Dear Sir/Madam,
We read with interest a review on peripartum cardiomyopathy (PPCM) by Pyatt and Dubey (1) that has recently been published in your journal. Reviewing the epidemiology of PPCM, the authors conclude that, "PPCM appears not to have a hereditary association", and this erroneous assertion is supported by the citation of three references.(2,3,4) However, all three of the papers cited, actually emphasise the current thinking that PPCM does indeed have heretidary and/or genetic underpinnings. We have recently demonstrated in a series of South African families with familial dilated cardiomyopathy (DCM) that PPCM can present as part of the spectrum of familial DCM.(5) Similarly, in 90 Dutch families with familial DCM, van Spaendonck-Zwarts and colleagues have found that PPCM may be the initial presentation of familial DCM and identified previously undiagnosed DCM in the families of PPCM patients who did not show full recovery.(6) In the US, 45 cases of PPCM were identified from 530 pedigrees of familial DCM, and in 19 PPCM cases offered molecular genetic screening the causative mutations were isolated in 6 patients.(7) Furthermore, familial clustering was noted in 23 (55%) of the 42 unrelated cases of PPCM in this study. In an editorial titled 'Birthing the Genetics of Peripartum Cardiomyopathy' Anderson and Horne argue that "PPCM may develop as a result of a complex interaction of pregnancy associated factors against a susceptible genetic background".(8)

We have previously reviewed the role of genetics in the aetiopathogenesis of PPCM.(9) Genetic susceptibility may account for up to a third of cases of PPCM. In a series of 17 PPCM patients, Pierce and colleagues found 3 (18%) to have a definite family history of PPCM.(4) Likewise, there have been many reports of familial clustering of PPCM, (10 -13) clearly showing that the disease can have a hereditary association.

Nevertheless, while genetic susceptibility seems to play a role in the development of PPCM, the majority of cases of PPCM do not have a family history of the disease, and other environmental and biological factors have been postulated to play a role (including inflammatory, infectious, autoimmune, metabolic, hormonal and biochemical factors).(9) The high incidence of PPCM in certain communities, (14) suggests that a common genetic founder mutation cannot be excluded, however. Within populations there is scope for variable genetic susceptibility, as well as incomplete penetrance and variable expression of the causative mutations, as with other forms of DCM.(15) It is clearly the interaction of pathogenic and modifier genes with pregnancy-specific environmental, clinical and biological factors that determines the final common expression of PPCM.

The picture painted by the family and molecular studies has implications for the management of patients with PPCM. First, in every patient with PPCM, the construction of a 3- to 5-generation pedigree is essential to exclude familial DCM. Second, clinical screening of first degree relatives is required in order to exclude cases of undiagnosed familial DCM. Finally, the management of PPCM requires a multidisciplinary team of physicians, obstetricians and medical geneticists in order to achieve optimal care.

References

1. Pyatt JR, Dubey G. Peripartum cardiomyopathy: current understanding, comprehensive management review and new developments. Postgrad J Med 2011; 87: 34-39.

2. Pearson GD, Veille JC, Rahimtoola S, et al. Peripartum cardiomyopathy: National Heart, Lung, Blood Institute and Office of Rare Diseases (National Institutes of Health). Workshop recommendations and review. JAMA 2000; 283: 1183-1188.

3. Witlin AG, Mabie WC, Sibai BM. Peripartum cardiomyopathy: an ominous diagnosis. Am J Obstet Gynecol 1997; 176: 182-188.

4. Pierce JA, Price BD, Joyce BW. Familial occurrence of postpartal heart failure. Arch Intern Med 1963; 111: 651-655.

5. Ntusi NBA, Wonkam A, Shaboodien G, et al. Frequency and clinical genetics of familial dilated cardiomyopathy in Cape Town: Implications for the evaluation of patients with unexplained cardiomyopathy. S Afr Med J 2011; 101: 394-398.

6. van Spaendonck-Zwarts KY, van Tintelen JP, van Veldhuisen DJ, et al. Peripartum Cardiomyopathy as a Part of Familial Dilated Cardiomyopathy. Circulation 2010; 121: 2169-2175.

7. Morales A, Painter T, Li R, et al. Rare variant mutations in Pregnancy-Associated or Peripartum Cardiomyopathy. Circulation 2010; 121: 2176-2182.

8. Anderson JL, Horne BD. Birthing the Genetics of Peripartum Cardiomyopathy. Circulation 2010; 121: 2157-2159.

9. Ntusi NBA, Mayosi BM. Peripartum cardiomyopathy: a systematic review. Int J Cardiol 2009; 131: 168-179.

10. Massad LS, Reiss CK, Mutch DG, Haskel EJ. Familial peripartum cardiomyopathy after molar pregnancy. Obstet Gynecol 1993; 81: 886-888.

11. Pearl W. Familial occurrence of peripartum cardiomyopathy. Am Heart J 1995; 129: 421-422.

12. Voss EG, Reddy CV, Detrano R, et al. Familial dilated cardiomyopathy. Am J Cardiol 1984; 54: 456-457.

13. Fett JD, Sundstrom BJ, Etta King M et al. Mother-daughter peripartum cardiomyopathy. Int J Cardiol 2002; 86: 331-332.

14. Ntusi NBA, Mayosi BM. Epidemiology of heart failure in sub- Saharan Africa. Expert Rev Cardiovasc Ther 2009; 7: 169-180.

15. Sliwa K, Hilfiker-Kleiner D, Petrie MC, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Working Group on peripartum cardiomyopathy. Eur J Heart Fail 2010; 12: 767-778.

Conflict of Interest:

None declared