High prevalence of viral genomes and inflammation in peripartum cardiomyopathy

doi:10.1016/j.ajog.2005.01.022

American Journal of Obstetrics and Gynecology

Volume 193, Issue 2, August 2005, Pages 363-365

https://doi.org/10.1016/j.ajog.2005.01.022 Get rights and content

Molecular pathologic investigation of endomyocardial biopsy specimens from 26 patients with peripartum cardiomyopathy revealed viral genomes (parvovirus B19, human herpes virus 6, Epstein-Barr virus, and human cytomegalovirus) in 8 patients (30.7%) that were associated immunohistologically with interstitial inflammation. These findings indicate a high prevalence of virus-associated inflammatory changes in peripartum cardiomyopathy.

Section snippets

Study population and methods

Review of our files (1993-2003) revealed EMBs from 769 women, 26 of whom (median age, 31.8 years; range, 22-38 years) had a clinical diagnosis of PPCM, according to the criteria of the National Heart, Lung, and Blood Institute and the Office of Rare Diseases of the National Institutes of Health workshop panel.¹ The main clinical, morphologic, and molecular pathologic data are summarized in the Table. As controls, we used EMBs from 33 women (median age, 31.3 years; range, 20-38 years) in whom

Results

PCR detected viral genomes in 8 of the 26 patients (30.7%): PVB19 (n = 4), HHV6 (n = 2), EBV (n = 1), and HCMV (n = 1). Specificity of the virus-specific PCR products was proved by automatic DNA sequencing, which revealed randomly distributed patient-specific point mutations as previously shown.2, 3 QRT-PCR disclosed a viral load of 3.5 × 10¹, 1.63 × 10², and 9.4 × 10⁴ genome equivalents per microgram of myocardial nucleic acid in 3 patients who had PVB19-positive EMBs. A follow-up EMB from the patient

Comment

This is the first study to show that (1) viral genomes are detectable by molecular pathologic investigation in EMBs of a large proportion (30.7%) of patients with PPCM, (2) the prevalence of these viruses is identical (30.3%) in female control subjects of the same age class with other non–virus-related CMPs, and (3) the presence of viral genomes in EMBs is associated with inflammatory CMP exclusively in patients with PPCM but not in control subjects. We recently demonstrated that the presence

References (8)

B.D. Bültmann et al.
Fatal parvovirus B19-associated myocarditis clinically mimicking ischemic heart disease: an endothelial cell-mediated disease
Hum Pathol
(2003)
M.N. Rizeq et al.
Incidence of myocarditis in peripartum cardiomyopathy
Am J Cardiol
(1994)
J.G. Murphy
Peripartum cardiomyopathy
U. Kühl et al.
Parvovirus B19 infection mimicking acute myocardial infarction
Circulation
(2003)

There are more references available in the full text version of this article.

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Heart failure (HF) is one of the leading causes of maternal mortality and morbidity in the United States. Peripartum cardiomyopathy (PPCM) constitutes up to 70% of all HF in pregnancy. Cardiac angiogenic imbalance caused by cleaved 16kDa prolactin has been hypothesized to contribute to the development of PPCM, fueling investigation of prolactin inhibitors for the management of PPCM. We conducted a systematic review and meta-analysis to assess the impact of prolactin inhibition on left ventricular (LV) function and mortality in patients with PPCM. We included English language articles from PubMed and EMBASE published upto March 2022. We pooled the mean difference (MD) for left ventricular ejection fraction (LVEF) at follow-up, odds ratio (OR) for LV recovery and risk ratio (RR) for all-cause mortality using random-effects meta-analysis. Among 548 studies screened, 10 studies (3 randomized control trials (RCTs), 2 retrospective and 5 prospective cohorts) were included in the systematic review. Patients in the Bromocriptine + standard guideline directed medical therapy (GDMT) group had higher LVEF% (pMD 12.56 (95% CI 5.84-19.28, I2=0%) from two cohorts and pMD 14.25 (95% CI 0.61-27.89, I2=88%) from two RCTs) at follow-up compared to standard GDMT alone group. Bromocriptine group also had higher odds of LV recovery (pOR 3.55 (95% CI 1.39-9.1, I2=62)). We did not find any difference in all-cause mortality between the groups. Our analysis demonstrates that the addition of Bromocriptine to standard GDMT was associated with a significant improvement in LVEF% and greater odds of LV recovery, without significant reduction in all-cause mortality.
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La cardiomyopathie du péripartum est une pathologie rare et imprévisible de la grossesse. Il s’agit d’une cardiomyopathie idiopathique se présentant comme une défaillance cardiaque secondaire à une dysfonction systolique ventriculaire gauche apparaissant vers la fin de la grossesse ou dans les mois qui suivent l’accouchement avec une présentation clinique peu spécifique. À travers une revue critique de la littérature scientifique actuelle, nous souhaitons améliorer la compréhension de sa physiopathologie, connaître les symptômes évocateurs du diagnostic, les éléments conditionnant le pronostic et, enfin, la prise en charge durant la grossesse et le post-partum. Le traitement est principalement symptomatique, d’autres traitements semblent prometteurs, mais sont encore à l’étude. En conclusion, la détection et la prise en charge précoce permettent une meilleure récupération de la fonction cardiaque réduisant le recours à la transplantation.
Peripartum cardiomyopathy is a rare and unpredictable pregnancy-related pathology. Idiopathic cardiomyopathy is characterized by a heart failure secondary to left ventricular systolic dysfunction appearing towards the end of pregnancy or in the months following delivery with a non-specific clinic presentation. Through reviewing previous research, our critical literature review wishes to bring a concise and objective summarize for a better understanding of physiopathology, evocative symptoms and knowing of factors influencing prognosis in order to standardize peripartum management. The treatment remains mainly symptomatic but other promising treatments are still in development. In conclusion, early detection and treatment allow a better cardiac function recovery reducing cardiac transplantation.
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A 34 year-old African American woman with a history of chronic hypertension and obesity presents with 1 week of dyspnea on exertion. She is a G3P2 and delivered a healthy baby girl at term gestation via cesarean section 4 weeks prior. Her pregnancy was complicated by superimposed preeclampsia diagnosed just prior to delivery. Her review of systems is notable for a nonproductive cough and lower extremity edema and is negative for fever, chills, and orthopnea. She is taking nifedipine for hypertension. On exam, she is afebrile. She has mild resting tachypnea, her heart rate is 98 beats per minute, and her blood pressure is 130/78. Her jugular venous pressure (JVP) is difficult to assess. Lungs have diminished breath sounds at the bases bilaterally. Her heart rate is regular, she does not have a gallop, and a 2/6 systolic murmur is heard at the apex. Her abdomen is soft with a healing scar. She has 1 + pitting edema of her lower extremities. Her chest X-ray shows multifocal airspace opacities suspicious for pneumonia and a mildly enlarged cardiac silhouette (see Figures 1). A computed tomography (CT) pulmonary angiogram is performed and demonstrates extensive multifocal patchy groundglass opacities and no pulmonary embolism. Her laboratory analysis is notable for a normal comprehensive metabolic panel and complete blood count. An N-terminal pro-B-type natriuretic peptide (NT-proBNP) level is 3908 pg/mL. A bedside echocardiogram shows severe dilatation of the left ventricle (LV) with an LV end-diastolic dimension of 7.3 cm with normal LV wall thickness (Figures 2). The LV ejection fraction is 25%. She has moderate-to-severe mitral regurgitation, trace tricuspid regurgitation, and an estimated pulmonary artery systolic pressure of 46 mmHg. What would be the next steps you would take in managing this patient’s dyspnea and depressed left ventricular function?
Peripartum cardiomyopathy (PPCM) is an often severe form of cardiomyopathy diagnosed in the peripartum period and is characterized by left ventricular systolic dysfunction and heart failure. The diagnosis is made in 1 in every 1000–4000 live births in the United States and is more commonly made in women of African ancestry. Other risk factors include advanced maternal age, preeclampsia, and twin gestations. The majority of women will recover cardiac function but short- and long-term complications are common. Heart failure-specific therapies are the mainstay of treatment and bromocriptine is currently under investigation as a disease-specific treatment in certain clinical cases. Recent mechanistic work has highlighted the role of toxic vascular hormones of late gestation and genetic predisposition in causing PPCM. In this chapter, we review the current literature on the epidemiology, pathophysiology, and clinical management of PPCM, as well as future research directions.
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Peripartum cardiomyopathy is a form of systolic heart failure affecting young women toward the end of pregnancy or in the months following delivery. Incidence is higher in African-American women and in women with older maternal age, hypertensive disorders of pregnancy, and multiple gestation pregnancies. Symptoms of heart failure mimic those of normal pregnancy, often resulting in a delay in diagnosis and preventable complications. Echocardiography showing decreased myocardial function is essential for the diagnosis. Medical management is similar to heart failure with reduced ejection fraction of other etiologies, but adjustments during pregnancy are necessary to ensure fetal safety. Variable outcomes include complete recovery, persistent heart failure, arrhythmias, thromboembolic events, and death. Subsequent pregnancy confers substantial risk of relapse and even death if there is incomplete myocardial recovery. Additional research about the etiology, optimal therapy including the use of bromocriptine, long-term outcomes, and duration of treatment after recovery are needed.
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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.

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^†: Burkhard D. Bültmann and Karin Klingel contributed equally to this study, and thus share first authorship.

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General Obstetrics and Gynecology: GynecologyHigh prevalence of viral genomes and inflammation in peripartum cardiomyopathy

Section snippets

Study population and methods

Results

Comment

Hum Pathol

Am J Cardiol

Peripartum cardiomyopathy

Parvovirus B19 infection mimicking acute myocardial infarction

Circulation

General Obstetrics and Gynecology: Gynecology
High prevalence of viral genomes and inflammation in peripartum cardiomyopathy