Posts Tagged ‘bosentan’

Management of  severe  pulmonary hypertension continues to be a difficult task .Medical therapy is not definitive, in-spite of the new prostocyclins, endothelin antagonists and  sildenafil analogues.Natural history  depends mainly on  the presence of  any treatable cause ( Especially ,connective tissue disorders)  ,  supportive management along with anticoagulation.

Ultimate  strategy  would involve a   plan  for a “Lung “or  “Heart -Lung”transplantation  , if feasible. Last decade saw an innovative modality of creating an  artificial inter atrial  shunt to decompress the right heart .This had varied response in the  real world  , still  most  showed some benefit .In fact , in 1998 the world symposium on PHT ,  formulated guidelines for BAS (Balloon atrial septostomy)

Principle of  Balloon atrial septostomy (BAS)  and mechanism of benefit

The symptomatology  of  pulmonary HT  is largely  determined by mean RA pressure .

Puncturing  the  IAS and diverting blood  flow into left atrium would decompress the RA ( or even the RV )  and reduce the Mean RAP.

The resultant  right to left to shunt  can   increase the cardiac output  only  slightly ,  still  good enough to  provide   relief from the fatigue.(Though at the cost of  desaturation.)

What is the risk involved in the BAS.

Procedural risk of  a cath study in a sick  patient with hypertensive lungs (Can be really high !)

In some patients  even a small  fall in systemic  oxygen saturation can be counter productive.

What is the balloon used ?

Mansfield or Tyshak balloons are good choices .

Balloon diameters are between 5 -14 mm


Involves standard Brockenborough needle /Mullin sheath /Guide wire in pulmonary vein.

Atrial anatomy to  be well  analysed prior to BAS  . (Please note even though it is similar to PTMC , anatomically we encounter a large right atrium rather than left atrium .)

Fluroscopy with  TEE guide optimal

Pulmonary angiogram might help.

Intra-cardiac  Echo may be  ideal.

Blade septostomy may be preferred if hardware is available

The endpoint of procedure

  • Size of ASD > 5mm
  • Fall of arterial saturation < 80 %
  • Sustained atrial fibrillation with hypotension
  • Any  disabling complication

Hemodynamic impact

  • Cardiac output increase by 750 ml to 1 liter
  • It is expected ,  RA  mean pressure  would fall at least 5mmhg from  the baseline value.
  • PA pressure , no significant impact expected.
  • Tricuspid regurgitation regresses.
  • RA,RV size marginal reduction observed.

Follow up and outcome

  1. Greatest  relief is from syncope.
  2. Functional class improvement  in >50% .
  3. One year survival benefit is substantial (75-90%)  .Beats the  natural history (40%) convincingly.
  4. Late deterioration  can occur as ASD gets closed in few.

When  BAS is contraindicated ?

  1. Critical RV failure
  2. Patient in class 4
  3. Mean RA pressure > 20mmhg
  4. Pulmonary vascular resistance index> 55 Wood units / sq.meter

* BAV should not be considered as a  live saving  procedure  in any dying patient with PAH.  It needs to be  selected early and carefully .In fact,  the very high procedural complication  rate is related to late selection of patients.

Natural foramen  PFO better than BAV ?

We do not know yet.It is highly possible  natural opening up of PFO is good thing to happen for patients with severe pulmonary hypertension.


1 . SS Kothari  et all  Indian heart journal 2002

2. http://content.onlinejacc.org/cgi/reprint/32/2/297.pdf

3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC484602/pdf/heart00028-0066.pdf

  4. http://erj.ersjournals.com/content/early/2011/02/24/09031936.00072210.abstract

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Bosentan an non selective endothelin  antagonist is an approved drug  for pulmonary arterial hypertension.

Even this drug has not fully proven it’s worth . Meanwhile ,  a relatively  unknown company manufactured sitaxentan a similar molecule with a  self claimed  selective endothelin blocking property .

Pfizer bought this company and marketed it as Thelien . The liver injury is less  than bosentan , they claimed and it was  prescribed once a day .The same old story unfolds.physiological endothelin  in liver was in appropriately blocked and caused dangerous forms of liver injury.

Only one difference this time , Pfizer self banned this drug and stopped all research activities  about this molecule.


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PAH  is  the major determinant of surgical outcome of left to right shunts. In this  modern era of cardiac care  allowing a child  with   left to right shunt   to progress to a  stage of   Eisenmenger syndrome  is  considered  as a  huge medical failure . But  , this is still rampant in many of the developing countries .

Cardiologists are divided over the issue of  operability of Eisenmenger syndrome .The confusion is largely due to the conflicting data of outcome in these patients. While  there is strong   data  when  PVR exceeds  SVR  ,  the death is imminent in the post operative period .

What has complicated the issue is   there are  many case reports  where severe PAH patients have been successfully operated. Most would think it is a statistical exception and one can  not alter the traditional criteria based on few case reports.

But ,it remains an irony as on 2009 ,  we do not have a proper methodology to assess reversibility of PAH in Eisenmenger syndrome . Further ,  there is a  significant number of  patients with high PVR  , who continue to experience  an  unabated left to right shunting .  We do not have an answer  for either the mechanism of such shunts and  how to manage these patients.

Click over the slide  to view full  PPT  presentation in PDF format .

This short paper was presented in the Annual scientific sessions of cardiological society of India 2009 regarding the usefulness of a new parameter to assess reversibility of PAH. This may not be called as  a study rather a report of  our experience  in  five  patients  with eisenmenger syndrome

Download the full PPT presentation in PDF  format.

pulmonary artery pulse pressure

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