Pulmonary vascular remodeling in the Fontan

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The Fontan circula on is a surgical pallia on for pa ents with a func onally univentricular heart, resul ng in a chronic non-‐pulsa le pulmonary flow. The Fontan.
Adverse  Pulmonary  Vascular  Remodeling  in  the  Fontan  CirculaKon    

F.J.S.  Ridderbos  BSc  1  •  D.  Wolff  BSc1  •  A.  Timmer  MD  PhD2  •  J.  van  Melle  MD  PhD3  •  T.  Ebels  MD  PhD4  •  M.G.  Dickinson  MD1  •    W.  Timens  MD  PhD2  •    R.M.F.  Berger  MD  PhD1                                           1Center  for  Congenital  Heart  Diseases,  Beatrix  Children's  Hospital,  Department  of  Pediatric  Cardiology,  2Department  of  Pathology,  3Department  of  Cardiology,  4Department  of  Cardiothoracic  Surgery,  University  Medical  Center  Groningen,  University  of  Groningen,  The  Netherlands  

Purpose   Purpose  

The  Fontan  circulaKon  is  a  surgical  palliaKon  for  paKents  with  a  funcKonally  univentricular  heart,  resulKng  in  a  chronic  non-­‐pulsaKle  pulmonary  flow.  The  Fontan   circulaKon  is  characterized  by  gradual  aSriKon  over  Kme.  An  increase  of  the  pulmonary  vascular  resistance  could  be  a  key  factor  in  the  long  term  failure  of  the   Fontan  circulaKon.  The  current  study  aimed  to  invesKgate  the  presence  of  pulmonary  vascular  remodeling  in  paKents  with  a  Fontan  circulaKon.    

Methods  

Pulmonary  vascular  histomorphometric  analysis  and  immunohistochemistry  were  performed  in  lung  Kssue  obtained  at  autopsy  from  12  Fontan  paKents.  The   Fontan   paKents   had   died   either   peri-­‐operaKvely   (group   A:   death   during   or     <   15   days   aXer   Fontan   compleKon;   N=5)   or   at   mid-­‐   to   long   term   follow   up         (group  B:  death  >  5  years  aXer  Fontan  compleKon;  N=7).  Two  age-­‐matched  control  groups  (N=10  and  N=14,  respecKvely)  were  included.    

Figure  1.  Wall  thickness  small  pulmonary  vessels   group  A  (peri-­‐operaKve  death)  

Wall  thickness  

Figure  3.  Wall  thickness  and  muscularizaKon  of   small  pulmonary  vessels  in  group  B  (long  term)  

Figure  4.  InKma  fibrosis  of  small  pulmonary  vessels  in  group  B  (long   term)  

Control  

Wall  thickness  

Figure  6.  CorrelaKon  age  at  death  and     vascular  remodeling  in  group  B  (long   term)  

Total  wall  thickness   One  control  vessel  and  four  typical  examples  of  eccentric  acellular  inHma  fibrosis   in  the  intra-­‐acinar  pulmonary  vessels  of  group  B  (long  term)  Fontan  paHents.  Note   the   acellular   thickened   vessel   wall   and   the   difference   with   the   control   vessel   in   lumen  area.  Verhoeff  staining,  scale  bar  =  50  µm  

Results  

Figure  5.  Histology  of  small  pulmonary  vessels  in  group  B  (long  term)  

p=0.028  for  total  wall  thickness   Figure  2.  Media  hypertrophy  in  group  A     (peri-­‐operaKve  death)  

 

p=0.002  for  total  wall  thickness;  p=0.028  for   media  thickness  and  p