Iatrogenic pathology of the heart:

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Iatrogenic pathology of the heart: Complications of mitral valve plasty and replacement Patrick Bruneval D pt of Pathology Hôpital Européen Georges Pompidou

Enterprise Interest None

Mitral valve surgery Frequent: 4,000 operations/year in France (and 12,000 for aortic valve) [http://www.academie-medecine.fr/wp-content/uploads/2016/11/chir-cardiaque-2025-version-seconderecommendations-fin1.pdf, 2016] In-hospital mortality for valve surgery in France: 4.4% [https://www.hassante.fr/portail/upload/docs/application/pdf/rapport_second_chirurgien_en_chir_cardiaque.pdf, 2007] Mortality and morbidity depending mainly now on patient parameters: age, cardiac, respiratory, renal functions [http://www.euroscore.org/calc.html] From a pioneer cardiac surgery in the 60s and from a technical development cardiac surgery in the 70s- 90s, to now a cardiac surgery which wants to be less invasive, more secure. Operative and early deaths less frequent. Operative diffuse myocardial ischemia (stone heart syndrome), inadequate myocardial preservation during valve surgery Myocardial rupture due to excessive pulling of the papillary muscle during mitral valve excision for replacement Massive mitral valve incompetence following excessive mitral valve commissurotomy

Complications of mitral valve plasty and replacement Mitral valve repair Mitral valve replacement: Mechanical prosthesis Bioprosthesis Valve homografts

Mitral valve repair Carpentier s procedure for mitral valve repair [Carpentier et al. Ann Throc Surg 1978]: quadrangular resection of the prolapsed leaflet segment [including the area with ruptured chordae tendinae (>70%)] remodeling of the annulus because of annular dilatation or deformation requiring the use of a Carpentier s ring. ±"sliding plasty" of the papillary muscle or a "shortening plasty" of the chordae for elongated chordae Mitral valve [from Foster NEJM 2010]

Carpentier s procedure mainly appropriate for degenerative mitral valve disease This is due to the characteristic lesions observed in degenerative mitral valve: mitral annulus dilatation, tissue excess in leaflets (most frequent in the posterior scallop P2), chordae tendinae rupture surgical margins free edge P3 P2 P1 A Normal mitral valve

Carpentier s procedure is efficient and secure Study from a single center (Carpentier s surgery department) [Jouan et al. JTCS 2012]: 200 Barlow s patients, mean follow-up 77.5 mo: Immediate postoperative echocardiography showed residual mitral regurgitation > 1+ in 6 pts (3%) all reoperated Operative mortality was 1.5% (n=3) Overall survival was 88.6% Freedom from reintervention was 95.3% Freedom from late recurrence of moderate mitral regurgitation ( 2+) was 90.2%

Carpentier s procedure failure: Immediate failure Unsatisfactory repair mitral valve incompetence detected at echo performed on beating heart just after unclamping the aorta with open chest most often leads to valve replacement. Anatomical causes for immediate failure are not often obvious for the pathologist on the resected mitral valve: spectrum of patterns: expected normal pattern of repaired leaflet pattern of shortage of leaflet tissue or thickened sutured area pattern the mitral valve disease which is not pure Barlow, showing some restriction by fibrosis and thickened chordae tendinae.

Carpentier s procedure failure: Late failure In the setting of immediate satisfactory repair Late recurrence of regurgitation ± stenosis, years after repair: Rule out endocarditis 2 mechanisms: Progression of the degenerative disease Postoperative scarring

Late failure: Progression of the degenerative disease Case: Mitral valve plasty 12 y. ago; Mitral valve and tricuspid valve incompetence; Cardiac failure; Cardiac transplantation. Anterior leaflet major doming, exces of tissue; Posterior leaflet scarring postplasty + Degenerative tricuspid valve incompetence

Late failure: Postoperative scarring The most frequent mechanism: due to scarring of operative damage from mild fibrous thickening to rheumatism pattern. Changes in the motion of the mitral valve: becomes more restrictive and stenosis can develop. Severe fibrosis Mild fibrous changes

Other procedures for mitral valve repair Pericardial patches: indicated for leaflet perforation (ex. endocarditis) or for restoring normal surface area in some cases of degenerative valve Pericardial patch from glutaraldehyde-treated autologous human or bovine pericardium Complications: retraction, shortening of the patch deformation of leaflet; fibrosis, calcification stiffness of leaflet, restrictive; degenerative opening of the suture; endocarditis. Calcification Hypertrophic cardiomyopathy with mitral valve regurgitation: pericardial patch; immediate failure Fibrosis of patch and chordae tendinae Opening of the suture Degenerative changes in the patch due to the absence of collagen renewal (see bioprosthesis)

Mitral valve replacement by prosthesis Mechanical prosthesis: the most used for mitral valve. Now bileaflets tilting disks in pyrolytic carbon (better flow properties, solidity) with Dacron sewing cuff Advantage: long duration ; Drawback: thrombosis lifetime anticoagulation mandatory First ball prosthesis, Starr, 1960 Björk-Shiley, Lillehei-Kaster 1970 Present Past

Complications of mechanical prosthesis Thrombosis (turbulent flow, thrombogenic materials) Fibrous overgrowth forming a pannus Endocarditis thrombosis, ring dehiscence, ring abscess Periprosthestic leak Cutter ball prosthesis Björk prosthesis All contribute to prosthesis dysfunction: regurgitation, stenosis, occlusion

Mitral valve replacement by prosthesis Bioprosthesis: 3 cusps made of animal tissue: porcine aortic valve (ex. historic Carpentier-Edwards, now Medtronics Hancock) or mainly now bovine pericardium (ex. Carpentier-Edwards Perimount, Magna Ease) sewed on a stent (or no: stentless and sutureless bioprosthesis). Advantage: less or no thrombosis, lifetime anticoagulation not mandatory; Drawback: limited duration Stent, struts 3 cusps of treated bovine pericardium (Carpentier- Edwards Perimount, Magna Ease) Left ventricle outflow aspect Left atrium inflow aspect

Bioprosthesis Bovine pericardium from abattoir company removal of adipose tissue on external side («rough» side) and keep «smooth side» to prepare cusps industrial process using aldehyde for crosslinking extracellular matrix proteins + trade secret process to delay collagen degeneration and calcifications (remove phospholipids, etc ). Hanging/sewing pericardium piece on a stent in a semilunar anatomy Preserved collagen fiber bundles and elastic fibers Dead tissue: acellular (native cells fixed by aldehydes, but dead by fixation, no rejection) So-called «biocompatible» material, but immediate adhesion of platelets, monocytes. Elastic stain Minimal leukocyte and platelet adhesion Monocyte adhesion Sirius red Early patterns of bioprothesis cusps, pericardial

Degeneration: the main complication of bioprothesis Occurs years after implantation structural defects of the cusps mitral valve dysfunction Wide variability among patients: factors influencing degenerative changes: Renal failure, hypercalcemia Young age: bioprosthesis contraindication in children Preparation of pericardium (handmade cleaning, different chemicals ) Less degenerative changes with bovine pericardium than with porcine valves porcine pericardial [Grunekemeier JTCS 2012]

Bioprothesis degeneration Basic phenomena: Calcification: on cell debris, used collagen and elastic fibers Absence of collagen renewal due to absence of synthesis because of absence of living cells Calcifications tears of cusps, perforations, stiffness of cusps Worn out collagen tears and perforations of cusps tissue fatigue prominent in areas with maximum tension (commissure cusp attachment) and maximum flexion/deformation (commissure cusp attachment and attachment margins).

Bioprothesis degeneration valve incompetence ± stenosis Perforations Tears Calcification (stiffness) Carpentier-Edwards 28 yearimplantation (1984 2012)

Hyalinization of collagen Splitting of collagen fiber bundles Calcifications Lipids deposits Bioprothesis degeneration fibrosa porcine Carpentier-Edwards 28 y implantation porcine Carpentier-Edwards 18 y implantation

Complications of bioprothesis: contribute to prosthesis dysfunction: regurgitation, stenosis, occlusion Thrombosis Fibrous overgrowth forming a pannus

Complications of bioprothesis: Contribute to prosthesis dysfunction: regurgitation, stenosis, occlusion Endocarditis thrombosis/vegetation, perforations, ring dehiscence, periannular abcess Periprosthetic leak

Mitral valve replacement by homografts Mitral valve homografts (cryopreserved without aldehydes from Assistance Publique-Hôpitaux de Paris tissue bank) 104 patients Early reoperation: 5 Pts, mainly due to size mismatch between graft and recipient Late reoperation (mean time 53 mo): 10 Pts including 2 for endocarditis and 8 for degenerative structural changes [Ali et al. JTCS 2004]

Mitral valve replacement by homografts Early failure, 2 mo Preserved structure Inflammation consistent with rejection Late failure Loss of structure. Hyalinization of collagen, Calcifications No inflammation

Conclusion Now and future Less surgery and more interventional procedures: MitraClip Explanted unlocked MitraClip devices in EVEREST trial Explanted for mitral valve regurgitation, residual or recurrent (and finally treated by surgery) Ancillary pathology study of removed devices: showed healing phenomenon from inflammation and hemostasis to scar fibrosis (embedding the device) according to time [Ladich et al. Circulation 2011]