James D. Fett

Clinical Outcomes for Peripartum Cardiomyopathy in North America Results of the IPAC Study (Investigations of Pregnancy-Associated Cardiomyopathy)

BACKGROUND Peripartum cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality. OBJECTIVES This study sought to prospectively evaluate recovery of the left ventricular ejection fraction (LVEF) and clinical outcomes in the multicenter IPAC (Investigations of Pregnancy Associated Cardiomyopathy) study. METHODS We enrolled and followed 100 women with PPCM through 1 year post-partum. The LVEF was assessed by echocardiography at baseline and at 2, 6, and 12 months post-partum. Survival free from major cardiovascular events (death, transplantation, or left ventricular [LV] assist device) was determined. Predictors of outcome, particularly race, parameters of LV dysfunction (LVEF), and remodeling (left ventricular end-diastolic diameter [LVEDD]) at presentation, were assessed by univariate and multivariate analyses. RESULTS The cohort was 30% black, 65% white, 5% other; the mean patient age was 30 ± 6 years; and 88% were receiving beta-blockers and 81% angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The LVEF at study entry was 0.35 ± 0.10, 0.51 ± 0.11 at 6 months, and 0.53 ± 0.10 at 12 months. By 1 year, 13% had experienced major events or had persistent severe cardiomyopathy with an LVEF <0.35, and 72% achieved an LVEF ≥0.50. An initial LVEF <0.30 (p = 0.001), an LVEDD ≥6.0 cm (p < 0.001), black race (p = 0.001), and presentation after 6 weeks post-partum (p = 0.02) were associated with a lower LVEF at 12 months. No subjects with both a baseline LVEF <0.30 and an LVEDD ≥6.0 cm recovered by 1 year post-partum, whereas 91% with both a baseline LVEF ≥0.30 and an LVEDD <6.0 cm recovered (p < 0.00001). CONCLUSIONS In a prospective cohort with PPCM, most women recovered; however, 13% had major events or persistent severe cardiomyopathy. Black women had more LV dysfunction at presentation and at 6 and 12 months post-partum. Severe LV dysfunction and greater remodeling at study entry were associated with less recovery. (Investigations of Pregnancy Associated Cardiomyopathy [IPAC]; NCT01085955).

Risk of heart failure relapse in subsequent pregnancy among peripartum cardiomyopathy mothers

To quantify the level of risk for heart failure relapse in a subsequent pregnancy in women who have had peripartum cardiomyopathy (PPCM), and to test the hypothesis that meeting additional criteria may help lower the risk.

Predictors of left ventricular recovery in a cohort of peripartum cardiomyopathy patients recruited via the internet

BACKGROUND Peripartum cardiomyopathy (PPCM) is the onset of acute heart failure without demonstrable cause during the last month of pregnancy or within five months after delivery. The purpose of this study was to create a prospective registry of PPCM patients with the assistance of the internet and identify clinical factors predictive of ejection fraction (EF) recovery. METHODS Patients with PPCM were identified by novel web-based methods. Subjects were categorized as recovered (EF>50) or nonrecovered (EF<50) and compared on the basis of demographic and clinical variables. RESULTS Fifty-five subjects met criteria for inclusion. There was a statistically significant association between diagnosis during third trimester and persistent systolic dysfunction (25% vs. 4.7%, p=0.03). Gestational hypertension and breastfeeding were significantly associated with EF recovery (48.8% vs. 16.7%, p=0.046, and 39.5% vs. 8.3%, p=0.04, respectively). EF normalization occurred in all patients with EF(1) ≥ 35%. CONCLUSIONS Presence of gHTN, EF ≥ 35% at diagnosis, breastfeeding, and postpartum diagnosis were all significantly associated with recovery of systolic function. Internet recruitment may be a valuable tool for studying PPCM.

Recovery from severe heart failure following peripartum cardiomyopathy

Traditional concepts surrounding peripartum cardiomyopathy (PPCM) hold that if recovery does not occur within 6 months of diagnosis, it is unlikely to happen. The purpose of the study was to determine the length of time required for recovery of left ventricular systolic function.

Is peripartum cardiomyopathy an organ-specific autoimmune disease? ☆

Peripartum cardiomyopathy (PPCM) is a rare and serious heart disease that exclusively afflicts women during childbearing years. Symptoms include rapid onset of cardiovascular insufficiency occurring during pregnancy, initiated anytime between the third trimester until 5 months post-partum in the absence of any other signs or history of heart disease. The rare incidence of PPCM and the absence of any relevant animal models have limited research and understanding of the pathogenic mechanisms involved. Several compelling sets of data support the view that PPCM is a form of autoimmune IDCM. However, PPCM differs from autoimmune IDCM in that (a) it is associated with unique sets of autoantibodies and autoantigens, (b) it has a relatively rapid onset, and (c) it exclusively affects pregnant women. Furthermore, the etiology of PPCM is dependent on the interaction of pregnancy associated factors, e.g. increased hemodynamic stress, vasoactive hormones and fetal microchimerism, that co-operate in the context of essential immune and genetic environments for disease progression. Our model of PPCM attempts to represent how multiple factors, e.g. pregnancy, genetics, immune dysregulation, and fetal microchimerism are held in a complex dynamic balance that can co-operate towards the maintenance of cardiovascular health or disease in the mother (Fig. 1). A more thorough study of the precise nature of the cardiac tissue autoantigens may lead to the identification of the mechanisms of breakdown of self-tolerance and perhaps also the putative etiologic agent(s). Further studies of the precise nature of the cardiac tissue autoantigens and the specific factors governing the balance between tolerance and autoimmunity in the periphery, e.g. expression of PD-L1 on cardiac tissues and the role of regulatory T cells, may help to elucidate the autoimmune mechanisms of PPCM.

Unrecognized peripartum cardiomyopathy in Haitian women

Objective: Haitian women have a high relative incidence of clinical presentation with peripartum cardiomyopathy (PPCM): an incidence estimated at one case per three hundred live births, a ten‐fold occurrence compared to American women. Our objective has been to test the hypothesis that some Haitian women may have a forme fruste of PPCM while still without clinical symptoms. Method: A preliminary case‐control study was conducted at the Hospital Albert Schweitzer (HAS), Deschapelles, Haiti, in which 25 apparently healthy postpartum women, without cardiovascular symptoms and with a normal cardiovascular clinical examination, were selected from a consecutive list of obstetrical deliveries and screened by echocardiography for left ventricular dysfunction. Result: Four out of 25 patients (16%) had asymptomatic left ventricular dysfunction that subsequently evolved towards either improvement or deterioration. Supporting evidence for the existence of asymptomatic left ventricular dysfunction or forme fruste PPCM is presented. A hypothetical schema of the pathophysiology of PPCM explains how a latent phase of variable duration may exist prior to onset of detectable clinical heart failure. Conclusion: Screening Haitian women during the last month of pregnancy or in the early postpartum period may help to detect asymptomatic left ventricular dysfunction. Early detection and treatment of PPCM in a known high risk population could lead to improvements in maternal and fetal mortality and morbidity.

Caution in the use of bromocriptine in peripartum cardiomyopathy.

It is premature to attribute the recovery of 2 “postpartum cardiomyopathy” patients to the blocking effect of bromocriptine against prolactin and to assign causal relationship of 16 kDa prolactin to human peripartum cardiomyopathy (PPCM) ([1,2][1]). Both patients in heart failure were treated

Inhibition of Progenitor Dendritic Cell Maturation by Plasma from Patients with Peripartum Cardiomyopathy: Role in Pregnancy-associated Heart Disease

Dendritic cells (DCs) play dual roles in innate and adaptive immunity based on their functional maturity, and both innate and adaptive immune responses have been implicated in myocardial tissue remodeling associated with cardiomyopathies. Peripartum cardiomyopathy (PPCM) is a rare disorder which affects women within one month antepartum to five months postpartum. A high occurrence of PPCM in central Haiti (1 in 300 live births) provided the unique opportunity to study the relationship of immune activation and DC maturation to the etiology of this disorder. Plasma samples from two groups (n = 12) of age- and parity-matched Haitian women with or without evidence of PPCM were tested for levels of biomarkers of cardiac tissue remodeling and immune activation. Significantly elevated levels of GM-CSF, endothelin-1, proBNP and CRP and decreased levels of TGF- were measured in PPCM subjects relative to controls. Yet despite these findings, in vitro maturation of normal human cord blood derived progenitor dendritic cells (CBDCs) was significantly reduced (p < 0.001) in the presence of plasma from PPCM patients relative to plasma from post-partum control subjects as determined by expression of CD80, CD86, CD83, CCR7, MHC class II and the ability of these matured CBDCs to induce allo-responses in PBMCs. These results represent the first findings linking inhibition of DC maturation to the dysregulation of normal physiologic cardiac tissue remodeling during pregnancy and the pathogenesis of PPCM.

Earlier detection can help avoid many serious complications of peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) has a remarkable potential for recovery. It may be within our capability to help almost all women with PPCM not only to survive, but also to completely recover heart function. Time-of-diagnosis left ventricular ejection fraction (LVEF) ≥0.35 is associated with better survival rates and higher full recovery rates. Increased mortality, chronic cardiomyopathy, thromboembolic complications and serious ventricular tachyarrhythmias are associated with diagnostic LVEF <0.30. Delays in diagnosis may result in lower LVEF at diagnosis and subsequent lower recovery rates. Greater awareness of the possibility of heart failure developing in previously healthy young women, with no history of heart disease, will contribute to earlier diagnosis, with potentially better preserved heart function. Women of African descent may be at higher risk for poorer outcomes. Recent investigations suggest newer biomarkers may help with earlier detection of PPCM.

Why do some recovered peripartum cardiomyopathy mothers experience heart failure with a subsequent pregnancy

Opinion statementAfter concerns about survival and recovery from peripartum cardiomyopathy (PPCM), the question commonly asked is, “Is it safe to have another pregnancy?” While important advances have been made in the past decade in the recognition and treatment of PPCM, we still do not know why some apparently recovered PPCM mothers have a relapse of heart failure in a subsequent pregnancy. Knowing that some risk for relapse is always present, careful monitoring of the post-PPCM pregnancy is currently the best way to enable earlier diagnosis with institution of effective evidence-based treatment. In that situation it is reassuring to observe that when a subsequent pregnancy begins with recovered left ventricular systolic function to echocardiographic ejection fraction ≥0.50, even with relapse, the response to treatment is good with much more favorable outcomes. On the other hand, beginning the subsequent pregnancy with echocardiographic ejection fraction <0.50 greatly increases the risk for less favorable outcomes. This article summarizes the current state of knowledge; addresses the important questions facing patients, their families, and caregivers; and identifies the need for a prospective multi-center study of women with post-PPCM pregnancies. The reality is that an estimated 10 % to 20 % of apparently recovered PPCM mothers are going to relapse in a post-PPCM pregnancy; but we do not yet know why. Nevertheless, the lowest risk for relapse is experienced by those who (1) recover to left ventricular ejection fraction 0.55 prior to another pregnancy; (2) have no deterioration of left ventricular ejection fraction after phasing out angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker treatment following recovery; and perhaps, (3) demonstrate adequate contractile reserve on exercise echocardiography.