Selected Aortic Valve Procedures: Ross Pulmonary Autograft and Aortic Valve-Sparing Re-implantation

Number: 0407

Policy

1. Aetna considers the Ross pulmonary autograft procedure medically necessary for members undergoing aortic valve replacement secondary to either congenital anomalies or aortic valve disease, such as:

   1. Aortic incompetence (including endocarditis, rheumatism of the heart); or
   2. Aortic stenosis; or
   3. Complex left ventricular outflow tract obstruction; or
   4. Congenital lesions.

   Contraindications to this procedure are presented as an Appendix to the Background section.

   Aetna considers the Ross pulmonary autograft experimental and investigational for all other indications (e.g., middle-aged or older adults when suitable alternatives to autograft replacement of the aortic valve are available with comparable results and without the need for replacement of the right ventricular outflow tract, and individuals with bicuspid valves and aortic regurgitation or aortic dilation if other alternatives are available) because its effectiveness for indications other than the ones listed above has not been established.

2. Aetna considers the minimally invasive approach to the aortic valve a medically necessary acceptable alternative to the conventional approach to aortic valve replacement.

3. Aetna considers aortic valve-sparing re-implantation medically necessary for the treatment of secondary aortic regurgitation due to aortic root dilatation as occurs in Marfan syndrome as well as for the treatment of type A acute aortic dissections (i.e., dissection of the ascending and descending aorta).

   Aetna considers aortic valve-sparing re-implanatation experimental and investigational for all other indications because its effectiveness for indications other than the ones listed above has not been established.

4. Aetna considers aortic valve-sparing procedures medically necessary for the treatment of aortic root ectasia, and dissection and aneurysms of the ascending aorta.

5. Aetna considers the decellularized Matrix P bioprosthesis experimental and investigational for pulmonary valve replacement for Ross procedures because the safety and effectiveness of this approach has not been established.

6. Aetna considers the Florida Sleeve valve-sparing procedure experimental and investigational for the treatment of aortic root ectasia and aneurysm because the long-term safety and effectiveness of this approach has not been established.

Background

Patients undergoing aortic valve replacement may consider 3 options:

1. a prosthetic valve,
2. a homograft valve, or
3. a pulmonary autograft (i.e., the Ross procedure).

Ross pulmonary autograft refers to essentially a double valve replacement in which the native pulmonic valve is substituted for the diseased aortic valve, while a homograft prosthetic valve replaces the pulmonic valve.  This procedure was first devised in 1967 and sought to provide a permanent aortic valve substitution, which would not degenerate like a homograft valve and would not require chronic anti-coagulation therapy like a prosthetic valve.  The risk:benefit ratio involves a balance between a more complicated surgical procedure (essentially a double valve replacement) and a potentially more durable and physiologic aortic valve replacement.  Furthermore, it is thought that the autografted pulmonary valve will grow with the young patient, thus obviating the need for re-operation.  Studies have also shown that the Ross procedure resulted in significant improvement in left ventricular wall thickness and outflow tract velocity not observed in allograft aortic valve replacements in children.  For these reasons, the Ross procedure is considered most appropriate for young adults.  Candidates for this procedure should be adequately counseled on the various valve replacement alternatives.

In a systematic review and meta-analysis, Takkenberg et al (2009) stated that the Ross procedure provides satisfactory results for both children and young adults (less than or equal to 50 years of age).  Furthermore, David (2009) noted that young adults with aortic stenosis and normal-size aortic root are the best candidates for the Ross procedure.

Aortic valve-sparing re-implantation is a valve-sparing technique employed for patients with aortic regugitation secondary to aortic root dilatation in which valvular insufficiency is due to outward displacement of the valve commissures.  This technique, which is different from aortic valve repair, has the advantages of lack of requirement for anti-coagulation and avoidance of other problems and complications associated with mechanical prosthetic valves.  Although primarily used for secondary aortic regurgitation due to root dilatation as occurs in Marfan syndrome, guidelines from the European Society of Cardiology (Erbel et al, 2001) stated that aortic valve-sparing re-implantation may also be indicated for patients with type A acute aortic dissections (i.e., dissection of the ascending and descending aorta).

The Society of Thoracic Surgeons’ “Aortic valve and ascending aorta guidelines for management and quality measures” (Svensson et al, 2013) stated that

• The Ross procedure is not recommended for middle-aged or older adults when suitable alternatives to autograft replacement of the aortic valve are available with comparable results and without the need for replacement of the right ventricular outflow tract (RVOT), as the latter adds the additional risk of pulmonary valve dysfunction and subsequent replacement.  (Level of evidence C)
• The Ross procedure is not recommended for patients with bicuspid valves and aortic regurgitation or aortic dilation if other alternatives are available.  (Level of evidence C)

Guidelines from the European Society of Cardiology (Erbel, et al., 2014) state that In most cases of aortic insufficiency associated with acute Type A dissection, the aortic valve is essentially normal and can be preserved by applying an aortic valve-sparing repair of the aortic root. In cases of aneurysms of the ascending aorta, where total replacement is indicated, the choice between a valve-sparing intervention and a composite graft with a valve prosthesis depends on the analysis of aortic valve function and anatomy, the size and site of TAA, life expectancy, desired anticoagulation status, and the experience of the surgical team.

Similarly, guidelines from the American College of Cardiology (Hiratzka, et al., 2010) state that extensive dissection of the aortic root should be treated with aortic root replacement with a composite graft or with a valve sparing root replacement.

Stephens et al (2014) examined if recurrent or residual mild aortic regurgitation, which occurs after valve-sparing aortic root replacement, progresses over time.  Between 2003 and 2008, a total of 154 patients underwent Tirone David-V valve-sparing aortic root replacement; 96 patients (62 %) had both 1-year (median of 12 ± 4 months) and mid-term (62 ± 22 months) transthoracic echocardiograms available for analysis.  Age of patients averaged 38 ± 13 years, 71 % were male, 31 % had a bicuspid aortic valve, 41 % had Marfan syndrome, and 51 % underwent aortic valve repair, predominantly cusp free margin shortening.  A total of 41 patients (43 %) had mild aortic regurgitation on 1-year echocardiogram.  In 85 % of patients (n = 35), mild aortic regurgitation remained stable on the most recent echocardiogram (median of 57 ± 20 months); progression to moderate aortic regurgitation occurred in 5 patients (12 %) at a median of 28 ± 18 months and remained stable thereafter; severe aortic regurgitation developed in 1 patient, eventually requiring re-operation.  Five patients (5 %) had moderate aortic regurgitation at 1 year, which did not progress subsequently.  Two patients (2 %) had more than moderate aortic regurgitation at 1 year, and both ultimately required re-operation.  The authors concluded that although mild aortic regurgitation occurs frequently after valve-sparing aortic root replacement, it is unlikely to progress over the next 5 years and should not be interpreted as failure of the valve-preservation concept.  Further, these investigators suggested that mild aortic regurgitation should not be considered non-structural valve dysfunction, as the 2008 valve reporting guidelines would indicate.  The authors noted that 10- to 15-year follow-up is needed to learn the long-term clinical consequences of mild aortic regurgitation early after valve-sparing aortic root replacement.

In a retrospective study, Gamba and colleagues (2015) evaluated their experience of using a simplified aortic valve sleeve procedure to treat aortic root ectasia and aneurysms with or without aortic regurgitation.  In experienced hands, 2 aortic valve-sparing procedures, namely, Yacoub and David, have yielded excellent long-term results in the treatment of aortic root aneurysms, with or without aortic regurgitation.  However, these techniques are demanding and not widely used.  Recently, a new and simplified valve-sparing technique, named "sleeve procedure", has been proposed, and has yielded encouraging early results.  A total of 90 consecutive patients with aortic root aneurysms underwent sleeve procedures from October 2006 to October 2012.  Follow-up data (clinical 100 % complete and echocardiographic 93 % complete) were acquired from the authors’ out-patient clinic or from the referring cardiologist.  The mean age of the patients was 61.5 ± 12.5 years, 79 % were male, 16 (18 %) had a bicuspid valve, 3 had Marfan syndrome, and 2 had aortic dissection.  Over a mean clinical follow-up of 34 ± 19 months, 2 patients died from non-cardiac causes and 1 was re-operated on for the recurrence of aortic regurgitation.  On follow-up echocardiography after a mean of 18 ± 9 months, aortic regurgitation was absent/negligible, mild or moderate in 62 %, 37 %, and 1 % of patients, respectively, and the diameters of the annulus, Valsalva sinuses, and sino-tubular junction were 27.3 + 2.2, 37.0 + 3.4, and 30.6 + 3.1 mm, respectively.  The authors concluded that these encouraging early and medium term results suggested that the sleeve procedure is a safe and effective aortic valve-sparing technique for the treatment of aortic root ectasia and aneurysm.  However, they stated that longer follow-up is needed in order to draw definitive conclusions.

Bavaria and colleagues (2015) noted that valve-sparing root reimplantation (VSRR) in tricuspid aortic valve (TAV) patients is well-established, but in bicuspid aortic valve (BAV) patients, it has been less widely adopted. These investigators examined if valve type affects mid-term outcomes with VSRR.  They performed a retrospective review of 186 patients who underwent an aortic valve-sparing root reimplantation operation between 2004 and 2013.  Of these, 129 patients underwent elective VSRR with the David V technique.  Outcomes were compared in this cohort by valve type: TAV (n = 89) versus BAV (n = 40).  Demographics were similar in the 2 groups – BAV patients had a higher degree of aortic insufficiency (AI) at presentation (p < 0.05), and an enlarged pre-operative annulus (30 ± 4 versus 28 ± 6 mm, p = 0.06).  All BAV patients required primary leaflet repair (6 % in the TAV group; p < 0.01).  Post-operative mortality (0), stroke (0 % versus 1 %), and pacemaker requirement (0 % versus 5 %) were similar.  Post-operative freedom from AI grade greater than or equal to 2+ was 100 % in the entire cohort, and trans-valvular gradients were similar.  At follow-up, a 1-year echocardiogram (ECG) showed higher peak and mean trans-valvular gradients in the BAV group (p < 0.01).  One TAV group patient died from an unknown cause.  The 5-year actuarial freedom from aortic valve reoperation was 100 % versus 97 % ± 3 % (p = 0.6); 3 patients in the entire cohort have had AI grade greater than 2+ on follow-up (n = 1 in the BAV group; n = 2 in the TAV group).  The authors concluded that even though BAV patients presented with higher AI grade and required concomitant primary valve repair, the VSRR David V technique offered excellent mid-term outcomes with both the BAV and TAV valve types.

Malvindi and associates (2015) stated that aortic valve-sparing operation has been progressively widely performed for the treatment of aortic root aneurysm. Nowadays, this procedure has been proposed even in presence of a BAV, severe aortic regurgitation or in primary aortic dissection repair.  These investigators presented their 10-year experience focusing on mid-term ECG follow-up.  Between June 2002 and February 2012, a total of 139 patients (mean age of 61 ± 12 years) underwent aortic valve-sparing operation with valve reimplantation; 27 patients (19 %) had BAV; in 18 cases (13 %) cusp motion or anatomical abnormalities concurred in determining aortic regurgitation and needed an adjunct cusp repair.  A Gelweave Valsalva graft was implanted in all the patients.  The mortality pre-discharge was 0.7 % (1 patient).  The cumulative 1-year, 5-years and 8-years survival rates were 99 %, 93 % and 87 %, respectively.  Post-operative aortic regurgitation more than mild degree (greater than 2+/4+) was the only significant risk factors for redo aortic valve surgery freedom from reoperation due to aortic valve regurgitation was 96 % at 1 year, 90 % at 5 years and 86 % at 8 years.  When comparing freedom from reoperation in patients with BAV versus TAV, no differences were found (p = 0.31) and the rate of aortic valve reoperation was significantly higher (p < 0.001) in patients who received leaflet's repair.  The authors concluded that the durability of valve reimplantation was found to be excellent in patients with TAV and normal or nearly normal cusps.  Cusp prolapse and complication after cusp repair turned out to be the main causes for early failure.

The Ross Procedure versus Other Aortic Valve Replacement

Um and colleagues (2018) noted that life expectancy in young adults undergoing mechanical or bioprosthetic aortic valve replacement (AVR) may be reduced by up to 20 years compared to age-matched controls.  The Ross procedure is a durable, anticoagulation-sparing alternative.  These investigators performed a systematic review and meta-analysis to compare the valve hemodynamics of the Ross procedure versus other AVR.  They searched Cochrane CENTRAL, Medline and Embase from inception to February 2017 for randomized controlled trials (RCTs) and observational studies (n of greater than or equal to 10 Ross).  Independently and in duplicate, these researchers performed title and abstract screening, full-text eligibility assessment, and data collection.  They evaluated the risk of bias with the Cochrane and CLARITY tools, and the quality of evidence with the GRADE framework.  The authors identified 2 RCTs and 13 observational studies that met eligibility criteria (n = 1,412).  In observational studies, the Ross procedure was associated with a lower mean aortic gradient at discharge (mean difference [MD] -9 mmHg, 95 % confidence interval [CI]: -13 to -5, p < 0.0001, I2 = 97 %) and latest follow-up (MD -5 mmHg, 95 % CI: -7 to -3, p < 0.0001, I2 = 92 %).  There was no significant difference in the incidence of severe aortic regurgitation at latest follow-up (relative risk [RR] 1.3, 95 % CI: 0.3 to 5.8, p = 0.70, I2 = 30 %).  In RCTs, the Ross procedure was associated with a lower mean gradient at latest follow-up (MD -15 mmHg, 95 % CI: -32 to 2, p = 0.08, I2 = 99 %).  The mean pulmonic gradient for the Ross procedure was 18.0 mmHg (95 % CI: 16 to 20, p < 0.0001) at latest follow-up.  The evidence for all outcomes from observational studies was deemed to be of very low quality, while the evidence from RCTs was down-graded for imprecision and moderately serious risk of bias.  The authors concluded that compared to conventional AVR, the Ross procedure was associated with better aortic valve hemodynamics.  These researchers stated that future studies should evaluate the impact of the Ross procedure on exercise capacity and quality of life (QOL).

In a propensity-matched study, Mazine and colleagues (2022) compared the long-term outcomes of patients undergoing the Ross procedure and those receiving bioprosthetic AVRs.  Consecutive patients aged 16 to 60 years who underwent a Ross procedure or surgical bioprosthetic AVR at the Toronto General Hospital between 1990 and 2014 were identified.  Propensity score matching was employed to account for differences in baseline characteristics.  The primary outcome was all-cause mortality; and secondary outcomes included valve re-intervention, valve deterioration, endocarditis, thrombo-embolic events, and permanent pace-maker implantation.  Propensity score matching yielded 108 pairs of patients.  The median age was 41 years (inter-quartile range [IQR]: 34 to 47 years).  Baseline characteristics were similar between the matched groups.  There was no operative mortality in either group.  Mean follow-up was 14.5 ± 7.2 years.  All-cause mortality was lower following the Ross procedure (hazard ratio [HR]: 0.35; 95 % CI: 0.14 to 0.90; p = 0.028).  Using death as a competing risk, the Ross procedure was associated with lower rates of re-intervention (HR: 0.21; 95 % CI: 0.10 to 0.41; p < 0.001), valve deterioration (HR: 0.25; 95 % CI: 0.14 to 0.45; p < 0.001), thrombo-embolic events (HR: 0.15; 95 % CI: 0.05 to 0.50; p = 0.002), and permanent pace-maker implantation (HR: 0.22; 95 % CI: 0.07 to 0.64; p = 0.006).  The authors concluded that the Ross procedure was associated with better long-term survival and freedom from adverse valve-related events compared with bioprosthetic AVR.  In specialized centers with sufficient expertise, the Ross procedure should be considered the primary option for young and middle-aged adults undergoing AVR.

Decellularized Matrix P Bioprosthesis for Pulmonary Valve Replacement for Ross Procedures

Christ and colleagues (2019) noted that since 1967, the Ross procedure has been performed to treat aortic valve disease using homografts for pulmonary valve replacement (PVR). The decellularized Matrix P bioprosthesis was developed to overcome (some) limitations of homografts.  Until now, the long-term outcome data have been unavailable.  Between 2002 and 2010, the Ross procedures using the Matrix P bioprosthesis were performed in 492 adult patients (mean age of 57.2 ± 10.6 years, range of 21 to 73 years) at the authors’ institution.  Patient data were prospectively collected and analyzed (3,617.3 patient-years, mean follow-up of 7.7  ±  4.3 years).  Completeness of follow-up at 1, 5 and 10 years was 98.4 %, 94.5 % and 91.0 %, respectively.  Hospital mortality was 3.9 % (n  = 19).  During follow-up, 121 patients died resulting in a survival rate at 5, 10 and 12.5 years of 82.8  ±  1.7 %, 70.4  ±  2.3 %, and 62.4  ±  2.9 %, respectively.  Echocardiography revealed a high incidence of relevant dysfunction of the Matrix P bioprosthesis and subsequent right ventricular failure.  Primary re-operation/re-intervention was necessary for 150 Matrix P and 48 autografts.  Freedom from pulmonary valve re-operation at 5, 10 and 12.5 years was 76.2  ±  2.1 %, 58.6  ±  2.9 % and 53.4  ±  3.4 %, respectively.  The autograft function and the left ventricular function showed similar results as previously reported with a freedom from autograft re-operation at 5, 10 and 12.5 years of 91.8  ±  1.4 %, 86.1  ±  2.0 %, and 86.1  ±  2.0 %, respectively.  The authors concluded that the Matrix P bioprosthesis used for the RVOT reconstruction in the Ross procedure showed unfavorable long-term echocardiographic results with a high rate of re-operation/re-intervention for structural pulmonary valve failure.  As a consequence, long-term survival of this patient cohort was impaired.  The authors concluded that based on these findings, the use of the Matrix P bioprosthesis for PVR for Ross procedures in adults should not be recommended.

The Florida Sleeve Valve-Sparing Procedure for the Treatment of Aortic Root Ectasia and Aneurysm

Aalaei-Andabili and associates (2019) stated that the Florida (FL) Sleeve procedure was introduced as a simplified approach for valve-sparing correction of functional type I aortic insufficiency (AI) associated with aortic root aneurysms.  In this study, these researchers examined the short- and long-term outcomes following the FL Sleeve procedure.  From May 2002 to January 2016, a total of 177 patients underwent the FL Sleeve procedure.  Left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), and degree of AI (none = 0, minimal = 1, mild = 2, moderate = 3, severe = 4) were evaluated by echocardiography.  Mean ± standard deviation of age was 49.41 ± 15.37 years.  Survival rate was 98 % at 1 year, 97 % at 5 years, and 93 % at 8 years.  Freedom from re-operation was 99 % at 1 year and 98 % at 2 to 8 years; 3 patients (1.69 %) died during hospitalization; 3 patients (1.69 %) developed peri-procedural stroke.  Post-operative follow-up echocardiography was available in 140 patients at 30 days, and 31 patients at 5 years.  AI grade significantly improved from baseline at 30 days (2.18 ± 1.26 versus 1.1 ± 0.93, p < 0.001) and at 5 years (2.0 ± 1.23 versus 1.45 ± 0.88, p = 0.04).  Pre-operative mean LVEDD significantly decreased from 52.20 ± 6.73 to 46.87 ± 8.40 (p < 0.001) at 30 days, and from 53.22 ± 7.07 to 46.61 ± 10.51 (p = 0.01) at 5 years.  The authors concluded that the FL Sleeve procedure was a safe, effective, and durable treatment of aortic root aneurysm and type I AI; long-term survival and freedom from re-operation rates were encouraging.

The authors stated that this study had several drawbacks.  First, this was a retrospective and single-center study.  Second, there were no comparison between outcomes of the FL Sleeve procedure and previous aortic valve-sparing (AVS) techniques.  Third, loss to follow-up of patients’ echocardiography measurements.

Wu and co-workers (2019) devised a simple modification of the FL Sleeve procedure to perform AVS surgery.  This technique was simple, quick, effective, and safe.  These researchers employed this technique in operations performed on 2 young patients with Marfan syndrome.  The initial and short-term results were satisfactory.  Moreover, these researchers stated that a larger number of cases and long-term follow-up are needed to prove its durability.

Tasca and colleagues (2020) noted that the Sleeve procedure is one of the options in patients with aortic root diseases and it might be suitable for patients with a bicuspid valve.  From October 2006 to December 2018, a total of 42 consecutive patients with bicuspid aortic valve and aortic root ectasia/aneurysm, with or without aortic regurgitation, were surgically treated with the Sleeve procedure.  In 20 patients (48 %) leaflets surgery was necessary and consisted of raphe mobilization/resection in 17 patients, plication of both leaflets in 2 patients and a 2-commissures re-suspension in 1 patient.  During a mean clinical follow-up time of 4.4 ± 3.1 years, the survival rate was 100 %, 1 patient required a re-operation at 6.1 years post-operatively, with an overall freedom from re-operation of 94 ± 5 %.  The rest of the patients (41/42), had no more than mild residual aortic valve regurgitation.  With a mean follow-up of 4.3 ± 1.7 years the magnetic resonance imaging (MRI) performed in 26 patients, did not show signs of aortic wall herniation through the key-holes or persisting creases of the aortic wall inside the prosthesis.  The authors concluded that patients with aortic root disease and bicuspid aortic valve may be treated with the Sleeve procedure with excellent mid-term results; however, a longer follow-up is needed before drawing any solid conclusion.

Furthermore, an UpToDate review on “Management of Marfan syndrome and related disorders” (Wright and Connolly, 2020) states that “Investigational approaches – We agree with the 2015 Professional Advisory Statement from the Marfan Foundation that there are insufficient data on alternative approaches that reinforce rather than replace an aortic aneurysm (e.g., personalized external aortic root support [PEARS] procedure and "Florida sleeve" repair) to support a recommendation for clinical use at the present time.  Potential advantages include theoretically simpler technique and for PEARS, potential avoidance of use of cardiopulmonary bypass and minimizing the size of the surgical incision.  However, data on these procedures are limited to small numbers of patients at a small number of centers with limited durations of follow-up”.

Holubec and colleagues (2022) compared short- and longer-term outcomes of David (DV) versus FL Sleeve procedure in patients requiring valve-sparing aortic root replacement.  Between January 1996 and December 2020, a total of 285 patients received a DV procedure (median age of 60 years; 26 % females) and 57 patients underwent an FL Sleeve procedure (median age of 64 years; 19 % females) in the authors’ department.  Propensity score matching using patient characteristics led to 58 (DV) versus 57 (FL Sleeve) patients.  Endpoints were defined as primary: freedom from aortic valve and/or aortic root-related re-operation and freedom from aortic regurgitation greater than or equal to moderate and secondary: early and late survival.  The 30-day mortality was 2 % (DV) and 0 % (FL Sleeve) (p = 0.319).  There was 1 early stroke in each group (p = 0.990).  Follow-up was complete in 99 % with only 1 patient (FL Sleeve) lost.  The 5- and 10-year freedom from aortic valve and/or aortic root related re-operation was 98 ± 2 % and 96 ± 3 % in the DV group and 92 ± 5 % and 84 ± 9 % in the FL Sleeve group, respectively (p = 0.095).  The 5- and 10-year freedom from aortic regurgitation greater than or equal to moderate was 88 ± 5 % and 80 ± 8 % in the DV group and 92 ± 5 % and 78 ± 1 % in the FL Sleeve group, respectively (p = 0.782).  The 5- and 10-year survival rates were 93 ± 4 % and 82 ± 6 % (DV) versus 75 ± 7 % and 67 ± 10 % (FL Sleeve), respectively (p = 0.058).  No case of endocarditis (DV) and 3 cases of endocarditis (FL Sleeve) (p = 0.055) were observed during follow-up.  The authors concluded that both DV and FL Sleeve resulted in similar early and longer-term outcomes with a trend to slightly better performance and survival in the DV group.  These researchers stated that the FL Sleeve procedure might be an alternative approach for patients with higher-risk profiles requiring valve-sparing aortic root replacement.

Ross Procedure for Middle-Aged or Older Adults

In a retrospective, single-center study, Guerreiro and colleagues (2019) examined the long-term clinical and echocardiographic outcomes of the Ross procedure.  This study analyzed the findings of 56 adult patients who underwent the Ross procedure.  Mean age at surgery was 44 ± 12 years (range of 16 to 65 years) and 55 % were male.  Clinical endpoints included overall mortality and the need for valve re-operation due to graft failure.  The echocardiographic endpoint was the presence of any graft deterioration.  Median clinical follow-up was 20 years (1,120 patient/years). Indications for surgery were dominant aortic stenosis in 50 % and isolated aortic regurgitation in 21 %.  Concomitant mitral valve repair was performed in 21 % and a sub-coronary technique was most commonly used (86 %).  Overall long-term survival was 91 %, 80 % and 77 % at 15, 20 and 24 years, respectively.  The survival rate was similar to the age- and gender-matched general population (p = 0.44).  During the follow-up period, freedom from graft re-operation was 80 %; 11 patients (31 %) developed moderate AV regurgitation, 3 (8.6 %) developed moderate pulmonary regurgitation, and 1 (2.9 %) presented moderate pulmonary stenosis.  The authors concluded that the Ross procedure, mostly using a sub-coronary approach, proved to have good clinical and hemodynamic results, with low re-operation rates in long-term follow-up.  Moderate autograft regurgitation was a frequent finding but had no significant clinical impact.

Oeser and co-workers (2019) examined the long-term durability and function of pulmonary homografts used for RVOT reconstruction in the Ross procedure at a single center with 25 years of experience.  The study included 274 patients (212 male patients and 62 female patients; age of 3 to 59 years), who underwent the Ross procedure between 1991 and 2014.  Homograft-related complications and re-interventions were evaluated.  Homograft hemodynamic function was determined using trans-thoracic echocardiography (TTE) undertaken by a single cardiologist.  The all-cause 30-day mortality was 1.1 % (3 patients), and there were 17 late deaths; 1 death was associated with a homograft-related complication.  During the observation period (median of 13.3 years; 3,327.5 cumulative patient-years), 21 patients (7.7 %) underwent at least 1 RVOT re-intervention.  Freedom from homograft re-intervention was 95.6 %, 90.4 % and 87.5 % at 10, 15 and 20 years, respectively.  Pediatric patients had a significant lower rate of freedom from re-intervention (log-rank p < 0.001).  Remarkably, all patients who underwent re-intervention were male (log-rank p = 0.009).  Female patients received homografts with a significantly higher (p < 0.001) indexed diameter than male patients, which might be causally related to absent re-interventions in women.  The linearized rate of homograft endocarditis was 0.2 % per patient-year.  At the latest echocardiography (median follow-up time of 14.7 years; 164 patients), the peak trans-homograft pressure gradient was less than 40 mmHg in 150 patients (91.5 %), and homograft incompetence was none or trivial in 111 patients (67.7 %), mild in 49 patients (29.9 %) and moderate in 3 patients (1.8 %).  In 1 patient (0.6 %), it was not possible to determine the degree of incompetence.  Younger patient age (p < 0.001), a smaller homograft diameter (p = 0.014) and an increase in the body surface area (BSA) during the follow-up time (p = 0.006) were significantly correlated with a higher peak trans-homograft pressure gradient.  Men had a significantly higher peak trans-homograft pressure gradient than women (p = 0.018).  The authors concluded that pulmonary homograft provided very satisfying long-term results after the Ross procedure; differences in long-term performance are related to under-sizing and young age.

Chauvette et al (2020) examined the safety and late outcomes of the Ross procedure for the treatment of active infective endocarditis (IE).  From 2000 to 2019, a total of 31 consecutive patients underwent a Ross procedure to treat active IE (mean age of 43 ± 12 years, 84 % male).  All patients were followed-up prospectively; 4 patients (13 %) were intravenous (IV) drug users and 6 patients (19 %) had prosthetic IE.  The most common infective organism was Streptococcus (58 %).  Median follow-up was 3.5 (0.9 to 4.5) years and 100 % complete.  There were no in-hospital deaths; 1 patient suffered a post-operative stroke (3 %) and 1 patient (3 %) required re-intervention for bleeding; 3 patients had a new occurrence endocarditis: 2 patients were limited to the pulmonary homograft and successfully managed with IV antibiotics, whereas 1 IV drug user patient developed concomitant autograft and homograft endocarditis.  Overall, cumulative incidence of IE recurrence was 13 ± 8 % at 8 years.  The cumulative incidence for autograft endocarditis was 5 ± 4 % at 8 years; 2 patients (6 %) died during follow-up, both from drug overdoses.  At 8 years, actuarial survival was 88 ± 8 %.  The authors concluded that in selected patients with IE, the Ross procedure was a safe and reasonable alternative with good mid-term outcomes.

Singh and colleagues (2022) noted that the Ross procedure is rarely considered in older patients.  These researchers compared the peri-operative and long-term outcomes of patients greater than 50 years of age with younger patients after the Ross Procedure.  Between 1992 and 2018, a total of 455 patients underwent the Ross procedure utilizing the inclusion technique.  Patients with redo-surgery, non-aortic procedures and unsupported root replacement were excluded.  The remaining were matched for native valve morphology, valve lesion and annular manipulation and yielded 96 matched pairs.  Pre-operative and operative characteristics, peri-operative outcomes, survival rates, valve related adverse events (AEs) and valve hemodynamics were evaluated.  There was no in-hospital mortality.  The median follow-up was 11 years for both cohorts.  Overall survival at 15 years was similar: 99 % (95 % CI: 89.8 % to 99.8 %) for patients greater than 50 years of age and 98 % (95 % CI: 89.3 % to 99.7 %) for younger patients.  Patients over 50 years had a notable freedom from ross related re-intervention at 15 years: 94 % (95 % CI: 84.8 % to 97.7 %) versus 90 % (95 % CI: 80.2 % to 95.6 %) in younger patients.  The mixed model analysis revealed being 50 years and older was not significantly associated with higher autograft gradient or regurgitation.  Interestingly, being 50 years and older correlated with decreased allograft regurgitation and stenosis.  The authors concluded that older patients undergoing the Ross procedure had comparable outcomes to younger patients.  Patients 50 years of age and over, who have high functioning with minimal co-morbidities, should be considered for the Ross procedure.

In a retrospective, international cohort, multi-center study, Romeo and associates (2021) examined the long-term clinical and echocardiographic outcomes in young and middle-aged patients undergoing the Ross procedure.  This trial had a median follow-up period of 9.2 years; and was carried out in 5 experienced centers regularly performing the Ross procedure.  Consecutive patients aged 18 to 65 years were included by each center between 1991 and 2018.  Main outcomes and measures included survival and autograft-related and homograft-related re-intervention.  Serial echocardiographic measurements of valve function were analyzed using mixed-effects modeling.  During the study period, a total of 1431 patients (74.3 % men; n = 1,063) were operated on at a median age of 48.5 years (mean [SD], 47.7 [9.5]; range of 18.1 to 65 years; inter-quartile range [IQR], 42.7 to 54.0 years).  Implantation techniques were root inclusion in 355 (24.9 %), root replacement in 485 (34.0 %), and sub-coronary implantation in 587 (41.1 %).  Right ventricular outflow tract reconstruction was carried out with homograft in 98.6 % (n = 1,189) and bioprosthesis in 1.4 % (n = 17); 10 patients (0.7 %) died before discharge.  Median follow-up was 9.2 years (13,015 total patient-years).  Survival after 10 and 15 years was 95.1 % (95 % CI: 93.8 % to 96.5 %) and 88.5 % (95 % CI: 85.9 % to 91.1 %), respectively.  Freedom from autograft and homograft re-intervention after 15 years was 92.0 % and 97.2 %, respectively.  Late events were autograft endocarditis in 14 patients (0.11 % per patient-year), homograft endocarditis in 11 patients (0.08 % per patient-year), and stroke in 37 patients (0.3 % per patient-year).  The authors concluded that given its excellent short-term and long-term outcome in young and middle-aged adults in this study, the Ross procedure should be considered in young and middle-aged adults who require aortic valve replacement.  Patients should be referred to an experienced center with a program dedicated to the Ross procedure.

Furthermore, an UpToDate review on “Choice of prosthetic heart valve for surgical aortic or mitral valve replacement” (Gaasch and Suri, 2021) states that “Use of the Ross procedure in adults is controversial and the procedure is performed at only a few experienced centers.  Reasons include its technical complexity; complications with both the aortic autograft and the pulmonic homograft, with long-term risk of requiring reoperation of 20 % or more; and the availability of simpler and effective alternatives (i.e., mechanical valves and bioprosthesis, including stentless bioprosthetic valves).  Even at experienced centers, use of this procedure has waned since the 1990s.  Given its limitations, the pulmonic autograft procedure is predominantly performed in children, as the autograft aortic annulus and valve may have the capacity to grow.  It has also been performed at a limited number of experienced centers in selected adults less than 50 years of age such as athletes or other young patients in whom anticoagulation is contraindicated and for whom optimal hemodynamics are desired (e.g., a woman contemplating pregnancy)”.

Appendix

The pulmonary autograft procedure is contraindicated in individuals with the following conditions:

• Extremes of age; or
• Marfan's syndrome; or
• Multiple pathology in which a second valve replacement device is needed; or
• Multi-vessel coronary artery disease; or
• Severely depressed left ventricular function.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes covered if selection criteria are met:
33390 - 33391	Valvuloplasty, aortic valve, open, with cardiopulmonary bypass
33413	Replacement, aortic valve; by translocation of autologous pulmonary valve with allograft replacement of pulmonary valve (Ross procedure)
33440	Replacement, aortic valve; by translocation of autologous pulmonary valve and transventricular aortic annulus enlargement of the left ventricular outflow tract with valved conduit replacement of pulmonary valve (Ross- Konno procedure)
CPT codes not covered for indications listed in the CPB:
Florida Sleeve valve-sparing procedure - no specific code:
HCPCS codes not covered for indications listed in the CPB:
Decellularized Matrix P bioprosthesis - no specific code:
ICD-10 codes covered if selection criteria are met:
I06.0	Rheumatic aortic stenosis
I06.1	Rheumatic aortic insufficiency
I35.0 - I35.9	Nonrheumatic aortic valve disorders [not covered for individuals with bicuspid valves and aortic regurgitation or aortic dilation if other alternatives are available]
I71.00 - I71.9	Aortic aneurysm and dissection
I77.810 - I77.819	Aortic ectasia [aortic dilation]
Q23.0	Congenital stenosis of aortic valve
Q23.1	Congenital insufficiency of aortic valve
Q25.21 - Q25.4, Q25.8 - Q25.9	Other congenital malformations of aorta

The above policy is based on the following references: