IMAC2 is the first investigation to prospectively compare outcomes in PPCM with other forms of recent onset non-ischemic cardiomyopathy. At both enrollment and six month follow up, subjects with PPCM had significantly higher mean values for LVEF than the subset of men with recent onset cardiomyopathy. The mean values for non-peripartum women were intermediate, suggesting that part of the greater recovery in PPCM may be related to female gender. This study also investigated the influence of PPCM risk factors such as race and blood pressure on subsequent recovery, and found that while recovery appears to be less evident in black subjects, blood pressure, maternal age and multi-parity had little impact on the degree of recovery achieved.
The percentage of women with PPCM achieving an LVEF of ≥0.50 at 6 months was far greater in peripartum women than in either non peripartum women or men. However, the percentage with significant cardiomyopathy at 6 months (LVEF<0.30) did not differ between groups. Indeed, in the PPCM cohort the LVEF 6 months after presentation appeared to have a bimodal distribution, with a majority of patients having marked recovery but a significant minority having persistent severe LV dysfunction. While an autoimmune pathogenesis has long been suspected for PPCM (11
), the question remains whether women with persistent cardiomyopathy have a more severe irreversible injury or represent a completely different etiology such as a “latent” cardiomyopathy brought out by pregnancy. Recent investigation in large cohorts of familial dilated cardiomyopathy reveals that genetic etiologies may indeed be identified in a substantial fraction of women presenting with PPCM (12
The incidence of PPCM varies throughout the world with an incidence observed in Africa and Haiti (15
) significantly higher than the incidence observed in the United States. Within the United States, African-American women have an estimated 15.7 fold higher risk of developing PPCM than non- African-American women (17
). While the differences by race in the current study failed to reach significance, the trends toward lower LVEF and less recovery in blacks were consistent with previous reports of poorer outcomes in black women with PPCM compared to whites (17
). In terms of other risk factors for PPCM neither systolic nor diastolic pressure at presentation was linked to recovery. In a similar fashion multi-parity and higher maternal age also did not affect outcome.
Treatment with beta blockers may assist improvements in LVEF in other forms of non-ischemic cardiomyopathy and may be partially responsible for the excellent recovery noted in the current report. In the absence of an appropriate control group, the current investigation can not address whether medical therapy facilitates recovery in PPCM. In addition, whether the lower degree of recovery in black subjects represents differences in genetic background or a decreased responsiveness to pharmacologic therapy cannot be determined.
The IMAC2 registry was limited by the small number of peripartum subjects, which diminished the ability to fully evaluate the prognostic impact of traditional risk factors. In addition, at enrollment PPCM subjects in IMAC2 were on average more than 2 months postpartum, by which time significant recovery may have already occurred. However this delay would be unlikely to affect the comparison with men and non-peripartum women, for while it is more difficult in these subjects to pinpoint the initiation of the disorder, they likely had similar delays from presentation to enrollment. Finally, enrollment of PPCM subjects was not equal across all centers and we cannot exclude an ascertainment bias in this registry. A subsequent NHLBI funded investigation of myocardial recovery specifically in PPCM, Investigations in Pregnancy Associated Cardiomyopathy (IPAC), was initiated at 30 North American centers in 2010 and is currently underway.
Recently, inhibition of prolactin secretion with bromocriptine has been reported to facilitate recovery in both murine models of PPCM and in clinical reports (19
). The degree of spontaneous recovery evident in the IMAC registry demonstrates that anecdotal reports of treatments linked to recovery must be interpreted with caution (22
). While the recovery evident is encouraging, the persistence of severe cardiomyopathy in a significant fraction of women warrants further investigation, and demonstrates the need for novel strategies to both delineate and treat women with PPCM destined for poor outcomes on conventional therapy.