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PERIPARTUM CARDIOMYOPATHY

 

 

 

 

 

 

 

 

 

 

 

 

James D.Fett, MD

Hôpital Albert Schweitzer

Deschapelles, Haiti 

c/o 611 Sumner Ave. 

Aberdeen, WA 98520

Tel. 360-533-5695, 

E-mail:  jdftlsc@techline.com.

10 October 2003, update 25 March 2004, update 1 September 2004, update 1 February 2005

 

 

 

 

 

 

 

 

 

 

Appendix I:

PROBABILITIES & POSSIBILITIES IN PERIPARTUM CARDIOMYOPATHY (PPCM)

 James D. Fett, MD

 

1.      At some stage of the disease many PPCM patients experience an irregularly distributed/ focal inflammatory process in the myocardium.  This process, identifiable as either an inflammatory cardiomyopathy or a myocarditis1, eventually leads to left ventricular dysfunction.  It also appears possible to have a cardiomyopathy without a typical inflammatory histological picture.2,3  The outcome of this process is a dilated cardiomyopathy and congestive heart failure, thus permitting the diagnosis of PPCM.

2.      There may be a genetic predisposition to the development of PPCM.4,5

3.      The pathobiology of PPCM may involve (at least):

a)Immature dendritic cells (iDC) (antigen-presenting cells).6,55,74,75,78

b)Cytokines, TNF, IL, TGF,  (negative inotropic effect) and C-Reactive Protein as marker (or by itself as potentially harmful80).1,7,8,9,10,55,81,89

c)Chemokines (negative inotropic effect).6,11,12,71

d)T-lymphocytes (cellular immune system).6,13

e)B-lymphocytes (humoral immune system).14

f)Autoantibodies (harmless epiphenomena or pathogenic?).15,16,17,18,56,84

g)Excess cardiac nitric oxide synthase (NOS) (negative inotropic effect).19,20,21,22,85

h)Virus and/or viral gênomes, especially  adenovirus and echovirus?23,24,25,71,73,82

i)Fetal microchimerism or other unknown antigens?16,25,26, 27

j)Hormones (estrogen, progesterone, prolactin, relaxin, testosterone).16

k)Toll-like receptors (TLR).28,29,30

l)Cardiac myocyte apoptosis31,32

     m)Enterovirus capsid protein VP133,34

      n)Cyclooxygenase (COX)-269

      o)Immune complexes71

      p)Cardiac dystrophin72

4.      The pathobiology of PPCM can be interrupted by:

a)Natural healing process, at the price of increased morbidity and mortality.

b)Potential therapeutic interventions:

   1—Angiotensin converting enzyme-inhibitors (ACE-inhibitors)and angiotensin II receptor blockers (ARB).35,36,68

   2—Beta-adrenergic blockers (Beta-blockers).37,38,54,83,86

   3—Diuretics

   4—HMC-CoA reductase inhibitors (statins)?39, 65,70,90

   5—Intravenous immune globulin (IVIg)?40,41

   6—Pentoxifylline as Tumor Necrosis Factor-a inhibitor?42,43

   7—Monoclonal antibodies?44,45,77

   8—Immunoadsorption and/or apheresis?46,47,48,79, 87,88

   9—Interferon B?23

  10—Calcium channel-blockers?49

  11—Prednisone and azathioprine?50

  12—Recombinant human erythropoietin?76

 13—Cellular cardiomyoplasty?66,67

  14—Inhibition of matrix metalloproteinases (MMPs)81

5.      Important questions to answer:

a) What is/are the precipitating antigen(s)?

b) Which HLA patterns could convey increased susceptibility to PPCM? 

c)What is the relative importance of the elements involved in the pathobiology of PPCM?  Are there others?

d)Which of the potential therapeutic regimens is/are most effective?

e)Can the development of PPCM be identified in the sub-clinical phase before significant cardiomyocyte damage is inflicted?  Are there useful early clinical markers of an inflammatory process? (?hs-CRP,3,39 ?sICAM-151)

f)Is there any possibility of developing a vaccine to prevent PPCM and/or other dilated cardiomyopathies?52,53

 

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4.      Fett, JD, Sundstrom JB, King ME, Ansari AA.  Mother-daughter peripartum cardiomyopathy.  Int J Cardiol 2002;86:331-32.

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