Methods

After procurement of the institutional review board’s approval, electronic medical records (2006 to 2013) were retrospectively screened to identify patients with peripartum HF. Specifically, patients who presented with PC and normal LVEFs as well as those with traditional PC (LVEF <45%) were identified.

PC with normal LVEF was defined by the following criteria: (1) patient meeting Framingham criteria for HF, (2) onset of HF during the last month of pregnancy or up to 5 months after delivery, (3) absence of an identifiable cause of HF, (4) absence of recognizable heart disease or HF before the last month of pregnancy, and (5) LVEF ≥55% on echocardiogram at the time of diagnosis of HF. Similarly, PC with low LVEF was defined by the criteria proposed by the National Heart, Lung, and Blood Institute and the European Society of Cardiology Working Group on peripartum cardiomyopathy. Considerable heterogeneity exists in the definition of HF with normal EF with multiple studies using variable cutoffs such as LVEF >40%, >45%, >50%, and ≥55%. Notably, this lack of consensus or uniformity in the LVEF cutoffs for HF with normal EF was acknowledged in the recent 2013 American College of Cardiology Foundation/American Heart Association guidelines. In a deliberate attempt to isolate pure groups of HF, we opted to define patients with PC with normal LVEF as those with an LVEF of ≥55% in this study. All echocardiographic parameters were obtained as per the American Society of Echocardiography guideline recommendations. The LVEF was calculated using Simpson’s biplane method. Pulmonary edema was defined as acute onset of dyspnea within the preceding 6 hours with chest x-ray findings of pulmonary interstitial or alveolar edema and increased bronchovascular markings. Cut-off values for cardiac troponin I positivity were based on the referenced normal value of <0.2 ng/ml (Bayer ADVIA Centaur chemiluminometric immunoassay, Bayer Health Care, Tarrytown, New York). At the time of this study, our institution provided B-type natriuretic peptide results using the Biosite Triage immunochromatographic assay (Biosite Inc., San Diego, California) (suggested cut-off value for clinical decision making: 100 pg/ml). B-type natriuretic peptide values twice as high as that in non-pregnant women and a lack of fluctuation during all trimesters have been demonstrated in pregnant women.

On review of confirmed cases of PC with normal LVEF by 2 board-certified cardiologists, clinical characteristics, echocardiographic data, and the mean 3-year follow-up outcomes were compared with age-matched controls with traditionally defined PC (LVEF <45%) identified during the same screening time frame. Follow-up data over a period of approximately 3 years were collected for recurrent HF, New York Heart Association functional class, and mortality (Social Security Death Index).

Statistical Analysis

Categorical data are summarized as percentages and continuous data as mean ± SDs. Patients were dichotomized into PC with normal LVEF (≥55%) and traditionally defined PC with low LVEF (<45%) groups. Subsequently, both groups were compared using the Fisher’s exact test for categorical variables, independent samples t test for normally distributed continuous variables, and the nonparametric Mann-Whitney test for continuous variables not following a normal distribution (SPSS Inc. v19.0, IBM, Chicago, Illinois). A p value of <0.05 was considered to be statistically significant.

Statistical Analysis

Categorical data are summarized as percentages and continuous data as mean ± SDs. Patients were dichotomized into PC with normal LVEF (≥55%) and traditionally defined PC with low LVEF (<45%) groups. Subsequently, both groups were compared using the Fisher’s exact test for categorical variables, independent samples t test for normally distributed continuous variables, and the nonparametric Mann-Whitney test for continuous variables not following a normal distribution (SPSS Inc. v19.0, IBM, Chicago, Illinois). A p value of <0.05 was considered to be statistically significant.

Results

Retrospective screening of medical records over a period of 5 years using keywords “peripartum,” “postpartum,” “partum,” and “heart failure” yielded a total of 297 patients for chart review. After assiduously excluding patients with known history of HF, those with other underlying heart diseases, those without a baseline index echocardiogram at our hospital during the prespecified window (1 month prepartum to 5 months postpartum), and patients who did not meet the Framingham criteria for HF, we identified a total of 25 patients with peripartum HF and normal LVEF. Exclusion of patients with hypertension (n = 9), preeclampsia (n = 1), and diabetes mellitus (n = 2) yielded 13 patients with PC and normal LVEF. Similarly identified age-matched traditional PC controls (LVEF <45%) during the same time window constituted the cohort of patients with PC and low LVEF (n = 16). None of the patients with PC were diagnosed with volume overload, severe anemia, sepsis, or acute respiratory distress syndrome in the peripartum period. The clinical characteristics, biochemical markers, and echocardiographic data from the index admission and outcomes of PC patients with normal and low LVEFs are listed in Tables 1 and 2 , respectively.

Table 1

Summary of the clinical, biochemical, echocardiographic parameters and outcomes of the 13 women with peripartum cardiomyopathy and normal left ventricular ejection fractions (≥55%)

Age (Years)	Ethnicity	Delivery to HF (Days)	BNP (pg/ml) ∗	Troponin I (ng/ml)	LVEF ∗	LVEDV (ml) ∗	LVESV (ml) ∗	Septal Tissue Doppler Velocities				Follow-Up Data
								S′ (cm/s) ∗	E (cm/s)	E′ (cm/s) ∗	E/E′	Duration (Months)	Mortality	Recurrent HF	NYHA Class ∗
20	AA	5 †	271	<0.02	58%	93	39	7	120	10	12	13	0	0	I
21	AA	1	—	<0.02	63%	119	44	12	114	10	11	14	0	0	I
22	AA	1 †	—	0.03	56%	98	43	8	143	11	13	19	0	0	I
25	AA	2	—	0.03	68%	124	40	8	116	9	13	20	0	0	I
25	AA	4	360	<0.02	65%	116	41	9	92	5	18	72	0	+	III
26	AA	5 †	875	0.03	73%	82	22	9	131	12	11	27	0	+	III
27	Other	1 †	—	—	64%	67	24	9	104	11	9	17	0	0	I
31	AA	5	—	—	63%	239	88	7	122	13	9	42	0	0	II
31	Other	40	—	—	64%	88	32	8	84	7	12	45	0	0	II
32	Other	2	536	—	57%	137	59	7	103	9	11	14	0	0	I
33	AA	0 † ‡	3630	0.63	67%	126	42	13	113	12	9	7	0	0	II
34	AA	3	202	<0.02	62%	159	61	8	97	10	10	46	0	+	III
40	C	−4 ‡	745	<0.02	66%	153	52	9	127	7	18	60	0	0	II

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