By Van Selby, MD
Assistant Professor of Medicine, UCSF Cardiology Division, Advanced Heart Failure Section, San Francisco
Dr. Selby reports no financial relationships relevant to this field of study.
SOURCE: McNamara DM, et al. Clinical outcomes for peripartum cardiomyopathy in North America: Results of the IPAC study (Investigations of Pregnancy-Associated Cardiomyopathy). J Am Coll Cardiol 2015;66:905-914.
Peripartum cardiomyopathy (PPCM) affects approximately one in every 2000 births. While the majority of patients with PPCM will recover left ventricular (LV) function, mortality remains high at 6-10%. Because PPCM is such a rare disease, the current evidence base is primarily limited to small, retrospective, single-center studies.
The Investigations of Pregnancy-Associated Cardiomyopathy (IPAC) study prospectively evaluated 100 women with newly diagnosed PPCM within the first 13 weeks postpartum. All subjects had an echocardiogram at baseline and again at 6 and 12 months postpartum. The mean age was 30 years, and the mean LV ejection fraction (EF) was 35 ± 0.1% at baseline. Beta-blockers were used in 88% of subjects, and angiotensin-converting-enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) were used in 81%. Only one patient was treated with bromocriptine.
At 1 year of follow-up, mean LVEF improved to 53 ± 1%, with 72% of all patients achieving an LVEF > 50%. Baseline LV function and LV dimensions were strong predictors of recovery. Ninety-one percent of subjects with both LVEF > 30% and left ventricular end-diastolic diameter (LVEDD) < 6 cm at baseline had full recovery of LV function at 1-year postpartum, compared to 0% of women with both LVEF < 30% and LVEDD > 6 cm. Overall, 1-year event-free survival was 93%. LVEF at baseline was also a powerful predictor of cardiovascular (CV) events. One-year event-free survival was 82% in those with LVEF < 30%, compared to 99% in those with LVEF ≥ 30% (P = 0.004).
Black women were a particularly high-risk subgroup, with significantly more LV dysfunction at baseline and at 1-year postpartum (P < 0.001). Black women were also more likely to have CV events. At 1 year, 26% of black women had some type of CV event or a final LVEF < 0.35%, compared to 8% of other subjects (P = 0.03). Multiparity, maternal age, and New York Heart Association functional class were not predictive of adverse outcomes. The authors concluded that poor baseline LVEF, greater degree of LV dilation, and black race predict poorer subsequent recovery with conventional therapy.
COMMENTARY
This is the largest prospective study of PPCM ever conducted, with 30 centers involved. Improvement in cardiac function is more common than previously reported, with most women achieving LVEF > 50% at 1 year. However, despite evidence-based medical therapy for heart failure, more than 20% of patients still have some degree of cardiomyopathy at 1 year and 7% have a serious adverse CV event (death, heart transplant, or LV assist device implantation). Identifying these patients early in the course of the disease has the potential to improve outcomes.
What is most impressive is the utility of standard echocardiographic parameters for risk-stratification in PPCM. The finding that among those with both low EF and LV dilation at baseline, none recovered function at 1 year is particularly valuable, as this identifies a subset that requires not only aggressive medical therapy for heart failure but possibly early referral to an advanced heart failure center for further evaluation. Black women also clearly have worse outcomes, a finding that is consistent with previous studies.
The IPAC analysis also found several previously identified predictors of poor prognosis were not significant in multivariate analyses. This includes multiparity, older maternal age, and blood pressure. It is also worth noting that breastfeeding was not associated with worse outcomes in this study. Because it increases prolactin in the postpartum period, some have suggested breastfeeding should be avoided in mothers with PPCM. Given the multiple proven benefits of breastfeeding, providers should reconsider this recommendation in women with PPCM.
There are several limitations worth mentioning. There was substantial heterogeneity in time to diagnosis. In particular, black women presented significantly later. Black women were also more likely to be hypertensive as well. Both of these factors could help explain the lower EF at baseline and worse outcomes in these patients.
There are currently no clinical guidelines with recommendations regarding the management of PPCM. Going forward, the risk factors identified in this study may serve as targets for investigation. Previous trials of agents such as bromocriptine, pentoxifylline, and intravenous immunoglobulin did not show clear benefit in PPCM. However, this may be due to the fact that a majority of PPCM patients will recover LV function regardless of the intervention. Designing clinical trials for PPCM patients at increased risk (i.e., reduced EF, LV remodeling, black race) may facilitate the identification of effective therapies.
Echocardiography is a relatively inexpensive and risk-free test. It should be considered in any pregnant woman presenting with dyspnea or other symptoms of heart failure, and is the most important prognostic tool in PPCM. Those with high-risk findings require aggressive medical therapy for heart failure, close monitoring, and consideration of early referral to an advanced heart failure center.
