Pregnancy-associated Cardiomyopathy Research Articles

Race, Hypertensive Disorders of Pregnancy and Outcomes in Peripartum Cardiomyopathy

BackgroundBlack women with peripartum cardiomyopathy (PPCM) have a higher prevalence of hypertensive disorders of pregnancy (HDP) and worse clinical outcomes compared with non-Black women. We examined the impact of HDP on myocardial recovery in Black women with PPCM. MethodsA total of 100 women were enrolled into the Investigation in Pregnancy Associated Cardiomyopathy (IPAC) study. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6, and 12-months post-partum (PP). Women were followed for 12 months postpartum and outcomes including persistent cardiomyopathy (LVEF≤35%), left ventricular assist device, (LVAD), cardiac transplantation, or death were examined in subsets based on race and the presence of HDP. ResultsBlack women with HDP were more likely to present earlier compared to Black women without HDP (days PP HDP: 34±21 vs 54±27 days, P=0.03). There was no difference in LVEF at study entry for Black women based on HDP, but better recovery with HDP at 6 (HDP:52±11% vs no HDP: 40±14%, P=0.03) and 12-months (HDP:53±10% vs no HDP:40±16%, P=0.02). At 12-months, Black women overall had a lower LVEF than non-Black women (P<0.001), driven by less recovery in Black women without HDP compared to non-Black women (P<0.001). In contrast, Black women with HDP had a similar LVEF at 12 months compared to non-Black women (P=0.56). ConclusionsIn women with PPCM, poorer outcomes evident in Black women were driven by women without a history of HDP. In Black women, a history of HDP was associated with earlier presentation and recovery which was comparable to non-Black women.

Association of activin A and postpartum blood pressure in peripartum cardiomyopathy

BackgroundActivin A has been implicated in the pathogenesis of patients with chronic hypertension and heart failure as well as patients with hypertensive disorders of pregnancy (HDP). Whether activin A correlates with blood pressure in patients with peripartum cardiomyopathy (PPCM) and HDP history has not previously been explored. Methods and results82 women with PPCM w/ and w/out HDP or hypertension history were selected for analysis from the Investigations in Pregnancy Associated Cardiomyopathy (IPAC) study. Serum biomarkers and blood pressure were assessed at the time of enrollment (median postpartum day 24). Levels of both sFlt-1 (SBP: r 0.47, p = 0.008; DBP: r 0.57, p < 0.001) and activin A (SBP: r 0.59, p < 0.001;DBP: r 0.68, p < 0.001) were noted to significantly correlate with blood pressure in patients with a history of HDP who went on to develop PPCM, but not in patients with chronic hypertension or no hypertensive history. The strongest correlation was between activin A levels and postpartum diastolic blood pressure for the subset with preeclampsia (DBP: r0.82, p < 0.001). This remained significant in multivariable linear regression analysis (DBP: β = 0.011, p = 0.015). ConclusionIn patients with PPCM, activin A and sFlt-1 levels had direct correlations with both systolic (SBP) and diastolic blood pressures (DBP), but only in participants with history of HDP. This correlation was more evident for activin A and strongest with a history of preeclampsia. Our findings suggest that activin A may play an important role in blood pressure modulation in women with HDP who subsequently develop PPCM.

Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways

BackgroundThe pathophysiology of peripartum cardiomyopathy (PPCM) and its distinctive biological features remain incompletely understood. High-throughput serum proteomic profiling, a powerful tool to gain insights into the pathophysiology of diseases at a systems biology level, has never been used to investigate PPCM relative to nonischemic cardiomyopathy. ObjectivesThe aim of this study was to characterize the pathophysiology of PPCM through serum proteomic analysis. MethodsAptamer-based proteomic analysis (SomaScan 7K) was performed on serum samples from women with PPCM (n = 67), women with nonischemic nonperipartum cardiomyopathy (NPCM) (n = 31), and age-matched healthy peripartum and nonperipartum women (n = 10 each). Serum samples were obtained from the IPAC (Investigation of Pregnancy-Associated Cardiomyopathy) and IMAC2 (Intervention in Myocarditis and Acute Cardiomyopathy) studies. ResultsPrincipal component analysis revealed unique clustering of each patient group (P for difference <0.001). Biological pathway analyses of differentially measured proteins in PPCM relative to NPCM, before and after normalization to pertinent healthy controls, highlighted specific dysregulation of inflammatory pathways in PPCM, including the upregulation of the cholesterol metabolism-related anti-inflammatory pathway liver-X receptor/retinoid-X receptor (LXR/RXR) (P < 0.01, Z-score 1.9-2.1). Cardiac recovery by 12 months in PPCM was associated with the downregulation of pro-inflammatory pathways and the upregulation of LXR/RXR, and an additional RXR-dependent pathway involved in the regulation of inflammation and metabolism, peroxisome proliferator-activated receptor α/RXRα signaling. ConclusionsSerum proteomic profiling of PPCM relative to NPCM and healthy controls indicated that PPCM is a distinct disease entity characterized by the unique dysregulation of inflammation-related pathways and cholesterol metabolism-related anti-inflammatory pathways. These findings provide insight into the pathophysiology of PPCM and point to novel potential therapeutic targets.

Peripartum cardiomyopathy: current theories about etiopathogenesis, potential biomarkers and treatment - a literature review

Background: Peripartum cardiomyopathy (PPCM) is a form of an idiopathic systolic heart failure, which occurs the most often in the last weeks of pregnancy or in the early postpartum period. Symptoms of this disease include exertional dyspnea, orthopnoea, paroxysmal nocturnal dyspnoea and edema. They are typical for a heart failure, but also can be attributed to late pregnancy or the effects of labor, which is a cause of common misdiagnosis or its delay and significantly affects the worsening of the prognosis and the high mortality rate. In more severe cases, cardiogenic shock, arrhythmias, thromboembolic complications may occur, leading to death. Aim of the study: The study aim is to summarize the current state of knowledge and the recent scientific reports on the potential etiopathogenesis, diagnostics including new biomarkers, and treatment of the peripartum cardiomyopathy. Material and methods: The study is based on the scientific literature available in the PubMed and Google Scholar databases, using the following keywords: „peripartum cardiomyopathy”, „pregnancy-associated cardiomyopathy” and “16-kDa prolactin”. Results and conclusions: The diagnosis of peripartum cardiomyopathy should be considered in every pregnant or postnatal woman with symptoms of heart failure. Despite great advances made in understanding and diagnosing PPCM over the last few years, the pathogenesis and complex interactions of genetics and the vascular and hormonal balance of late pregnancy are still unclear. Further research is needed to determine the benefits and risks of bromocriptine treatment and the use of new markers in the diagnostics of PPCM.

Serum proteomic analysis of peripartum cardiomyopathy reveals a unique disease with distinctive dysregulation of inflammatory and cholesterol metabolism pathways

Abstract Background: The pathophysiology of peripartum cardiomyopathy (PPCM) and its defining features when compared to other forms of cardiomyopathy remain unclear, thus limiting the development of targeted therapies. Methods: To address this knowledge gap, we utilized a systems biology approach and performed high-throughput aptamer-based proteomic analysis (SOMAscan 7K) of serum samples from women with PPCM (n = 67) or non-peripartum cardiomyopathy (NPCM, n = 31), and age-matched peripartum and non-peripartum healthy women (n = 10 each). Samples were obtained from the Investigation in Pregnancy-Associated Cardiomyopathy and the Intervention in Myocarditis and Acute Cardiomyopathy studies. Comparative analyses were performed based on the presence of cardiomyopathy and peripartum status. Results: Principal component analysis revealed distinct proteomic signatures of PPCM, NPCM, and each healthy control group (p&amp;lt;0.00001 for all pairwise comparisons). Comparative analyses of PPCM and NPCM identified hundreds of differentially expressed serum proteins before and after normalization to healthy controls. Pathway enrichment analyses of proteins differentially expressed in PPCM highlighted dysregulation of several biological pathways related to inflammation and cholesterol metabolism, including upregulation of the anti-inflammatory liver-X receptor/retinoid X receptor (LXR/RXR) pathway. Conclusions: Serum proteomic profiling of PPCM indicates that PPCM is a unique disease entity characterized by the dysregulation of pro-inflammatory and cholesterol metabolism-related anti-inflammatory pathways. These pathways may represent potential novel therapeutic targets in PPCM.

Pregnancy-Associated Cardiomyopathy (PACM) in a Preeclamptic Woman with Twin Pregnancy: A Case Report

Peripartální kardiomyopatie (peripartum cardiomyopathy, PPCM) není časté onemocnění; jedná se o typ dilatační kardiomyopatie postihující ženy v posledním měsíci těhotenství a v prvních pěti měsících po porodu. Tomuto onemocnění předchází podobné, označované jako těhotenská kardiomyopatie (pregnancy-associ- ated cardiomyopathy, PACM). Morbidita i mortalita v souvislosti s oběma onemocněními jsou vysoké. U žen s preeklampsií a vícečetným těhotenstvím existuje výrazně vyšší riziko rozvoje PACM/PPCM. Na oddělení urgentního příjmu se dostavila 40letá multipara ve 20. týdnu vícečetného těhotenství s kašlem, dyspnoe, výraznými bilaterálními chrůpky, otoky končetin, kardiomegalií, hypertenzí, proteinurií a s hodnotou ejekční frakce levé komory 26 %. Byla u ní stanovena diagnóza akutního otoku plic, PACM a preeklampsie. Těhotenství bylo ukončeno a byla zahájena farmakologická léčba srdečního selhání. Při PACM může být odklad diagnostického vyšetření spojen se závažnou morbiditou matek a mortalitou novorozenců. Případ poukázal na nutnost věnovat pozornost preeklampsii a vícečetnému těhotenství jako rizikovým faktorům; tyto ženy mohou být i kandidátkami monitorování funkce levé komory. Časné a vhodné řešení může zabránit rozvoji ireverzibilní PACM.

Perhexiline treatment improves toxic effects of β‐adrenergic receptor stimulation in experimental peripartum cardiomyopathy

AimsPeripartum cardiomyopathy (PPCM) is a pregnancy‐associated cardiomyopathy that occurs in previously heart‐healthy women towards the end of pregnancy or in the first months after delivery and is characterized by heart failure due to systolic dysfunction. The clinical course of PPCM differs between mild symptoms and severe forms with acute heart failure complicated by cardiogenic shock (CS). Treatment of CS complicating PPCM is challenging, as β‐adrenergic receptor (β‐AR) stimulation seems to be associated with progression of heart failure and adverse outcome. This experimental study aims to examine whether postpartum treatment with the glucose uptake‐promoting drug perhexiline alone or as co‐treatment with β‐AR stimulation prevents heart failure in the experimental PPCM mouse model.Methods and resultsPostpartum (PP) female PPCM‐prone mice with a cardiomyocyte‐restricted STAT3‐deficiency (αMHC‐Cretg/+;Stat3fl/fl; CKO) were treated with perhexiline over two to three pregnancies and nursing periods (2/3PP) or were co‐treated with perhexiline after one pregnancy (1PP) under chronic β‐AR stimulation using isoproterenol (Iso) infusion. Perhexiline was not able to prevent onset of PPCM in CKO mice (FS: CKO Pexsig‐2/3PP: 25 ± 12% vs. CKO Ctrl‐2/3PP: 24 ± 9%, n.s.) but attenuated worsening of left ventricular function in response to treatment with the β‐AR agonist Iso (FS: CKO Pexsig‐Iso‐1PP: 19 ± 4% vs. CKO Ctrl‐Iso‐1PP: 11 ± 5%, P < 0.05).ConclusionsTreatment of PPCM patients with β‐AR agonists should be avoided whenever possible. In cases with CS complicating PPCM, when treatment with β‐AR agonists cannot be prevented, co‐medication with perhexiline might help to reduce the cardiotoxic side effects of β‐AR stimulation. Clinical data are necessary to further validate this therapeutic approach.

Pregnant in the United States in the COVID-19 pandemic: A collision of crises we cannot ignore

NO abstract intended, Introduction is listed here The COVID-19 pandemic and call for social justice is occurring when the United States, unlike its peer countries, has already experienced a steady 20-year rise in maternal morbidity and mortality with pregnant women today facing a 50 percent higher risk of mortality than their mothers. 1 Most vulnerable are women of color, black and American Indian/Alaska Native women, who have experienced longstanding disparities in access to and quality of healthcare and may begin pregnancy with hypertension, diabetes, and obesity, complications known to be more common in women enduring segregation. 2–4 Initially, the race-related health disparities and resultant disproportionately higher rates of COVID-19 cases and mortality in indigenous communities and black, latinx, or other communities of color were mistakenly considered innate racial differences. More recently, these higher rates have been attributed to underlying social, structural, and environmental determinants of health including resource inequities, inadequate housing, and occupational and environmental hazards that result in greater exposure to and less protection from COVID-19. 5,6 Augmented by the added physiologic stress of pregnancy, these comorbidities and disparities compound the risk of pregnancy-associated cardiomyopathy, thromboembolism, and hemorrhage, often resulting in lasting physical and mental health consequences.

Differences in the clinical characteristics and long-term outcome of peripartum tako-tsubo cardiomyopathy and peripartum cardiomyopathy

Abstract Background Some peripartum-associated cardiomyopathy patients present similarly to those of tako-tsubo cardiomyopathy (TCM), little is known about the clinical course of peripartum TCM. Purpose To know clinicial characteristics and outcomes of peripartum TCM, in comparison with peripartum cardiomyopathy (PPCM) Methods and results Of 31 pregnancy-associated cardiomyopathy patients in a tertiary hospital, 10 cases of peripartum TCM and 21 cases of PPCM were found. Maternal near-missed death was significantly more common in the peripartum TCM group than in the PPCM group (100.0% vs. 76.2%, p=0.030). Complete recovery was observed with all peripartum TCM cases, while 23.8% of the PPCM cases had residual left ventricle (LV) dysfunction. LV ejection fraction greater than 30% on the initial echocardiogram independently predicted early echocardiographic recovery of left ventricular systolic function (odds ratio 331.33, 95% confidence interval 3.87–28402.60, p=0.011). There was no difference between the two groups in terms of the rate of adverse clinical events at 3 years of follow-up (PPCM group: 26.3% [5/19] vs. TCM group: 33.3% [3/9], p=0.750). Conclusions One-third of pregnancy-associated cardiomyopathy patients had peripartum TCM. With contemporary supportive care, both PPCM and peripartum TCM patients had a low mortality rate and excellent long-term outcomes. Kaplan-Meier survival curves for death, Funding Acknowledgement Type of funding source: None

Clinical characteristics and long-term outcomes of peripartum takotsubo cardiomyopathy and peripartum cardiomyopathy.

AimsAlthough some peripartum‐associated cardiomyopathy patients present with features that are clinically and echocardiographically similar to those of takotsubo cardiomyopathy (TCM), little is known about the diagnosis and clinical course of peripartum TCM.Methods and resultsIn a tertiary hospital in Seoul, Korea, we searched the hospital database to find cardiomyopathy cases that were associated with pregnancy from January 1995 to May 2019. Applying the published diagnostic criteria, we sought peripartum cardiomyopathy (PPCM) and peripartum TCM patients for comparison. Of 31 pregnancy‐associated cardiomyopathy patients, 10 cases of peripartum TCM and 21 cases of PPCM were found. Maternal near‐miss death was significantly more common in the peripartum TCM group than in the PPCM group (100.0% vs. 57.1%, P = 0.030). Complete recovery was observed with all peripartum TCM cases, while 23.8% of the PPCM cases had residual left ventricular dysfunction. One death and one heart transplantation occurred in the PPCM group, while neither occurred in the peripartum TCM group. There was no difference between the two groups in terms of the rate of major adverse clinical events at 3 years of follow‐up [PPCM group: 26.3% (5/19) vs. TCM group: 33.3% (3/9), P = 0.750].ConclusionsOne‐third of pregnancy‐associated cardiomyopathy patients had peripartum TCM. With contemporary supportive care, both PPCM and peripartum TCM patients had a low mortality rate and excellent long‐term outcomes.

33-Year-Old Woman With Postpartum Acute Shortness of Breath

33-Year-Old Woman With Postpartum Acute Shortness of Breath

26-Year-Old Woman With Shortness of Breath and Chest Pain

26-Year-Old Woman With Shortness of Breath and Chest Pain

Angiotensin II receptor blocker LCZ696 attenuates cardiac remodeling through the inhibition of the ERK signaling pathway in mice with pregnancy-associated cardiomyopathy

Pregnancy-associated cardiomyopathy (PAH) represents a pregnancy-associated myocardial disease that is characterized by the progression of heart failure due to marked left ventricular systolic dysfunction. Compelling evidence has highlighted the potential of angiotensin (Ang) receptor inhibitors as therapeutic targets in PAH treatment. The present study aims to elucidate the molecular mechanisms underlying Ang II receptor inhibitor LCZ696 treatment in PAH. Initially, a PAH mouse model was induced, followed by intraperitoneal injection of LCZ696. Subsequently, cardiomyocytes and fibroblasts were isolated, cultured, and treated with Ang II and LCZ696, followed by detection of the total survival rate, cardiac injury, cardiac fibrosis and apoptosis. Moreover, in order to quantify the cardiac hypertrophy and fibrosis degree of cardiac fibroblasts, the expression levels of markers of cardiac hypertrophy (ANP, βMHC and TIMP2) and markers of fibrosis (collagen I, collagen III and TGF-β) were evaluated. Furthermore, the potential effect of LCZ696 on the extracellular signal-regulated kinase (ERK) signaling pathway was examined. The acquired findings revealed that LCZ696 increased the total survival rate of PAH mice, but decreased cardiac injury, cardiac fibrosis, and apoptosis in vitro. LCZ696 attenuated cardiac injury induced by Ang II through the inhibition the expression of markers of cardiac hypertrophy, fibrosis and apoptosis by inhibiting ERK phosphorylation in vivo and in vitro. Altogether, LCZ676 could potentially alleviate cardiac remodeling in mice with PAH via blockade of the ERK signaling pathway activation. Our findings suggest that LCZ696 could be a potential target for PAH therapy.

Global Left Ventricular Strain at Presentation Is Associated with Subsequent Recovery in Patients with Peripartum Cardiomyopathy

Peripartum cardiomyopathy (PPCM) is a serious complication of pregnancy associated with variable degrees of left ventricular (LV) recovery. The aim of this study was to test the hypothesis that global LV strain at presentation has prognostic value in patients with PPCM. One hundred patients with PPCM aged 30±6years were enrolled in the multicenter Investigation in Pregnancy Associated Cardiomyopathy study along with 21 normal female control subjects. Speckle-tracking global longitudinal strain (GLS) and global circumferential strain (GCS) analysis was performed. The predefined primary combined outcome variable was death, transplantation, LV assist device implantation, or evidence of persistent LV dysfunction (LV ejection fraction [LVEF]<50%) at 1year. GLS measurement was feasible in 110 subjects: 89 of 90 patients with PPCM (99%) with echocardiographic data and all 21 control subjects. Of 84 patients (94%) with 1-year follow-up, 21 (25%) had unfavorable primary outcomes: four LV assist device placements, two deaths, and 15 patients with persistent LV dysfunction. GLS at presentation with a cutoff of 10.6% (absolute value) was specifically associated with the subsequent primary outcome with 75% sensitivity and 95% specificity. GCS at presentation with a cutoff of 10.1% was associated with the primary outcome with 78% sensitivity and 84% specificity. GLS and GCS remained significantly associated with outcomes after adjusting for LVEF (GLS odds ratio, 2.07; P<.001; GCS odds ratio, 1.37; P=.005). GLS was significantly additive to LVEF (C statistic=0.76-0.91, net reclassification improvement=1.32, P<.001). GLS and GCS in patients with PPCM at presentation were associated with subsequent clinical outcomes, including death, LV assist device implantation, and evidence of persistent LV dysfunction. Strain measures may add prognostic information over LVEF for risk stratification.

Breastfeeding, Cellular Immune Activation, and Myocardial Recovery in Peripartum Cardiomyopathy

The etiology of peripartum cardiomyopathy remains unknown. One hypothesis is that an increase in the 16-kDa form of prolactin is pathogenic and suggests that breastfeeding may worsen peripartum cardiomyopathy by increasing prolactin, while bromocriptine, which blocks prolactin release, may be therapeutic. An autoimmune etiology has also been proposed. The authors investigated the impact of breastfeeding on cellular immunity and myocardial recovery for women with peripartum cardiomyopathy in the IPAC (Investigations in Pregnancy Associated Cardiomyopathy) study. Women who breastfed had elevated prolactin, and prolactin levels correlated with elevations in CD8+ T cells. However, despite elevated prolactin and cytotoxic T cell subsets,myocardial recovery was not impaired in breastfeeding women.

Electrocardiographic findings in peripartum cardiomyopathy.

BackgroundThere is limited data on electrocardiographic (ECG) abnormalities and their prognostic significance in women with peripartum cardiomyopathy (PPCM). We sought to characterize ECG findings in PPCM and explore the association of ECG findings with myocardial recovery and clinical outcomes.HypothesisWe hypothesized that ECG indicators of myocardial remodeling would portend worse systolic function and outcomes.MethodsStandard 12‐lead ECGs were obtained at enrollment in the Investigations of Pregnancy‐Associated Cardiomyopathy study and analyzed for 88 women. Left ventricular ejection fraction (LVEF) was measured by echocardiography at baseline, 6 months, and 12 months. Women were followed for clinical events (death, mechanical circulatory support, and/or cardiac transplantation) until 1 year.ResultsHalf of women had an “abnormal” ECG, defined as atrial abnormality, ventricular hypertrophy, ST‐segment deviation, and/or bundle branch block. Women with left atrial abnormality (LAA) had lower LVEF at 6 months (44% vs 52%, P = 0.02) and 12 months (46% vs 54%, P = 0.03). LAA also predicted decreased event‐free survival at 1 year (76% vs 97%, P = 0.008). Neither left ventricular hypertrophy by ECG nor T‐wave abnormalities predicted outcomes. A normal ECG was associated with recovery in LVEF to ≥50% (84% vs 49%, P = 0.001) and event‐free survival at 1 year (100% vs 85%, P = 0.01).ConclusionsECG abnormalities are common in women with PPCM, but a normal ECG does not rule out the presence of PPCM. LAA predicted lower likelihood of myocardial recovery and event‐free survival, and a normal ECG predicted favorable event‐free survival.

PREGNANCY-ASSOCIATED CARDIOMYOPATHY: A TEAM-BASED APPROACH FOR A COMPLEX, HIGH RISK DELIVERY

Pregnancy associated cardiomyopathy (PAC) expands the time frame of peripartum cardiomyopathy (last month of pregnancy through five months post-partum) to earlier in the pregnancy. This case illustrates the importance of a multidisciplinary team at a tertiary center planning a complicated delivery

Revisiting Peripartum Cardiomyopathy: A Subsequent Pregnancy

Peripartum cardiomyopathy, or pregnancy-associated cardiomyopathy, is the development of left ventricular dysfunction usually occurring during the last trimester of pregnancy, shortly after delivery, or five months postpartum. As a result of the cardiovascular strain of pregnancy, patients who have developed peripartum cardiomyopathy, particularly those with persistent left ventricular dysfunction, are strongly advised against subsequent pregnancies. If a subsequent pregnancy should occur in the setting of a diminished left ventricular ejection fraction, the risk of fetal and maternal morbidity and mortality increases significantly. This case describes a 25-year-old Caucasian female patient who became pregnant eighteen months after developing peripartum cardiomyopathy. The association between barriers to adequate care and increased development of peripartum cardiomyopathy in both a rural and global setting has been recognized by several researchers. Literature has shown that expectant mothers from underserved areas, those of African descent and those who smoke, have hypertension, or use cocaine carry a greater risk of developing peripartum cardiomyopathy. Therefore, in addition to the related complications of peripartum cardiomyopathy, practitioners in underserved areas with high-risk populations should be aware of the risk factors and pathophysiologic manifestations inherent with the disease.

Maternal Obesity Affects Cardiac Remodeling and Recovery in Women with Peripartum Cardiomyopathy.

To examine the association between maternal obesity on left ventricular (LV) size and recovery in women with peripartum cardiomyopathy (PPCM). This was a prospective analysis of 100 women enrolled within 13 weeks of PPCM diagnosis and followed for a year in the Investigation of Pregnancy Associated Cardiomyopathy study. Adiposity was defined by standard body mass index (BMI) definitions for under/normal weight, overweight, and obesity. Demographic, clinical, and biomarker variables were compared across weight categories. LV end-diastolic diameter (LVEDD) and ejection fraction were measured at entry, 6, and 12 months postpartum. Multivariable regression models examined the relationship between adiposity, LV size, and leptin levels with cardiac recovery at 6 and 12 months postpartum. Obese and nonobese women had similar LV dysfunction at entry. Obese women had greater LV size and less LV recovery at 6 and 12 months postpartum. BMI was positively associated with leptin and ventricular diameter. Greater BMI at entry remained associated with less ventricular recovery at 6 months (p = 0.02) in adjusted race-stratified models. LVEDD at entry predicted lower ejection fraction at 6 months (p < 0.001) and similarly at 12 months. Obese women with PPCM had greater cardiac remodeling, higher leptin levels, and diminished cardiac recovery.

Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy: Results From the Multicenter IPAC Study

ObjectiveThe aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women. BackgroundPPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis. MethodsThe Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non–pregnancy-associated recent-onset cardiomyopathy (ROCM). ResultsEntry NK cell levels (CD3–CD56+CD16+; reported as % of CD3– cells) were significantly (P < .0003) reduced in PPCM (6.6 ± 4.9% of CD3– cells) compared to HP (11.9 ± 5%). Of T-cell subtypes, CD3+CD4–CD8–CD38+ cells differed significantly (P < .004) between PPCM (24.5 ± 12.5% of CD3+CD4–CD8– cells) and HP (12.5 ± 6.4%). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4–CD8–CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM. ConclusionsCompared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4–CD8–CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and “double negative” (CD4–CD8–) T regulatory cells in PPCM requires further investigation.