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1.
BMJ Open ; 9(9): e030097, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481563

RESUMO

PURPOSE: The LipidCardio Study was established for in-depth analyses of cardiovascular risk factors, providing well-defined cardiovascular and metabolic phenotypes. In particular, the role of lipoproteins in the pathobiological process and treatment of cardiovascular disease (CVD) will be a main focus. PARTICIPANTS: 1005 individuals aged 21 years and older undergoing cardiac catheterisation during 17 months at a tertiary academic cardiology centre were enrolled (troponin-positive acute coronary syndrome was exclusion criterion). The baseline data not only contain detailed phenotyping, broad biochemical parameters, genetic data, but also standardised personal and family history, a screening test for cognitive impairment, pulse wave analysis and measurements of hand grip strength, among others. Blood samples were stored in a biobank for future analyses. FINDINGS TO DATE: The mean age of the participants at enrolment was 70.9±11.1 years (70% male). Coronary angiography provided evidence of obstructive coronary artery disease (CAD) in 69.9% of participants. Those with evidence of CAD were significantly more likely to be male, inactive, diabetic and with a family history of CVD than participants without CAD.About 20% of patients had lipoprotein(a) (Lp(a)) concentrations above 106.9 nmol/L (fifth quintile). These patients had significantly increased odds of obstructive CAD compared with participants in quintiles 1-4 (crude OR 1.70, 95% CI 1.17 to 2.48, p=0.005). There was reasonable evidence that with increasing severity of CAD the odds of having elevated Lp(a) increased. We were able to replicate the established strong association between specified single nucleotide polymorphisms (SNPs) in the LPA gene (rs10455872, rs3798220 and rs186696265) and the APOE gene (rs7412), and the concentration of Lp(a), validating our phenotype database and biobank. FUTURE PLANS: Mortality information will be obtained in 2 year intervals. Follow-up phone interviews will be conducted at 3 and 6 years after enrolment. We seek to cooperate with other researchers, for example, by sharing data and biobank samples.

2.
N Engl J Med ; 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31475799

RESUMO

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary-end point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).

4.
Artigo em Inglês | MEDLINE | ID: mdl-31464553

RESUMO

Objectives: Understanding sex differences in myocarditis is crucial to improve clinical care. We sought to investigate sex differences focusing on clinical presentation and laboratory parameters. Methods: From 2011 to 2018, 77 patients were diagnosed with myocarditis according to European Society of Cardiology (ESC) criteria with available clinical, laboratory, and cardiac magnetic resonance imaging data. First, we investigated sex differences of clinical and laboratory parameters in the entire cohort of 77 patients. Second, we focused on patients with acute myocarditis (n = 51) defined as recent symptom onset (≤10 days). Results: Myocarditis was present in 63 men (82%) and 14 women (18%). While men most frequently presented with chest pain (78%), a considerable amount of women presented with dyspnea as the only symptom (40%). Within the entire cohort, only creatinine kinase (CK) was higher in men versus women (364 ± 286 vs. 147 ± 148 U/L, p = 0.007), while in patients with acute myocarditis both CK and myoglobin (Mb) were higher in men versus women (CK: 327 ± 223 vs. 112 ± 65 U/L, p = 0.004 and Mb: 111 ± 126 vs. 25 ± 29 µg/L, p = 0.04). No sex differences were found for high-sensitivity troponin T, C-reactive protein, and NT-probrain natriuretic peptide. Conclusions: This is the first study reporting sex differences in clinical presentation and routine laboratory parameters in myocarditis. While clinical presentation appeared to be subtle in women with dyspnea being the only presenting symptom of myocarditis in a considerable part, men typically complained of chest pain. Similarly to observations in myocardial infarction, atypical symptoms and underdiagnosis may be a cause for under-representation of women in cohorts of myocarditis.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31448867

RESUMO

OBJECTIVES: We sought to compare the procedural and clinical performance of dual- versus single-catheter strategy for transradial coronary angiography. BACKGROUND: The radial artery (RA) is recommended as the vascular access of choice in patients undergoing coronary angiography and intervention. The procedural and clinical performance of dual- versus single-catheter strategy in patients undergoing transradial coronary angiography remains a matter of debate. METHODS: This is a study-level meta-analysis of randomized trials. The primary outcome was procedure time. The main secondary outcome was fluoroscopy time. Other outcomes of interest were contrast volume, crossover to other catheter strategy and RA spasm. RESULTS: A total of 2,062 patients (978 randomly assigned to dual-catheter and 1,084 to single-catheter strategy) included in seven trials were available for the quantitative synthesis. A dual-catheter strategy was associated with procedure time (standardized mean difference [95% confidence intervals (CI)], 0.55 [-0.69, 1.78]; p = .32), fluoroscopy time (-0.36 [-2.39, 1.67]; p = .68) and contrast volume (-0.93 [-3.79, 1.94]; p = .44) comparable to a single-catheter strategy. The risk for crossover was lower (risk ratio [95% CI], 0.14 [0.03, 0.70]; p = .025) while the risk for RA spasm was higher (1.81 [1.54, 2.12]; p < .001) among patients assigned to dual- versus single-catheter strategy. CONCLUSIONS: This meta-analysis provides evidence for a comparable procedural performance of either dual- or single-catheter strategy for transradial coronary angiography. The fewer crossovers with dual-catheter strategy occur at the expense of more frequent radial artery spasm.

6.
JACC Cardiovasc Imaging ; 12(7 Pt 1): 1294-1296, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31272610
7.
Int J Cardiol ; 292: 73-77, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31256990

RESUMO

BACKGROUND: The obesity paradox has been recognized in patients with cardiovascular disease. The association between obesity and outcomes in elderly patients undergoing percutaneous coronary intervention (PCI) has not been investigated, yet. METHODS: A total of 990 elderly (≥80 years) patients undergoing PCI at our institution between January 2009 and December 2017 and with available data on body mass index (BMI) were divided according to BMI tertiles (lowest BMI tertile: ≪24.1 kg/m2, middle BMI tertile: 24.1-27.2 kg/m2, and highest BMI tertile: ≫27.2 kg/m2). The primary endpoint was all-cause mortality at a median follow-up of 233 [34-862] days. RESULTS: All-cause mortality was 11.2%, 7.6%, and 5.8% in the lowest, the middle, and the highest BMI tertiles (Log Rank p = 0.008). Belonging to the lowest BMI tertile was associated with an increased risk of all-cause mortality (HR 2.14, 95% CI 1.23-3.73, p = 0.007), and associations remained significant after multivariable adjustments (adjusted HR 1.92, 95% CI 1.05-3.52, p = 0.03). While belonging to the lowest BMI tertile was independently associated with an increased all-cause mortality in patients with acute coronary syndromes (HR 2.32, 95% CI 1.24-4.35, p = 0.009; adjusted HR 2.40, 95% CI 1.19-4.84, p = 0.01), relations were not significant in patients with stable coronary artery disease (HR 1.32, 95% CI 0.38-4.56, p = 0.67; adjusted HR 0.80, 95% CI 0.21-3.05, p = 0.75). CONCLUSIONS: In elderly (≥80 years) patients undergoing PCI, belonging to the lowest BMI tertile was associated with an increased mortality, mainly in acute coronary syndromes. Hence, the BMI should be incorporated into the risk stratification of elderly patients with coronary artery disease.

8.
J Electrocardiol ; 56: 38-42, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31255952

RESUMO

BACKGROUND: Left atrial low voltage areas (LVA) are associated with increased recurrence rates of atrial fibrillation (AF) after catheter ablation and can be a potential ablation target during the procedure. Therefore, noninvasive prediction of the presence and the distribution of LVA may help physicians to predict ablation outcomes and to guide antiarrhythmic management. MATERIAL AND METHODS: Seventy-three consecutive patients with atrial fibrillation undergoing first time left atrial ablation for paroxysmal or persistent AF were enrolled. P-wave properties (amplitude and duration) were measured in all limb and precordial leads in pre-interventional sinus rhythm surface ECGs and correlated with total LVA size. LVA were detected via high density low voltage maps of the left atrium in sinus rhythm. LVA were then manually encircled, their total size was calculated and given as a percentage of the total LA surface area. RESULTS: A significant, inverse correlation with LVA size was shown for P-wave amplitude for leads I, II, aVR, aVF, V1, V4, V5 and V6. Additionally, a significant positive correlation between LVA size and P-wave duration was shown for leads V1, V2 and V3. As the strongest correlation was shown for the amplitude in lead I (R = -0.578), this lead was used to find a potential cutoff for LVA prediction. The best cut-off for a P-wave amplitude in lead I to predict severe scarring (defined as LVA size >35%, according to UTAH stadium IV) was 0.062 mV with an area-under-the receiver-operating-characteristic curve of 0.935, a sensitivity of 85% and a specificity of 88%. CONCLUSIONS: P-wave duration and amplitude show significant correlations with LVA size and may be used as a noninvasive tool to predict severe scarring. Amplitudes in lead I smaller than 0.062 mV were found to be predictive of LVA >35%.

9.
Swiss Med Wkly ; 149: w20098, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31269222

RESUMO

BACKGROUND: Systematic work-up of patients with myocardial infarction and non-obstructive coronary artery disease (MINOCA) using cardiac magnetic resonance imaging (CMR) led to a more than six-fold increase in the detection rate of myocarditis. In this study, we expanded on our prior two-year analysis by including preceding and subsequent years. METHODS: We performed a retrospective chart review of patients with angina-like symptoms and elevated high-sensitivity troponin T (TnT-hs ≥14 ng/l) but without significant coronary artery disease, from 2011 to 2017. Patients underwent CMR to test for myocarditis. From 2011 to 2015, only patients with elevated TnT-hs, no significant coronary artery disease and moderate to high clinical likelihood of suffering from myocarditis, underwent CMR. In 2016 and 2017, CMR images were obtained from all patients with MINOCA, independent of the clinical likelihood that patients were suffering from myocarditis. RESULTS: A total of 556 patients who underwent CMR (70.5% male, 57 ± 17 years, with an average left ventricular ejection fraction of 51 ± 15%) qualified for inclusion in this study’s analysis. From 2011 to 2015, 240 CMR examinations were performed, with the number increasing to 316 between 2016 and 2017. In total, myocarditis was diagnosed in 76 out of the 556 patients (13.7%). Between 2011 and 2015, the detection rate of myocarditis was 12.7 per 100,000 hospitalisations and increased 4.9-fold (p <0.0001), to 62.5 per 100,000 hospitalisations, between 2016 and 2017. CONCLUSION: A novel diagnostic algorithm led to an average 4.9-fold increase in the rate of myocarditis detection in our hospital over the two subsequent years. This highlights that myocarditis continues to be underdiagnosed when CMR is not systematically used in patients with MINOCA.  .

10.
N Engl J Med ; 380(26): 2529-2540, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31242362

RESUMO

BACKGROUND: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. METHODS: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. RESULTS: Among 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. CONCLUSIONS: A risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov numbers, NCT00470587, NCT02355457, NCT01852123, NCT01994577, and NCT03227159; and Australian New Zealand Clinical Trials Registry numbers, ACTRN12611001069943, ACTRN12610000766011, ACTRN12613000745741, and ACTRN12611000206921.).


Assuntos
Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Medição de Risco/métodos , Troponina/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade , Troponina I/sangue
11.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31036510

RESUMO

INTRODUCTION AND OBJECTIVES: Despite the efficacy of oral anticoagulant (OAC) therapy, some patients continue to have a high residual risk and develop a stroke on OAC therapy (resistant stroke [RS]), and there is a lack of evidence on the management of these patients. The aim of this study was to analyze the safety and efficacy of left atrial appendage occlusion (LAAO) as secondary prevention in patients with nonvalvular atrial fibrillation who have experienced a stroke/transient ischemic attack despite OAC treatment. METHODS: We analyzed data from the Amplatzer Cardiac Plug multicenter registry on 1047 consecutive patients with nonvalvular atrial fibrillation undergoing LAAO. Patientes with previous stroke on OAC therapy as indication for LAAO were identified and compared with patients with other indications. RESULTS: A total of 115 patients (11%) with RS were identified. The CHA2DS2-VASc and the HAS-BLED score were significantly higher in the RS group (respectively 5.5±1.5 vs 4.3±1.6; P <.001; 3.9±1.3 vs 3.1±1.2; P <.001). No significant differences were observed in periprocedural major safety events (7.8 vs 4.5%; P=.1). With a mean clinical follow-up of 16.2±12.2 months, the observed annual stroke/transient ischemic attack rate for the RS group was 2.6% (65% risk reduction) and the observed annual major bleeding rate was 0% (100% risk reduction). CONCLUSIONS: Patients with RS undergoing LAAO showed similar safety outcomes to patients without RS, with a significant reduction in stroke/transient ischemic attack and major bleeding events during follow-up. Adequately powered controlled trials are needed to further investigate the use of LAAO in RS patients.

12.
Cerebrovasc Dis Extra ; 9(1): 19-24, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039572

RESUMO

BACKGROUND: Elevated high-sensitive cardiac troponin (hs-cTn) can be found in more than 50% of the patients with acute ischemic stroke. The observational TRoponin ELevation in Acute ischemic Stroke (TRELAS) study revealed that about 25% of all stroke patients with elevated troponin had a coronary angiography-detected culprit lesion affording immediate intervention, and about 50% of all patients did not have any obstructive coronary artery disease. Given the risk of procedure-related complications, the identification of stroke patients in urgent need of invasive coronary angiography is desirable. METHODS: TRELAS patients were prospectively enrolled into this sub-study. In addition to conventional coronary angiography, a cardiac magnetic resonance imaging (MRI) at 3T was performed during the in-hospital stay after acute ischemic stroke to compare the diagnostic value of both imaging modalities. RESULTS: Nine stroke patients (median age 73 years [range 58-87]; four females; median NIH Stroke Severity score on admission 4 [range 0-6] with elevated hs-cTnT [median 74 ng/L, interquartile range 41-247] on admission) completed cardiac MRI and underwent coronary angiography. The absence of MRI-detected wall motion abnormalities and/or late gadolinium enhancement in 5 stroke patients corresponded with the exclusion of culprit lesions or significant coronary artery disease by coronary angiography. Four patients had abnormal MRI findings, whereof 2 showed evidence of myocardial infarction and in whom coronary angiography demonstrated a >70% stenosis of a coronary artery. CONCLUSIONS: The TRELAS sub-study indicates that noninvasive cardiac MRI may provide helpful information to identify stroke patients with or without acute coronary syndrome. Our findings might help to select stroke patients in urgent need of coronary angiography.

13.
Curr Cardiol Rep ; 21(6): 51, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31041621

RESUMO

PURPOSE OF REVIEW: Current guidelines on the management of patients with dyslipidemias recommend specific risk-dependent low-density lipoprotein cholesterol (LDL-C) treatment goals. Recently, several randomized clinical trials have investigated further lowering of LDL-C in addition to statin therapy using novel therapeutic approaches and examined their effects on cardiovascular (CV) risk. This review summarizes newly available data on efficacy and safety of lowering LDL-C beyond statin therapy and below current treatment targets. RECENT FINDINGS: In patients at very high risk for CV events, a significant residual risk remains when failing to achieve significant LDL-C reduction on maximally tolerated statin therapy alone. Further lowering of LDL-C, even beyond current treatment targets, has been shown to be safe and was associated with a further reduced CV risk reduction. The relative risk reduction per change in LDL-C levels has been observed to be consistent even in patient populations achieving extremely low levels of LDL-C. In patients at very high CV risk, further lowering of LDL-C beyond statin therapy and present treatment targets has been observed to further reduce CV risk, which may be foremost relevant for patients at a particular high absolute CV risk, e.g., for patients with progressive and/or very extensive coronary disease.

14.
J Am Coll Cardiol ; 73(16): 2089-2105, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31023434

RESUMO

Despite major strides in reducing cardiovascular disease (CVD) burden with modification of classic CVD risk factors, significant residual risks remain. Recent discoveries that linked intestinal microbiota and CVD have broadened our understanding of how dietary nutrients may affect cardiovascular health and disease. Although next-generation sequencing techniques can identify gut microbial community participants and provide insights into microbial composition shifts in response to physiological responses and dietary exposures, provisions of prebiotics or probiotics have yet to show therapeutic benefit for CVD. Our evolving understanding of intestinal microbiota-derived physiological modulators (e.g., short-chain fatty acids) and pathogenic mediators (e.g., trimethylamine N-oxide) of host disease susceptibility have created novel potential therapeutic opportunities for improved cardiovascular health. This review discusses the roles of human intestinal microbiota in normal physiology, their associations with CVD susceptibilities, and the potential of modulating intestinal microbiota composition and metabolism as a novel therapeutic target for CVD.

15.
Eur Heart J ; 2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31004144

RESUMO

AIMS: Heart failure with preserved ejection fraction (HFpEF) and pathological cardiac aging share a complex pathophysiology, including extracellular matrix remodelling (EMR). Protease-activated receptor 2 (PAR2) deficiency is associated with EMR. The roles of PAR1 and PAR2 have not been studied in HFpEF, age-dependent cardiac fibrosis, or diastolic dysfunction (DD). METHODS AND RESULTS: Evaluation of endomyocardial biopsies from patients with HFpEF (n = 14) revealed that a reduced cardiac PAR2 expression was associated with aggravated DD and increased myocardial fibrosis (r = -0.7336, P = 0.0028). In line, 1-year-old PAR2-knockout (PAR2ko) mice suffered from DD with preserved systolic function, associated with an increased age-dependent α-smooth muscle actin expression, collagen deposition (1.7-fold increase, P = 0.0003), lysyl oxidase activity, collagen cross-linking (2.2-fold increase, P = 0.0008), endothelial activation, and inflammation. In the absence of PAR2, the receptor-regulating protein caveolin-1 was down-regulated, contributing to an augmented profibrotic PAR1 and transforming growth factor beta (TGF-ß)-dependent signalling. This enhanced TGF-ß/PAR1 signalling caused N-proteinase (ADAMTS3) and C-proteinase (BMP1)-related increased collagen I production from cardiac fibroblasts (CFs). PAR2 overexpression in PAR2ko CFs reversed these effects. The treatment with the PAR1 antagonist, vorapaxar, reduced cardiac fibrosis by 44% (P = 0.03) and reduced inflammation in a metabolic disease model (apolipoprotein E-ko mice). Patients with HFpEF with upstream PAR inhibition via FXa inhibitors (n = 40) also exhibited reduced circulating markers of fibrosis and DD compared with patients treated with vitamin K antagonists (n = 20). CONCLUSIONS: Protease-activated receptor 2 is an important regulator of profibrotic PAR1 and TGF-ß signalling in the heart. Modulation of the FXa/FIIa-PAR1/PAR2/TGF-ß-axis might be a promising therapeutic approach to reduce HFpEF.

16.
Cardiovasc Res ; 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30924864

RESUMO

BACKGROUND: Inflammation is a key driver of atherosclerosis and myocardial infarction (MI), and beyond proteins and microRNAs (miRs), long noncoding RNAs (lncRNAs) have been implicated in inflammation control. To obtain further information on the possible role of lncRNAs in the context of atherosclerosis, we obtained comprehensive transcriptome maps of circulating immune cells (PBMCs) of early onset MI patients. One lncRNA significantly suppressed in post-MI patients was further investigated in a murine knockout model. METHODS AND RESULTS: Individual RNA-sequencing (RNA-seq) was conducted on PBMCs from 28 post-MI patients with a history of MI at age ≤50 years and stable disease ≥3 months before study participation, and from 31 healthy individuals without manifest cardiovascular disease or family history of MI as controls. RNA-seq revealed deregulated protein-coding transcripts and lncRNAs in post-MI PBMCs, among which NEAT1 was the most highly expressed lncRNA, and the only one significantly suppressed in patients. Multivariate statistical analysis of validation cohorts of 106 post-MI patients and 85 controls indicated that the PBMC NEAT1 levels were influenced (p = 0.001) by post MI status independent of statin intake, left ventricular ejection fraction, LDL or HDL cholesterol, or age. We investigated NEAT1-/- mice as a model of NEAT1 deficiency to evaluate if NEAT1 depletion may directly and causally alter immune regulation. RNA-seq of NEAT1-/- splenocytes identified disturbed expression and regulation of chemokines/receptors, innate immunity genes, TNF and caspases, and increased production of reactive oxygen species (ROS) under baseline conditions. NEAT1-/- spleen displayed anomalous Treg and TH cell differentiation. NEAT1-/- bone marrow derived macrophages (BMDMs) displayed altered transcriptomes with disturbed chemokine/chemokine receptor expression, increased baseline phagocytosis (p < 0.0001), and attenuated proliferation (p = 0.0013). NEAT1-/- BMDMs responded to LPS with increased (p < 0.0001) ROS production and disturbed phagocytic activity (p = 0.0318). Monocyte-macrophage differentiation was deregulated in NEAT1-/- bone marrow and blood. NEAT1-/- mice displayed aortic wall CD68+ cell infiltration and there was evidence of myocardial inflammation which could lead to severe and potentially life-threatening structural damage in some of these animals. CONCLUSIONS: The study indicates distinctive alterations of lncRNA expression in post-MI patient PBMCs. Regarding the monocyte-enriched NEAT1 suppressed in post-MI patients, the data from NEAT1-/- mice identify NEAT1 as a novel lncRNA-type immunoregulator affecting monocyte-macrophage functions and T cell differentiation. NEAT1 is part of a molecular circuit also involving several chemokines and interleukins persistently deregulated post-MI. Individual profiling of this circuit may contribute to identify high risk patients likely to benefit from immunomodulatory therapies. It also appears reasonable to look for new therapeutic targets within this circuit.

17.
Clin Res Cardiol ; 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30900010

RESUMO

AIMS: Patients suffering from cardiogenic shock (CS) have a high mortality and morbidity. The Impella percutaneous left-ventricular assist device (LVAD) decreases LV preload, increases cardiac output, and improves coronary blood flow. We aimed to review and meta-analyze available data comparing Impella versus intra-aortic pump (IABP) counterpulsation or medical treatment in CS due to acute myocardial infarction or post-cardiac arrest. METHODS AND RESULTS: Study-level data were analyzed. Heterogeneity was assessed using the I2 statistic. Risk rates were calculated and obtained using a random-effects model (DerSimonian and Laird). Four studies were found suitable for the final analysis, including 588 patients. Primary endpoint was short-term mortality (in-hospital or 30-day mortality). In a meta-analysis of four studies comparing Impella versus control, Impella was not associated with improved short-term mortality (in-hospital or 30-day mortality; RR 0.84; 95% CI 0.57-1.24; p = 0.38; I2 55%). Stroke risk was not increased (RR 1.00; 95% CI 0.36-2.81; p = 1.00; I22 0%), but risk for major bleeding (RR 3.11 95% CI 1.50-6.44; p = 0.002; I2 0%) and peripheral ischemia complications (RR 2.58; 95% CI 1.24-5.34; p = 0.01; I2 0%) were increased in the Impella group. CONCLUSION: In patients suffering from severe CS due to AMI, the use of Impella is not associated with improved short-time survival but with higher complications rates compared to IABP and medical treatment. Better patient selection avoiding Impella implantation in futile situations or in possible lower risk CS might be necessary to elucidate possible advantages of Impella in future studies.

18.
Am J Cardiol ; 123(11): 1806-1811, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30910227

RESUMO

Data on the prevalence of infections in patients who underwent percutaneous coronary intervention (PCI) and their impact on outcomes are scarce. In this study, a total of 644 patients ≥80 years of age who underwent PCI were stratified according to the presence/absence of infections requiring antibiotic therapy. The primary end point was major adverse cardiovascular events (MACE) after discharge, a composite of all-cause mortality, nonfatal myocardial infarction, and rehospitalization for heart failure. Median follow-up was 1.2 (interquartile range 0.1 to 3.4) years. Of the 644 patients, 186 (28.9%) had infections during index hospitalization, with 84 (13%) and 59 (9.2%) patients having pneumonia and urinary tract infections, respectively. Patients with infections were older, more often women, and had an increased prevalence of atrial fibrillation and congestive heart failure. Infections prolonged hospital stay (10 [7 to 16] vs 5 [3 to 7] days, p <0.001), but were not related to rates of MACE (20% vs 19%, adjusted hazard ratio [HR] 1.41, 95% confidence intervals 0.84 to 2.38, p = 0.20). Pneumonia was significantly associated with increased rates of MACE (27% vs 18%, adjusted HR 2.19, 95% confidence intervals 1.23 to 3.91, p = 0.008) and rehospitalization for heart failure (17% vs 10%, adjusted HR 2.66 (1.25 to 5.63, p = 0.01), whereas urinary tract infections were not. In conclusion, concomitant infections are frequent in patients ≥80 years of age who underwent PCI, and associated with an increased risk of adverse events when affecting the respiratory system.

19.
J Cachexia Sarcopenia Muscle ; 10(1): 22-34, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30920776

RESUMO

BACKGROUND: Cachexia has significant impact on the patients' quality of life and prognosis. It is frequently observed in patients with cancer, especially in advanced stages, but prevalence data for the overall population are lacking. Good quality estimates of cancer cachexia in general and for each of the major cancer types would be highly relevant for potential treatment development efforts in this field. Both the USA and European Union (EU) have implemented special clinical development rules for such rare disorders what are called 'orphan diseases'. The cut-off level for a disease to be considered an orphan disease in the USA is 200 000 people (0.06% of the population) and EU is 5 per 10 000 people (0.05% of the population). METHODS: For this systematic review, we searched at PubMed (from inception to 31 January 2018) to identify clinical studies that assessed the prevalence of cachexia in cancer patients at risk. Studies reporting the prevalence of either cancer cachexia or wasting disease in the top-10 cancer types and 4 other selected cancer types known to be particularly commonly complicated by cachexia were included in this analysis (i.e. prostate cancer, breast cancer, colorectal cancer, melanoma, endometrial cancer, thyroid cancer, urinary bladder cancer, non-hodgkin lymphoma, lung cancer, kidney and renal pelvis cancer, head and neck cancer, gastric cancer, liver cancer, and pancreatic cancer). We calculated the current burden of cancer cachexia, disease by disease, in the USA and in the EU and compared them to the current guidelines for the definition of orphan disease status. RESULTS: We estimate that in 2014 in the USA, a total of 527 100 patients (16.5 subjects per 10 000 people of the total population), and in 2013 in the EU, a total of 800 300 patients (15.8 subjects per 10 000 people of the total population) suffered from cancer cachexia (of any kind). In the 14 separately analysed cancer types, the prevalence of cancer cachexia in the USA ranged between 11 300 (0.4/10 000, gastric cancer) and 92 000 patients (2.9/10 000, lung cancer) and in the EU between 14 300 (0.3/10 000, melanoma of the skin) and 150 100 (3.0/10 000, colorectal cancer). CONCLUSIONS: The absolute number of patients affected by cancer cachexia in each cancer group is lower than the defined thresholds for orphan diseases in the USA and EU. Cancer cachexia in each subgroup separately should be considered an orphan disease.

20.
Clin Res Cardiol ; 108(8): 921-930, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30737532

RESUMO

INTRODUCTION: Transcatheter aortic valve replacement (TAVR) has become the mainstay of treatment for aortic stenosis in patients with high surgical risk. Pure aortic regurgitation (PAR) is considered a relative contraindication for TAVR; however, TAVR is increasingly performed in PAR patients with unfavorable risk profile. Herein, we aim to summarize available data on TAVR for PAR with special emphasis on "on-label" versus "off-label" TAVR devices. METHODS AND RESULTS: Pubmed was searched for studies of patients undergoing TAVR for PAR. Primary outcome was 30 day-mortality. Pooled estimated event rates were calculated. Twelve studies including a total of 640 patients were identified until December 2017. Among these, 208 (33%) patients were treated with devices with CE-mark approval for PAR ("on-label"; JenaValve and J valve). Overall, the procedural success rate was 89.9% (95% CI 81.1-96.1%; I2 80%). Major bleeding was reported in 6.4% (95% CI 2.9-10.8%; I2 48%). All-cause mortality at 30 days was 10.4% (95% CI 7.1-14.2%; I2 20%). Stroke occurred in 2.2% (95% CI 0.9-3.9%; I2 0%). A permanent pacemaker was required in 10.7% (95% CI 7.3-14.6%; I2 23%). At 30 days after TAVR, ≥ moderate AR post-interventional was observed in 11.5% (95% CI 2.9-23.6%; I2 90%). In the "on-label"-group, success rate was 93.0% (95% CI 85.9-98.1%; I2 52%). 30-day-mortality was 9.1% (95% CI 3.7-16.0%; I2 36%). More than trace AR was present in 2.8% (95% CI 0.1-7.6%; I2 0%). Compared to first-generation devices, second-generation devices were associated with significantly lower 30-day-mortality (r = - 0.10; p = 0.02), and significantly higher procedural success rates (r = 0.28; p < 0.001). Compared to other second-generation devices, the use of J valve or JenaValve was not associated with altered mortality (r = 0.04; p = 0.50), rates of > trace residual AR (r = - 0.05; p = 0.65) but with a significantly higher procedural success (r = 0.15; p = 0.042). CONCLUSION: Based on this summary of available observational data TAVR for PAR is feasible and safe in patients deemed inoperable. First-generation TAVR devices are associated with inferior outcome and should be avoided. The "on-label" use of PAR-certified TAVR devices is associated with a significantly higher procedural success rate and might be favorable compared to other second-generation devices.

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