Molecular mechanisms of peripartum cardiomyopathy: A vascular/hormonal hypothesis
Section snippets
Vignette
A 40-year-old woman delivered her second child by C-section uneventfully at 39 weeks of gestation. Three days later she developed shortness of breath and swelling in her legs. Two days later she experienced chest pain with exertion and went to the emergency room. On presentation, her blood pressure and heart rate were mildly elevated, and blood tests, EKG, and chest x-ray were unremarkable. Two hours later, while still in the emergency room, she developed anxiety, much worsened shortness of
Clinical presentation and treatment
At the time of presentation, women usually present with wet/warm heart failure, although fulminant cardiovascular collapse can be seen when presentation for care is delayed. The symptoms of heart failure include shortness of breath (dyspnea) on exertion or at rest, difficulty breathing while supine (orthopnea), awakening abruptly due to shortness of breath (paroxysmal nocturnal dyspnea), and cough. Swelling of the feet, ankles, and abdomen, fatigue, weakness, and decreased exercise tolerance
PPCM as a vascular and hormonal disease
The cause of PPCM has remained unclear. Numerous hypotheses have been proposed, including myocarditis, autoimmunity against fetal antigens, fetal microchimerism, and dietary deficiencies of selenium or excessive salt intake. Recent research, however, suggests that PPCM is a vascular disease, triggered by late-gestational secretion of potent anti-angiogenic agents from the placenta and pituitary. Although this idea has been proposed in the past [28], experimental support for it has been lacking
A two-hit hypothesis
Taken together, these recent developments suggest that PPCM stems from the coincidence of two “hits”: one hit is the late-gestational vasculotoxic hormonal environment, including sFlt1 and prolactin, and the second hit is an inability, in some women, to withstand this vasculotoxic insult.
The hormonal hypothesis of the first hit is consistent with the timing of PPCM. Pregnancy presents significant hemodynamic and metabolic challenges to the heart, including large increases in heart rate, stroke
Conclusions and future studies
The recent findings outlined above paint a compelling picture of PPCM as a disease caused by a vasculotoxic hormonal state of late gestation, superimposed on a permissive heart with insufficient pro-vascular defenses. Evidence for the model rests on both significant experimental mouse data and clinical epidemiological observations. Nevertheless, the proposition that PPCM is a vascular and hormonal disease is still in its early stages and remains poorly discussed, if at all, in most current
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The authors have indicated there are no conflicts of interest.