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1.
J Mol Cell Cardiol ; 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32305360

RESUMO

BACKGROUND: Cardiac troponins are the preferred biomarkers of acute myocardial infarction. Despite superior sensitivity, serial testing of Troponins to identify patients suffering acute coronary syndromes is still required in many cases to overcome limited specificity. Moreover, unstable angina pectoris relies on reported symptoms in the troponin-negative group. In this study, we investigated genome-wide miRNA levels in a prospective cohort of patients with clinically suspected ACS and determined their diagnostic value by applying an in silico neural network. METHODS: PAXgene blood and serum samples were drawn and hsTnT was measured in patients at initial presentation to our Chest-Pain Unit. After clinical and diagnostic workup, patients were adjudicated by senior cardiologists in duty to their final diagnosis: STEMI, NSTEMI, unstable angina pectoris and non-ACS patients. ACS patients and a cohort of healthy controls underwent deep transcriptome sequencing. Machine learning was implemented to construct diagnostic miRNA classifiers. RESULTS: We developed a neural network model which incorporates 34 validated ACS miRNAs, showing excellent classification results. By further developing additional machine learning models and selecting the best miRNAs, we achieved an accuracy of 0.96 (95% CI 0.96-0.97), sensitivity of 0.95, specificity of 0.96 and AUC of 0.99. The one-point hsTnT value reached an accuracy of 0.89, sensitivity of 0.82, specificity of 0.96, and AUC of 0.96. CONCLUSIONS: Here we show the concept of neural network based biomarkers for ACS. This approach also opens the possibility to include multi-modal data points to further increase precision and perform classification of other ACS differential diagnoses.

2.
Heart ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245882

RESUMO

OBJECTIVE: The European Society of Cardiology (ESC) 0/1 hour algorithm has been primarily validated in Europe, America and Australasia with less knowledge of its performance outside of these settings. We aim to evaluate the performance of the ESC 0/1 hour algorithm across different contexts. METHODS: We searched PubMed, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials for relevant studies published between 1 January 2008 and 31 May 2019. The primary outcome was index myocardial infarction and the secondary outcome was major adverse cardiac event or mortality. A bivariate random-effects meta-analysis was used to derive the pooled estimate of each outcome. RESULTS: A total of 11 014 patients from 10 cohorts were analysed for the primary outcome. The algorithm based on high-sensitivity cardiac troponin (hs-cTn)T (Roche), hs-cTnI (Abbott) and hs-cTnI (Siemens) had pooled sensitivity of 98.4% (95% CI=95.1% to 99.5%), 98.1% (95% CI=94.6% to 99.3%) and 98.7% (95% CI=97.3% to 99.3%), respectively. The algorithm based on hs-cTnT (Roche) and hs-cTnI (Siemens) had pooled specificity of 91.2% (95% CI=86.0% to 94.6%) and 95.9% (95% CI=94.1% to 97.2%), respectively. Among patients in the rule-out category, the pooled mortality rate at 30 days and at 1 year was 0.1% (95% CI=0.0% to 0.4%) and 0.8% (95% CI=0.5% to 1.2%), respectively. Among patients in the observation zone, the pooled mortality rate was 0.7% (95% CI=0.3% to 1.2%) at 30 days but increased to 8.1% (95% CI=6.1% to 10.4%) at 1 year, comparable to the mortality rate in the rule-in group. CONCLUSION: The ESC 0/1 hour algorithm has high diagnostic accuracy but may not be sufficiently safe if the 1% miss-rate for myocardial infarction is desired. PROSPERO REGISTRATION NUMBER: CRD42019142280.

3.
ESC Heart Fail ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32285648

RESUMO

AIMS: Patients with non-ischaemic dilated cardiomyopathy (DCM) are at increased risk of sudden cardiac death. Identification of patients that may benefit from implantable cardioverter-defibrillator implantation remains challenging. In this study, we aimed to determine predictors of sustained ventricular arrhythmias in patients with DCM. METHODS AND RESULTS: We searched MEDLINE/Embase for studies describing predictors of sustained ventricular arrhythmias in patients with DCM. Quality and bias were assessed using the Quality in Prognostic Studies tool, articles with high risk of bias in ≥2 areas were excluded. Unadjusted hazard ratios (HRs) of uniformly defined predictors were pooled, while all other predictors were evaluated in a systematic review. We included 55 studies (11 451 patients and 3.7 ± 2.3 years follow-up). Crude annual event rate was 4.5%. Younger age [HR 0.82; 95% CI (0.74-1.00)], hypertension [HR 1.95; 95% CI (1.26-3.00)], prior sustained ventricular arrhythmia [HR 4.15; 95% CI (1.32-13.02)], left ventricular ejection fraction on ultrasound [HR 1.45; 95% CI (1.19-1.78)], left ventricular dilatation (HR 1.10), and presence of late gadolinium enhancement [HR 5.55; 95% CI (4.02-7.67)] were associated with arrhythmic outcome in pooled analyses. Prior non-sustained ventricular arrhythmia and several genotypes [mutations in Phospholamban (PLN), Lamin A/C (LMNA), and Filamin-C (FLNC)] were associated with arrhythmic outcome in non-pooled analyses. Quality of evidence was moderate, and heterogeneity among studies was moderate to high. CONCLUSIONS: In patients with DCM, the annual event rate of sustained ventricular arrhythmias is approximately 4.5%. This risk is considerably higher in younger patients with hypertension, prior (non-)sustained ventricular arrhythmia, decreased left ventricular ejection fraction, left ventricular dilatation, late gadolinium enhancement, and genetic mutations (PLN, LMNA, and FLNC). These results may help determine appropriate candidates for implantable cardioverter-defibrillator implantation.

4.
ESC Heart Fail ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31802644

RESUMO

Cardiac sarcoidosis is a chronic inflammatory disease with a large spectrum of symptoms that can mimic diseases such as dilated, hypertrophic, or arrhythmogenic cardiomyopathies. It can be asymptomatic but can also present with ventricular arrhythmias, conduction disease, and heart failure (HF) or even sudden cardiac death (SCD). We present here the case of a patient transplanted due to end-stage arrhythmogenic right ventricular cardiomyopathy (ARVC), fulfilling the task force criteria. A few years after successful heart transplantation (HTX), the patient developed similar symptoms and morphofunctional changes of the heart, which led to critical re-evaluation of his primary diagnosis.

5.
Clin Res Cardiol ; 108(11): 1297-1308, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30980206

RESUMO

BACKGROUND: Left ventricular non-compaction has been increasingly diagnosed in recent years. However, it is still debated whether non-compaction is a pathological condition or a physiological trait. In this meta-analysis and systematic review, we compare studies, which investigated these two different perspectives. Furthermore, we provide a comprehensive overview on the clinical outcome as well as genetic background of left ventricular non-compaction cardiomyopathy in adult patients. METHODS AND RESULTS: We retrieved PubMed/Medline literatures in English language from 2000 to 19/09/2018 on clinical outcome and genotype of patients with non-compaction. We summarized and extensively reviewed all studies that passed selection criteria and performed a meta-analysis on key phenotypic parameters. Altogether, 35 studies with 2271 non-compaction patients were included in our meta-analysis. The mean age at diagnosis was the mid of their fifth decade. Two-thirds of patients were male. Congenital heart diseases including atrial or ventricular septum defect or Ebstein anomaly were reported in 7% of patients. Twenty-four percent presented with family history of cardiomyopathy. The mean frequency of neuromuscular diseases was 5%. Heart rhythm abnormalities were reported frequently: conduction disease in 26%, supraventricular tachycardia in 17%, and sustained or non-sustained ventricular tachycardia in 18% of patients. Three important outcome measures were reported including systemic thromboembolic events with a mean frequency of 9%, heart transplantation with 4%, and adequate ICD therapy with 15%. Nine studies investigated the genetics of non-compaction cardiomyopathy. The most frequently mutated gene was TTN with a pooled frequency of 11%. The average frequency of MYH7 mutations was 9%, for MYBPC3 mutations 5%, and for CASQ2 and LDB3 3% each. TPM1, MIB1, ACTC1, and LMNA mutations had an average frequency of 2% each. Mutations in PLN, HCN4, TAZ, DTNA, TNNT2, and RBM20 were reported with a frequency of 1% each. We also summarized the results of eight studies investigating the non-compaction in altogether 5327 athletes, pregnant women, patients with sickle cell disease, as well as individuals from population-based cohorts, in which the presence of left ventricular hypertrabeculation ranged from 1.3 to 37%. CONCLUSION: The summarized data indicate that non-compaction may lead to unfavorable outcome in different cardiomyopathy entities. The presence of key features in a multimodal diagnostic approach could distinguish between benign morphological trait and manifest cardiomyopathy.

6.
Biomark Med ; 10(3): 329-42, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26860036

RESUMO

AIM: Galectin-3 (Gal-3) is a new biomarker for assessing prognosis of heart failure (HF) patients. This systemic review and meta-analysis aims to examine Gal-3's ability in assessing prognosis of HF patients. METHOD: We searched MEDLINE and Embase up to November 2014. Test performance characteristics were summarized using forest plots and hierarchical summary receiver operating characteristic curves. RESULTS: The diagnostic odds ratio of Gal-3 in predicting mortality in chronic HF patients was 2.36 (95% CI: 1.71-3.26) and 2.30 (95% CI: 1.76-3.01) in acute HF patients. CONCLUSION: Elevated levels of Gal-3 are associated with mortality in both acute and chronic HF patients. However, current evidence does not support sole use of Gal-3 for prognosis evaluation of HF patients.


Assuntos
Galectina 3/metabolismo , Insuficiência Cardíaca/mortalidade , Doença Aguda , Doença Crônica , Humanos , Infarto do Miocárdio/mortalidade
7.
Am J Emerg Med ; 32(12): 1450-4, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25245283

RESUMO

OBJECTIVES: The objective of the study is to describe the epidemiology and outcome of community-acquired bloodstream infection (BSI) in type 2 diabetic patients in emergency department (ED). METHODS: All patients admitted to the ED of the university hospital from June 2010 to June 2011 with a history of type 2 diabetes mellitus and microbiologically documented BSI were retrospectively enrolled. Demographic characteristics, Charlson comorbidity index, antibiotic therapy, clinical severity, microbiological etiology, and diabetes-related complications were recorded in a standardized form. The major outcome measure was 30-day survival. χ2 Or Student t test was used for univariate analysis, and Cox proportional hazards models were used for multivariate analysis. RESULTS: Among 250 enrolled emergency patients with BSI, the overall 30-day mortality rate was 15.5%. Twenty-seven patients (10.7%) developed diabetic ketoacidosis (DKA), and 22 patients (8.8%) developed hyperosmolar hyperglycemic state. On univariate analysis, DKA rather than hyperosmolar hyperglycemic state was associated with adverse outcome. Other risk factors include higher mean glycated hemoglobin level, presence of underlying malignancy, long-term use of steroids, lower respiratory tract infection, and higher Charlson scores. Multivariate analysis identified 3 independent risk factors for early mortality when severity, comorbidity, age, and sex were under control: DKA (hazard ratio, 3.89; 95% confidence interval, 1.6-8.9), inappropriate antibiotics (2.25, 1.05-4.82), and chronic use of steroid (3.89, 1.1-13.2). CONCLUSION: In type 2 diabetic patients with BSI, a substantial proportion of patients developed DKA. This condition was probably underrecognized by clinicians and constituted an independent risk factor for short-term mortality. Other identified risk factors are potentially correctable and may allow preventive efforts to individuals at greatest potential benefit.


Assuntos
Bacteriemia/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Serviço Hospitalar de Emergência , Idoso , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/etiologia , Diabetes Mellitus Tipo 2/microbiologia , Cetoacidose Diabética/etiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hemoglobina A Glicada/análise , Humanos , Coma Hiperglicêmico Hiperosmolar não Cetótico/etiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida
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