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BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure (HF), presenting with left ventricular (LV) systolic dysfunction either at the end of pregnancy or in the months following delivery. In rare cases, PPCM leads to severe impairment of LV function, refractory cardiogenic shock or advanced HF. LV assist devices (LVAD) have been shown to be a feasible treatment option in advanced HF. However, little is known about long-term outcomes and prognosis of PPCM patients undergoing LVAD implantation. METHODS: A retrospective analysis of data from PPCM patients undergoing LVAD implantation in two tertiary centers with respect to long-term outcomes was performed. RESULTS: Twelve patients of median age 30 (18-39) years were included. Eight patients were experiencing cardiogenic shock (INTERMACS 1) at implantation. Seven patients were implanted within 1 month of their PPCM diagnosis. Median duration of LVAD support was 19 (2-92) months with median follow up of 67 (18-136) months (100% complete). In-hospital and 1-year mortality were 0% and 8.3%, respectively. Two patients died on LVAD support, four patients were successfully bridged to transplantation, two patients are still on LVAD, and four were successfully weaned due to sufficient LV recovery (one died after LV function deteriorated again). CONCLUSION: LVAD treatment of decompensated end-stage PPCM is feasible. Early LVAD provision led to hemodynamic stabilization in our cohort and facilitated safe LV recovery in one third of these young female patients.
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Cardiomiopatias , Insuficiência Cardíaca , Coração Auxiliar , Disfunção Ventricular Esquerda , Gravidez , Humanos , Feminino , Adulto , Choque Cardiogênico/terapia , Estudos Retrospectivos , Coração Auxiliar/efeitos adversos , Período Periparto , Resultado do Tratamento , Cardiomiopatias/complicações , Cardiomiopatias/cirurgia , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/complicações , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/terapiaRESUMO
Peripartum cardiomyopathy is a myocardial disease process which occurs in young women either in late pregnancy or the early postpartum period. Due to the young age of women effected by this disease, many of these patients elect to pursue a subsequent pregnancy after their initial diagnosis. Currently, echocardiography is used to better elucidate the cardiovascular risks these young patients face when undergoing a subsequent pregnancy; however, the most accurate modality to determine these risks is debatable. In this review, we explore the current literature regarding the use and accuracy of resting transthoracic echocardiography, exercise stress echocardiography, and dobutamine stress echocardiography in risk stratification of a subsequent pregnancy in a patient with peripartum cardiomyopathy.
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Cardiomiopatias , Complicações Cardiovasculares na Gravidez , Transtornos Puerperais , Cardiomiopatias/diagnóstico , Cardiomiopatias/epidemiologia , Feminino , Humanos , Período Periparto , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Complicações Cardiovasculares na Gravidez/epidemiologia , Prognóstico , Transtornos Puerperais/diagnósticoRESUMO
In patients with newly diagnosed heart failure with reduced ejection fraction (HFrEF), three months of optimal therapy are recommended before considering a primary preventive implantable cardioverter-defibrillator (ICD). It is unclear which patients benefit from a prolonged waiting period under protection of the wearable cardioverter-defibrillator (WCD) to avoid unnecessary ICD implantations. This study included all patients receiving a WCD for newly diagnosed HFrEF (n = 353) at our center between 2012 and 2017. Median follow-up was 2.7 years. From baseline until three months, LVEF improved in patients with all peripartum cardiomyopathy (PPCM), myocarditis, dilated cardiomyopathy (DCM), or ischemic cardiomyopathy (ICM). Beyond this time, LVEF improved in PPCM and DCM only (10 ± 8% and 10 ± 12%, respectively), whereas patients with ICM showed no further improvement. The patients with newly diagnosed HFrEF were compared to 29 patients with a distinct WCD indication, which is an explantation of an infected ICD. This latter group had a higher incidence of WCD shocks and poorer overall survival. All-cause mortality should be considered when deciding on WCD prescription. In patients with newly diagnosed HFrEF, the potential for delayed LVEF recovery should be considered when timing ICD implantation, especially in patients with PPCM and DCM.
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Desfibriladores Implantáveis , Insuficiência Cardíaca , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Humanos , Volume Sistólico , Função Ventricular EsquerdaRESUMO
Increased expression and activity of cardiac and circulating cathepsin D and soluble fms-like tyrosine kinase-1 (sFlt-1) have been demonstrated to induce and promote peripartum cardiomyopathy (PPCM) via promoting cleavage of 23-kD prolactin (PRL) to 16-kD PRL and neutralizing vascular endothelial growth factor (VEGF), respectively. We hypothesized that activation of Hes1 is proposed to suppress cathepsin D via activating Stat3, leading to alleviated development of PPCM. In the present study, we aimed to investigate the role of Notch1/Hes1 pathway in PPCM. Pregnant mice between prenatal 3 days and postpartum 3 weeks were fed with LY-411575 (a notch inhibitor, 10 mg/kg/d). Ventricular function and pathology were evaluated by echocardiography and histological analysis. Western blotting analysis was used to examine the expression at the protein level. The results found that inhibition of Notch1 significantly promoted postpartum ventricular dilatation, myocardial hypertrophy and myocardial interstitial fibrosis and suppressed myocardial angiogenesis. Western blotting analysis showed that inhibition of Notch1 markedly increased cathepsin D and sFlt-1, reduced Hes1, phosphorylated Stat3 (p-Stat3), VEGFA and PDGFB, and promoted cleavage of 23k-D PRL to 16-kD PRL. Collectively, inhibition of Notch1/Hes1 pathway induced and promoted PPCM via increasing the expressions of cathepsin D and sFlt-1. Notch1/Hes1 was a promising target for prevention and therapeutic regimen of PPCM.
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Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Período Periparto/metabolismo , Receptor Notch1/metabolismo , Transdução de Sinais , Animais , Biomarcadores , Cardiomegalia/diagnóstico , Cardiomegalia/etiologia , Cardiomegalia/metabolismo , Cardiomiopatias/sangue , Cardiomiopatias/diagnóstico , Catepsina D/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Ecocardiografia , Feminino , Fibrose , Proteínas de Membrana/metabolismo , Camundongos , Gravidez , Proteólise , Remodelação VentricularRESUMO
BACKGROUND: This case report highlights the rare occurrence of postpartum psychosis in the setting of peripartum cardiomyopathy, which can have rare presentations like arrhythmias and pulmonary edema; and the challenges one should anticipate while managing these conditions together. Caution is advised whenever antipsychotic drugs are to be administered to a patient with a cardiac condition as these drugs potentially increase the risk of arrhythmias and sudden death. CASE PRESENTATION: A 35 year old grand multiparous woman who was 1 week into puerperium was admitted with severe difficulty in breathing at rest, chest congestion and pain. She also had easy fatigability, orthopnea, paroxysmal nocturnal dyspnea, edema, tachycardia, tachypnea, irregularly irregular heart rate with a pulse deficit, elevated jugular venous pressure, cardiomegaly, hepatomegaly and pulmonary crepitations. On the sixth day while improving on standard drugs for heart failure, she developed bizarre behavior and confusion. She also had auditory, visual and olfactory hallucinations; violence to the baby and the husband; and refusal to feed and take medication. There was no altered sensorium and the vital signs were normal. She was diagnosed with puerperal psychosis during the management of peripartum cardiomyopathy. CONCLUSION: In the rare occurrence of puerperal psychosis in the course of management of peripartum cardiomyopathy one must be acutely aware of the risk of sudden cardiac death occasioned by use of antipsychotics, either directly or due to arrhythmias. Continuous electrocardiogram (ECG) monitoring or use of alternative management modalities is thus highly advised.
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Cardiomiopatias/complicações , Cardiomiopatias/terapia , Período Periparto , Período Pós-Parto , Transtornos Psicóticos/complicações , Transtornos Puerperais/terapia , Adulto , Cesárea , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
Peripartum cardiomyopathy (PPCM) is a condition of unknown etiology that presents as heart failure due to left ventricular systolic dysfunction in the last of month of pregnancy and up to six months after giving birth. PPCM predisposes towards thrombo-embolism and an acute limb ischaemia can be a manifestation of this disease. We present a case of a 23-year-old lady presenting an acute lower limb ischaemia four months post-partum. Doppler ultrasound showed bilateral femoral emboli and cardiac ECHO showed a 24% ejection fraction. Amputation was performed on both limbs, below her right knee and above her left knee. The patient was started on heart failure medication and her symptoms improved with diuretic therapy, confirming the diagnoses of PPCM. It is important to recognise acute limb ischaemia as a rare manifestation of PPCM, as a timely diagnosis and effective treatment of the disease can improve the prognosis. We believe this is the first case to be reported in medical literature from Pakistan of a patient presenting PPCM with bilateral acute limb ischaemia and gangrene.
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Cardiomiopatias/complicações , Embolia/etiologia , Artéria Femoral/diagnóstico por imagem , Gangrena/etiologia , Isquemia/etiologia , Transtornos Puerperais/diagnóstico por imagem , Amputação Cirúrgica , Cardiomiopatias/diagnóstico por imagem , Ecocardiografia , Embolectomia , Embolia/diagnóstico por imagem , Embolia/cirurgia , Feminino , Gangrena/cirurgia , Humanos , Isquemia/diagnóstico por imagem , Extremidade Inferior , Volume Sistólico , Falha de Tratamento , Ultrassonografia Doppler , Adulto JovemRESUMO
Background and objecives: Adverse cardiovascular outcomes during pregnancy have increased over the past few decades, with increased numbers of women delivering later in their reproductive life. Other factors include higher rates of female obesity, diabetes, hypertension, cardiovascular diseases and assisted reproductive technology, which has extended fertility. Those at risk require extensive prenatal maternal screening, constant pregnancy supervising, monitoring during labor, delivery and puerperium and careful anesthetic evaluation during delivery. Materials and Methods: The present review reports the relevant information available on cardiovascular outcomes in advanced maternal age delivering women and related medico-legal issues. The search was performed on Pubmed, Cochrane, Semantic Scholar, Medline and Embase databases, accessed by Ovid, including among others the terms "cardiomyopathy", "ischaemic heart disease", "arrhythmias", "hypertension", "peripartum period", "diabetes", "advanced maternal age" "anesthesia", "maternal morbidity and mortality" and "litigation". Results: To the extent that underestimating risk factors for peripartum cardiomyopathy (PPCM) can adversely impact maternal and fetal outcomes, the legal implications of misdiagnosis or mismanagement can result in high compensatory damages. Substantial indemnity payments drive up costs of insurance coverage. Conclusions: Multidisciplinary approaches are necessary from obstetricians, cardiologists, anesthesiologists and perinatologists for pregnancy monitoring and delivery outcomes.
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Doenças Cardiovasculares/etiologia , Idade Materna , Complicações Cardiovasculares na Gravidez/etiologia , Adulto , Doenças Cardiovasculares/diagnóstico , Feminino , Humanos , Responsabilidade Legal , Pessoa de Meia-Idade , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Fatores de RiscoRESUMO
BACKGROUND: Concentrations of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) are altered in peripartum cardiomyopathy (PPCM). In this study we investigated changes in the angiogenesis balance in PPCM.MethodsâandâResults:Plasma concentrations of sFlt-1 and the pro-angiogenic placenta growth factor (PlGF) were determined in patients with PPCM during the post-partum phase (n=83), in healthy women at delivery (n=30), and in patients with acute heart failure (AHF; n=65). Women with cardiac failure prepartum or associated with any form of hypertension, including pre-eclampsia, were excluded. Compared with non-pregnant women, in women with AHF and PPCM, median PlGF concentrations were greater (19 [IQR 16-22] and 98 [IQR 78-126] ng/mL, respectively; P<0.001) and the sFlt-1/PlGF ratio was lower (9.8 [6.6-11.3] and 1.2 [0.9-2.8], respectively; P<0.001). The sFlt-1/PlGF ratio was lower in PPCM than in normal deliveries (1.2 [0.9-2.8] vs. 94.8 [68.8-194.1], respectively; P<0.0001). The area under the curve for PlGF (cut-off value: 50ng/mL) and/or the sFlt-1/PlGF ratio (cut-off value: 4) to distinguish PPCM from either normal delivery or AHF was >0.94. Median plasma concentrations of the anti-angiogenic factor relaxin-2 were lower in PPCM and AHF (0.3 [IQR 0.3-1.7] and 0.3 [IQR 0.3-1] ng/mL, respectively) compared with normal deliveries (1,807 [IQR 1,101-4,050] ng/mL; P<0.001). CONCLUSIONS: Plasma of PPCM patients shows imbalanced angiogenesis. High PlGF and/or low sFlt-1/PlGF may be used to diagnose PPCM.
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Cardiomiopatias/sangue , Neovascularização Patológica/sangue , Fator de Crescimento Placentário/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Cardiomiopatias/diagnóstico , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Período Periparto , GravidezRESUMO
Earlier this year, 200 researchers from across the globe gathered at the Omni New Haven Hotel at Yale University in New Haven, Connecticut, for 3 days of talks from 30 of the leading pioneers in modern cardiovascular medicine. From May 8 to 10, 2014, scientists discussed and dissected topics ranging from the clinical treatment of atherosclerosis to the molecular biology of leukocyte-endothelial cell interactions. With other sessions exploring vascular malformation and aneurysm, hypertension, the endothelial-mesenchymal transition (endo-MT), and the role of metabolism in cardiovascular disease, conference participants gained striking insights into rapid advances and ongoing challenges in the field of cardiovascular inflammation and remodeling.
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Sistema Cardiovascular/patologia , Inflamação/patologia , Sociedades Médicas , Animais , Doenças Cardiovasculares/patologia , Connecticut , Estudo de Associação Genômica Ampla , Humanos , CamundongosRESUMO
Background: Due to the rarity of peripartum cardiomyopathy (PPCM) globally, baseline characteristic data for PPCM patients are still scarce. Therefore, this study aims to determine the baseline characteristics and 6-month outcomes of PPCM patients in Indonesia. Methods: From January 2014 to December 2021, all PPCM patients aged ≥18 years who were admitted to Dr. Hasan Sadikin General Hospital in Bandung, Indonesia, participated in this single-center, prospective cohort study. All patients were re-evaluated within 6 months of PPCM diagnosis. Results: A total of 138 patients with PPCM were admitted to Dr. Hasan Sadikin General Hospital in Bandung. The mean age of all patients was 30.4 ± 6.4 years old. Approximately 60% patients were multipara and had preeclampsia. All guideline-directed medical therapy for heart failure was received by most patients, excluding mineralocorticoid receptor antagonists (25.2%) and bromocriptine (14.1%). The neonatal mortality rate was 5.1%. Among those who survived, 61.2% had normal weight, 31.8% had low birth weight, and 7% had very low birth weight. At the 6-month follow-up, 6.7% of the patients died, 63.3% recovered, and 1.9% were rehospitalized. Conclusion: The present study found a high incidence of PPCM in Indonesia. Our patients frequently had preeclampsia, which contributed to the higher rate of miscarriage and low birth weight. Our liberal use of beta-blockers and ACEi/ARB may have contributed to the higher 6-month recovery rate than that in other countries.
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Background: Women with peripartum cardiomyopathy (PPCM) are at an increased risk of arterial and venous thromboembolic events. The review summarizes the evidence on the incidence of thromboembolic complications in women with PPCM, diagnostic approaches, related outcomes, and effects of therapies that have been used. Methods: English articles were retrieved from Web of Science and PubMed using search terms to capture studies related to PPCM (or postpartum cardiomyopathy) and all combinations of thrombosis- and embolism-related keywords. A total of 347 articles from PubMed and 85 from Web of Science were obtained, and after removing duplicates, 327 articles were screened for original data and classified into four domains: epidemiology, risk factors, diagnosis, and therapy of thromboembolism in PPCM. Ultimately, 30 articles were included. Data were synthesized in summary tables for each domain. Results: Studies in the United States and Europe reported varying incidence for thromboembolism in PPCM, up to 14% in 6 months. Risk factors include elevated levels of coagulation factors, decreased protein C and S activity, decreased fibrinolysis, and a low left ventricular ejection fraction (LVEF). Cesarean delivery and post-operative status were correlated with a higher incidence of thromboembolic complications. Diagnosis relied mostly on ultrasonography and magnetic resonance and depended on the suspected location of thrombus. Anticoagulation has been used mostly for PPCM patients with a reduced LVEF, with the duration varying across guidelines and healthcare systems. Unfractionated heparin and low molecular weight heparin (LMWH) were considered safe choices during pregnancy, while warfarin and novel oral anticoagulants (NOACs) were used postpartum. The association of bromocriptine with risk of thromboembolic complications remains debated. Conclusions: There are important gaps in our understanding of the epidemiology, risk stratification, and optimal secondary prevention of thromboembolism in PPCM. Larger prospective studies with detailed phenotyping are required.
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Background: Peripartum cardiomyopathy (PPCM) is a common cause of heart failure (HF) in the peripartum. Some medications are considered safe while breastfeeding. However, sacubitril/valsartan (Entresto), while efficacious, is not recommended in breastfeeding women due to concerns about adverse infant development, and no published data suggest otherwise. Objectives: This study aimed to assess the transfer of sacubitril/valsartan into human milk and evaluate the infant's risk of drug exposure. Methods: The InfantRisk Human Milk Biorepository released samples and corresponding health information from five breastfeeding maternal-infant dyads exposed to sacubitril/valsartan. Sacubitril, valsartan, and LBQ657 (sacubitril active metabolite) concentrations were determined using liquid chromatography-mass spectrometry (LC/MS/MS) from timed samples 0, 1, 2, 4, 6, 8, 10, and 12 h following medication administration at steady state conditions. Results: Valsartan levels were below the detection limit of 0.19 ng/mL in all milk samples. Sacubitril was measurable in all milk samples of the five participants, peaking 1 h after drug administration at a mean concentration of 1.52 ng/mL for a total infant dose of 0.00049 mg/kg/12 h and a relative infant dose (RID) calculated at 0.01%. The maximum concentration of its active metabolite LBQ657 in the milk samples was observed 4 h after medication administration and declined over the remaining 12-h dosing interval, for an average concentration of 9.5 ng/mL. The total infant dose was 0.00071 mg/kg/12 h, and the RID was 0.22%. Two mothers reported continuing to breastfeed while taking sacubitril/valsartan; both mothers stated observing no negative effects in their breastfed infants. Conclusion: The transfer of sacubitril/valsartan into human milk is minimal. These concentrations are unlikely to pose a significant risk to breastfeeding infants, with a combined calculated RID of <0.25%, which is far lower than the industry safety standards (RID <10%).
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Aminobutiratos , Compostos de Bifenilo , Aleitamento Materno , Combinação de Medicamentos , Leite Humano , Valsartana , Humanos , Leite Humano/química , Leite Humano/metabolismo , Feminino , Aminobutiratos/análise , Adulto , Cromatografia Líquida , Gravidez , Espectrometria de Massas em Tandem , Recém-Nascido , Tetrazóis , Lactente , Antagonistas de Receptores de Angiotensina/administração & dosagem , CardiomiopatiasRESUMO
Peripartum Cardiomyopathy (PPCM) is a polymorphic myocardial disease occurring late during pregnancy or early after delivery. While reduced systolic function and heart failure (HF) symptoms have been widely described, there is still a lack of reports about the arrhythmic manifestations of the disease. Most importantly, a broad range of unidentified pre-existing conditions, which may be missed by general practitioners and gynecologists, must be considered in differential diagnosis. The issue is relevant since some arrhythmias are associated to sudden cardiac death occurring in young patients, and the overall risk does not cease during the early postpartum period. This is why multimodality diagnostic workup and multidisciplinary management are highly suggested for these patients. We reported a series of 16 patients diagnosed with PPCM following arrhythmic clinical presentation. Both inpatients and outpatients were identified retrospectively. We performed several tests to identify the arrhythmic phenomena, inflammation and fibrosis presence. Cardiomyopathies phenotypes were reclassified in compliance with the updated ESC guidelines recommendations. Arrhythmias were documented in all the patients during the first cardiological assessment. PVC were the most common recorder arrhythmias, followed by VF, NSVT, AF, CSD.
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BACKGROUND: Over the past decades the use of assisted reproduction technology (ART) increased worldwide. ARTs are associated with an elevated risk for cardiovascular complications. However, a potential relation between subfertility/ARTs and the heart disease peripartum cardiomyopathy (PPCM) has not been systematically analyzed yet. METHODS: A retrospective cohort study was carried out, including n = 111 PPCM patients from the German PPCM registry. Data from PPCM patients were compared to those from postpartum women in the German general population. RESULTS: The prevalence of reported subfertility was high among PPCM patients (30%; 33/111). Most of the subfertile PPCM patients (55%; 18/33) obtained vitro fertilizations (IVF) or intracytoplasmic sperm injections (ICSI). PPCM patients were older (p < 0.0001), the percentage of born infants conceived by IVF/ICSI was higher (p < 0.0001) with a higher multiple birth (p < 0.0001), C-section (p < 0.0001) and preeclampsia rate (p < 0.0001), compared to postpartum women. The cardiac outcome was comparable between subfertile and fertile PPCM patients. Whole exome sequencing in a subset of n = 15 subfertile PPCM patients revealed that 33% (5/15) carried pathogenic or likely pathogenic gene variants associated with cardiomyopathies and/or cancer predisposition syndrome. CONCLUSIONS: Subfertility occurred frequently among PPCM patients and was associated with increased age, hormonal disorders, higher twin pregnancy rate and high prevalence of pathogenic gene variants suggesting a causal relationship between subfertility and PPCM. Although this study found no evidence that the ART treatment per se increases the risk for PPCM or the risk for an adverse outcome, women with subfertility should be closely monitored for signs of peripartum heart failure.
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Cardiomiopatias , Infertilidade , Complicações Cardiovasculares na Gravidez , Masculino , Gravidez , Lactente , Humanos , Feminino , Estudos Retrospectivos , Período Periparto , Prevalência , Sêmen , Cardiomiopatias/complicações , Técnicas de Reprodução Assistida/efeitos adversos , Fertilidade , Infertilidade/complicações , Complicações Cardiovasculares na Gravidez/epidemiologiaRESUMO
Peripartum cardiomyopathy (PPCM) is a form of new-onset heart failure that has a high rate of maternal morbidity and mortality. This was the first study to systematically investigate and compare clinical factors and echocardiographic findings between women with PPCM and co-incident hypertensive pregnancy disorders (HPD-PPCM) and PPCM-only women. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) framework. We used four databases and a single search engine, namely PubMed/Medline, Scopus, Web of Science, and Cochrane. We used Cochrane Risk of Bias (RoB) 2.0 for quality assessment. Databases were searched for relevant articles published from 2013 to the end of April 2023. The meta-analysis used the DerSimonian-Laird random-effects model to analyze the pooled mean difference (MD) and its p-value. We included four studies with a total of 64,649 participants and found that systolic blood pressure was significantly more likely to be associated with the PPCM group than the HPD-PPCM group (SMD = -1.63) (95% CI; -4.92,0.28, p = 0.01), while the other clinical profiles were not significant. HPD-PPCM was less likely to be associated with LVEF reduction (SMD = -1.55, [CI: -2.89, -0.21], p = 0.02). HPD-PPCM was significantly associated with less LV dilation (SMD = 1.81; 95% (CI 0.07-3.01), p = 0.04). Moreover, HPD-PPCM was less likely to be associated with relative wall thickness reduction (SMD = 0.70; 95% CI (-1.08--0.33), p = 0.0003). In conclusion, PPCM and HPD-PPCM shared different clinical profiles and remodeling types, which may affect each disease's response to pharmacological treatment. Patients with HPD-PPCM exhibited less eccentric remodeling and seemed to have a higher chance of recovering their LV ejection fraction, which means they might not benefit as much from ACEi/ARB and beta-blockers. The findings of this study will guide the development of guidelines for women with PPCM and HPD-PPCM from early detection to further management.
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AIMS: Peripartum cardiomyopathy (PPCM) is a rare heart disease, occurring in previously heart-healthy women during the last month of pregnancy or the first months after delivery due to left ventricular (LV) systolic dysfunction. A common pathomechanistic pathway of PPCM includes increased oxidative stress and the subsequent generation of a cleaved prolactin fragment (16 kDa PRL), which promotes the onset of heart failure (HF) in a microRNA (miR)-146a-dependent manner. Inhibition of prolactin secretion with the dopamine D2 receptor (D2R) agonist bromocriptine combined with standard HF therapy supports cardiac recovery. This study examined whether treatment with the more selective D2R agonist cabergoline prevents HF development in an experimental PPCM mouse model and might be used as an alternative treatment regime for PPCM. METHODS AND RESULTS: Postpartum (PP) female PPCM-prone mice with a cardiomyocyte restricted STAT3-deficiency (αMHC-Cretg/+ ; Stat3fl/fl ; CKO) were treated over two consecutive nursing periods with cabergoline (CKO Cab, 0.5 mg/kg/day) and were compared with bromocriptine treated CKO (CKO Br) and postpartum-matched WT and CKO mice. Cabergoline treatment in CKO PP mice preserved cardiac function [fractional shortening (FS): CKO Cab: 34.5 ± 9.4% vs. CKO: 22.1 ± 9%, P < 0.05] and prevented the development of cardiac hypertrophy, fibrosis, and inflammation as effective as bromocriptine therapy (FS: CKO Br: 33.4 ± 5.6%). The myocardial up-regulation of the PPCM biomarkers plasminogen inhibitor activator 1 (PAI-1) and miR-146a were prevented by both cabergoline and bromocriptine therapy. A small cohort of three PPCM patients from the German PPCM Registry was treated with cabergoline (1 mg per week for 2 weeks, followed by 0.5 mg per week for another 6 weeks) due to a temporary unavailability of bromocriptine. All PPCM patients initially presented with a severely reduced LV ejection fraction (LVEF: 26 ± 2%). However, at 6 months of follow-up, LV function (LVEF: 56 ± 2%) fully recovered in all three PPCM patients, and no adverse events were detected. CONCLUSIONS: In the experimental PPCM mouse model, the selective D2R agonist cabergoline prevents the onset of postpartum HF similar to bromocriptine. In PPCM patients, cabergoline treatment was safe and effective as all patients fully recovered. Cabergoline might serve as a promising alternative to bromocriptine. However, these findings are based on experimental data and a small case series and thus have to be interpreted with caution and should be validated in a larger clinical trial.
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Cardiomiopatias , Insuficiência Cardíaca , MicroRNAs , Disfunção Ventricular Esquerda , Gravidez , Feminino , Camundongos , Animais , Bromocriptina , Cabergolina/metabolismo , Cabergolina/uso terapêutico , Período Periparto , Prolactina/metabolismo , Prolactina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Miócitos Cardíacos/metabolismo , Agonistas de Dopamina , Disfunção Ventricular Esquerda/tratamento farmacológico , MicroRNAs/metabolismoRESUMO
We report a case of successful continuous spinal anesthesia (CSA) for labor analgesia and cesarean delivery in a patient with familial dilated cardiomyopathy (DCM). A 33-year-old pregnant woman diagnosed with DCM was scheduled for a vaginal delivery under labor analgesia. An accidental intrathecal catheter was placed, and labor analgesia was provided by CSA. The vaginal delivery was converted to a cesarean delivery, and an intrathecal catheter was used for transition, which avoided hemodynamic changes and allowed the patient to safely undergo cesarean delivery. CSA is a reliable and rapidly titratable technique that provides excellent analgesia without hemodynamic changes in patients with DCM undergoing labor analgesia and subsequent cesarean delivery.
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Background: Cardiac arrest (CA) caused by peripartum cardiomyopathy (PPCM) is a catastrophic disease that can lead to a high mortality rate in young women. Cardiopulmonary resuscitation (CPR) is the initial first aid measure to be taken and unfortunately, does not always lead to the restoration of spontaneous circulation (ROSC). We shared a rare successful case of extracorporeal cardiopulmonary oxygenation-assisted resuscitation (ECPR) in a patient with CA for up to 5.5 hours due to PPCM. Case Description: A previously healthy 31-year-old woman at 34 weeks of gestation was admitted to the emergency department with fever and arrhythmia. Two days later, the patient had postpartum CA. She underwent CPR for up to 5 hours before receiving V-A extracorporeal membrane oxygenation (ECMO) support and eventually regained spontaneous circulation after half an hour. Based on the clinical manifestations, the patient was diagnosed with PPCM and received treatment. The patient was successfully removed from ECMO after 9 days. The patient experienced ECMO-related complications, including thrombocytopenia and intracranial hemorrhage (ICH). Although treatment was difficult, the patient was discharged after 2 months without any neurological complications. We followed up for 1 year and the patient was able to work normally as a teacher. In our mini-review, we found that the success rate of ECPR in perinatal CA was high, and ECPR is worthy of promotion and application. Conclusions: As an advanced life support method, ECPR can save patients undergoing postpartum CA. However, effective CPR and avoidance of ICH are necessary for the recovery of brain function.
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Introduction: Peripartum cardiomyopathy (PPCM) is a potentially life-threatening pregnancy-related heart disease. Genetic roles such as gene polymorphisms may relate to the etiology of PPCM. This study analyzes the association between single nucleotide gene polymorphism (SNP) guanine nucleotide-binding protein beta-3 subunit (GNB3) C825T and insertion/deletion (I/D) of the angiotensin-converting enzyme (ACE) gene with the incidence of PPCM. Methods: An analytic observational study with a case-control design was conducted at the Integrated Cardiac Service Center of Dr. Soetomo General Hospital, Surabaya, Indonesia. PPCM patients of the case and control groups were enrolled. Baseline characteristic data were collected and blood samples were analyzed for SNP in the GNB3 C825T gene and for I/D in the ACE gene by using the polymerase chain reaction, restriction fragment length polymorphism, and Sanger sequencing. We also assessed ACE levels among different ACE genotypes using a sandwich-ELISA test. Results: A total of 100 patients were included in this study, with 34 PPCM cases and 66 controls. There were significant differences in GNB3 TT and TC genotypes in the case group compared with that in the control group (TT: 35.3% vs. 10.6%, p = 0.003; TC: 41.2% vs. 62.5%, p = 0.022). The TT genotype increased the risk of PPCM by 4.6-fold. There was also a significant difference in the ACE DD genotype in the case group compared with that in the control group (26.5% vs. 9.1%, p = 0.021). DD genotypes increased the risk of PPCM by 3.6-fold. ACE levels were significantly higher in the DD genotype group than in the ID and II genotype groups (4,356.88 ± 232.44â pg/mL vs. 3,980.91 ± 77.79â pg/mL vs. 3,679.94 ± 325.77â pg/mL, p < 0.001). Conclusion: The TT genotype of GNB3 and the DD genotype of the ACE are likely to increase the risk of PPCM. Therefore, these polymorphisms may be predisposing risk factors for PPCM incidence. ACE levels were significantly higher in the DD genotype group, which certainly had clinical implications for the management of PPCM patients in the administration of ACE inhibitors as one of the therapy options.
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Peripartum cardiomyopathy is a life-threatening condition that requires urgent diagnosis and management. Bromocriptine was established as disease specific therapy; less data is known about Cabergolin which is another prolactin secretion inhibitor. In this paper we report 4 peripartum cardiomyopathy cases treated successfully with Cabergoline, including a cardiogenic shock case requiring mechanical circulatory support.