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1.
HGG Adv ; 2(3)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34888534

RESUMO

Bicuspid aortic valve (BAV) with ~1%-2% prevalence is the most common congenital heart defect (CHD). It frequently results in valve disease and aorta dilation and is a major cause of adult cardiac surgery. BAV is genetically linked to rare left-heart obstructions (left ventricular outflow tract obstructions [LVOTOs]), including hypoplastic left heart syndrome (HLHS) and coarctation of the aorta (CoA). Mouse and human studies indicate LVOTO is genetically heterogeneous with a complex genetic etiology. Homozygous mutation in the Pcdha protocadherin gene cluster in mice can cause BAV, and also HLHS and other LVOTO phenotypes when accompanied by a second mutation. Here we show two common deletion copy number variants (delCNVs) within the PCDHA gene cluster are associated with LVOTO. Analysis of 1,218 white individuals with LVOTO versus 463 disease-free local control individuals yielded odds ratios (ORs) at 1.47 (95% confidence interval [CI], 1.13-1.92; p = 4.2 × 10-3) for LVOTO, 1.47 (95% CI, 1.10-1.97; p = 0.01) for BAV, 6.13 (95% CI, 2.75-13.7; p = 9.7 × 10-6) for CoA, and 1.49 (95% CI, 1.07-2.08; p = 0.019) for HLHS. Increased OR was observed for all LVOTO phenotypes in homozygous or compound heterozygous PCDHA delCNV genotype comparison versus wild type. Analysis of an independent white cohort (381 affected individuals, 1,352 control individuals) replicated the PCDHA delCNV association with LVOTO. Generalizability of these findings is suggested by similar observations in Black and Chinese individuals with LVOTO. Analysis of Pcdha mutant mice showed reduced PCDHA expression at regions of cell-cell contact in aortic smooth muscle and cushion mesenchyme, suggesting potential mechanisms for BAV pathogenesis and aortopathy. Together, these findings indicate common variants causing PCDHA deficiency play a significant role in the genetic etiology of common and rare LVOTO-CHD.

2.
Int J Cardiol ; 339: 93-98, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34224767

RESUMO

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.


Assuntos
Cardiomiopatias , Período Periparto , Cardiomiopatias/diagnóstico por imagem , Citocinas , Feminino , Humanos , Índice de Gravidade de Doença , Células Th17
3.
Eur J Heart Fail ; 23(6): 854-871, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34010472

RESUMO

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant (HTx) rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples have significantly improved diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (i) an overview of the practical approach to EMB, (ii) an update on indications for EMB, (iii) a revised plan for HTx rejection surveillance, (iv) the impact of multimodality imaging on EMB, and (v) the current clinical practice in the worldwide use of EMB.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Biópsia , Endocárdio , Insuficiência Cardíaca/diagnóstico , Humanos , Japão , Miocárdio
4.
J Card Fail ; 27(7): 727-743, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34022400

RESUMO

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumors. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples has significantly improved the diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (1) an overview of the practical approach to EMB, (2) an update on indications for EMB, (3) a revised plan for heart transplant rejection surveillance, (4) the impact of multimodality imaging on EMB, and (5) the current clinical practice in the worldwide use of EMB.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Biópsia , Endocárdio , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Japão/epidemiologia , Miocárdio
5.
Circulation ; 143(19): 1852-1862, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33874732

RESUMO

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.

6.
JACC Heart Fail ; 9(3): 226-236, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33549559

RESUMO

OBJECTIVES: This study sought to determine cardiopulmonary exercise (CPX) predictors of the combined outcome of durable mechanical circulatory support (MCS), transplantation, or death at 1 year among patients with ambulatory advanced heart failure (HF). BACKGROUND: Optimal CPX predictors of outcomes in contemporary ambulatory advanced HF patients are unclear. METHODS: REVIVAL (Registry Evaluation of Vital Information for ventricular assist devices [VADs] in Ambulatory Life) enrolled 400 systolic HF patients, INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profiles 4-7. CPX was performed by 273 subjects 2 ± 1 months after study enrollment. Discriminative power of maximal (peak oxygen consumption [peak VO2]; VO2 pulse, circulatory power [CP]; peak systolic blood pressure â€¢ peak VO2], peak end-tidal pressure CO2 [PEtCO2], and peak Borg scale score) and submaximal CPX parameters (ventilatory efficiency [VE/VCO2 slope]; VO2 at anaerobic threshold [VO2AT]; and oxygen uptake efficiency slope [OUES]) to predict the composite outcome were assessed by univariate and multivariate Cox regression and Harrell's concordance statistic. RESULTS: At 1 year, there were 39 events (6 transplants, 15 deaths, 18 MCS implantations). Peak VO2, VO2AT, OUES, peak PEtCO2, and CP were higher in the no-event group (all p < 0.001), whereas VE/VCO2 slope was lower (p < 0.0001); respiratory exchange ratio was not different. CP (hazard ratio [HR]: 0.89; p = 0.001), VE/VCO2 slope (HR: 1.05; p = 0.001), and peak Borg scale score (HR: 1.20; p = 0.005) were significant predictors on multivariate analysis (model C-statistic: 0.80). CONCLUSIONS: Among patients with ambulatory advanced HF, the strongest maximal and submaximal CPX predictor of MCS implantation, transplantation, or death at 1 year were CP and VE/VCO2, respectively. The patient-reported measure of exercise effort (Borg scale score) contributed substantially to the prediction of outcomes, a surprising and novel finding that warrants further investigation. (Registry Evaluation of Vital Information for VADs in Ambulatory Life [REVIVAL]; NCT01369407).


Assuntos
Insuficiência Cardíaca Sistólica , Insuficiência Cardíaca , Coração Auxiliar , Limiar Anaeróbio , Teste de Esforço , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Consumo de Oxigênio , Prognóstico
7.
J Card Surg ; 36(2): 643-650, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33295043

RESUMO

BACKGROUND: This study evaluated 20-year survival after adult orthotopic heart transplantation (OHT). METHODS: The United Network of Organ Sharing Registry database was queried to study adult OHT recipients between 1987 and 1998 with over 20-year posttransplant follow-up. The primary and secondary outcomes were 20-year survival and cause of death after OHT, respectively. Multivariable logistic regression was used to identify significant independent predictors of long-term survival, and long-term survival was compared among cohorts stratified by number of predictors using Kaplan Meier survival analysis. RESULTS: 20,658 patients undergoing OHT were included, with a median follow-up of 9.0 (IQR, 3.2-15.4) years. Kaplan-Meier estimates of 10-, 15-, and 20-year survival were 50.2%, 30.1%, and 17.2%, respectively. Median survival was 10.1 (IQR, 3.9-16.9) years. Increasing recipient age (>65 years), increasing donor age (>40 years), increasing recipient body mass index (>30), black race, ischemic cardiomyopathy, and longer cold ischemic time (>4 h) were adversely associated with a 20-year survival. Of these 6 negative predictors, presence of 0 risk factors had the greatest 10-year (59.7%) and 20-year survival (26.2%), with decreasing survival with additional negative predictors. The most common cause of death in 20-year survivors was renal, liver, and/or multisystem organ failure whereas graft failure more greatly impacted earlier mortality. CONCLUSIONS: This study identifies six negative preoperative predictors of 20-year survival with 20-year survival rates exceeding 25% in the absence of these factors. These data highlight the potential for very long-term survival after OHT in patients with end-stage heart failure and may be useful for patient selection and prognostication.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Adulto , Idoso , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Estudos Retrospectivos , Taxa de Sobrevida , Doadores de Tecidos , Estados Unidos/epidemiologia
8.
Transplantation ; 105(3): 608-619, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32345866

RESUMO

BACKGROUND: Psychosocial evaluations are required for long-term mechanical circulatory support (MCS) candidates, no matter whether MCS will be destination therapy (DT) or a bridge to heart transplantation. Although guidelines specify psychosocial contraindications to MCS, there is no comprehensive examination of which psychosocial evaluation domains are most prognostic for clinical outcomes. We evaluated whether overall psychosocial risk, determined across all psychosocial domains, predicted outcomes, and which specific domains appeared responsible for any effects. METHODS: A single-site retrospective analysis was performed for adults receiving MCS between April 2004 and December 2017. Using an established rating system, we coded psychosocial evaluations to identify patients at low, moderate, or high overall risk. We similarly determined risk within each of 10 individual psychosocial domains. Multivariable analyses evaluated whether psychosocial risk predicted clinical decisions about MCS use (DT versus bridge), and postimplantation mortality, transplantation, rehospitalization, MCS pump exchange, and standardly defined adverse medical events (AEs). RESULTS: In 241 MCS recipients, greater overall psychosocial risk increased the likelihood of a DT decision (odds ratio, 1.76; P = 0.017); and postimplantation pump exchange and occurrence of AEs (hazard ratios [HRs] ≥ 1.25; P ≤ 0.042). The individual AEs most strongly predicted were cardiac arrhythmias and device malfunctions (HRs ≥ 1.39; P ≤ 0.032). The specific psychosocial domains predicting at least 1 study outcome were mental health problem severity, poorer medical adherence, and substance use (odds ratios and HRs ≥ 1.32; P ≤ 0.010). CONCLUSIONS: The psychosocial evaluation predicts not only clinical decisions about MCS use (DT versus bridge) but important postimplantation outcomes. Strategies to address psychosocial risk factors before or soon after implantation may help to reduce postimplantation clinical risks.


Assuntos
Insuficiência Cardíaca/terapia , Transplante de Coração/psicologia , Coração Auxiliar , Feminino , Seguimentos , Insuficiência Cardíaca/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Tempo
9.
JACC Heart Fail ; 8(7): 557-568, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32535125

RESUMO

OBJECTIVES: This study aims to understand the complex factors affecting heart transplant survival and to determine the importance of possible sex-specific risk factors. BACKGROUND: Heart transplant allocation is primarily focused on preventing waitlist mortality. To prevent organ wastage, future allocation must balance risk of waitlist mortality with post-transplantation mortality. However, more information regarding risk factors after heart transplantation is needed. METHODS: We included all adults (30,606) in the Scientific Registry of Transplant Recipients database who underwent isolated heart transplantation from January 1, 2004, to July 1, 2018. Mortality (8,278 deaths) was verified with the complete Social Security Death Index with a median follow-up of 3.9 years. Temporal decomposition was used to identify phases of survival and phase-specific risk factors. The random survival forests method was used to determine importance of mortality risk factors and their interactions. RESULTS: We identified 3 phases of mortality risk: early post-transplantation, constant, and late. Sex was not a significant risk factor. There were several interactions predicting early mortality such as pretransplantation mechanical ventilation with presence of end-organ function (bilirubin, renal function) and interactions predicting later mortality such as diabetes and older age (donor and recipient). More complex interactions predicting early-, mid-, and late-mortality existed and were identified with machine learning (i.e., elevated bilirubin, mechanical ventilation, and dialysis). CONCLUSIONS: Post-heart transplant mortality risk is complex and dynamic, changing with time and events. Sex is not an important mortality risk factor. To prevent organ wastage, end-organ dysfunction should be resolved before transplantation as much as possible.


Assuntos
Insuficiência Cardíaca/cirurgia , Transplante de Coração/mortalidade , Sistema de Registros , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Adulto , Fatores Etários , Feminino , Seguimentos , Sobrevivência de Enxerto , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida/tendências , Fatores de Tempo , Estados Unidos/epidemiologia , Listas de Espera/mortalidade
10.
Cardiovasc Pathol ; 47: 107211, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32268262

RESUMO

Immune checkpoint inhibitor (ICI)-induced myocarditis carries a poor prognosis and is not fully understood. Similar to lymphocytic myocarditis and acute cellular rejection in heart transplant, ICI-induced myocarditis requires immune suppressive strategies. We aimed to describe ICI-induced myocarditis by presenting findings of comprehensive cardiovascular evaluations and outcomes of patients following a therapeutic approach similar to autoimmune disorders or allograft transplant rejection, and to discuss the molecular basis of the benefits of immune modulation and statins in ICI-myocarditis. Three patients with ICI-induced myocarditis (2 with positive biopsies and 1 based on cardiac magnetic resonance imaging with negative biopsy) underwent a complete cardiovascular workup, including cardiac catheterization with endomyocardial biopsy. Treatment was with intravenous immunoglobulins (IVIG) and statins in all cases, with additional colchicine (2 cases) or hydroxychloroquine (1 case). Immunohistochemical analysis demonstrated varied subsets of T cells involved in the inflammatory response. Therapy with IVIG and statins led to symptom resolution and cardiac function normalization at 1-month follow-up in all patients. Cancer therapy was resumed in all patients. One patient expired 10 months after the myocarditis episode due to advanced malignancy; two patients were alive, free of heart failure symptoms and cancer progression, at 1-year follow-up, and 1 patient was rechallenged with ICI. We suggest that treatment with IVIG and statins may allow for a prompt resumption of anti-cancer therapy (including ICI) and improve outcomes.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Ipilimumab/efeitos adversos , Melanoma/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Miocardite/tratamento farmacológico , Nivolumabe/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Cardiotoxicidade , Colchicina/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Melanoma/imunologia , Melanoma/secundário , Síndromes Mielodisplásicas/imunologia , Síndromes Mielodisplásicas/patologia , Miocardite/induzido quimicamente , Miocardite/imunologia , Miocardite/patologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Resultado do Tratamento
11.
J Am Coll Cardiol ; 75(2): 207-221, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31948651

RESUMO

Peripartum cardiomyopathy is a form of systolic heart failure affecting young women toward the end of pregnancy or in the months following delivery. Incidence is higher in African-American women and in women with older maternal age, hypertensive disorders of pregnancy, and multiple gestation pregnancies. Symptoms of heart failure mimic those of normal pregnancy, often resulting in a delay in diagnosis and preventable complications. Echocardiography showing decreased myocardial function is essential for the diagnosis. Medical management is similar to heart failure with reduced ejection fraction of other etiologies, but adjustments during pregnancy are necessary to ensure fetal safety. Variable outcomes include complete recovery, persistent heart failure, arrhythmias, thromboembolic events, and death. Subsequent pregnancy confers substantial risk of relapse and even death if there is incomplete myocardial recovery. Additional research about the etiology, optimal therapy including the use of bromocriptine, long-term outcomes, and duration of treatment after recovery are needed.


Assuntos
Cardiomiopatias/diagnóstico , Cardiomiopatias/terapia , Complicações Cardiovasculares na Gravidez/diagnóstico , Complicações Cardiovasculares na Gravidez/terapia , Transtornos Puerperais/diagnóstico , Transtornos Puerperais/terapia , Cardiomiopatias/epidemiologia , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Feminino , Humanos , Período Periparto/fisiologia , Gravidez , Complicações Cardiovasculares na Gravidez/epidemiologia , Transtornos Puerperais/epidemiologia , Literatura de Revisão como Assunto
12.
J Heart Lung Transplant ; 39(1): 7-15, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31679943

RESUMO

INTRODUCTION: Improved understanding of the clinical course of ambulatory advanced chronic systolic heart failure may improve the provision of appropriate care and is central to the design of clinical trials in this population. METHODS: Twenty-one implanting ventricular assist device (VAD) centers enrolled 400 subjects in the Registry Evaluation of Vital Information for VADs in Ambulatory Life (REVIVAL), a prospective, observational study in ambulatory, chronic, advanced systolic heart failure, designed to identify a cohort with an approximately 25% 1-year risk of the primary composite outcome of death, urgent transplant, or durable mechanical circulatory support. Inclusion criteria utilized only information collected during routine clinical care. Exclusion criteria identified patients with contraindications to VAD. Study inclusion required at least 1 of 10 high-risk criteria derived from established hospitalization and non-hospitalization markers of increased mortality risk. We evaluated the test performance characteristics of the high-risk criteria. RESULTS: Data on 373 subjects evaluable for the primary composite outcome at the 1-year visit are presented. Baseline data were consistent with a less advanced cohort than Medical Arm for Mechanically Assisted Circulatory Support or Risk Assessment (MedaMACS) and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients (ROADMAP). Freedom from the primary composite outcome was 75.9%. Non-hospitalization inclusion criteria identified 89% of patients with events. CONCLUSIONS: Using routinely obtained clinical information for enrollment, REVIVAL successfully recruited an ambulatory chronic systolic heart failure cohort with an approximately 25% annual risk of the primary composite outcome. Information from this registry will be relevant to the planning of future trials of earlier VAD use and of other interventions in this population.


Assuntos
Insuficiência Cardíaca/terapia , Coração Auxiliar , Pacientes Ambulatoriais/estatística & dados numéricos , Qualidade de Vida , Sistema de Registros , Medição de Risco/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
13.
J Card Fail ; 26(4): 316-323, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31809791

RESUMO

BACKGROUND: Worsening heart failure (HF) and health-related quality of life (HRQOL) have been shown to impact the decision to proceed with left ventricular assist device (LVAD) implantation, but little is known about how socioeconomic factors influence expressed patient preference for LVAD. METHODS AND RESULTS: Ambulatory patients with advanced systolic HF (n=353) reviewed written information about LVAD therapy and completed a brief survey to indicate whether they would want an LVAD to treat their current level of HF. Ordinal logistic regression analyses identified clinical and demographic predictors of LVAD preference. Higher New York Heart Association (NYHA) class, worse HRQOL measured by Kansas City Cardiomyopathy Questionnaire, lower education level, and lower income were significant univariable predictors of patients wanting an LVAD. In the multivariable model, higher NYHA class (OR [odds ratio]: 1.43, CI [confidence interval]: 1.08-1.90, P = .013) and lower income level (OR: 2.10, CI: 1.18 - 3.76, P = .012 for <$40,000 vs >$80,000) remained significantly associated with wanting an LVAD. CONCLUSION: Among ambulatory patients with advanced systolic HF, treatment preference for LVAD was influenced by level of income independent of HF severity. Understanding the impact of socioeconomic factors on willingness to consider LVAD therapy may help tailor counseling towards individual needs.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Insuficiência Cardíaca/terapia , Humanos , Estudos Prospectivos , Qualidade de Vida , Fatores Socioeconômicos , Resultado do Tratamento
14.
JACC Basic Transl Sci ; 4(3): 291-300, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31312753

RESUMO

The etiology of peripartum cardiomyopathy remains unknown. One hypothesis is that an increase in the 16-kDa form of prolactin is pathogenic and suggests that breastfeeding may worsen peripartum cardiomyopathy by increasing prolactin, while bromocriptine, which blocks prolactin release, may be therapeutic. An autoimmune etiology has also been proposed. The authors investigated the impact of breastfeeding on cellular immunity and myocardial recovery for women with peripartum cardiomyopathy in the IPAC (Investigations in Pregnancy Associated Cardiomyopathy) study. Women who breastfed had elevated prolactin, and prolactin levels correlated with elevations in CD8+ T cells. However, despite elevated prolactin and cytotoxic T cell subsets, myocardial recovery was not impaired in breastfeeding women.

15.
J Card Fail ; 25(7): 553-560, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30978507

RESUMO

BACKGROUND: Polymorphisms in adrenergic signaling affect the molecular function of adrenergic receptors and related proteins. The ß1 adrenergic receptor (ADRB1) Arg389Gly, G-protein receptor kinase type 5 (GRK5) Gln41Leu, G-protein ß-3 subunit (GNB3) 825 C/T, and α2c deletion affect adrenergic tone, impact heart failure outcomes and differ in prevalence by ethnicity. Their combined effect within black cohorts remains unknown. METHODS AND RESULTS: We analyzed subjects from the African American Heart Failure Trial (A-HeFT) by assessing event-free survival, quality of life, and gene coinheritance. Significant coinheritance effects on survival included GRK5 Leu41 among subjects co-inheriting GNB3 825 C alleles (n = 166, 90.4% vs 69.0%, P < 0.001). By contrast, the impact of ADRB1 Arg389Arg genotype was magnified among subjects with GNB3 825 TT genotype (n = 181, 66.3% vs 85.7%, P = .002). The lack of the α2c deletion (ie, insertion) led to a greater impact of the ARG389Arg genotype (n = 289, 76.4% vs 86.1%, P = .007). CONCLUSIONS: Polymorphisms in adrenergic signaling affects outcomes in black subjects with heart failure. Coinheritance patterns in genetic variation may help determine heart failure survival.


Assuntos
Afro-Americanos/genética , Insuficiência Cardíaca , Proteínas Heterotriméricas de Ligação ao GTP/genética , Receptores Adrenérgicos beta 1/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prevalência , Intervalo Livre de Progressão , Volume Sistólico
16.
Clin Cardiol ; 42(5): 524-529, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30843220

RESUMO

BACKGROUND: There is limited data on electrocardiographic (ECG) abnormalities and their prognostic significance in women with peripartum cardiomyopathy (PPCM). We sought to characterize ECG findings in PPCM and explore the association of ECG findings with myocardial recovery and clinical outcomes. HYPOTHESIS: We hypothesized that ECG indicators of myocardial remodeling would portend worse systolic function and outcomes. METHODS: Standard 12-lead ECGs were obtained at enrollment in the Investigations of Pregnancy-Associated Cardiomyopathy study and analyzed for 88 women. Left ventricular ejection fraction (LVEF) was measured by echocardiography at baseline, 6 months, and 12 months. Women were followed for clinical events (death, mechanical circulatory support, and/or cardiac transplantation) until 1 year. RESULTS: Half of women had an "abnormal" ECG, defined as atrial abnormality, ventricular hypertrophy, ST-segment deviation, and/or bundle branch block. Women with left atrial abnormality (LAA) had lower LVEF at 6 months (44% vs 52%, P = 0.02) and 12 months (46% vs 54%, P = 0.03). LAA also predicted decreased event-free survival at 1 year (76% vs 97%, P = 0.008). Neither left ventricular hypertrophy by ECG nor T-wave abnormalities predicted outcomes. A normal ECG was associated with recovery in LVEF to ≥50% (84% vs 49%, P = 0.001) and event-free survival at 1 year (100% vs 85%, P = 0.01). CONCLUSIONS: ECG abnormalities are common in women with PPCM, but a normal ECG does not rule out the presence of PPCM. LAA predicted lower likelihood of myocardial recovery and event-free survival, and a normal ECG predicted favorable event-free survival.


Assuntos
Potenciais de Ação , Cardiomiopatias/diagnóstico , Eletrocardiografia , Frequência Cardíaca , Período Periparto , Transtornos Puerperais/diagnóstico , Adulto , Cardiomiopatias/mortalidade , Cardiomiopatias/fisiopatologia , Cardiomiopatias/terapia , Feminino , Humanos , América do Norte , Valor Preditivo dos Testes , Gravidez , Intervalo Livre de Progressão , Transtornos Puerperais/mortalidade , Transtornos Puerperais/fisiopatologia , Transtornos Puerperais/terapia , Recuperação de Função Fisiológica , Volume Sistólico , Fatores de Tempo , Função Ventricular Esquerda , Adulto Jovem
17.
Am J Transplant ; 19(7): 2067-2076, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30659754

RESUMO

The prelisting variables essential for creating an accurate heart transplant allocation score based on survival are unknown. To identify these we studied mortality of adults on the active heart transplant waiting list in the Scientific Registry of Transplant Recipients database from January 1, 2004 to August 31, 2015. There were 33 069 candidates awaiting heart transplantation: 7681 UNOS Status 1A, 13 027 Status 1B, and 12 361 Status 2. During a median waitlist follow-up of 4.3 months, 5514 candidates died. Variables of importance for waitlist mortality were identified by machine learning using Random Survival Forests. Strong correlates predicting survival were estimated glomerular filtration rate (eGFR), serum albumin, extracorporeal membrane oxygenation, ventricular assist device, mechanical ventilation, peak oxygen capacity, hemodynamics, inotrope support, and type of heart disease with less predictive variables including antiarrhythmic agents, history of stroke, vascular disease, prior malignancy, and prior tobacco use. Complex interactions were identified such as an additive risk in mortality based on renal function and serum albumin, and sex-differences in mortality when eGFR >40 mL/min/1.73 m. Most predictive variables for waitlist mortality are in the current tiered allocation system except for eGFR and serum albumin which have an additive risk and complex interactions.


Assuntos
Bases de Dados Factuais , Insuficiência Cardíaca/mortalidade , Transplante de Coração/mortalidade , Sistema de Registros/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/métodos , Transplantados/estatística & dados numéricos , Listas de Espera/mortalidade , Feminino , Seguimentos , Insuficiência Cardíaca/cirurgia , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Prognóstico , Alocação de Recursos/métodos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
18.
J Am Heart Assoc ; 8(2): e008968, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30638108

RESUMO

Background Myocarditis is an important cause of acute and chronic heart failure. Men with myocarditis have worse recovery and an increased need for transplantation compared with women, but the reason for the sex difference remains unclear. Elevated sera soluble (s) ST2 predicts mortality from acute and chronic heart failure, but has not been studied in myocarditis patients. Methods and Results Adults with a diagnosis of clinically suspected myocarditis (n=303, 78% male) were identified according to the 2013 European Society of Cardiology position statement. Sera sST2 levels were examined by ELISA in humans and mice and correlated with heart function according to sex and age. Sera sST2 levels were higher in healthy men ( P=8×10-6) and men with myocarditis ( P=0.004) compared with women. sST2 levels were elevated in patients with myocarditis and New York Heart Association class III - IV heart failure ( P=0.002), predominantly in men ( P=0.0003). Sera sST2 levels were associated with New York Heart Association class in men with myocarditis who were ≤50 years old ( r=0.231, P=0.0006), but not in women ( r=0.172, P=0.57). Sera sST2 levels were also significantly higher in male mice with myocarditis ( P=0.005) where levels were associated with cardiac inflammation. Gonadectomy with hormone replacement showed that testosterone ( P<0.001), but not estradiol ( P=0.32), increased sera sST2 levels in male mice with myocarditis. Conclusions We show in a well-characterized subset of heart failure patients with clinically suspected and biopsy-confirmed myocarditis that elevated sera sST2 is associated with an increased risk of heart failure based on New York Heart Association class in men ≤50 years old.


Assuntos
Insuficiência Cardíaca/sangue , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Miocardite/sangue , Miocárdio/patologia , Adulto , Fatores Etários , Animais , Biomarcadores/sangue , Biópsia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Miocardite/complicações , Miocardite/diagnóstico , Prognóstico , Estudos Retrospectivos , Fatores Sexuais
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