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1.
Circ Res ; 124(11): 1568-1583, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31120823

RESUMO

Myocarditis is generally a mild and self-limited consequence of systemic infection of cardiotropic viruses. However, patients can develop a temporary or permanent impairment of cardiac function including acute cardiomyopathy with hemodynamic compromise or severe arrhythmias. In this setting, specific causes of inflammation are associated with variable risks of death and transplantation. Recent translational studies suggest that treatments tailored to specific causes of myocarditis may impact clinical outcomes when added to guideline-directed medical care. This review summarizes recent advances in translational research that influence the utility of endomyocardial biopsy for the management of inflammatory cardiomyopathies. Emerging therapies for myocarditis based on these mechanistic hypotheses are entering clinical trials and may add to the benefits of established heart failure treatment.

2.
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.

3.
J Am Coll Cardiol ; 72(24): 3158-3176, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30545455

RESUMO

This JACC Scientific Expert Panel provides consensus recommendations for an update of the cardiovascular magnetic resonance (CMR) diagnostic criteria for myocardial inflammation in patients with suspected acute or active myocardial inflammation (Lake Louise Criteria) that include options to use parametric mapping techniques. While each parameter may indicate myocardial inflammation, the authors propose that CMR provides strong evidence for myocardial inflammation, with increasing specificity, if the CMR scan demonstrates the combination of myocardial edema with other CMR markers of inflammatory myocardial injury. This is based on at least one T2-based criterion (global or regional increase of myocardial T2 relaxation time or an increased signal intensity in T2-weighted CMR images), with at least one T1-based criterion (increased myocardial T1, extracellular volume, or late gadolinium enhancement). While having both a positive T2-based marker and a T1-based marker will increase specificity for diagnosing acute myocardial inflammation, having only one (i.e., T2-based OR T1-based) marker may still support a diagnosis of acute myocardial inflammation in an appropriate clinical scenario, albeit with less specificity. The update is expected to improve the diagnostic accuracy of CMR further in detecting myocardial inflammation.

4.
Eur J Heart Fail ; 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30378224

RESUMO

AIMS: Cardiac sarcoidosis (CS) often presents with ventricular arrhythmias, heart block, and cardiomyopathy. The prognosis of CS with contemporary management is uncertain. We estimated the impact of baseline and treatment variables on left ventricular ejection fraction (LVEF), ventricular assist device placement, heart transplant, and death. METHODS AND RESULTS: We identified patients with CS seen from 1994-2014 at two large academic medical centres. All met the 2014 Heart Rhythm Society expert consensus criteria for diagnosis. From the 574 patients identified, 91 met inclusion criteria. Twenty-two (24.2%) were diagnosed by endomyocardial biopsy. Cardiomyopathy was the primary presentation in 47 patients (51.6%). Within 90 days of diagnosis, 41 patients (45.0%) received prednisone alone, 29 (31.9%) received alternative immunosuppression with or without prednisone, and 21 (23.1%) received no immunosuppression. During follow-up, 31 of 47 cardiomyopathy patients experienced improvement in LVEF, while 23 experienced decline in LVEF or clinical exacerbation, and 15 of 22 patients presenting with ventricular arrhythmia had recurrence. These results did not differ by treatment group. During a median follow-up of 44 months for our cohort, 14 patients reached the composite endpoint of ventricular assist device placement, heart transplant, or death. Survival without the composite outcome did not differ by treatment group, but was worse among patients presenting with cardiomyopathy (log-rank = 0.005). CONCLUSION: In a large series of CS subjects, rates of ventricular arrhythmia and heart failure events remain high with no treatment regimen clearly associated with better outcome. Patients with cardiomyopathy at diagnosis were more likely to reach the composite endpoint.

6.
Am J Perinatol ; 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30184556

RESUMO

OBJECTIVE: To examine the association between maternal obesity on left ventricular (LV) size and recovery in women with peripartum cardiomyopathy (PPCM). STUDY DESIGN: This was a prospective analysis of 100 women enrolled within 13 weeks of PPCM diagnosis and followed for a year in the Investigation of Pregnancy Associated Cardiomyopathy study. Adiposity was defined by standard body mass index (BMI) definitions for under/normal weight, overweight, and obesity. Demographic, clinical, and biomarker variables were compared across weight categories. OUTCOMES: LV end-diastolic diameter (LVEDD) and ejection fraction were measured at entry, 6, and 12 months postpartum. Multivariable regression models examined the relationship between adiposity, LV size, and leptin levels with cardiac recovery at 6 and 12 months postpartum. RESULTS: Obese and nonobese women had similar LV dysfunction at entry. Obese women had greater LV size and less LV recovery at 6 and 12 months postpartum. BMI was positively associated with leptin and ventricular diameter. Greater BMI at entry remained associated with less ventricular recovery at 6 months (p = 0.02) in adjusted race-stratified models. LVEDD at entry predicted lower ejection fraction at 6 months (p < 0.001) and similarly at 12 months. CONCLUSION: Obese women with PPCM had greater cardiac remodeling, higher leptin levels, and diminished cardiac recovery.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30003460

RESUMO

PURPOSE: Electroanatomic mapping (EAM) has been utilized as a modality to improve the sensitivity of endomyocardial biopsy (EMB). We sought to systematically review published medical literature on the efficacy and safety of EAM-guided EMB. METHODS: We searched Ovid MEDLINE, Ovid Embase, Ovid CDR, Cochrane Central, Scopus, and Web of Science for studies where EAM was used for EMB. Data abstracted included demographics, indications, final diagnoses, histology findings, and technical details of biopsy extraction. Test characteristics including sensitivity (Se), specificity (Sp), and area under curve (AUC) were calculated on a per-patient and per-biopsy level. RESULTS: Seventeen studies (9 case series, 8 case reports) were included in this systematic review. EAM-guided EMB was performed in 148 patients and results of 207 individual biopsies were available for analysis. The most common indications for EAM-guided EMB were suspected arrhythmogenic right ventricular cardiomyopathy (ARVC), myocarditis, and cardiac sarcoidosis (CS). The pooled sensitivity and specificity for EAM-guided EMB for the diagnosis of cardiomyopathies (ARVC, myocarditis, CS, and other specific diagnoses) were 92 and 58% on per-biopsy analysis and 100 and 39% on per-patient analysis. Among the individual components of abnormal EGMs, abnormal unipolar EGM had the best AUC on per-biopsy (0.81, 95% CI 0.68-0.90) and per-patient analysis (0.84, 95% CI 0.68-0.92). EAM-guided EMB appears safe. Adverse events included 1 hemopericardium, 2 minimal asymptomatic pericardial effusions, and 1 femoral hematoma. CONCLUSIONS: EAM-guided EMB is a safe and efficacious method and might improve test characteristics over conventional fluoroscopy-guided biopsy.

8.
Am J Cardiol ; 121(11): 1373-1379, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29580630

RESUMO

In patients with unexplained cardiomyopathy, electroanatomical mapping can identify abnormal tissue to target during electrophysiology-guided endomyocardial biopsy (EP-guided EMB). The objective of this study is to determine whether catheter ablation performed in the same setting as EP-guided EMB increases procedural risk. Sixty-seven patients (mean age 54.4 ± 13.8, 57% male) undergoing EP-guided EMB were included. Radiofrequency catheter ablation was performed in 17 patients (25%) for ventricular arrhythmias and in 2 (3%) for typical atrial flutter. Femoral arterial access was obtained in 90% ablation patients and 40% biopsy-only patients; vascular access complications were more common in the ablation group than in the EMB-only group (p = 0.02). There were no significant differences in rate of tricuspid regurgitation, thromboembolism, or pericardial effusion, whether procedural anticoagulation was used. In conclusion, catheter ablation and procedural anticoagulation can be combined with EP-guided EMB with an increased risk of vascular access complications, but no significant increase in intracardiac complications.

9.
J Card Fail ; 24(1): 33-42, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29079307

RESUMO

OBJECTIVE: The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women. BACKGROUND: PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis. METHODS: The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non-pregnancy-associated recent-onset cardiomyopathy (ROCM). RESULTS: Entry NK cell levels (CD3-CD56+CD16+; reported as % of CD3- cells) were significantly (P < .0003) reduced in PPCM (6.6 ± 4.9% of CD3- cells) compared to HP (11.9 ± 5%). Of T-cell subtypes, CD3+CD4-CD8-CD38+ cells differed significantly (P < .004) between PPCM (24.5 ± 12.5% of CD3+CD4-CD8- cells) and HP (12.5 ± 6.4%). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4-CD8-CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM. CONCLUSIONS: Compared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4-CD8-CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and "double negative" (CD4-CD8-) T regulatory cells in PPCM requires further investigation.

11.
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16.
J Am Heart Assoc ; 6(4)2017 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-28373243

RESUMO

BACKGROUND: In peripartum cardiomyopathy, the prevalence of focal myocardial damage detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance is important to elucidate mechanisms of myocardial injury and cardiac dysfunction. LGE equates irreversible myocardial injury, but LGE prevalence in peripartum cardiomyopathy is uncertain. METHODS AND RESULTS: Among 100 women enrolled within the Investigations of Pregnancy Associated Cardiomyopathy cohort, we recruited 40 women at 13 centers to undergo LGE cardiovascular magnetic resonance, enrolled within the first 13 weeks postpartum. Follow-up scans occurred at 6 months postpartum, and death/transplant rates at 12 months. Baseline characteristics did not differ significantly in the parent cohort according to cardiovascular magnetic resonance enrollment except for mechanical circulatory support. LGE was noted only in 2 women (5%) at baseline. While left ventricular dysfunction with enlargement was prevalent at baseline cardiovascular magnetic resonance scans (eg, ejection fraction 38% [Q1-Q3 31-50%], end diastolic volume index=108 mL/m2 [Q1-Q3 83-134 mL/m2]), most women demonstrated significant improvements at 6 months, consistent with a low prevalence of LGE. LGE was not related to baseline clinical variables, ejection fraction, New York Heart Association heart failure class, or mortality. Neither of the 2 women who died exhibited LGE. LGE was inversely associated with persistent left ventricular ejection fraction at 6 months (P=0.006). CONCLUSIONS: Factors other than focal myocardial damage detectable by LGE explain the initial transient depressions in baseline left ventricular ejection fraction, yet focal myocardial damage may contribute to persistent myocardial dysfunction and hinder recovery in a small minority. Most women exhibit favorable changes in ventricular function over 6 months. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01085955.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Compostos Heterocíclicos/administração & dosagem , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Compostos Organometálicos/administração & dosagem , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Remodelação Ventricular , Canadá , Cardiomiopatias/mortalidade , Cardiomiopatias/fisiopatologia , Cardiomiopatias/terapia , Feminino , Fibrose , Gadolínio/administração & dosagem , Transplante de Coração , Humanos , Período Periparto , Valor Preditivo dos Testes , Gravidez , Complicações Cardiovasculares na Gravidez/mortalidade , Complicações Cardiovasculares na Gravidez/fisiopatologia , Complicações Cardiovasculares na Gravidez/terapia , Estudos Prospectivos , Recuperação de Função Fisiológica , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapia , Função Ventricular Direita
17.
J Am Coll Cardiol ; 69(8): 968-977, 2017 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-28231950

RESUMO

BACKGROUND: Among various cardiac autoantibodies (AAbs), those recognizing the ß1-adrenergic receptor (ß1AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by ß-blockers and immunoglobulin G3 (IgG3) immunoadsorption. OBJECTIVES: The goal of this study was to investigate the role of ß1AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. METHODS: Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). The presence of IgG and IgG3-ß1AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months. RESULTS: Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-ß1AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-ß1AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, ß = 0.20, p = 0.01; change in LVEF, ß = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. CONCLUSIONS: IgG3-ß1AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Autoanticorpos/sangue , Insuficiência Cardíaca Sistólica/sangue , Receptores Adrenérgicos beta 1/imunologia , Adulto , Feminino , Seguimentos , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica , Resultado do Tratamento , Função Ventricular Esquerda
18.
J Am Coll Cardiol ; 68(21): 2348-2364, 2016 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-27884253

RESUMO

Myocarditis is a diverse group of heart-specific immune processes classified by clinical and histopathological manifestations. Up to 40% of dilated cardiomyopathy is associated with inflammation or viral infection. Recent experimental studies revealed complex regulatory roles for several microribonucleic acids and T-cell and macrophage subtypes. Although the prevalence of myocarditis remained stable between 1990 and 2013 at about 22 per 100,000 people, overall mortality from cardiomyopathy and myocarditis has decreased since 2005. The diagnostic and prognostic value of cardiac magnetic resonance has increased with new, higher-sensitivity sequences. Positron emission tomography has emerged as a useful tool for diagnosis of cardiac sarcoidosis. The sensitivity of endomyocardial biopsy may be increased, especially in suspected sarcoidosis, by the use of electrogram guidance to target regions of abnormal signal. Investigational treatments on the basis of mechanistic advances are entering clinical trials. Revised management recommendations regarding athletic participation after acute myocarditis have heightened the importance of early diagnosis.


Assuntos
Cardiomiopatias , Imunidade Celular , Miocardite , Miocárdio/patologia , Linfócitos T/imunologia , Viroses/complicações , Biópsia , Cardiomiopatias/diagnóstico , Cardiomiopatias/epidemiologia , Cardiomiopatias/etiologia , Saúde Global , Humanos , Incidência , Miocardite/diagnóstico , Miocardite/epidemiologia , Miocardite/imunologia , Prognóstico
20.
JCI Insight ; 1(9)2016 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-27366791

RESUMO

In human myocarditis and its sequela dilated cardiomyopathy (DCM), the mechanisms and immune phenotype governing disease and subsequent heart failure are not known. Here, we identified a Th17 cell immunophenotype of human myocarditis/DCM with elevated CD4+IL17+ T cells and Th17-promoting cytokines IL-6, TGF-ß, and IL-23 as well as GM-CSF-secreting CD4+ T cells. The Th17 phenotype was linked with the effects of cardiac myosin on CD14+ monocytes, TLR2, and heart failure. Persistent heart failure was associated with high percentages of IL-17-producing T cells and IL-17-promoting cytokines, and the myocarditis/DCM phenotype included significantly low percentages of FOXP3+ Tregs, which may contribute to disease severity. We demonstrate a potentially novel mechanism in human myocarditis/DCM in which TLR2 peptide ligands from human cardiac myosin stimulated exaggerated Th17-related cytokines including TGF-ß, IL-6, and IL-23 from myocarditic CD14+ monocytes in vitro, and an anti-TLR2 antibody abrogated the cytokine response. Our translational study explains how an immune phenotype may be initiated by cardiac myosin TLR ligand stimulation of monocytes to generate Th17-promoting cytokines and development of pathogenic Th17 cells in human myocarditis and heart failure, and provides a rationale for targeting IL-17A as a therapeutic option.

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