Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 99
Filtrar
Filtros adicionais











País/Região como assunto
Intervalo de ano
1.
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.

2.
J Am Coll Cardiol ; 72(20): 2471-2481, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30442290

RESUMO

BACKGROUND: The BAG3 (BLC2-associated athanogene 3) gene codes for an antiapoptotic protein located on the sarcomere Z-disc. Mutations in BAG3 are associated with dilated cardiomyopathy (DCM), but only a small number of cases have been reported to date, and the natural history of BAG3 cardiomyopathy is poorly understood. OBJECTIVES: This study sought to describe the phenotype and prognosis of BAG3 mutations in a large multicenter DCM cohort. METHODS: The study cohort comprised 129 individuals with a BAG3 mutation (62% males, 35.1 ± 15.0 years of age) followed at 18 European centers. Localization of BAG3 in cardiac tissue was analyzed in patients with truncating BAG3 mutations using immunohistochemistry. RESULTS: At first evaluation, 57.4% of patients had DCM. After a median follow-up of 38 months (interquartile range: 7 to 95 months), 68.4% of patients had DCM and 26.1% who were initially phenotype-negative developed DCM. Disease penetrance in individuals >40 years of age was 80% at last evaluation, and there was a trend towards an earlier onset of DCM in men (age 34.6 ± 13.2 years vs. 40.7 ± 12.2 years; p = 0.053). The incidence of adverse cardiac events (death, left ventricular assist device, heart transplantation, and sustained ventricular arrhythmia) was 5.1% per year among individuals with DCM. Male sex, decreased left ventricular ejection fraction. and increased left ventricular end-diastolic diameter were associated with adverse cardiac events. Myocardial tissue from patients with a BAG3 mutation showed myofibril disarray and a relocation of BAG3 protein in the sarcomeric Z-disc. CONCLUSIONS: DCM caused by mutations in BAG3 is characterized by high penetrance in carriers >40 years of age and a high risk of progressive heart failure. Male sex, decreased left ventricular ejection fraction, and enlarged left ventricular end-diastolic diameter are associated with adverse outcomes in patients with BAG3 mutations.

3.
J Cardiothorac Surg ; 13(1): 95, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30223867

RESUMO

BACKGROUND: Treatment of heart failure remains one of the most challenging task for intensive care medicine, cardiology and cardiac surgery. New options and better indicators are always required. Understanding the basic mechanisms underlying heart failure promote the development of adjusted therapy e.g. assist devices and monitoring of recovery. If cardiac failure is related to compromised cellular respiration of the heart, remains unclear. Myocardial respiration depends on Cytochrome c- Oxidase (CytOx) activity representing the rate limiting step for the mitochondrial respiratory chain. The enzymatic activity as well as mRNA expression of enzyme's mitochondrial encoded catalytic subunit 2, nuclear encoded regulatory subunit 4 and protein contents were studied in biopsies of cardiac patients suffering from myocardial insufficiency and dilated cardiomyopathy (DCM). METHODS: Fifty-four patients were enrolled in the study and underwent coronary angiography. Thirty male patients (mean age: 45 +/- 15 yrs.) had a reduced ejection fraction (EF) 35 ± 12% below 45% and a left ventricular end diastolic diameter (LVEDD) of 71 ± 10 mm bigger than 56 mm. They were diagnosed as having idiopathic dilated cardiomyopathy (DCM) without coronary heart disease and NYHA-class 3 and 4. Additionally, 24 male patients (mean age: 52 +/- 11 yrs.) after exclusion of secondary cardiomyopathies, coronary artery or valve disease, served as control (EF: 68 ± 7, LVEDD: 51 ± 7 mm). Total RNA was extracted from two biopsies of each person. Real-time PCR analysis was performed with specific primers followed by a melt curve analysis. Corresponding protein expression in the tissue was studied with immune-histochemistry while enzymatic activity was evaluated by spectroscopy. RESULTS: Gene and protein expression analysis of patients showed a significant decrease of subunit 4 (1.1 vs. 0.6, p < 0.001; 7.7 ± 3.1% vs. 2.8 ± 1.4%, p < 0.0001) but no differences in subunit 2. Correlations were found between reduced subunit 2 expression, low EF (r = 0.766, p < 0.00045) and increased LVEDD (r = 0.492, p < 0.0068). In case of DCM less subunit 4 expression and reduced shortening fraction (r = 0.524, p < 0.017) was found, but enzymatic activity was higher (0.08 ± 0.06 vs. 0.26 ± 0.08 U/mg, p < 0.001) although myocardial oxygen consumption continued to the same extent. CONCLUSION: In case of myocardial insufficiency and DCM, decreased expression of COX 4 results in an impaired CytOx activity. Higher enzymatic activity but equal oxygen consumption contribute to the pathophysiology of the myocardial insufficiency and appears as an indicator of oxidative stress. This kind of dysregulation should be in the focus for the development of diagnostic and therapy procedures.


Assuntos
Cardiomiopatia Dilatada/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Insuficiência Cardíaca/metabolismo , Miocárdio/metabolismo , Adulto , Cardiomiopatia Dilatada/complicações , Coração/fisiopatologia , Insuficiência Cardíaca/etiologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Consumo de Oxigênio/fisiologia , Reação em Cadeia da Polimerase em Tempo Real
4.
Dis Markers ; 2018: 2958219, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30018673

RESUMO

Objectives: Studies have evaluated the association of galectin-3 and outcome in patients with heart failure. However, there is still scarce evidence concerning the clinical usefulness and predictive value of galectin-3 for left ventricular reverse remodeling (LVRR) in patients with recent-onset dilated cardiomyopathy (RODCM). Patients and Methods: Baseline galectin-3 was measured in 57 patients with RODCM. All patients were followed for at least 12 months. The study end point was LVRR at 12 months, defined as an absolute improvement of the left ventricular ejection fraction of ≥10% to a final value of ≥35%, accompanied by a decrease in the left ventricular end diastolic diameter of at least 10%, as assessed by echocardiography. In receiver operating characteristic curve analysis, the optimum cut-off value for baseline galectin-3 with the highest Youden index was 59 ng/ml. Results: Overall, LVRR at 12 months was observed in 38 patients (66%). In a univariate analysis, NYHA functional class and baseline galectin-3 levels were associated with LVRR. After adjustment for covariates, galectin-3 remained an independent predictor for LVRR. Conclusions: Our study suggests that baseline galectin-3 is an independent predictor of LVRR. Low levels of galectin-3 may be regarded a useful biomarker of favorable ventricular remodeling in patients with RODCM.


Assuntos
Cardiomiopatia Dilatada/sangue , Galectina 3/sangue , Remodelação Ventricular , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Cardiomiopatia Dilatada/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Open Heart ; 5(1): e000750, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29531765

RESUMO

Objective: Several studies indicate a prognostic value of sST2 and galectin-3 in heart failure (HF). While previous studies focused on ischaemic cause of HF, we investigated the role of sST2 and galectin-3 in patients with non-ischaemic dilated cardiomyopathy (DCM). Methods: sST2 and galectin-3 serum concentrations were measured in 262 subjects with DCM. Survival rates were determined for all-cause mortality (ACM) and cardiac mortality (CM). Results: In a univariate model, sST2 as a continuous variable was a predictor of ACM (HR 1.05; 95% CI 1.03 to 1.07, P<0.001) and CM (HR 1.03; 95% CI 1.00 to 1.06, P=0.040). In the subgroup of patients with inflammatory and/or viral DCM (DCMi⋎viral), the endpoints ACM (HR 1.10; 95% CI 1.05 to 1.17, P<0.001) and CM (HR 1.10; 95% CI 1.02 to 1.18, P=0.013) were significant. In the subgroup of patients with idiopathic DCM, the endpoint ACM (HR 1.04; 95% CI 1.01 to 1.07, P=0.019) was significant. In a multivariate model, the prognostic value of the sST2 main group remained intact for ACM (HR 1.04; 95% CI 1.02 to 1.07, P=0.003).Univariate and multivariate analysis of galectin-3 as continuous variable did not show any significant result. However, in a quartile model, intermediate values of galectin-3 were significantly associated with a lower event rate of ACM and CM. Conclusion: The study revealed that sST2 predicts ACM and CM in patients with non-ischaemic HF and could be useful especially in patients with inflammatory background. Our findings that intermediate levels of galectin-3 allow for better prognosis were new and different to other investigations. Trial registration number: NCT03090425; Results.

6.
Eur Heart J ; 39(10): 861-863, 2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29165585
7.
PLoS One ; 12(12): e0188491, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29267340

RESUMO

OBJECTIVES: The study objectives were to identify predictors of outcome in patients with inflammatory dilated cardiomyopathy (DCMi). METHODS: From 2004 to 2008, 55 patients with biopsy-proven DCMi were identified and followed up for 58.2±19.8 months. Predictors of outcome were identified in a multivariable analysis with a Cox proportional hazards analysis. The primary endpoint was a composite of death, heart transplantation and hospitalization for heart failure or ventricular arrhythmias. RESULTS: For the primary endpoint, a QTc interval >440msec (HR 2.84; 95% CI 1.03-7.87; p = 0.044), a glomerular filtration rate (GFR) <60ml/min/1.73m2 (HR 3.19; 95% CI 1.35-7.51; p = 0.008) and worsening of NYHA classification during follow-up (HR 2.48; 95% CI 1.01-6.10; p = 0.048) were univariate predictors, whereas left ventricular ejection fraction at baseline, NYHA class at entry, atrial fibrillation, treatment with digitalis or viral genome detection were not significantly related to outcome. After multivariable analysis, a GFR <60ml/min/1.73m2 (HR 3.04; 95% CI 1.21-7.66; p = 0.018) remained a predictor of adverse outcome. CONCLUSIONS: In patients with DCMi, a prolonged QTc interval >440msec, a GFR<60ml/min/1.73m2 and worsening of NYHA classification during follow-up were univariate predictors of adverse prognosis. In contrast, NYHA classification at baseline, left ventricular ejection fraction, atrial fibrillation, treatment with digitalis or viral genome detection were not related to outcome. After multivariable analysis, a GFR <60ml/min/1.73m2 remained independently associated with adverse outcome.


Assuntos
Cardiomiopatia Dilatada/patologia , Inflamação/patologia , Avaliação de Resultados (Cuidados de Saúde) , Adulto , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/terapia , Eletrocardiografia , Feminino , Taxa de Filtração Glomerular , Transplante de Coração , Hospitalização , Humanos , Inflamação/terapia , Masculino , Pessoa de Meia-Idade
8.
Cardiol Clin ; 35(4): 567-588, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29025548

RESUMO

Interventional procedures for pericardial diseases include pericardiocentesis, drainage of pericardial effusion, intrapericardial therapy, and percutaneous balloon pericardiotomy or percutaneous pericardiostomy. Echocardiographic and fluoroscopic guidance have greatly increased safety and feasibility. Several devices for pericardiocentesis have been tested (PerDucer, PeriAttacher, visual puncture systems, Grasper, Scissors, and Reverse slitter), mainly to facilitate access to the pericardium in the absence of effusion for epicardial ablations or left atrial appendage ligation. In selected patients with pericardial effusions that cannot be managed medically or with prolonged drainage, various medications can be applied intrapericardially to prevent further recurrences or induce sclerosis of the pericardial space.


Assuntos
Tamponamento Cardíaco/cirurgia , Derrame Pericárdico/cirurgia , Pericardiectomia/métodos , Pericardiocentese/métodos , Pericardite/cirurgia , Apêndice Atrial/cirurgia , Ecocardiografia , Fluoroscopia , Humanos , Complicações Pós-Operatórias/epidemiologia , Cirurgia Assistida por Computador
9.
ESC Heart Fail ; 4(3): 224-231, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28772053

RESUMO

AIMS: Previous studies demonstrated poor public awareness of heart failure (HF) compared with myocardial infarction and stroke. With respect to several activities to improve HF awareness in recent years, we present data on the development of HF awareness and information sources in Germany over 8 years. METHODS AND RESULTS: In 2007, 2012, and 2015, respectively, 2531, 359, and 171 respondents answered questions about causes, presentation, prognosis, and treatment of HF from a survey developed by the German Competence Network HF. Relationships between respondents' sociodemographic data and their HF knowledge were explored and changes in knowledge and use of information sources analysed. Sixty-eight per cent of respondents knew HF as 'weakness of the heart'. Seventy-nine per cent knew shortness of breath, 74% reduced exercise tolerance, and 52% knew leg edema as symptoms. Only 40% knew all three symptoms. Although up to 34% of the respondents were directly or indirectly affected by HF, they demonstrated poor knowledge about severity and prognosis. Between 2007 and 2015, overall HF awareness has not changed; awareness about treatment has dropped significantly. Younger respondents used all media, especially internet, for information about health; older respondents preferred printed/verbal media and their physician. CONCLUSIONS: We found rather insufficient public knowledge on HF etiology and symptoms but especially about management, severity, and prognosis, which is essential for good self-care and adherence of patients. Heart failure awareness has not improved even though awareness campaigns were held over the years. It seems that especially older patients should be much more approached by their family physicians.

10.
JAMA ; 315(24): 2683-93, 2016 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-27367876

RESUMO

IMPORTANCE: Depression is frequent in patients with heart failure and is associated with adverse clinical outcomes. Long-term efficacy and safety of selective serotonin reuptake inhibitors in these patients are unknown. OBJECTIVE: To determine whether 24 months of treatment with escitalopram improves mortality, morbidity, and mood in patients with chronic systolic heart failure and depression. DESIGN, SETTING, AND PARTICIPANTS: The Effects of Selective Serotonin Re-Uptake Inhibition on Morbidity, Mortality, and Mood in Depressed Heart Failure Patients (MOOD-HF) study was a double-blind, placebo-controlled randomized clinical trial conducted at 16 tertiary medical centers in Germany. Between March 2009 and February 2014, patients at outpatient clinics with New York Heart Association class II-IV heart failure and reduced left ventricular ejection fraction (<45%) were screened for depression using the 9-item Patient Health Questionnaire. Patients with suspected depression were then invited to undergo a Structured Clinical Interview based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) to establish the diagnosis. INTERVENTIONS: Patients were randomized 1:1 to receive escitalopram (10-20 mg) or matching placebo in addition to optimal heart failure therapy. Study duration was 24 months. MAIN OUTCOMES AND MEASURES: The composite primary outcome was time to all-cause death or hospitalization. Prespecified secondary outcomes included safety and depression severity at 12 weeks of treatment (including the titration period), which were determined using the 10-item Montgomery-Åsberg Depression Rating Scale (total possible score, 0 to 60; higher scores indicate more severe depression). RESULTS: A total of 372 patients (mean age, 62 years; 24% female) were randomized and had taken at least 1 dose of study medication when the data and safety monitoring committee recommended the trial be stopped early. During a median participation time of 18.4 months (n = 185) for the escitalopram group and 18.7 months (n = 187) for the placebo group, the primary outcome of death or hospitalization occurred in 116 (63%) patients and 119 (64%) patients, respectively (hazard ratio, 0.99 [95% CI, 0.76 to 1.27]; P = .92). The mean Montgomery-Åsberg Depression Rating Scale sum score changed from 20.2 at baseline to 11.2 at 12 weeks in the escitalopram group and from 21.4 to 12.5 in the placebo group (between-group difference, -0.9 [95% CI,-2.6 to 0.7]; P = .26). Safety parameters were comparable between groups. CONCLUSIONS AND RELEVANCE: In patients with chronic heart failure with reduced ejection fraction and depression, 18 months of treatment with escitalopram compared with placebo did not significantly reduce all-cause mortality or hospitalization, and there was no significant improvement in depression. These findings do not support the use of escitalopram in patients with chronic systolic heart failure and depression. TRIAL REGISTRATION: isrctn.com Identifier: ISRCTN33128015.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Citalopram/uso terapêutico , Depressão/tratamento farmacológico , Insuficiência Cardíaca/psicologia , Afeto , Idoso , Doença Crônica , Depressão/complicações , Esquema de Medicação , Feminino , Insuficiência Cardíaca/complicações , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Escalas de Graduação Psiquiátrica , Volume Sistólico , Resultado do Tratamento
11.
Int J Cardiol ; 220: 608-12, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27390998

RESUMO

BACKGROUND: The study objectives were to identify predictors of outcome and to assess the long-term outcome in patients with non-ischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: From 2004 to 2008, 206 consecutive patients (age 52.1±12.6years) with non-ischemic DCM were prospectively enrolled in the study and followed up for a mean of 55.6±18.4months. Predictors of outcome were identified in a multivariable analysis with a Cox proportional hazards analysis. The primary endpoint was a composite of all-cause mortality or heart transplantation. During the follow-up period 47 patients died (22.8%) and 5 patients (2.4%) underwent heart transplantation for end-stage heart failure. For the primary end point, a systolic LVEF <35% (hazard ratio 2.56; 95% confidence interval 1.21-5.45; p=0.014), a prolonged QTc interval >440ms (hazard ratio 2.56; 95% confidence interval 1.24-3.83; p=0.007) and a GFR <60ml/min/1.73m(2) (hazard ratio 2.42; 95% confidence interval 1.36-4.29; p=0.003) were identified as independent predictors, whereas the presence of an LBBB, atrial fibrillation, mild mitral regurgitation or treatment with digitalis were not significantly related to outcome. CONCLUSIONS: In patients with non-ischemic DCM, a reduced systolic LVEF <35%, a prolonged QTc interval >440ms and an abnormal renal function with a GFR <60ml/min/1.73m(2) are independent predictors of death or need for heart transplantation.


Assuntos
Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Taxa de Filtração Glomerular/fisiologia , Volume Sistólico/fisiologia , Adulto , Feminino , Seguimentos , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
12.
Dis Markers ; 2016: 9262741, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26941472

RESUMO

OBJECTIVES: Chronic pericardial effusion may be challenging in terms of diagnosis and treatment. Specific laboratory parameters predicting the frequency and severity of recurrences after initial drainage of pericardial effusion are lacking. MATERIALS AND METHODS: Pericardial fluid (PF) and serum (SE) samples from 30 patients with chronic pericardial effusion (PE) who underwent pericardiocentesis and pericardioscopically guided pericardial biopsy were compared with SE and PF samples from 26 control patients. The levels of antimyolemmal (AMLA) and antifibrillary antibodies (AFA) in PE and SE from patients with pericardial effusion as well as PF and SE from controls were determined and compared. RESULTS: AMLAs and AFAs in PF and SE were significantly higher in patients with chronic pericardial effusion than in the control group (AMLAs: p = 0,01 for PF and p = 0,004 for serum; AFAs: p < 0,001 for PF and p = 0,003 for serum). Patients with recurrence of PE within 3 months after pericardiocentesis had significantly higher levels of AMLAs in SE (p = 0,029) than patients without recurrence of PE. CONCLUSIONS: The identification of elevated anticardiac antibodies in PE and SE indicates increased immunological reactivity in chronic pericardial effusion. High titer serum levels of AMLAs also correlate with recurrence of pericardial effusion.


Assuntos
Anticorpos/metabolismo , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/imunologia , Pericardite/diagnóstico , Pericardite/imunologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pericárdico/cirurgia , Pericardiocentese , Pericardite/cirurgia , Prognóstico , Recidiva , Cirurgia Torácica Vídeoassistida , Resultado do Tratamento
14.
Eur J Clin Invest ; 45(9): 906-17, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26094644

RESUMO

BACKGROUND: The clinical phenotype dilated cardiomyopathy is assumed to be the endstage of a multifactorial aetiopathogenetic pathophysiology which includes a not satisfactorily defined group of patients with inflammatory cardiomyopathy. METHODS: Within the German Competence Network Heart Failure patients with heart failure due to dilated cardiomyopathy of viral/inflammatory (DCMi/v) and nonviral/noninflammatory (DCM) aetiology were enrolled. After 1 year 237 patients (180 male/57 female) were re-examined including complete clinical work-up. The association of different clinical courses with the time from initial diagnosis of heart failure (newly: ≤ 1 year; late: > 1 year) was investigated. RESULTS: After 1-year-follow-up New York Heart Association (NYHA) class (by -0.48 in newly diagnosed DCM and -0.82 in newly diagnosed DCMi/v in addition to -0.24 in late diagnosed DCM and -0.17 in late diagnosed DCMi/v) as well as left ventricular ejection fraction (+14% in newly diagnosed DCM and DCMi/v and +6% in later diagnosed DCM and DCMi/v) were significantly improved in all patients. In patients with early diagnosed dilated cardiomyopathy a strong improvement of NYHA class could be demonstrated. CONCLUSIONS: This study demonstrates for the first time a significant interaction between duration of disease, NYHA class and left ventricular ejection fraction in patients with DCM. Our results clearly demonstrate that in patients with DCM an early diagnosis within 1 year after occurrence of clinical signs is associated with a strong improvement in the clinical course, whereas late diagnosis results in a loss of change in clinical course and outcome.


Assuntos
Cardiomiopatia Dilatada/etiologia , Miocardite/complicações , Disfunção Ventricular Esquerda/etiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/terapia , Progressão da Doença , Diuréticos/uso terapêutico , Feminino , Seguimentos , Humanos , Hipolipemiantes/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Inflamação , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Miocardite/terapia , Miocardite/virologia , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapia
17.
Diagn Pathol ; 9: 114, 2014 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-24912374

RESUMO

BACKGROUND: Cardiac fibrosis disrupts the normal myocardial structure and has a direct impact on heart function and survival. Despite already available digital methods, the pathologist's visual score is still widely considered as ground truth and used as a primary method in histomorphometric evaluations. The aim of this study was to compare the accuracy of digital image analysis tools and the pathologist's visual scoring for evaluating fibrosis in human myocardial biopsies, based on reference data obtained by point counting performed on the same images. METHODS: Endomyocardial biopsy material from 38 patients diagnosed with inflammatory dilated cardiomyopathy was used. The extent of total cardiac fibrosis was assessed by image analysis on Masson's trichrome-stained tissue specimens using automated Colocalization and Genie software, by Stereology grid count and manually by Pathologist's visual score. RESULTS: A total of 116 slides were analyzed. The mean results obtained by the Colocalization software (13.72 ± 12.24%) were closest to the reference value of stereology (RVS), while the Genie software and Pathologist score gave a slight underestimation. RVS values correlated strongly with values obtained using the Colocalization and Genie (r>0.9, p<0.001) software as well as the pathologist visual score. Differences in fibrosis quantification by Colocalization and RVS were statistically insignificant. However, significant bias was found in the results obtained by using Genie versus RVS and pathologist score versus RVS with mean difference values of: -1.61% and 2.24%. Bland-Altman plots showed a bidirectional bias dependent on the magnitude of the measurement: Colocalization software overestimated the area fraction of fibrosis in the lower end, and underestimated in the higher end of the RVS values. Meanwhile, Genie software as well as the pathologist score showed more uniform results throughout the values, with a slight underestimation in the mid-range for both. CONCLUSION: Both applied digital image analysis methods revealed almost perfect correlation with the criterion standard obtained by stereology grid count and, in terms of accuracy, outperformed the pathologist's visual score. Genie algorithm proved to be the method of choice with the only drawback of a slight underestimation bias, which is considered acceptable for both clinical and research evaluations. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9857909611227193.


Assuntos
Cardiomiopatia Dilatada/patologia , Interpretação de Imagem Assistida por Computador , Microscopia , Miocárdio/patologia , Adulto , Algoritmos , Biópsia , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Software
18.
Curr Heart Fail Rep ; 11(2): 166-77, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24723087

RESUMO

Fulminant myocarditis is a clinical syndrome with signs of acute heart failure, cardiogenic shock, or life-threating rhythm disturbances in the context of suspected myocarditis. It is not an etiological diagnosis, but may have different underlying causes and pathogenetic processes - viral, bacterial, toxic, and autoreactive. Clinical management of the disease entity at the acute stage involves hemodynamic monitoring in an intensive care unit or similar setting. Rapid routine work-up is mandatory with serial EKGs, echocardiography, cardiac MRI, heart catheterization with endomyocardial biopsy for histology, immunohistology, and molecular analysis for the underlying infection and pathogenesis. Heart failure therapy is warranted in all cases according to current guidelines. For fulminant autoreactive myocarditis, immunosuppressive treatment is beneficial; for viral myocarditis, IVIg can resolve the inflammation, reduce the viral load, and even eradicate the microbial agent. ECMO, IABP, ventricular assist devices, LifeVest, or ICD implantation can bridge to recovery or to heart transplantation.


Assuntos
Miocardite/diagnóstico , Miocardite/etiologia , Algoritmos , Animais , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Cardiomiopatias/terapia , Modelos Animais de Doenças , Coração Auxiliar , Humanos , Incidência , Miocardite/epidemiologia , Miocardite/terapia , Fenótipo , Terminologia como Assunto
20.
Eur Heart J ; 35(16): 1069-77, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23853074

RESUMO

AIMS: Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM. METHODS AND RESULTS: Applying a three-staged study design, we analysed more than 4100 DCM cases and 7600 controls. We identified and successfully replicated multiple single nucleotide polymorphism on chromosome 6p21. In the combined analysis, the most significant association signal was obtained for rs9262636 (P = 4.90 × 10(-9)) located in HCG22, which could again be replicated in an independent cohort. Taking advantage of expression quantitative trait loci (eQTL) as molecular phenotypes, we identified rs9262636 as an eQTL for several closely located genes encoding class I and class II major histocompatibility complex heavy chain receptors. CONCLUSION: The present study reveals a novel genetic susceptibility locus that clearly underlines the role of genetically driven, inflammatory processes in the pathogenesis of idiopathic DCM.


Assuntos
Cardiomiopatia Dilatada/genética , Cromossomos Humanos Par 6/genética , Antígenos HLA-C/genética , Polimorfismo de Nucleotídeo Único/genética , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA