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Pubblicazioni recenti - peripartum cardiomyopathy
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Inhibition of cardiac PERK signaling promotes peripartum cardiac dysfunction.
Sci Rep2021 Sep;11(1):18687. doi: 10.1038/s41598-021-98344-7.
Shimizu Takashi, Taguchi Akashi, Higashijima Yoshiki, Kanki Yasuharu, Nakaki Ryo, Urade Yoshihiro, Wada Youichiro,
Abstract
Peripartum cardiomyopathy (PPCM) is a life-threatening heart failure occurring in the peripartum period. Although mal-angiogenesis, induced by the 16-kDa N-terminal prolactin fragment (16 K PRL), is involved in the pathogenesis, the effect of full-length prolactin (23 K PRL) is poorly understood. We transfected neonate rat cardiomyocytes with plasmids containing 23 K PRL or 16 K PRL in vitro and found that 23 K PRL, but not 16 K PRL, upregulated protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling, and hypoxia promoted this effect. During the perinatal period, cardiomyocyte-specific PERK homogenous knockout (CM-KO) mice showed PPCM phenotypes after consecutive deliveries. Downregulation of PERK or JAK/STAT signaling and upregulation of apoptosis were observed in CM-KO mouse hearts. Moreover, in bromocriptine-treated CM-KO mice, cardiac function did not improve and cardiomyocyte apoptosis was not suppressed during the peripartum period. These results demonstrate that interaction between 23 K PRL and PERK signaling is cardioprotective during the peripartum term.
© 2021. The Author(s).
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Complex Pathology and Management in the Obstetric Patient: A Narrative Review for the Anesthesiologist.
Cureus2021 Aug;13(8):e17196. doi: 10.7759/cureus.17196.
Metzger Lia, Teitelbaum Menachem, Weber Garret, Kumaraswami Sangeeta,
Abstract
Pregnant patients may present with multiple complex comorbidities that can affect peripartum management and anesthetic care. The preanesthesia clinic is the ideal setting for early evaluation of high-risk pregnant patients. Comorbidities may include cardiovascular pathology such as valvular abnormalities, septal defects, aortopathies, arrythmias and cardiomyopathies. Additional comorbidities include pulmonary conditions such as obstructive sleep apnea as well as preexisting neuromuscular and skeletal disorders that may impact anesthetic management. Hematologic conditions involving both bleeding diathesis and thrombophilias may present unique challenges for the anesthesiologist. Patients may also present with endocrinopathies including diabetes and obesity. While not as common, high-risk patients may also have preexisting gastrointestinal conditions such as liver dysfunction, renal failure, and even post-transplant status. Ongoing and prior substance abuse, obstetric conditions such as placenta accreta spectrum disorders, and fetal conditions needing ex utero Intrapartum treatment also require advanced planning. Preanesthesia evaluations also help address important ethical and cultural considerations. Counseling patients regarding anesthetic considerations as well as addressing concerns will play a role in reducing racial and ethnic disparities. Anticipatory guidance by means of pre-anesthetic planning can facilitate multidisciplinary communication and planning. This can allow for an impactful and meaningful role in the care provided, allowing for safe maternal care and optimal outcomes.
Copyright © 2021, Metzger et al.
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[PERIPARTUM CARDIOMYOPATHY: A REVIEW OF THE LITERATURE].
Gynecol Obstet Fertil Senol2021 Sep;():. doi: S2468-7189(21)00209-9.
Benson Betty, Theret Pierrick, Tonini Flavio, Marang Amélie, Sergent Fabrice, Gondry Jean, Foulon Arthur,
Abstract
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.
Copyright © 2021. Published by Elsevier Masson SAS.
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Cardiovascular and Obstetric Delivery Complications in Pregnant Women With Valvular Heart Disease.
Am J Cardiol2021 Aug;():. doi: S0002-9149(21)00724-4.
Minhas Anum S, Rahman Faisal, Gavin Nicole, Cedars Ari, Vaught Arthur Jason, Zakaria Sammy, Resar Jon, Schena Stefano, Schulman Steven, Zhao Di, Hays Allison G, Michos Erin D,
Abstract
Women with valvular heart disease may be more likely to have adverse obstetric and cardiovascular complications during pregnancy. Most current recommendations focus on stenotic lesions with less guidance regarding regurgitant lesions. We aimed to compare adverse events at delivery for women with various stenotic and regurgitant valvular diseases. We used the 2016 to 2018 National Inpatient Sample data to compare demographics, comorbidities, and obstetric and cardiovascular complications during delivery hospitalizations. After adjusting for clinical and socioeconomic factors, logistic regression was performed to investigate associations between valvular disease and outcomes. Among >11.2 million deliveries, 20,349 were in women with valvular disease. Women with valvular disease were older, had longer length of stays, and higher costs associated with delivery. They had higher prevalence of underlying cardiovascular comorbidities compared with women without valvular disease (hypertension: 5.1 vs 0.25%; pulmonary hypertension: 7.0 vs
Copyright © 2021 Elsevier Inc. All rights reserved.
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A Case of Peripartum Ventricular Tachycardia due to Arrhythmogenic Right Ventricular Dysplasia.
S D Med2021 Jul;74(7):314-317.
Desai Chirag K, Sheikh Maryam, Klippenstein Kade, Boyle Jeffrey, De Berg Kristen, Pham Scott,
Abstract
Arrhythmogenic right ventricular cardiomyopathy is a predominantly inherited structural disease with a heterogeneous set of implicated genetic defects. For those patients not identified by targeted population screening programs, ventricular tachycardia can be their first presentation. We report a case of a female from the genetically isolated Hutterite colonies who presented with recurrent ventricular tachycardia. She was found to be homozygous for a truncated desmocollin-2 gene, with both severe right ventricular dysfunction and left ventricular involvement. Her medical management was complicated by the finding of concomitant pre-term pregnancy. Management options for arrhythmia suppression and treatment are reviewed taking into account her decompensated biventricular dysfunction and possible fetal effects.
Copyright© South Dakota State Medical Association.
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Peripartum Cardiomyopathy.
Obstet Gynecol Surv2021 Aug;76(8):485-492. doi: 10.1097/OGX.0000000000000903.
Farrell Amanda S, Kuller Jeffrey A, Goldstein Sarah A, Dotters-Katz Sarah K,
Abstract
Importance:
Peripartum cardiomyopathy is a rare form of heart failure due to left ventricular systolic dysfunction that affects women late in pregnancy and the postpartum period. A diagnosis of exclusion, peripartum cardiomyopathy can be difficult to diagnose in the context of the normal physiologic changes of pregnancy and requires a high index of suspicion.
Evidence Acquisition:
Original research articles, review articles, and guidelines on peripartum cardiomyopathy were reviewed.
Results:
The etiology of peripartum cardiomyopathy remains poorly defined, but theories include genetic predisposition, as well as myocardial inflammation and angiogenic dysregulation. Risk factors for this condition include hypertensive disorders of pregnancy, Black race, and maternal age older than 30 years. Patients with peripartum cardiomyopathy are at increased risk of acute clinical decompensation, cardiac arrhythmias, thromboembolic complications, and death. Primary treatment modalities include initiation of a medication regimen aimed at the optimization of preload and reduction of afterload. Maternal clinical status is the primary determinant for timing of delivery.
Conclusions:
Prompt diagnosis and medical management by an interdisciplinary care team are vital for improving outcomes in patients with peripartum cardiomyopathy.
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Peripartum cardiomyopathy and acute heart failure associated with prolonged tocolytic therapy in pregnancy: A case report.
Medicine (Baltimore)2021 Aug;100(34):e27080. doi: 10.1097/MD.0000000000027080.
Li Pei-Chen, Chang Huai-Ren, Kao Sheng-Po,
Abstract
RATIONALE:
Peripartum cardiomyopathy (PPCM) is a rare and sometimes fatal systolic heart failure that affects women during late pregnancy or the early postpartum period. Heart failure symptoms can mimic the physiological changes of normal pregnancy, and the diagnosis is based on echocardiography.
PATIENT CONCERNS:
A 38-year-old multiparous woman with a history of cervical incompetence underwent cervical cerclage and received tocolysis for 100?days.
DIAGNOSES:
She delivered vaginally at 37?weeks of gestation but developed postpartum decompensated acute heart failure with low left ventricular ejection fraction (LVEF: 34%) and was diagnosed with PPCM.
INTERVENTIONS:
She received standard therapy for acute heart failure.
OUTCOMES:
The patient's pulmonary edema cleared, and she was fully ambulatory 6?days after admission. A follow-up echocardiogram 3?months later demonstrated recovery of LVEF to 66%.
LESSONS:
Prolonged tocolysis may contribute to cardiomyopathy and should be used with caution. PPCM management requires standard treatments for acute heart failure with modifications for fetal safety.
Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.
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Process of Care and a Practical Toolkit for Evaluating and Managing Arrhythmic Risk in the Cardiogenetic Pregnant Patient.
Can J Cardiol2021 Aug;():. doi: S0828-282X(21)00647-4.
Cheung Christopher C, Roston Thomas, Davies Brianna, Grewal Jasmine, Laksman Zachary W, Krahn Andrew D,
Abstract
Patients with inherited arrhythmia syndromes (IAS) and inherited cardiomyopathies (IC) are periodically encountered in both general and specialist practices. These syndromes include long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, early repolarization syndrome, and hypertrophic and arrhythmogenic cardiomyopathies. In general, the presence of an IAS or IC is not a contraindication to pregnancy, but do require additional expertise and patient engagement. In this review, we summarize the various pregnancy-related considerations in patients with IAS and IC, including the impact of physiologic/hemodynamic changes on heart failure progression or arrhythmia propensity, maternal and fetal pregnancy risk stratification, prenatal genetic testing and the specialized care and monitoring required through pregnancy, labour and delivery, and into the post-partum period. Management of patients with IAS and IC during pregnancy and the post-partum period requires collaboration between patient and provider, with a shared understanding of the general safety and potential risks during the pregnancy and post-partum period. Patients should be aware of the safety of various medications throughout pregnancy, and those with ICDs should be managed as per device guidelines. A peripartum care and delivery plan should be established, with multidisciplinary input from various specialists including obstetrics, cardiac obstetrics, and inherited arrhythmia specialists wherever appropriate.
Copyright © 2021. Published by Elsevier Inc.
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Frequency of Peripartum Cardiomyopathy Among Women With Idiopathic Dilated Cardiomyopathy.
Am J Cardiol2021 Oct;157():101-106. doi: S0002-9149(21)00682-2.
Roberts William C, Jeong Minseob,
Abstract
Among women with idiopathic dilated cardiomyopathy (IDC), the percent who develop heart failure (HF) in the peripartum period (during pregnancy or within 6 months of parturition) compared with those women who develop HF outside the peripartum period is unclear. We studied 72 women with IDC who underwent orthotopic heart transplantation for severe HF, the onset of which was in the peripartum period in 8 (11%) and outside the period in 64 (89%). Comparison of many clinical and morphologic variables between these 2 groups showed significant differences only in the ages of onset of HF, age when orthotopic heart transplantation was performed, and the frequency of the presence of diabetes mellitus. Examination of the hearts in the 2 groups disclosed no significant differences. Thus, separation of the peripartum IDC cases from the nonperipartum IDC cases by either clinical or cardiac morphologic variables is difficult.
Copyright © 2021 Elsevier Inc. All rights reserved.
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Gestational Diabetes and Incident Heart Failure: A Cohort Study.
Diabetes Care2021 Aug;():. doi: dc210552.
Echouffo-Tcheugui Justin B, Guan Jun, Retnakaran Ravi, Shah Baiju R,
Abstract
OBJECTIVE:
To assess whether gestational diabetes mellitus (GDM) is associated with an increased risk of heart failure (HF).
RESEARCH DESIGN AND METHODS:
We conducted a population-based cohort study using information from the Ministry of Health and Long-Term Care of Ontario (Canada) health care administrative databases. We identified all women in Ontario with a GDM diagnosis with a live birth singleton delivery between 1 July 2007 and 31 March 2018. Women with diabetes or HF before pregnancy were excluded. GDM was defined based on laboratory test results and diagnosis coding. The primary outcome was incident HF hospitalization over a period extending from the index pregnancy until 31 March 2019. The secondary outcome was prevalent peripartum cardiomyopathy at index pregnancy. Estimates of association were adjusted for relevant cardiometabolic risk factors.
RESULTS:
Among 906,319 eligible women (mean age 30 years [SD 5.6], 50,193 with GDM [5.5%]), there were 763 HF events over a median follow-up period of 7 years. GDM was associated with a higher risk of incident HF (adjusted hazard ratio [aHR] 1.62 [95% CI 1.28, 2.05]) compared with no GDM. This association remained significant after accounting for chronic kidney disease, postpartum diabetes, hypertension, and coronary artery disease (aHR 1.39 [95% CI 1.09, 1.79]). GDM increased the odds of peripartum cardiomyopathy (adjusted odds ratio 1.83 [95% CI 1.45, 2.33]).
CONCLUSIONS:
In a large observational study, GDM was associated with an increased risk of HF. Consequently, diabetes screening during pregnancy is suggested to identify women at risk for HF.
© 2021 by the American Diabetes Association.
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Heart failure in pregnancy: what is the long-term impact of pregnancy on cardiac function? A tertiary care centre experience and systematic review.
Open Heart2021 Aug;8(2):. doi: e001587.
Dodeja Anudeep K, Siegel Francesca, Dodd Katherine, Ma'ayeh Marwan, Mehta Laxmi S, Fuchs Margaret M, Rood Kara M, Mah May Ling, Bradley Elisa A,
Abstract
BACKGROUND:
Women with cardiomyopathy (CM) are often advised against pregnancy due to risk for major adverse cardiovascular events (MACE). However, the impact of CM subtype on maternal MACE is not understood, and so we sought to evaluate the influence of CM phenotype on maternal outcomes, as well as the effect on immediate and late left ventricular function.
METHODS:
We evaluated all pregnant women in our high-risk maternal cardiovascular programme (2009-2019). Composite maternal MACE included: death, inotrope use, left ventricular assist device, orthotopic heart transplant and/or escalation in transplant listing status, acute decompensated heart failure and sustained ventricular arrhythmia.
RESULTS:
Among 875 women followed, 32 had CM (29±7 years old, left ventricular ejection fraction (LVEF) 41%±12%): 3 ischaemic CM (ICM), 10 peripartum CM (PPCM) and 19 non-ICM (NICM). MACE events occurred in 6 (18%) women (PPCM: 2 (33%), NICM: 4 (67%)). There was no difference in LVEF at baseline, however, women with MACE had significantly lower LVEF both early (LVEF: 27±5% vs . 41±2%, p
CONCLUSIONS:
In this contemporary cohort of women with CM, maternal MACE rates were lower than previously reported, and were less common in PPCM as compared with ICM and NICM. Heart function in women with MACE was negatively impacted immediately after delivery and in late postpartum follow-up, suggesting that pregnancy itself likely has influence on future left ventricular function in women with underlying CM.
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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Peripartum cardiomyopathy: from genetics to management.
Eur Heart J2021 08;42(32):3094-3102. doi: 10.1093/eurheartj/ehab458.
Sliwa Karen, Bauersachs Johann, Arany Zolt, Spracklen Timothy F, Hilfiker-Kleiner Denise,
Abstract
Peripartum cardiomyopathy (PPCM) is a disease that occurs globally in all ethnic groups and should be suspected in any peripartum women presenting with symptoms and signs of heart failure, towards the end of pregnancy or in the months following delivery, with confirmed left ventricular dysfunction. After good history taking, all women should be thoroughly assessed, and alternative causes should be excluded. Urgent cardiac investigations with electrocardiogram and natriuretic peptide measurement (if available) should be performed. Echocardiography follows as the next step in investigation. Patients with abnormal cardiac investigations should be urgently referred to a cardiology team for expert management. Referral for genetic work-up should be considered if there is a family history of cardiomyopathy or sudden death. PPCM is a disease with substantial maternal and neonatal morbidity and mortality. Maternal mortality rates range widely, from 0% to 30%, depending on the ethnic background and geographic region. Just under half of women experience myocardial recovery. Remarkable advances in the comprehension of the pathogenesis and in patient management and therapy have been achieved, largely due to team efforts and close collaboration between basic scientists, cardiologists, intensive care specialists, and obstetricians. This review summarizes current knowledge of PPCM genetics, pathophysiology, diagnostic approach, management, and outcome.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.
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Severe peripartum cardiomyopathy complicated by COVID-19 infection and small intestinal obstruction.
Clin Case Rep2021 Jul;9(7):e04505. doi: 10.1002/ccr3.4505.
Abdulraheem Ekhlas, Shaikhoun Mazin, Kung David,
Abstract
COVID-19 infection can be a possible trigger for peripartum cardiomyopathy. Multidisciplinary teamwork was crucial for the favorable outcome in our patient. Small bowel strangulation is a rare complication post-cesarean section.
© 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.
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Resynchronization in the cardiogenic shock of peripartum cardiomyopathy.
Med Clin (Barc)2021 Jul;():. doi: S0025-7753(21)00361-4.
de Dios Inmaculada, Fernández Pedro, Rodríguez Teresa,
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Characteristics shifting of heart disease in pregnancy: A report from low middle-income country.
J Public Health Res2021 Jul;():. doi: 10.4081/jphr.2021.2137.
Puspa Pitaloka Cyntia, Secka Absa, Ernawati Ernawati, Sulistyono Agus, Juwono Hermanto Tri, Gumilar Dachlan Erry, Aditiawarman Aditiawarman,
Abstract
BACKGROUND:
Heart disease in pregnancy is one of the leading causes of maternal mortality and morbidity in developing countries. However, the characteristics of the disease vary between countries and regions. This study aimed to present the characteristics of pregnant women with heart disease in an economically advantageous region of a developing country.
DESIGN AND METHODS:
A cross-sectional study was conducted using data from the Weekly Report of Obstetrics and Gynaecology Department to assess pregnant women with heart disease characteristics and pregnancy outcomes. A total sample of 69 pregnant women with heart disease regarding their gestational age was included in the study. Variables observed were maternal characteristics, heart disease's clinical parameters, and maternal and neonatal outcomes. Chi-square test was used to examine the different characteristics of congenital and acquired heart disease groups.
RESULTS:
The prevalence of cardiac disease in pregnancy was 5.19%. Fifty-three point six percent of pregnant women with heart disease were suffered from congenital heart disease (CHD), while 46.4% were acquired heart disease (AHD). Most labor methods were Cesarean delivery, and 69.6% of women experienced cardiac complications. Maternal death was reported in 8.69% of cases. Four cases were CHD complicated by pulmonary hypertension, which leads to Eisenmenger syndrome. Two other cases were AHD complicated by Peripartum Cardiomyopathies. Although statistically insignificant, complications are more common in the AHD group than CHD.
CONCLUSION:
Cardiac disease prevalence in pregnancy is considered high, with CHD as the most common case, which significantly differs from other developing countries.
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In-Hospital Complications in Pregnant Women With Current or Historical Cancer Diagnoses.
Mayo Clin Proc2021 Jul;():. doi: S0025-6196(21)00357-8.
Wu Pensée, Jordan Kelvin P, Chew-Graham Carolyn A, Mohamed Mohamed O, Barac Ana, Lundberg Gina P, Chappell Lucy C, Michos Erin D, Maas Angela H E M, Mamas Mamas A,
Abstract
OBJECTIVE:
To assess the temporal trends, characteristics and comorbidities, and in-hospital cardiovascular and obstetric complications and outcomes of pregnant women with current or historical cancer diagnosis at the time of admission for delivery.
METHODS:
We analyzed delivery hospitalizations with or without current or historical cancer between January 1, 2004, and December 31, 2014, from the US National Inpatient Sample database.
RESULTS:
We included 43,132,097 delivery hospitalizations with no cancer, 39,118 with current cancer, and 67,336 with historical diagnosis of cancer. The 5 most common types of current cancer were hematologic, thyroid, cervical, skin, and breast cancer. Women with current and historical cancer were older (29 years and 32 years vs 27 years) and incurred higher hospital costs ($4131 and $4078 vs $3521) compared with women without cancer. Most of the cancer types were associated with preterm birth (hematologic: adjusted odds ratio [aOR], 1.48 [95% CI, 1.35 to 1.62]; cervical: aOR, 1.47 [95% CI, 1.32 to 1.63]; breast: aOR, 1.93 [95% CI, 1.72 to 2.16]). Current hematologic cancer was associated with the highest risk of peripartum cardiomyopathy (aOR, 12.19 [95% CI, 7.75 to 19.19]), all-cause mortality (aOR, 6.50 [95% CI, 2.22 to 19.07]), arrhythmia (aOR, 3.82 [95% CI, 2.04 to 7.15]), and postpartum hemorrhage (aOR, 1.31 [95% CI, 1.11 to 1.54]). Having a current or historical cancer diagnosis did not confer additional risk for stillbirth; however, metastases increased the risk of maternal mortality and preterm birth.
CONCLUSION:
Women with a current or historical diagnosis of cancer at delivery have more comorbidities compared with women without cancer. Clinicians should communicate the risks of multisystem complications to these complex patients.
Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
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Peripartum cardiomyopathy and pre-eclampsia: two tips of the same iceberg.
Eur J Heart Fail2021 Jul;():. doi: 10.1002/ejhf.2300.
Halliday Brian P, de Marvao Antonio, Thilaganathan Basky,
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ERBB4 and Multiple MicroRNAs That Target ERBB4 Participate in Pregnancy-Related Cardiomyopathy.
Circ Heart Fail2021 Jul;14(7):e006898. doi: 10.1161/CIRCHEARTFAILURE.120.006898.
Feyen Eline, Ricke-Hoch Melanie, Van Fraeyenhove Jens, Vermeulen Zarha, Scherr Michaela, Dugaucquier Lindsey, Viereck Janika, Bruyns Tine, Thum Thomas, Segers Vincent F M, Hilfiker-Kleiner Denise, De Keulenaer Gilles W,
Abstract
BACKGROUND:
Peripartum cardiomyopathy (PPCM) is a life-threatening disease in women without previously known cardiovascular disease. It is characterized by a sudden onset of heart failure before or after delivery. Previous studies revealed that the generation of a 16-kDa PRL (prolactin) metabolite, the subsequent upregulation of miR-146a, and the downregulation of the target gene is a common driving factor of PPCM.
METHODS:
miRNA profiling was performed in plasma of PPCM patients (n=33) and postpartum-matched healthy CTRLs (controls; n=36). Elevated miRNAs in PPCM plasma, potentially targeting ERBB4 (erythroblastic leukemia viral oncogene homolog 4), were overexpressed in cardiomyocytes using lentiviral vectors. Next, cardiac function, cardiac morphology, and PPCM phenotype were investigated after recurrent pregnancies of HZ (heterozygous) cardiomyocyte-specific mice (, n=9) with their age-matched nonpregnant CTRLs (n=9-10).
RESULTS:
Here, we identify 9 additional highly conserved miRNAs (miR-199a-5p and miR-199a-3p, miR-145a-5p, miR-130a-3p, miR-135a-5p, miR-221-3p, miR-222-3p, miR-23a-3p, and miR19b-3p) that target tyrosine kinase receptor ERBB4 and are over 4-fold upregulated in plasma of PPCM patients at the time of diagnosis. We confirmed that miR-146a, miR-199a-5p, miR-221-3p, miR-222-3p, miR-23a-3p, miR-130a-5p, and miR-135-3p overexpression decreases ERBB4 expression in cardiomyocytes (-29% to -50%;
CONCLUSIONS:
ERBB4 is essential to protect the maternal heart from peripartum stress. Downregulation of ERBB4 in cardiomyocytes induced by multiple miRNAs in the peripartum period may be crucial in PPCM pathophysiology. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00998556.
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Proinflammatory TH17 cytokine activation, disease severity and outcomes in peripartum cardiomyopathy.
Int J Cardiol2021 Sep;339():93-98. doi: S0167-5273(21)00981-5.
Koczo Agnes, Marino Amy, Rocco Joseph, Ewald Gregory, Givertz Michael M, Rajagopalan Navin, Bozkurt Biykem, Elkayam Uri, Cooper Leslie T, Fett James, McTiernan Charles F, Morel Penelope A, Hanley-Yanez Karen, McNamara Dennis M, ,
Abstract
BACKGROUND:
Immune dysregulation is implicated in the development and clinical outcomes of peripartum cardiomyopathy (PPCM).
METHODS AND RESULTS:
98 women with PPCM were enrolled and followed for 1 year postpartum (PP). LVEF was assessed at entry, 6-, and 12-months PP by echocardiography. Serum levels of soluble interleukin (IL)-2 receptor (sIL2R), IL-2, IL-4, IL-17, IL-22, tumor necrosis factor (TNF)-?, and interferon (IFN)-? were measured by ELISA at entry. Cytokine levels were compared between women with PPCM by NYHA class. Outcomes including myocardial recovery and event-free survival were compared by cytokine tertiles. For cytokines found to impact survival outcomes, parameters indicative of disease severity including baseline LVEF, medications, and use of inotropic and mechanical support were analyzed. Levels of proinflammatory cytokines including IL-17, IL-22, and sIL2R, were elevated in higher NYHA classes at baseline. Subjects with higher IL-22 levels were more likely to require inotropic or mechanical support. Higher levels of TNF-? and IL-22 were associated with poorer event-free survival. Higher TNF-? levels were associated with lower mean LVEF at entry and 12 months. In contrast, higher levels of immune-regulatory cytokines such as IL-4 and IL-2 were associated with higher LVEF during follow up.
CONCLUSION:
Proinflammatory cytokines IL-22 and TNF-? were associated with adverse event-free survival. IL-17 and IL-22 were associated with more severe disease. In contrast, higher levels of IL-2 and IL-4 corresponded with higher subsequent LVEF. Increased production of TH17 type cytokines in PPCM correlated with worse disease and outcomes, while an increased immune-regulatory response seems to be protective.
Copyright © 2021. Published by Elsevier B.V.
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Heat Shock Proteins: Potential Modulators and Candidate Biomarkers of Peripartum Cardiomyopathy.
Front Cardiovasc Med2021 ;8():633013. doi: 10.3389/fcvm.2021.633013.
Chakafana Graham, Spracklen Timothy F, Kamuli Stephen, Zininga Tawanda, Shonhai Addmore, Ntusi Ntobeko A B, Sliwa Karen,
Abstract
Peripartum cardiomyopathy (PPCM) is a potentially life-threatening condition in which heart failure and systolic dysfunction occur late in pregnancy or within months following delivery. To date, no reliable biomarkers or therapeutic interventions for the condition exist, thus necessitating an urgent need for identification of novel PPCM drug targets and candidate biomarkers. Leads for novel treatments and biomarkers are therefore being investigated worldwide. Pregnancy is generally accompanied by dramatic hemodynamic changes, including a reduced afterload and a 50% increase in cardiac output. These increased cardiac stresses during pregnancy potentially impair protein folding processes within the cardiac tissue. The accumulation of misfolded proteins results in increased toxicity and cardiac insults that trigger heart failure. Under stress conditions, molecular chaperones such as heat shock proteins (Hsps) play crucial roles in maintaining cellular proteostasis. Here, we critically assess the potential role of Hsps in PPCM. We further predict specific associations between the Hsp types Hsp70, Hsp90 and small Hsps with several proteins implicated in PPCM pathophysiology. Furthermore, we explore the possibility of select Hsps as novel candidate PPCM biomarkers and drug targets. A better understanding of how these Hsps modulate PPCM pathogenesis holds promise in improving treatment, prognosis and management of the condition, and possibly other forms of acute heart failure.
Copyright © 2021 Chakafana, Spracklen, Kamuli, Zininga, Shonhai, Ntusi and Sliwa.
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