barnes-Jewish Hospital, Campus Box 8234, 660 S Euclid Ave, St Louis, MO 63110.
Division of Cardiothoracic Surgery, Department of SurgeryDivision of Cardiovascular and Thoracic Surgery, Missouri Baptist Medical Center, BJC Health Care, St Louis, Mo
This study evaluated the impact of anatomic aortic root parameters during valve-sparing root replacement on the probability of postoperative aortic insufficiency and freedom from aortic valve reoperation.
Methods
From 1995 to 2020, 177 patients underwent valve-sparing root replacement (163 reimplantations, 14 remodeling). Preoperative and postoperative echocardiograms were analyzed to measure annulus and sinus diameters, effective height of leaflet coaptation, and degree of aortic insufficiency. Logistic regression was used to evaluate predictors of 2+ or greater late postoperative aortic insufficiency. Fine-Gray regression determined predictors for aortic valve reintervention.
Results
The study population included 122 (69%) men with a mean age of 43 ± 15 years. A total of 119 patients (67%) had an identified connective tissue disorder. The cumulative incidence of aortic valve reoperation was estimated as 7% at 5 years and 12% at 10 years. The probability of 2+ or greater late postoperative aortic insufficiency was inversely related to effective height during valve-sparing root replacement (P = .018). As postoperative effective height fell below 11 mm, the probability of 2+ or greater aortic insufficiency exceeded 10%. On multivariable logistic regression, effective height (odds ratio, 0.53; 0.33-0.86; P = .010), preoperative annulus diameter (odds ratio, 1.44; 1.13-1.82; P = .003), and degree of preoperative aortic insufficiency (odds ratio, 2.57; 1.45-4.52; P = .001) were associated with increased incidence of 2+ or greater late postoperative aortic insufficiency. On multivariable Fine-Gray regression, risk factors for aortic valve reintervention included preoperative annulus diameter (subdistribution hazard ratio, 1.28 [1.03-1.59], P = .027), history of 3+ or greater aortic insufficiency (subdistribution hazard ratio, 4.28; 1.60-11.44; P = .004), and 2+ or greater early postoperative aortic insufficiency (subdistribution hazard ratio, 5.22; 2.29-11.90; P < .001).
Conclusions
Measures to increase effective height during valve-sparing root replacement may decrease the risk of more than mild postoperative aortic insufficiency after repair and the need for aortic valve reoperation.
VSRR is deemed to be a safe but technically challenging procedure to repair the aortic root. Its advantages are offset by the complexity of repair that may be required. Increasing leaflet coaptation and stabilization of a large annulus may correct abnormal aortic root geometry and prevent future aortic valve reinterventions.
Valve-sparing root replacement (VSRR) has been demonstrated to be a safe and effective treatment for aneurysmal disease of the aortic root.
Systematic review and meta-analysis of surgical outcomes in Marfan patients undergoing aortic root surgery by composite-valve graft or valve sparing root replacement.
The ability to treat aortic root aneurysms with a durable valve-sparing repair is ideal for patients of all age groups and is especially beneficial for younger patients who would otherwise be subject to prosthetic valve degeneration or thromboembolic complications after mechanical valve replacement. Several studies have demonstrated its efficacy in patients with connective tissue disorders and bicuspid valves.
Systematic review and meta-analysis of surgical outcomes in Marfan patients undergoing aortic root surgery by composite-valve graft or valve sparing root replacement.
Despite introduction of aortic valve-sparing techniques in the early 1990s, they have not been widely adopted and remain a daunting reparative strategy for early career surgeons.
The durability of repair is likely dependent on more than 1 factor and is generally assessed by the degree of aortic insufficiency (AI) postrepair. Mild AI at 1 year has been noted after VSSR in a high percentage of patients, and initial midterm results indicated that mild postoperative AI may remain stable over time.
A recent study demonstrated progression of postoperative AI over time, particularly in patients who had more than mild AI after repair, and the authors recommended continued monitoring after VSRR.
The severity of regurgitation after aortic valve repair has been shown to be dependent on the restoration of normal 3-dimensional configuration of the aortic valve. Few studies have evaluated the components of anatomic aortic root to evaluate possible variables predictive of durable repair. Effective height has been highlighted as a potential factor for failure after valve repair.
We sought to identify anatomic variables, measured by 2-dimensional echocardiography, to determine the relationship between these variables and the development of postoperative AI and the need for reoperation.
Materials and Methods
Data Sources
This study was approved by the Washington University School of Medicine and the Missouri Baptist Medical Center Institutional Review Boards with a waiver for patient consent. Preoperative data, operative details, and perioperative results were obtained from our institutional Society of Thoracic Surgeons database supplemented by review of electronic medical records, including review of every operative report. Longitudinal outcomes were obtained through chart review of electronic medical records and contact with physicians and patients when necessary. Follow-up was 100% complete.
Patient Population
From August 1995 to September 2020, 191 patients underwent VSSR at 2 affiliated hospitals (Barnes Jewish and Missouri Baptist Medical Center). Fourteen patients who underwent prior cardiac surgery, including those with history of previous Ross procedure, were excluded, leaving 177 patients for this retrospective analysis (Figure E1). In general, the indication for VSRR included aortic root diameters 4.5 cm or greater or 5 cm for patients with Loeys-Dietz and Marfan syndrome, respectively, and 5.5 cm or greater in patients without connective tissue disorders and patients with acute type A aortic dissection. Patients with bicuspid valves, who required concomitant procedures (valve, coronary, or arrhythmia surgeries), and who required more extensive aortic reconstructions were included. The decisions regarding type of repair (reimplantation vs remodeling) or type of graft (tube vs Valsalva) were made by the operating surgeon. The operating surgeon's decision to select a certain graft size was not routinely described in the operative reports.
Echocardiogram Evaluation
The following anatomic variables were measured on the intraoperative prerepair and immediate postrepair transesophageal echocardiograms (TEEs) and on later postoperative TEE or transthoracic echocardiograms (TTEs): diameters of the preoperative aortic annulus or aortoventricular junction, sinuses of Valsalva, sinotubular junction (STJ), and ascending aorta (Figure E2). The effective height, defined as the distance from the virtual basal ring to the central tip of the leaflets, after repair was also determined. The degree of AI was assessed by color Doppler and graded as follows: 0 (none), 1+ (trace), 2+ (mild), 3+ (moderate), and 4+ (severe). To minimize reporter variability in interpretation, all echocardiographic parameters were retrospectively reviewed by a single experienced cardiac surgeon. All intraoperative TEE findings were corroborated by our cardiac anesthesiologists, and all late TTE findings were corroborated by our institutional cardiologists. The primary and secondary end points for the study were the presence of late 2+ or greater postoperative AI and reintervention on the aortic valve, respectively. We also recorded the need for additional interventions for other nonvalve-related procedures. The median echocardiographic follow-up was 5.7 (1.1-11.3) years.
Statistical Analysis
Continuous variables were reported as mean ± standard deviation or median with interquartile range as appropriate. The Shapiro–Wilk test was used for initial evaluation from normality, and departures from normality were secondarily evaluated graphically with a histogram of the data and normal probability plot. Categorical variables were expressed both as frequencies and percentages. All data analysis was performed using R version 3.6.1 (The R Foundation for Statistical Computing) statistical software using the cmprsk package.
For the outcome of 2+ or greater AI immediately postrepair, potential variables were evaluated using binary logistic regression. Significant covariates on univariate analysis with P less than .2 were entered into a multivariable binary regression model using stepwise selection. Survival over time was evaluated by Kaplan–Meier methodology.
Durability of the operation was assessed by aortic valve reintervention rates over time. Reintervention was evaluated using competing risks methodology. Composite end point survival (freedom from reintervention and death) was reported as a Kaplan–Meier estimate. Cumulative incidence functions were generated for reintervention and death during the follow-up period. The probability of being both alive and free from reintervention was equivalent to the probability of experiencing neither of the competing risks. This composite end point was presented alongside the cumulative incidence functions for both death and reintervention. These 3 states were considered mutually exclusive, with the first temporal event (death or reoperation) dictating transition to that terminal state. Variables of reintervention were identified using Fine-Gray subdistribution hazards regression. A P value less than .2 threshold was used for inclusion into the multivariable model.
Results
Baseline Characteristics
The study population included 122 (69%) male and 55 (31%) female patients with a mean age of 43 ± 15 years. Mean body mass index was 26.4 ± 5.9, and a small proportion of patients (8%; 15) were African American. A total of 119 patients (67%) had syndromic heritable thoracic aortic disease (HTAD) (Loeys-Dietz syndrome, n = 22; Marfan syndrome, n = 84, other, n = 13). The most commonly occurring comorbidities were hypertension (44%; 78) and current tobacco abuse (32%; 56) (Table 1).
Table 1Baseline characteristics
Demographics n = 177
Age (y)
43 ± 15
BMI (kg/m2)
26.4 ± 5.9
African American race
15 (8%)
Male gender
122 (69%)
Comorbidities
Diabetes
6 (3%)
Current tobacco abuse
56 (32%)
Peripheral vascular disease
14 (8%)
Chronic lung disease
17 (10%)
Hypertension
78 (44%)
NYHA class III/IV
14 (8%)
Pulmonary hypertension
4 (2%)
Arrhythmia
12 (7%)
Dialysis
2 (1%)
Prior MI
5 (3%)
Prior stroke
7 (4%)
Prior cardiovascular intervention
17 (10%)
Connective tissue disorder (n = 119; 67%)
119 (67%)
Marfan
83 (47%)
Loeys-Dietz
24 (13%)
Other
12 (8%)
Values are n (%) or mean ± standard deviation, unless otherwise indicated. BMI, Body mass index; NYHA, New York Heart Association; MI, myocardial infarction.
The intraoperative and postoperative details are shown in Table 2. A total of 163 patients (92%) underwent the reimplantation David I technique, and 14 patients (8%) had the remodeling procedure. The median aortic graft size was 30 (28-32) mm. Stabilization or reduction of the annulus diameter was not used in any of the patients who underwent the remodeling procedure. The majority of procedures were performed electively (94%; 167). The median duration of cardiopulmonary bypass was 178 (161-198) minutes, and the median duration of aortic occlusion was 151 (136-167) minutes.
Table 2Operative variables
Outcome n = 177
Operative characteristics
Status
Elective
167 (94%)
Urgent/emergency
10 (6%)
Cardiopulmonary bypass time (min)
178 [161-198]
Aortic crossclamp time (min)
151 [136-167]
Graft size
30 [28-32]
Additional aortic operation
Total aortic arch replacement
4 (2%)
Hemiarch replacement
28 (16%)
Remaining ascending aorta replacement
69 (39%)
Concomitant procedures
AV repair
8 (5%)
MV repair
9 (5%)
CABG
9 (5%)
VSD closure
1 (1%)
Cox-Maze IV
4 (2%)
30-d postoperative outcomes
Reoperation for bleeding
10 (6%)
Pneumothorax
1 (1%)
Sepsis
1 (1%)
Pneumonia
3 (2%)
Prolonged ventilation
8 (5%)
Renal failure
1 (1%)
Permanent stroke
0 (0%)
Postoperative atrial fibrillation
35 (20%)
Pacemaker
3 (2%)
Pericardial window
1 (1%)
Sternal wound infection
3 (2%)
Multisystem organ failure
1 (1%)
30-d mortality
0 (0%)
Values are n (%) or median with interquartile range [IQR], unless otherwise indicated. AV, Aortic valve; MV, mitral valve; CABG, coronary artery bypass graft; VSD, ventricular septal defect.
The most commonly performed concomitant aortic operations were replacement of the remaining ascending aortic (39%; 69) and hemiarch (16%; 28). Replacement of the entire arch was performed in 4 patients (2%). Eight patients (5%) underwent concomitant cusp or commissural repair. Other procedures performed were mitral valve repair (5%; 9), coronary artery bypass grafting (9; 5%), Cox-Maze IV (2%; 4), and ventricular septal defect closure (1%; 1).
Complications
There was no 30-day or hospital mortality in this cohort. The most common early postoperative complication was atrial fibrillation (20%; 35). Three patients (2%) required postoperative pacemaker implantation. Ten patients (6%) underwent reoperation for bleeding, and 8 patients (5%) required prolonged ventilation. Other complications occurred at lower frequency and are detailed in Table 2. No patient had a stroke in the early postoperative period.
Echocardiographic findings over time with respect to AI are shown in Figure 1 and Table 3. Preoperative echocardiograms were available for 168 patients. The mean ejection fraction before surgery was 57% ± 9%. At the time of surgery, 67 patients (40%) had 2+ or greater AI, 45 patients (27%) had 1+ AI, and 56 patients (33%) had no AI. The median annulus diameter was 25 (23, 27) mm, and the median sinus diameter was 5.0 (4.6, 5.2) cm.
Figure 1Degree of AI over time with VSRR. TEE or TTE from the early preoperative (n = 168), immediately after repair (n = 170), and late follow-up (n = 162) time periods was used to measure degree of AI. Corresponding estimates are shown in Table 3.
Early postrepair echocardiograms were available for 170 patients. No patients had 4+ AI, and 2 patients had 3+ AI. The percentage of patients with 2+ or greater AI decreased from 40% (67 patients) to 8% (14 patients). Fifty-two patients (31%) had greater than 1+ AI, and 104 patients (61%) had 0 AI. The median effective height was measured at 12 (11, 13) mm.
Late echocardiograms were available for 162 patients. If serial echocardiograms were performed, the most recent was used for analysis. Twenty-eight patients (17%) had 2+ or greater AI (6 with 3+ and 9 with 4+), 63 (39%) had 1+ AI, and 71 (44%) had 0 AI.
Predictors of 2+ or Greater Aortic Insufficiency
The probability of 2+ or greater postoperative AI was inversely related to effective height during VSRR (P = .018). As postoperative effective height fell below 11 mm, the probability of 2+ or greater AI exceeded 10% (Figure 2). On multivariable logistic regression, effective height (mm) (odds ratio [OR], 0.53 [0.33-0.86], P = .010), preoperative annulus diameter (mm) (OR, 1.44 [1.13-1.82], P = .003), and each degree of preoperative AI (OR, 2.57 [1.45-4.52], P = .001) were associated with increased incidence of late 2+ or greater postoperative AI (Table E1). History of 3+ or greater AI on prior echocardiogram (P = .202) and graft size (mm) (P = .333) were not significant on multivariable analysis.
Figure 2Probability of 2+ or greater AI as a function of effective height after VSSR. AI, Aortic insufficiency.
The 10- and 20-year survivals were 91% and 88%, respectively (Figure 3). A total of 16 patients required aortic valve reintervention for replacement over the study period. The cumulative incidence of aortic valve reoperation was estimated to be 7% at 5 years and 12% at 10 years (Figure 4 and Table E2). The causes for valve failure leading to reintervention were cusp prolapse (n = 7), retraction of leaflets (n = 6), leaflet calcification, and subsequent stenosis (n = 1), dehiscence of sinus from graft (n = 1), and disruption due to biological glue (n = 1). The time to intervention from the index procedure ranged from as early as 1 month to 13 years later.
Figure 3Kaplan–Meier depiction of late survival for patients who underwent VSSR (red) with 95% CIs (grey).
Figure 4Competing risks graph shows the probability of aortic valve reintervention (blue) and death (green) as cumulative incidence functions and probability of survival without reintervention (orange) by Kaplan–Meier composite end point. Corresponding estimates are shown in Table E2.
On multivariable Fine-Gray regression, independent risk factors for aortic valve reintervention included preoperative annulus diameter (mm) (subdistribution hazard ratio [SHR], 1.28 [1.03-1.59], P = .027), history of 3+ or greater AI (SHR 4.28 [1.60-11.44], P = .004), and 2+ or greater postoperative AI (SHR 5.22 [2.29-11.90], P < .001) (Table E3). Effective height (mm) (P = .271) and graft size (mm) (P = .318) were not associated with reintervention on multivariable analysis.
Discussion
Changes in the complex geometry of the aortic root occur with a root aneurysm, including dilation of the sinuses of Valsalva, the STJ (when the wall tension increases), and the aortic annulus. These changes may also result in alteration of cusp anatomy and function, resulting in cusp prolapse or retraction and unrepairable fenestrations.
The goal of surgery to repair the aortic root is to restore the normal anatomy and function not only at the levels of the STJ and ascending aorta but also by addressing the basal and commissural regions of the annulus. Patlolla and colleagues
suggested that valve-sparing strategies that stabilize the aortic annulus may result in a more durable repair, with lower shear stresses on the cusp surfaces. These reports are consistent with our findings that increased preoperative aortic annulus diameter is associated with an increased incidence of 2+ or greater AI and reintervention. Bierbach and colleagues
evaluated cusp geometry and found that effective height (measured directly at operation and by TTE) was highest in patients without residual AI. The majority of patients in their study who had effective height 9 mm or greater did not have any or only trivial AI. In our study, effective height was inversely related to probability of 2+ or greater AI and the probability exceeded 10% when effective height was less than 11 mm (Figure 5). Le Polain de Waroux and colleagues
identified parameters from postrepair TEE that predicted late failure. These included residual, especially eccentric, AI, dilated annulus, short coaptation length, and coaptation below the level of the annulus. The major abnormality associated with recurrent severe AI was cusp prolapse. Pethig and colleagues
described the type of coaptation (type A: within the prosthetic graft; type B: at the lower border of the graft; type C: 2 mm or greater below the graft) and observed that type C was associated with significantly higher prevalence of AI at both early and 1 year postoperatively. We did not identify any patients in our study who left the operating room with type C prolapse.
Figure 5A total of 177 patients underwent VSRR in whom several risk factors for postoperative AI and aortic valve reintervention were identified. Ultimately, increasing effective height during VSRR may decrease AI and risk of reoperation. AI, Aortic insufficiency.
Regarding the role of VSRR in patients with acute type A aortic dissection, Kunihara and colleagues demonstrated valve durability with the remodeling technique that was comparable to that observed with graft replacement of the ascending aorta.
They measured effective height since 2004 and added annuloplasty procedures in 2009. They reported excellent results in the setting of type A aortic dissection, with only 7% in hospital mortality and 8% reoperation rate for bleeding since 2007. Our experience with VSRR for acute type A aortic dissection was limited to 10 patients, but the outcomes were comparable to those of the remaining 167 patients.
evaluated 1015 patients who underwent VSRR in a German multicenter study to determine mortality and need for subsequent valve replacement. They did not demonstrate a negative impact of preoperative AI on freedom from aortic valve reintervention at 8 years (84% if no AI present vs 89% if any degree of AI was present preoperatively). Our study demonstrated a statistically significant higher prevalence of reintervention for patients with a history of moderate to severe AI and those with 2+ or greater AI postrepair. Stephens and colleagues,
using the David V Stanford Modification of VSRR, found that mild AI was common after repair, but that this did not increase the risk of long-term failure. In our study, only 2 patients had 3+ AI after repair, and correction of the AI was not undertaken. Although no patient had 4+ AI early postoperatively, 9 patients (5%) developed 4+ AI during the follow-up interval and required reintervention. The time to reintervention ranged from 1 month to 13 years postoperatively.
The majority of patients in our study had connective tissue disorders. Annular dilation is common in these conditions, and the remodeling technique has been identified as a risk factor for late failure.
We did not observe higher rates of failure for patients with HTAD or observe a higher rate of late AI or reintervention among the patients who underwent the reimplantation procedure (Video 1).
Study Limitations
The operations were performed mainly by 2 experienced surgeons at 2 institutions with established aortic surgery programs, and the results may not be generalizable. The reimplantation technique was used in all but 14 patients, and the study was not powered to compare the differences in outcome between this technique and the reimplantation technique. Analysis of outcomes for patients with bicuspid aortic valves was also not undertaken because of the small sample size. The majority of patients in our study had HTAD, which limited analysis of this condition as a risk factor for either reintervention or 2+ or more postoperative AI. Given the asymmetry of the aortic root, 2-dimensional measurements of the aortic root obtained by TTE are not likely to be as accurate as measurements obtained by intraoperative or 3-dimensional echocardiography. Using the parasternal long-axis view from TTEs, we focused mainly on the right and noncoronary cusps. We were able to standardize our measurements against those from other studies.
Conclusions
VSRR remains an excellent, durable option for treating aortic root pathology in patients with different aortic valve pathology or connective tissue disorders, and in select patients with acute type A aortic dissection. The results of our study suggest that measures to increase the effective height of leaflet coaptation may reduce the risk of more than mild AI after repair and the need for aortic valve reintervention. Interventions to stabilize a large aortic annulus may also improve late outcomes.
M.R.M.: Consultant for Medtronic. All other authors reported no conflicts of interest.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
Systematic review and meta-analysis of surgical outcomes in Marfan patients undergoing aortic root surgery by composite-valve graft or valve sparing root replacement.
This work was supported by grants from the Barnes-Jewish Foundation.
Washington University School of Medicine Institutional Review Board (IRB): IRB ID #201908191, current approval date: 9/9/2020. This study was approved by the Washington University School of Medicine IRB with a waiver for patient consent.
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