Long-term results (22 years) of the Ross Operation a single institutional experience

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Long-term results (22 years) of the Ross Operation a single institutional experience Authors: Costa FDA, Schnorr GM, Veloso M,Calixto A, Colatusso D, Balbi EM, Torres R, Ferreira ADA, Colatusso C Department of Cardiovascular Surgery INC- Cardio

Ross Operation - 22 Years Results Evaluate the long-term results (22 Years) of the Ross Operation with emphasis on: Late survival Causes and incidence of reoperations Late functional evaluation of the Pulmonary Autograft (PA) Late functional evaluation of the RVOT allograft Department of Cardiovascular Surgery INC- Cardio

Ross Operation - 22 Years Results Study Period: May 1995 thru October 2017 Total experience 526 patients Patients: n = 477 (includes all consecutive patients operated at the author s official institution) Age: 31.1 ± 13.1 years (min = 3, max = 60) Sex: Male 351 (73.6%), Female 126 (26.3%). 38 with concomitant mitral valve disease 8 with Ascending Aortic Aneurysm 26 with Bacterial Endocarditis 5 with Coronary Insufficiency Department of Cardiovascular Surgery INC- Cardio

Ross Operation Patient Demographics Ross Operation - 22 Years Results Etiology Bicuspid/Unicuspid valves 264 (55,3) Rheumatic 138 (28,9) Degenerative 28 (5,9) Endocarditis (Native + Prosthetic Valves) 26 (5,5) Others 21 (4,4) Predominant aortic hemodynamics Stenosis 150 (31,4) Regurgitation 183 (38,4) Mixed lesion 144 (30,2) Rhythm Sinus 459 (97,6) Atrial fibrillation 8 (1,7) Pacemaker 9 (0,5) Complete AV block 1 (0,2) LV ejection fraction 50% 432 (90,6) 31% to 49% 40 (8,4) 30% 5 (1,0) NYHA functional class I 108 (22,7) II 211 (44,2) III 135 (28,3) IV 23 (4,8) Previous aortic valve interventions 67 (14,0)

Ross Operation - 22 Years Results Total Root Replacement 419 Inclusion Technique (MiniRoot) 58 Myocardial Protection Intermittent Cold Blood Cardioplegia Cross Clamp Time 113 ± 26 min (min = 37, max = 226) ECC Bypass Time 138 ± 33 min (min = 58, max = 300) Department of Cardiovascular Surgery INC- Cardio

Ross Operation Operative Data Ross Operation - 22 Years Results Operative Technique Root Replacement 419 (87,8) Inclusion 58 (12,2) Additional Aortic Procedures External Annular Reduction 44 (9,2) Comissural Plication 9 (1,9) Mannouguian 9 (1,9) Konno 11 (2,3) Reduction Aortoplasty 59 (12,3) Concomitant Procedures Mitral Valve Repair 38 (8,0) CABG 15 (3,1) Congenital Anomalies Repair 10 (2,0) Ascending Aorta Replacement 8 (1,7) Aortic Annulus Diameter < 27mm 345 (72,3) 27mm 132 (27,6)

Ross Operation 22 Years Results RVOT Reconstrucion Group I Cryo Allografts...202 Group II- Cryo + DOA Dcell valves...42 Group III Cryo + SDS Dcell Valves... 37 Group IV Fresh + SDS Dcell Valves...196 Department of Cardiovascular Surgery INC- Cardio

Ross Operation 22 Years Results Postoperative Evaluation Clinical Examination Echocardiography Before hospital discharge 6/12 months PO, annualy thereafter CT scan studies Follow-up Clinical Follow-up 451 patients (94,5% complete) Mean clinical follow-up time = 9,4 years (0,1 22,0) Mean echo follow-up time = 7,6 years (0,1 21,9) Department of Cardiovascular Surgery INC- Cardio

Ross Operation - 22Years Results Statistical Analysis Actuarial Survival and Event-Free Survival for Pulmonary Autograft or RVOT Allograft Dysfunction or Reoperation- Kaplan-Meier Method Time related events- Risk factors for Pulmonary Autograft and RVOT Allograft Dysfunctionunivariate analysis with the Log Rank Mantel Cox Test and multivariable analysis with Cox Regression models Department of Cardiovascular Surgery INC- Cardio

Ross Operation - 22 Years Results Results - Early Mortality 2,5% (12/477) Low Cardiac Output Syndrome 5 Intraoperative Hemorrhage 3 Intractable Ventricular Fibrillation 1 Anomalous Circumflex Artery Injury 1 First Septal Injury 1 Left Main Angulation 1 Last 150 cases 2 deaths = 1.3% mortality Department of Cardiovascular Surgery INC- Cardio

Ross Operation - 22 Years Results Results - Late Mortality 31 cases (31/451) 6,8% Valve-Related 10 Sudden death 7 Endocarditis PA and/or RVOT allograft 2 Stroke 1 Cardiac -Related 11 Progressive CHF 7 Acute Myocardial Infarction 2 Pulmonary Embolism 2 Non- cardiac causes 10 Car accident 2 HIV + Meningitis 1 Drowning 1 Acute Abdomen 1 Murder 1 Colon cancer 1 Unknown 3 Department of Cardiovascular Surgery INC- Cardio

Ross Operation Actuarial Survival Survival at 20 years = 81.6% (CI95% = 75.3 88.4%)

Ross Operation - 22 Years Results Clinical Follow-up Late Functional Status NYHA I - 374 patients NYHA II - 77 patients NYHA III - 12 patients NYHA IV 1 patient 11 cases of Thromboembolism 0,28%/patient-year 2 Major Bleeding 0,05%/patient-year 9 cases of Bacterial Endocarditis- 0,23%/patient-year Department of Cardiovascular Surgery INC- Cardio

Ross Operation - 22 Years Results Reoperations (n=65 patients, 70 procedures) Pulmonary Autograft (PA) 38 RVOT Allograft 14 Mitral Valve 9 Myocardial Revascularization 4 Department of Cardiovascular Surgery INC- Cardio

Indications for Reoperations on the Pulmonary Autograft Conservative Approach Severe Aortic Regurgitation Root Aneurysm 55 mm or with documented increase > 3mm/year Moderate AR + Root Size 50 mm Endocarditis with valvular lesion or nonresponsive to medical therapy Pseudo-aneurysms at suture lines Ross Operation 22 Years Results

Ross Operation 22 Years Results Indications for Reoperation on the Pulmonary Autograft (n=38) Root Dilatation + AI 17 Endocarditis 4 Pure AI 11 Quadricuspid pulmonary autograft 1 Proximal Pseudo-Aneurysm 2 Rheumatic involvement 1 Supra-aortic stenosis 1 Technical distortion 1

Mean time to reoperation = 7,8 years ( min =0,1 y max =21 years) Reoperative Mortality = 7,7% (Both in endocarditis cases) No Mortality in Elective Reoperations 20 Patients (52%) retained their original PA Reoperations on the PA Operations Performed Ross Operation 22 Years Results Ao Homograft 9 David/Yacoub 15 Valve repair 3 Ao Bioprosthesis 4 Fistula closure 2 Bentall operation 4 Supra-aortic repair 1

Aortic Valve Repair for Pulmonary Autograft Dilatation with AR

Table 5. Risk Factors for More than Mild AI at Late Follow-up Risk Factor Hazard Ratio (95% CI) p value Sex (male) 1,45 (0,79 to 2,69) 0,23 Age 20 40 0,63 (0,35 to 1,13) 0,12 > 40 0,76 (0,39 to 1,47) 0,41 Valve Lesion AI 1,70 (0,87 to 3,33) 0,12 Mixed 1,29 (0,63 to 2,63) 0,47 Etiology Bicuspid (congenital) 1,14 (0,66 to 1,98) 0,63 Etiology Degenerative 1,30 (0,45 to 3,78) 0,63 Etiology Endocarditis 2,72 (0,93 to 7,96) 0,06 Etiology Others 1,16 (0,27 to 4,98) 0,83 Implantation Technique: inclusion 1,19 (0,57 to 2,53) 0.63 Aortic Annulus 27mm 2,00 (1,14 to 3,50) 0,01 Annulus Reduction 2,12 (1,10 to 4,07) 0,02 Aortoplasty 1,74 (0,82 to 3,69) 0,14 Previous Operation 1,08 (0,56 2,07) 0,81 Multivariable Cox Regression: Aortic Annulus > 27mm HR 1,76 95% CI 0,98-3,15: p= 0,05 Aortic Annulus Reduction HR 2,05 CI 1,02 4,09: p=0,04

Table 6. Risk Factors for Root Diameter 45mm at Late Follow-up Risk Factor Hazard Ratio (95% CI) p value Sex (males vs females) 9,09 (2,20 to 37,60) 0,0023 Age 20 40 0,92 (0,44 to 1,89) 0,82 > 40 0,94 (0,40 to 2,18) 0,89 Valve Lesion AI 3,88 (1,33 to 11,28) 0,01 Mixed 3,41 (1,15 to 10,10) 0,02 Etiology Bicuspid (congenital) 1,48 (0,73 to 3,01) 0,27 Etiology Degenerative 4,55 (1,69 to 12,22) 0,026 Etiology Endocarditis 4,023 (1,19 to 15,05) 0,02 Etiology Others 2,85 (0,63 to 12,86) 0,17 Implantation Technique: inclusion 1,64 (0,50 to 5,33) 0,40 Aortic Annulus 27mm 10,30 (4,04 to 26,21) <0,0001 Annulus Reduction 3,20 (1,62 to 6,33) 0,0008 Aortoplasty 1,35 (0,47 to 3,82) 0,56 Previous Operation 1,35 (0,64 12,82) 0,41 Multivariable Cox Regression : Aortic Annulus > 27mm (HR 7.51 95% CI 2.91-19.35; p=0.000) Males (HR 4.28 95% CI 1.01-18.00; p=0.04) Aortic Insuf. (HR 2.54 95% CI 0.87-7.44; p=0.08) Mixed (HR 2.82 95% CI 0.94-8.46; p=0.06)

Ross Operation Risk Factors for Root Dilatation

FRESH DECELLULARIZED VERSUS STANDARD CRYOPRESERVED PULMONARY ALLOGRAFTS FOR RVOT RECONSTRUCTION DURING THE ROSS OPERATION A PROPENSITY MATCHED STUDY Authors: Jonathan Etnel, Paula H Suss, Danielle F. Collatusso, Eduardo M. Balbi Filho, Gabriela M. Schnorr, Myrian Wisniewski, Francisco Diniz Affonso da Costa

PATIENTS AND METHODS Ross Operations - 521 119 RVOT RECONSTRUCTION WITH DIFFERENT ALLOGRAFTS (EXCLUDED) GROUP SCA (N=202) Standard Cryopreserved Allografts GROUP DA (N=200) Fresh Decellularized Allografts PROPENSITY MATCHING GROUP SCA (N=130) GROUP DA (N=130)

Freedom from Allograft Dysfunction Unmatched Matched SCA = 43 events (1.82%/year) DA = 10 events (1.47%/year) HR = 0.68, (95% CI: 0.32-1.44, p=0,311) Freedom from Dysfunction at 8 years DA = 87.1% ( 95%CI: 67.8-95.2) SCA = 84.4% ( 95%CI: 78.4-88.9) SCA = 25 events (1.55%/year) DA = 7 events (1.28%/year) HR = 0.54, (95%CI:0.26-1.12, p=0,09) Freedom from Dysfunction at 8 years DA = 86.7% (95%CI: 63.6-95.6) SCA = 87.3%( 95%CI: 80.1-92.0)

LONGITUDINAL ECHO ANALYSIS

Decellularized Pulmonary Allograft with Decellularized Human Pericardium Extension Patent Pending

Ross Operation - 22Years Results The Ross Operation is associated with excellent functional recovery and long-term survival up to 20 years of followup. The Pulmonary Autograft, when implanted as a root replacement has acceptable durability, especially in patients with pure Aortic Stenosis. Males, with a dilated aortic annulus and preoperative diagnosis of AI are at incresead risk for developing late AI and root dilatation. Progressive AI/PA dilatation may indicate the need for future reoperations after the second decade of follow-up Technical Aspects/Patient Selection.

Ross Operation - 22 Years Results Although cryopreserved allografts provides good long-term results for the RVOT reconstruction, the incidence of elevated peak gradients is not negligible. The use of fresh decellularized allografts valves is emerging as a better alternative to RVOT reconstruction. Proximal Pericardium extension may improve RVOT allograft function even further.