EPIDEMIOLOGIA ED EZiOPATOLOGIA DELLE VALVULOPATIE AORTICHE G EPIDEMIOLOGIA ED EZiOPATOLOGIA DELLE VALVULOPATIE AORTICHE G. Caruso anatomia patologica Universita ‘ di Bari Heartline IRCCS S. Martino Genova Cardiology meeting 14-15 novembre 2014

MALATTIE VALVOLARI AORTICHE STENOSI INSUFFICIENZA FORME MISTE Prevalente stenosi Prevalente insufficienza

La stenosi aortica è la più diffusa malattia delle valvole cardiache Secondo le stime più recenti, questa affezione colpisce il 4,6% della popolazione oltre i 75 anni, un quinto dei quali deve essere operato nel giro di 2-3 anni di anni, altrimenti non può sopravvivere. Nonostante la gravità, questa per gli esperti è una malattia sottovalutata e spesso non trattata in maniera appropriata Da una ricerca dell’istituto britannico Opinion Matters su un campione rappresentativo della popolazione italiana over 60 è emerso che solo il 7,7% delle persone è preoccupata per le valvole cardiache. Sono i tumori (24,6%) e il morbo di Alzheimer (20%) le malattie che spaventano di più. The Huffington Post

Eziopatologia delle valvulopatie aortiche Congenite Valvola uni/bicuspide Acquisite Displasia senile fibro-calcifica Malattia reumatica

valvulopatie aortiche: acquisizioni recenti Congenite Valvola uni/bicuspide patologia di per sé? Acquisite Displasia senile fibro-calcifica malattia aterosclerotica? Malattia reumatica simile patogenesi? Altre rare patologie Patologie acquisite su base congenita? Fibrosi e calcificazione su valvole tricuspidi/bicuspidi asimmetriche?

Anatomia vs Patologia Abbiamo in mente un aspetto “ideale” di una valvola cardiaca Più ci si allontana da questo ideale più aumenta il rischio di patologia acquisita Varianti anatomiche Senilità sono perfetti substrati per vere patologie 6

varianti anatomiche/patologie congenite Anomalo numero delle cuspidi Unicuspide Bicuspide Quadricuspide Atresia Anomala proporzione fra le cuspidi Anomala struttura Cuspidi displastiche Quadricuspid valve AO valve atresia

Modificazioni senili della valvola aortica Accentuazione delle lunule Fenestrazioni Vegetazioni marantiche escrescenze di Lambl formazioni trombotiche con evoluzione fibrotica

Numerose varianti Patologiche Bicuspid and dysplastic valve with both coronary arteries arising from the anterior facing sinus. Bicuspid valve with the leaflets and sinuses arranged in left–right fashion. A raphe is present in the right leaflet A valve with three thickened leaflets. One of the leaflets is considerably larger than the other two. This valve with three leaflets has been cut longitudinally to show the thick and gelatinous looking leaflets. There are abundant calcific nodules in this severely stenotic valve from an elderly patient. This unicommisural and unifoliate valve has a tiny eccentric orifice. Ho S Y Eur J Echocardiogr 2009;10:i3-i10

Quadro anatomo-patologico della valvola e chirugia Lo stato della valvola riguarda il cardiochirurgo? Opzione chirurgica Solo la valvola Valvola e radice aortica Solo radice aortica Morfologia della valvola Numbero delle cuspidi Fibrosi/calcificazione Patologie associate Coronarie Bulbo/Aorta ascendente

Bulbo e aorta ascendente Aortic bulbus The enlarged part where the cusps are situated Diameter 1.5 superior in respect to proximal ascending aorta Ascending aorta From the bulbus up to the first bifurcation of the aortic arch Sinutubular junction Immediately above the three aortic sinuses   11 11

Valvola aortica Bicuspide 1 –2 % della popolazione maschio/femmina 3:1 Familiarità Cuspidi spesso asimmetriche Ostio di aspetto semilunare Cuspidi: “antero-posteriore” 60-70% 2 coronarie nel seno anteriore “lato a lato” 30-40% 1 coronaria per seno Presenza variabile di un rafe o falsa commissura 36-59% Distribuzione coronarica a dominanza sinistra 4 volte piu comune origine sovracommissurale dell’ostio cor. sin. 2 volte più comune

Aortic valve disease and clinical implications Aortic valve disease is one of the most common congenital cardiac defects, occurring in 5% of all children with heart disease. Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, affecting 1-2% of the population, with strong male predominance. Individuals may have a normally functioning BAV, and may be unaware of its presence and the potential risk of impending complications. They may typically remain asymptomatic until the third or fourth decade of life, when the valve becomes dysfunctional. BAV is associated with both valve disease and aortic disease, thereby leading to increased morbidity and mortality, including other cardiovascular malformations coronary anomalies, coartaction etc. aortic valve disorders aortic wall abnormalities endocarditis Bicuspid aortic valve phenotype and aortic disease: a magnetic resonance study David W Fitz*, James C Carr and Edwin Wu J Cardiovasc MR 2011

Classification of bicuspid aortic valve Four valve morphologies on 217 cases: type 1, fusion of the right and left cusps (n=152); type 2, fusion of the right and non-coronary cusps (n=48); type 3, fusion of the left and non-coronary cusps (n=9); and unicuspid, two fusions (n=8). further characterized by the number of sinuses, two or three, and the presence or absence of a raphe. Conclusion Type 1 BAV is the most frequent phenotype. Two sinus valves are more common among type 2 and type 3 phenotypes. Type 2 is associated with moderate to severe aortic stenosis a larger mid-ascending aortic diameter. Bicuspid aortic valve phenotype and aortic disease: a magnetic resonance study David W Fitz*, James C Carr and Edwin Wu J Cardiovasc MR 2011 Type 1 Type 2

Bav and ascending aorta pathology Anatomo-Clinical demonstration of progressive aortic dilatation Abnormalities in components of the extracellular matrix or aberrant vascular matrix remodeling might contribute to abnormal valvulogenesis and a structurally weakened aortic root. Other studies supports the concept of an independent aortic remodeling process throughout childhood among patients with a bicuspid aortic valve may precede frank aneurysm formation.

Complications of the bicuspid aortic valve Fibrosis Calcification Thrombosis Infections Hemolisis DISSECTION Sudden death? Fibrosis and Calcification

Bav vs tav Ascending aortic dilatation is rarely associated with coronary artery disease regardless of aortic valve morphology Differences in clinical presentation between patients with tricuspid aortic valves (TAVs) or bicuspid aortic valves (BAVs) and aortic valve disease are evident. METHODS: 702 patients with aortic valve and/or ascending aortic pathology; 202 also had concomitant coronary artery disease. RESULTS: A BAV was commonly found in patients with isolated valve disease (BAV 47%, TAV 53%) and frequently associated with ascending aortic dilatation (BAV 80%, TAV 20%). In patients with coronary artery disease, a TAV was commonly found (TAV 84%, BAV 16%). The combination of ascending aortic dilatation and coronary artery disease was markedly rare regardless of valve morphology (TAV, 7 out of 38; BAV, 6 out of 127). The distribution of valve pathology and clinical parameters was similar in patients with TAV and BAV with coronary artery disease (P ≥ .12). Without coronary artery disease, parameters associated with cardiovascular risks were more often seen in patients with TAV than in patients with BAV (P ≤ .0001). J Thorac Cardiovasc Surg. 2014 Aug 17. pii: S0022-5223(14)01114-3. doi: Jackson V1, Eriksson MJ2, Caidahl K2, Eriksson P3, Franco-Cereceda A4

Ascending aortic dilatation is rarely associated with coronary artery disease regardless of aortic valve morphology (2) CONCLUSIONS: Coronary artery disease is uncommon in surgical patients with BAV, but it is associated with TAV, advanced age, and male gender. Coronary artery disease and ascending aortic dilatation rarely coexist, regardless of valve phenotype. Differences in the prevalence of coronary artery disease or ascending aortic dilatation between patients with TAV and BAV are not explained by differences in cardiovascular risks or the distribution of valve pathology. J Thorac Cardiovasc Surg. 2014 Aug 17. pii: S0022- 5223(14)01114-3. doi: Jackson V1, Eriksson MJ2, Caidahl K2, Eriksson P3, Franco-Cereceda A4.

Stenosi valvolare senile calcifica non patologia displastica - patogenesi simil-aterosclerotica

Fattori aterogeni/genetici

Valvola aortica calcifica The process of valve disease is believed to be initiated with the development of atherosclerosis along the aortic surface of the valve which, subsequent to aortic valvular osteoblast differentiation, calcifies. Early in the disease process, the thickened aortic valve is said to be sclerotic; that is, although thickening of the valves is present, there is not yet obstruction of the valve orifice.  Later in the disease process, as the thickening of the valve progresses and the valve orifice becomes significantly obstructed, the valve is said to be frankly calcific. Comparsa di elementi infiammatori Ruolo patogenetico? Secondaria alla fibrosi?

Malattia reumatica In rheumatic fever, antistreptococcal antibodies produced by B lymphocytes cross- react with host-tissue epitopes, producing inflammation in a number of organ systems, including the heart and its mitral and aortic valves. Any or all 4 valves may be involved. Inflammation induces angiogenesis in the normally avascular valve layers; over a period of months or years, thickening of the valve develops as inflamed elastic tissue becomes replaced by irregular masses of collagen fibers. Recurrent episodes of rheumatic fever produce progressive damage to the host’s valves.

Cause rare di stenosi valvolare aortica renal failure, familial hypercholesterolemia, Paget disease, systemic lupus erythematosus, ochronosis with alkaptonuria, Radiation left ventricular noncompaction systemic lupus erythematosus

Cause rare e nuove di stenosi valvolare aortica IgG4-related disease of the aortic valve: a report of two cases and review of the literature. Cardiovasc Pathol. 2014 Sep 28. pii: S1054-8807(14)00085-4. doi: 10.1016/j.carpath.2014.08.001. Maleszewski JJ1, Tazelaar HD2, Horcher HM3, Hinkamp TJ4, Conte JV5, Porterfield JK6, Halushka MK7. A case of aortic and mitral valve involvement in granulomatosis with polyangiitis. Cardiovasc Pathol. 2014 Aug 4. Espitia O1, Droy L2, Pattier S3, Naudin F4, Mugniot A5, Cavailles A4, Hamidou M6, Bruneval P7, Agard C6, Toquet C2. Aortic valve replacement in systemic sclerosis. J Cardiovasc Med (Hagerstown). 2014 Mar 12. Ferrari G1, Pratali S, Pucci A, Bortolotti U.

Valvulopatie aortiche diverse Patogenesi simile? Forme infiammatorie Fusione delle cuspidi Calcificazione Inizia dal margine aortico Forme diverse all’inizio Alla fine si somigliano tutte

Patologie valvolari aortiche ed eta’ Bicuspidia Associazione con lesioni aortiche Post-infiammatorie Possibili recidive, quadri sistemici Forme senili Progressivo aumento