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BACKGROUND: Black 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. METHODS: A 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. RESULTS: Black 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 = .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 = .03) and 12-months (HDP:53 ± 10% vs no HDP:40 ± 16%, P = .02). At 12-months, Black women overall had a lower LVEF than non-Black women (P < .001), driven by less recovery in Black women without HDP compared to non-Black women (P < .001). In contrast, Black women with HDP had a similar LVEF at 12 months compared to non-Black women (P = .56). CONCLUSIONS: In 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.
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Negro ou Afro-Americano , Cardiomiopatias , Hipertensão Induzida pela Gravidez , Período Periparto , Complicações Cardiovasculares na Gravidez , Volume Sistólico , Humanos , Feminino , Gravidez , Adulto , Cardiomiopatias/fisiopatologia , Cardiomiopatias/etnologia , Cardiomiopatias/epidemiologia , Complicações Cardiovasculares na Gravidez/fisiopatologia , Complicações Cardiovasculares na Gravidez/etnologia , Complicações Cardiovasculares na Gravidez/epidemiologia , Hipertensão Induzida pela Gravidez/fisiopatologia , Hipertensão Induzida pela Gravidez/etnologia , Hipertensão Induzida pela Gravidez/epidemiologia , Volume Sistólico/fisiologia , Negro ou Afro-Americano/estatística & dados numéricos , Ecocardiografia , Função Ventricular Esquerda/fisiologia , Transplante de Coração/estatística & dados numéricos , Coração Auxiliar/estatística & dados numéricosRESUMO
A 36 year old woman with history of heart failure and left ventricular assist device (LVAD) implantation, with subsequent explantation after myocardial recovery, presented for management of preconception counseling and subsequent pregnancy. To our knowledge, this case represents the first documented successful pregnancy after LVAD explantation. Management details are provided, and relevant literature is reviewed.
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Insuficiência Cardíaca , Coração Auxiliar , Humanos , Feminino , Gravidez , Adulto , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/terapia , Complicações Cardiovasculares na Gravidez/terapia , Complicações Cardiovasculares na Gravidez/cirurgia , Remoção de Dispositivo/métodos , Resultado da GravidezAssuntos
Cardiomiopatias , Transtornos Puerperais , Feminino , Gravidez , Humanos , Período PeripartoRESUMO
PURPOSE: The 2021 European Society of Cardiology guidelines on acute and chronic heart failure (HF) recommend that non-dihydropyridine calcium channel blockers (NDCC) should be avoided in patients with HF with reduced ejection fraction. It also emphasizes that beta-blockers only be initiated in clinically stable, euvolemic patients. Despite these recommendations, NDCC and beta-blockers are often still employed in patients with AF with rapid ventricular response and acute decompensated HF. The relative safety and efficacy of these therapies in this setting is unclear. METHODS: To address the question of the safety and efficacy of NDCC and beta-blockers for acute rate control in decompensated HF, we provide a perspective on the literature of NDCC and beta-blockers in chronic HF with reduced and preserved ejection fraction and AF, including trials on the management of AF with rapid ventricular response with and without HF. RESULTS: Robust data demonstrates mortality benefits when beta-blockers are used in patients with chronic HF with reduced ejection fraction. The data that inform the contraindication of NDCC in HF with reduced ejection fraction are outdated and were not primarily designed to address the efficacy and safety of rate control of AF in patients with HF. Several studies indicate that for acute rate control, NDCC and beta-blockers are both efficacious therapies, especially in the setting of tachycardia-induced cardiomyopathy. CONCLUSION: Future studies are needed to assess the safety and efficacy of beta-blockers and NDCC in both acute and chronic AF with HF with reduced and preserved ejection fraction.
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Fibrilação Atrial , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/efeitos adversos , Volume Sistólico/fisiologia , Antagonistas Adrenérgicos beta/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Doença CrônicaRESUMO
Background Information on maternal and fetal outcomes of pregnancy in women with D-transposition of the great arteries is limited. We conducted a systematic literature review on pregnancies in women with transposition of the great arteries after atrial and arterial switch operations to better define maternal and fetal risk. Methods and Results A systematic review was performed on studies between 2000 and 2021 that identified 676 pregnancies in 444 women with transposition of the great arteries. A total of 556 pregnancies in women with atrial switch operation were tolerated by most cases with low mortality (0.6%). Most common maternal complications, however, were arrhythmias (9%) and heart failure (8%) associated with serious morbidity in some patients. Worsening functional capacity, right ventricular function, and tricuspid regurgitation occurred in ≈20% of the cases. Rate of fetal and neonatal mortality was 1.4% and 0.8%, respectively, and rate of prematurity was 32%. A total of 120 pregnancies in women with arterial switch operation were associated with no maternal mortality, numerically lower rates of arrhythmias and heart failure (6% and 5%, respectively), significantly lower rate of prematurity (11%; P<0.001), and only 1 fetal loss. Conclusions Pregnancy is tolerated by most women with transposition of the great arteries and atrial switch operation with low mortality but important morbidity. Most common maternal complications were arrhythmias, heart failure, worsening of right ventricular function, and tricuspid regurgitation. There was also a high incidence of prematurity and increased rate of fetal loss and neonatal mortality. Outcome of pregnancy in women after arterial switch operations is more favorable, with reduced incidence of maternal complications and fetal outcomes similar to women without underlying cardiac disease.
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Insuficiência Cardíaca , Transposição dos Grandes Vasos , Recém-Nascido , Humanos , Feminino , Gravidez , Transposição dos Grandes Vasos/cirurgia , ArtériasRESUMO
AIMS: To describe the effect of subsequent pregnancies (SSP) on left ventricular (LV) function and outcomes in patients with peripartum cardiomyopathy (PPCM). METHODS: Among146 women with PPCM who were prospectively followed at two medical centres in Israel (2007-2019), 75 SSPs (in 50 women) were identified: 8 miscarriages, 8 terminations, and 59 life birth. RESULTS: Forty-five patients with 59 full-term SSPs [mean age was 32.9 ± 4.1 years, LV ejection fraction (LVEF) 57.7 ± 5.1%] were analysed. Data on LVEF at 1-month post-delivery were available in 46 and at 6 months in 36 SSPs. There was a small decrease in the mean LVEF, mostly at third trimester (57.2 ± 5.6 vs. 54.4. ± 7.3, P < 0.001); and at 1-mont (57.9 ± 5.7% vs. 55.4 ± 6.1%, P = 0.001) and at 6-month post-delivery (57.4 ± 6.1 vs. 55.3 ± 7.9%, P = 0.03). In patients with pre-SSP LV LVEF ≥55%, a mild reduction in the mean group LVEF was seen at 1-month post-delivery (P = 0.009). One patient with pre-SSP LVEF ≥55% developed severe relapse. In patients with pre-SSP LVEF <55%, a mild reduction in LVEF was obtained mostly at third trimester (51.1 ± 5.6 vs 47.0 ± 7.4%, P < 0.001), which persisted at 6 months (P = 0.03). A relapse was observed in three (25%) women with LVEF <55%. There was no maternal mortality, 32 patients delivered by caesarean section, and there were no foetal complications. CONCLUSIONS: Our study indicates a favourable outcome and low likelihood of maternal mortality associated with SSP in women with a history of PPCM and recovered LV systolic function. SSP was associated with a slight reduction in LVEF mostly during the third trimester, which persisted up to 6 months after delivery.
Assuntos
Cardiomiopatias , Complicações Cardiovasculares na Gravidez , Gravidez , Humanos , Feminino , Adulto , Masculino , Período Periparto , Cesárea/efeitos adversos , Complicações Cardiovasculares na Gravidez/epidemiologia , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico , Cardiomiopatias/epidemiologia , RecidivaRESUMO
AIMS: Hypertensive disorders of pregnancy (HDP) occur in 10% of pregnancies in the general population, pre-eclampsia specifically in 3-5%. Hypertensive disorders of pregnancy may have a high prevalence in, and be poorly tolerated by, women with heart disease. METHODS AND RESULTS: The prevalence and outcomes of HDP (chronic hypertension, gestational hypertension or pre-eclampsia) were assessed in the ESC EORP ROPAC (n = 5739), a worldwide prospective registry of pregnancies in women with heart disease.The overall prevalence of HDP was 10.3%, made up of chronic hypertension (5.9%), gestational hypertension (1.3%), and pre-eclampsia (3%), with significant differences between the types of underlying heart disease (P < 0.05). Pre-eclampsia rates were highest in women with pulmonary arterial hypertension (PAH) (11.1%), cardiomyopathy (CMP) (7.1%), and ischaemic heart disease (IHD) (6.3%). Maternal mortality was 1.4 and 0.6% in women with vs. without HDP (P = 0.04), and even 3.5% in those with pre-eclampsia. All pre-eclampsia-related deaths were post-partum and 50% were due to heart failure. Heart failure occurred in 18.5 vs. 10.6% of women with vs. without HDP (P < 0.001) and in 29.1% of those with pre-eclampsia. Perinatal mortality was 3.1 vs. 1.7% in women with vs. without HDP (P = 0.019) and 4.7% in those with pre-eclampsia. CONCLUSION: Hypertensive disorders of pregnancy and pre-eclampsia rates were higher in women with CMP, IHD, and PAH than in the general population. Adverse outcomes were increased in women with HDP, and maternal mortality was strikingly high in women with pre-eclampsia. The combination of HDP and heart disease should prompt close surveillance in a multidisciplinary context and the diagnosis of pre-eclampsia requires hospital admission and continued monitoring during the post-partum period.
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Cardiopatias , Insuficiência Cardíaca , Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Monofosfato de Citidina , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Gestantes , Sistema de RegistrosRESUMO
Pregnancy in individuals with a mechanical heart valve has been classified as very high risk because of a substantially increased risk of maternal mortality or severe morbidity. Lifelong therapeutic anticoagulation is a principal component of the medical management of mechanical heart valves to prevent valve thrombosis. Anticoagulation regimens indicated outside of pregnancy for patients with mechanical valves should be continued during pregnancy with the possibility of modifications based on the type of valve, the trimester of pregnancy, individual risk tolerance, and circumstances around the time of delivery. The purpose of this document is to provide recommendations regarding the management of anticoagulation for common cardiac conditions complicating pregnancy, including mechanical heart valves, atrial fibrillation, systolic heart failure, and congenital heart disease.
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Complicações Cardiovasculares na Gravidez , Tromboembolia , Anticoagulantes/uso terapêutico , Arritmias Cardíacas , Feminino , Humanos , Perinatologia , Gravidez , Complicações Cardiovasculares na Gravidez/induzido quimicamente , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/prevenção & controle , Tromboembolia/prevenção & controleRESUMO
Heart failure affects over 2.6 million women and 3.4 million men in the United States with known sex differences in epidemiology, management, response to treatment, and outcomes across a wide spectrum of cardiomyopathies that include peripartum cardiomyopathy, hypertrophic cardiomyopathy, stress cardiomyopathy, cardiac amyloidosis, and sarcoidosis. Some of these sex-specific considerations are driven by the cellular effects of sex hormones on the renin-angiotensin-aldosterone system, endothelial response to injury, vascular aging, and left ventricular remodeling. Other sex differences are perpetuated by implicit bias leading to undertreatment and underrepresentation in clinical trials. The goal of this narrative review is to comprehensively examine the existing literature over the last decade regarding sex differences in various heart failure syndromes from pathophysiological insights to clinical practice.
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Cardiomiopatias/fisiopatologia , Cardiomiopatias/terapia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Caracteres Sexuais , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Terapia de Ressincronização Cardíaca/métodos , Cardiomiopatias/sangue , Cardiomiopatias/diagnóstico , Feminino , Hormônios Esteroides Gonadais/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Humanos , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/fisiologiaRESUMO
Increasing maternal mortality and incidence of arrhythmias in pregnancy have been noted over the past 2 decades in the United States. Pregnancy is associated with a greater risk of arrhythmias, and patients with a history of arrhythmias are at significant risk of arrhythmia recurrence during pregnancy. The incidence of atrial fibrillation in pregnancy is rising. This review discusses the management of tachyarrhythmias and bradyarrhythmias in pregnancy, including management of cardiac arrest. Management of fetal arrhythmias are also reviewed. For patients without structural heart disease, ß-blocker therapy, especially propranolol and metoprolol, and antiarrhythmic drugs, such as flecainide and sotalol, can be safely used to treat tachyarrhythmias. As a last resort, catheter ablation with minimal fluoroscopy can be performed. Device implantation can be safely performed with minimal fluoroscopy and under echocardiographic or ultrasound guidance in patients with clear indications for devices during pregnancy. Because of rising maternal mortality in the United States, which is partly driven by increasing maternal age and comorbidities, a multidisciplinary and/or integrative approach to arrhythmia management from the prepartum to the postpartum period is needed.
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Fibrilação Atrial , Sotalol , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Feminino , Flecainida , Humanos , Gravidez , Taquicardia/tratamento farmacológicoRESUMO
Pregnancy is associated with a significant increase in hemodynamic burden. These changes can lead to maternal morbidity and mortality as well as unfavorable fetal outcomes in patients with valvular heart disease and limited cardiac reserve. Mechanical interventions may be needed for the management of severe hemodynamic deterioration not responding to medical therapy. Catheter-based percutaneous interventions can provide an alternative therapy to surgery during pregnancy. The purpose of this article is to review indications, potential advantages, and limitations of catheter-based interventions for the management of women with valvular heart disease in pregnancy.
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Background The objective of this study was to evaluate the temporal trends in pregnancy-associated myocardial infarction (PAMI) in the State of California and explore potential risk factors and mechanisms. Methods and Results The California State Inpatient Database was analyzed from 2003 to 2011 for patients with International Classification of Diseases, Ninth Revision (ICD-9) codes for acute myocardial infarction and pregnancy or postpartum admissions; risk factors were analyzed and compared with pregnant patients without myocardial infarction. A total of 341 patients were identified with PAMI from a total of 5 266 380 pregnancies (incidence of 6.5 per 100 000 pregnancies). Inpatient maternal mortality rate was 7%, and infant mortality rate was 3.5% among patients with PAMI. There was a nonsignificant trend toward an increase in PAMI incidence from 2003 to 2011, possibly attributable to higher incidence of spontaneous coronary artery dissection, vasospasm, and Takotsubo syndrome. PAMI, when compared with pregnant patients without myocardial infarction, was significant for older age (aged >30 years in 72% versus 37%, P<0.0005), higher preponderance of Black race (12% versus 6%, P<0.00005), lower socioeconomic status (median household income in lowest quartile 26% versus 20%, P=0.04), higher prevalence of hypertension (26% versus 7%, P<0.0005), diabetes (7% versus 1%, P<0.0005), anemia (31% versus 7%, P<0.0001), amphetamine use (1% versus 0%, P<0.00005), cocaine use (2% versus 0.2%, P<0.0001), and smoking (6% versus 1%, P=0.0001). Conclusions There has been a trend toward an increase in PAMI incidence in California over the past decade, with an increasing trend in spontaneous coronary artery dissection, vasospasm, and Takotsubo syndrome as mechanisms. These findings warrant further investigation.
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Infarto do Miocárdio , Cardiomiopatia de Takotsubo , Adulto , Anomalias dos Vasos Coronários , Feminino , Humanos , Incidência , Infarto do Miocárdio/epidemiologia , Gravidez , Estudos Retrospectivos , Fatores de Risco , Doenças Vasculares/congênitoRESUMO
Women with dilated cardiomyopathy or left ventricular (LV) dysfunction (LV ejection fraction [LVEF] < 40%) from other etiology are at increased risk of maternal and fetal mortality and morbidity. They should undergo preconception evaluation, risk assessment, and treatment modification including discontinuation and replacement of contraindicated medications. A close follow-up and treatment by a multidisciplinary team is recommended at all stages: preconception, gestation, delivery, and postpartum. An early gestational and delivery plan has to be prepared to face complications and to achieve a successful delivery and outcome. Long-term postpartum cardiac follow-up is recommended anticipating potential adverse effects of pregnancy. The recommended mode of delivery for most patients is vaginal. The indications for cesarian section are mainly obstetric, unless the patient is in severely decompensated heart failure or urgent delivery if the patient is receiving warfarin therapy. Cardiac events during pregnancy or in the first months postpartum occur in 32%-60% of patients. Prepregnancy signs of heart failure, atrial fibrillation, and New York Heart Association functional classification (NYHA FC) > II were associated with a poor cardiac outcome. Predictors of deterioration during pregnancy that are considered very high risk and should be advised to avoid pregnancy are: patients with NYHA FC III/IV unless improved under treatment and LVEF < 20%. Predictors for high risk of adverse outcome include: LVEF < 30%, NYHA FC II, ventricular tachyarrhythmias (including patients with implantable cardioverter defibrillator or cardiac resynchronization therapy defibrillator),atrial fibrillation with rapid ventricular rate, severe mitral regurgitation, significant right ventricular failure, and hypotension. Overall, despite a high rate of complications, most women with LV dysfunction can undergo a successful pregnancy.
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Cardiomiopatias/diagnóstico , Diagnóstico por Imagem/métodos , Complicações Cardiovasculares na Gravidez/diagnóstico , Disfunção Ventricular Esquerda/diagnóstico , Cardiomiopatias/complicações , Cardiomiopatias/epidemiologia , Feminino , Saúde Global , Humanos , Incidência , Gravidade do Paciente , Gravidez , Complicações Cardiovasculares na Gravidez/epidemiologia , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/etiologiaRESUMO
Methamphetamine-associated cardiomyopathy (MACM) in an increasingly prevalent disease yet presenting clinical characteristics have not been well studied. We studied consecutive patients with MACM presenting between June 2018 and March 2020 who were interviewed for drug use and medical history. We retrospectively identified an age- and gender-matched cohort of Non-MACM (NMACM) patients and compared clinical characteristics. 140 patients (70 MACM and 70 NMACM) were studied. MACM patients were young (49.6 ± 10 years) and predominantly male (94%). Compared to NMACM, MACM patients were more likely to be Caucasian (21% vs 6%, p = 0.007) and homeless (47% vs 7%, p = 0.001). MACM was characterized by lower left ventricular ejection fraction (EF) (p <0.001) and greater LV end diastolic volume (LVEDV) (p = 0.024). Right ventricular (RV) dilation was present more often (p = s0.001) and was more often severe (p = 0.03). Among MACM cases, half of the cohort developed MACM within 5 years of starting MA (18% within 1 year). There was no apparent relationship between frequency or amount of MA used weekly with time until heart failure onset. Drug use patterns were not clearly related to the degree of LV structural change however there were more consistent, significant associations with RV and right atrial (RA) size parameters. In conclusion, patients with MACM have more severe myocardial impairment with lower EF, greater LVEDV and RV dilation. Drug use patterns do not clearly impact degree of LV structural changes by echocardiography however may be related to RV and RA size.
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Transtornos Relacionados ao Uso de Anfetaminas , Cardiomiopatias/fisiopatologia , Estimulantes do Sistema Nervoso Central/efeitos adversos , Metanfetamina/efeitos adversos , Administração Intranasal , Adulto , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/epidemiologia , Cardiotoxicidade , Estudos de Casos e Controles , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fumar , Volume Sistólico , Disfunção Ventricular EsquerdaRESUMO
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)-α, and interferon (IFN)-γ 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-α and IL-22 were associated with poorer event-free survival. Higher TNF-α 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-α 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.
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Cardiomiopatias , Período Periparto , Cardiomiopatias/diagnóstico por imagem , Citocinas , Feminino , Humanos , Índice de Gravidade de Doença , Células Th17RESUMO
BACKGROUND: Peripartum cardiomyopathy (PPCM) occurs in ≈1:2000 deliveries in the United States and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in TTN (TTNtvs). Whether mutations in other genes can predispose to PPCM is not known. It is also not known if the presence of TTNtvs predicts clinical presentation or outcomes. Nor is it known if the prevalence of TTNtvs differs in women with PPCM and preeclampsia, the strongest risk factor for PPCM. METHODS: Women with PPCM were retrospectively identified from several US and international academic centers, and clinical information and DNA samples were acquired. Next-generation sequencing was performed on 67 genes, including TTN, and evaluated for burden of truncating and missense variants. The impact of TTNtvs on the severity of clinical presentation, and on clinical outcomes, was evaluated. RESULTS: Four hundred sixty-nine women met inclusion criteria. Of the women with PPCM, 10.4% bore TTNtvs (odds ratio=9.4 compared with 1.2% in the reference population; Bonferroni-corrected P [P*]=1.2×10-46). We additionally identified overrepresentation of truncating variants in FLNC (odds ratio=24.8, P*=7.0×10-8), DSP (odds ratio=14.9, P*=1.0×10-8), and BAG3 (odds ratio=53.1, P*=0.02), genes not previously associated with PPCM. This profile is highly similar to that found in nonischemic dilated cardiomyopathy. Women with TTNtvs had lower left ventricular ejection fraction on presentation than did women without TTNtvs (23.5% versus 29%, P=2.5×10-4), but did not differ significantly in timing of presentation after delivery, in prevalence of preeclampsia, or in rates of clinical recovery. CONCLUSIONS: This study provides the first extensive genetic and phenotypic landscape of PPCM and demonstrates that predisposition to heart failure is an important risk factor for PPCM. The work reveals a degree of genetic similarity between PPCM and dilated cardiomyopathy, suggesting that gene-specific therapeutic approaches being developed for dilated cardiomyopathy may also apply to PPCM, and that approaches to genetic testing in PPCM should mirror those taken in dilated cardiomyopathy. Last, the clarification of genotype/phenotype associations has important implications for genetic counseling.
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Cardiomiopatias/genética , Período Periparto/genética , Adulto , Cardiomiopatias/fisiopatologia , Feminino , Humanos , Fenótipo , Gravidez , Estudos RetrospectivosRESUMO
AIMS: Sacubitril/valsartan combines renin-angiotensin-aldosterone system inhibition with amplification of natriuretic peptides. In addition to well-described effects, natriuretic peptides exert direct effects on pulmonary vasculature. The effect of sacubitril/valsartan on pulmonary artery pressure (PAP) has not been fully defined. METHODS AND RESULTS: This was a retrospective case-series of PAP changes following transition from angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) to sacubitril/valsartan in patients with heart failure reduced ejection fraction and a previously implanted CardioMEMS™ sensor. Pre-sacubitril/valsartan and post-sacubitril/valsartan PAPs were compared for each patient by examining averaged consecutive daily pressure readings from 1 to 5 days before and after sacubitril/valsartan exposure. PAP changes were also compared between patients based on elevated trans-pulmonary gradients (trans-pulmonary gradient ≥ 12 mmHg) at time of CardioMEMS™ sensor implantation. The cohort included 18 patients, 72% male, mean age 60.1 ± 13.6 years. There was a significant decrease in PAPs associated with transition from ACEI/ARB to sacubitril/valsartan. The median (interquartile range) pre-treatment and post-treatment change in mean, systolic and diastolic PAPs were -3.6 (-9.8, -0.7) mmHg (P < 0.001), -6.5 (-15.0, -2.0) mmHg (P = 0.001), and -2.5 (-5.7, -0.7) (P = 0.001), respectively. The decrease in PAPs was independent of trans-pulmonary gradient (F(1,16) = 0.49, P = 0.49). CONCLUSIONS: In this retrospective case series, transition from ACEI/ARB to sacubitril/valsartan was associated with an early and significant decrease in PAPs.