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1.
Heart Fail Rev ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31396762

RESUMO

Meta-analysis on immunohistological (IHC) concepts for the detection of inflammatory cardiomyopathy (InfCM) in endomyocardial biopsies (EMB). We included 61 publications, with 10,491 patients (mean age 47.1 years; men 66%) who underwent EMB and IHC evaluation. The 460 control patients were devoid of IHC proof of InfCM. The mean IHC detection rate of InfCM was 50.8% (95% CI 47.7-53.8%; range 18.4-91.7%). A publication bias was excluded (Funnel Plot p = 0.4264). This IHC detection rate was significantly (p < 0.0001) higher compared to the histological detection of myocarditis according to the Dallas criteria (mean 8.04%; 95% CI 5.08-12.5%; subset of 3274 patients in 30 publications). However, 13 different diagnostic IHC criteria were described in the publications, with various thresholds of diverse phenotypes of quantified infiltrates, and endothelial expression of diverse cell adhesion molecules (CAM), quantified either visually or by digital image analysis (DIA). The comparison of IHC with cardiac magnetic resonance (CMR) data available in a subset of 13 publications with 1185 patients revealed a sensitivity for CMR of 69% (95% CI 58-79%), a specificity of 73% (95% CI 59-84%), and a ROC-AUC of 0.77 (95% CI 0.73-0.81). This meta-analysis encompassing 10,491 patients confirms a mean detection rate of InfCM in 50.8% of EMB, being significantly more sensitive compared to the histological Dallas criteria. IHC cannot be fully substituted by CMR. However, standardization of the diverse IHC markers and protocols seems pertinent, especially considering the published adverse prognostic impact of IHC-confirmed InfCM and its published suitability for the selection of candidates responding favorably to immunosuppression.

2.
JCI Insight ; 52019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31393858

RESUMO

Dual peroxisome proliferator-activated receptor (PPAR)α/γ agonists that were developed to target hyperlipidemia and hyperglycemia in type 2 diabetes patients, caused cardiac dysfunction or other adverse effects. We studied the mechanisms that underlie the cardiotoxic effects of a dual PPARα/γ agonist, tesaglitazar, in wild type and diabetic (leptin receptor deficient - db/db) mice. Mice treated with tesaglitazar-containing chow or high fat diet developed cardiac dysfunction despite lower plasma triglycerides and glucose levels. Expression of cardiac peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which promotes mitochondrial biogenesis, had the most profound reduction among various fatty acid metabolism genes. Furthermore, we observed increased acetylation of PGC1α, which suggests PGC1α inhibition and lowered sirtuin 1 (SIRT1) expression. This change was associated with lower mitochondrial abundance. Combined pharmacological activation of PPARα and PPARγ in C57BL/6 mice reproduced the reduction of PGC1α expression and mitochondrial abundance. Resveratrol-mediated SIRT1 activation attenuated tesaglitazar-induced cardiac dysfunction and corrected myocardial mitochondrial respiration in C57BL/6 and diabetic mice but not in cardiomyocyte-specific Sirt1-/- mice. Our data shows that drugs, which activate both PPARα and PPARγ lead to cardiac dysfunction associated with PGC1α suppression and lower mitochondrial abundance likely due to competition between these two transcription factors.

3.
Heart Lung Circ ; 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31327702

RESUMO

BACKGROUND: Due to the non-specific clinical presentation of patients with pulmonary hypertension (PH), diagnosis is often delayed, consequently resulting in limited therapeutic success and an impaired prognosis. In this trial, we analysed the plasma concentrations of novel cardiovascular biomarkers that reflect different pathobiological pathways (sST2: soluble suppression of tumorigenicity 2, H-FABP: heart type fatty acid binding protein, suPAR: soluble urokinase plasminogen activator receptor and GDF-15: growth-differentiation factor-15) potentially involved in PH associated vascular and right ventricular remodelling. Thus, these markers could contribute to the development of a non-invasive approach for diagnosis and therapy surveillance of PH patients in the future. METHODS: In total, we enrolled 162 patients in this single-centre retrospective analysis consisting of 88 patients suffering from PH and 74 controls. The latter were admitted for elective coronary angiography and coronary artery disease was excluded. Plasma samples of all patients were obtained and analysed for sST2, H-FABP, GDF-15 and suPAR serum concentrations by means of enzyme-linked immunosorbent assay (ELISA) kits (DuoSet ELISA, DY523B, DY957, DY807, DGAL30, R&D Systems, Minneapolis, MN, USA) after obtaining informed consent. RESULTS: Compared with controls, all of the investigated biomarkers were significantly elevated in patients with pulmonary hypertension (H-FABP median 3.5 ng/ml vs. median 0.0 ng/ml, p < 0.001; sST2 median 6364.6 pg/ml vs. median 5015.9 pg/ml, p = 0.004; GDF-15 median 1829.3 pg/ml vs. median 514.1 pg/ml, p < 0.001; suPAR median 4878.7 pg/ml vs. median 2227.0 pg/ml, p < 0.001). Interestingly, we found a significant difference in the biomarker concentrations of H-FABP, GDF-15 and suPAR between the five groups of pulmonary hypertension. In fact, we found that H-FABP levels were primarily elevated in group 2 and 3 PH, whereas the concentrations of GDF-15 and suPAR were primarily associated with pulmonary hypertension due to left sided heart disease (group 2). CONCLUSIONS: While sST2 constitutes a general biomarkerof pulmonary hypertension regardless of the subtype, H-FABP, GDF-15 and suPAR represent indicators of postcapillary PH. Thereby, they could constitute potential discriminators between pre- and postcapillary PH.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31156142

RESUMO

Growing evidence suggests that inflammation is crucially involved in the pathogenesis of pulmonary hypertension (PH) and consecutive right heart failure. The present study analyzed the inflammatory response in lung and right ventricle in a rat model of PH and evaluated the effects of the dual endothelin receptor antagonist (ERA) Macitentan. PH was induced by monocrotalin (60 mg/kg body weight s.c.) in Sprague-Dawley rats (PH, n = 10) and compared to healthy controls (CON, n = 10) as well as monocrotalin-induced, macitentan-treated rats (THER, n = 10). Detection of Dendritic cells (DCs), regulatory T cells (Tregs) and others as well as RT-PCR based inflammatory gene expression analysis were performed. Circulating DCs and Tregs were quantified by flow cytometry in the rat model and in PH patients (n = 70) compared to controls (n = 52). Inflammatory cells were increased in lung and right ventricular tissue, whereas DCs and Tregs were decreased in blood. Expression of 17 genes in the lung and 20 genes in the right ventricle were relevantly (>2.0 fold) regulated in the PH group. These effects were, at least in part, attenuated in response to Macitentan treatment. In humans as well as rats, immune cells showed significant correlations to clinical, echocardiographic, and haemodynamic parameters. PH is accompanied by a distinct inflammatory response in lung and right but not left ventricular tissue attenuated by Macitentan. Correlations of circulating DCs as well as tissue resident immune cells with parameters reflecting right ventricular function raise the idea of both, promising biomarkers and novel treatment strategies.

5.
Biochim Biophys Acta Mol Cell Res ; 1866(9): 1398-1411, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31150695

RESUMO

Emerging evidence suggests that arginase contributes to endothelial dysfunction in diabetes. Intracellular signaling pathways, which interplay between arginase and eNOS enzyme activity leading to the development of endothelial dysfunction in hyperglycemia are not fully understood. Here, we analyzed the possible involvement of hyperglycemia (HG) induced arginase expression in eNOS protein regulation and activity and also the impact of arginase inhibition on eNOS activity. Furthermore, the roles of p38 MAPK and Erk1/2 phosphorylation in upregulation of arginase expression and eNOS dysregulation in endothelial cells (ECs) under hyperglycemia were evaluated. Protein analysis showed a concurrent increase in arginase I expression and decrease in eNOS expression and phosphorylation at Ser1177 under HG conditions. There was no simultaneous change in phosphorylation of eNOS at Thr495 in HG. Arginase inhibition prevented increased arginase activity, restored impaired NO bioavailability and reduced superoxide anion generation. Inhibition of MAP-kinases demonstrated that, unlike Erk1/2, p38 MAPK is an upstream activator in a signaling cascade leading to increased arginase I in HG conditions. P38 MAPK protein expression and phosphorylation were increased in response to HG. In the presence of a p38 MAPK inhibitor, HG-induced arginase expression was blunted. Although Erk1/2 was activated in HG, increased arginase expression was not blocked by co-treatment with an Erk1/2 inhibitor. Activation of both, p38 MAPK and Erk1/2 in HG, induced a downregulation in eNOS activity. Hence, applying MAPK inhibitors increased eNOS phosphorylation in HG. In conclusion, these findings demonstrate contributions of arginase I in the development of endothelial cell dysfunction under HG conditions via impaired eNOS regulation, which maybe mediated by p38 MAPK.

6.
Int J Cardiol ; 291: 96-104, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31155332

RESUMO

For patients with myocardial infarct-related cardiogenic shock (CS), urgent percutaneous coronary intervention is the recommended treatment strategy to limit cardiac and systemic ischemia. However, a specific therapeutic intervention is often missing in non-ischemic CS cases. Though drug treatment with inotropes and/or vasopressors may be required to stabilize the patient initially, their ongoing use is associated with excess mortality. Coronary intervention in unstable patients often leads to further hemodynamic compromise either during or shortly after revascularization. Support devices like the intra-aortic balloon pump failed to improve clinical outcomes in infarct-related CS. Currently, more powerful and active hemodynamic support devices unloading the left ventricle such as transvalvular microaxial pumps are available and are being increasingly used. However, as for other devices large randomized trials are not yet available, and device use is based on registry data and expert consensus. In this article, a multidisciplinary group of experienced users of transvalvular microaxial pumps outlines the pathophysiological background on hemodynamic changes in CS, the available mechanical support devices, and current guideline recommendations. Furthermore, different hemodynamic situations in several case-based scenarios are used to illustrate candidate settings and to provide the theoretic and scientific rationale for left-ventricular unloading in these scenarios. Finally, organization of shock networks, monitoring, weaning, and typical complications and their prevention are discussed.

7.
J Am Heart Assoc ; 8(10): e012260, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31112430

RESUMO

Background Sepsis is the overwhelming host response to infection leading to shock and multiple organ dysfunction. Cardiovascular complications greatly increase sepsis-associated mortality. Although murine models are routinely used for preclinical studies, the benefit of using genetically engineered mice in sepsis is countered by discrepancies between human and mouse sepsis pathophysiology. Therefore, recent guidelines have called for standardization of preclinical methods to document organ dysfunction. We investigated the course of cardiac dysfunction and myocardial load in different mouse models of sepsis to identify the optimal measurements for early systolic and diastolic dysfunction. Methods and Results We performed speckle-tracking echocardiography and assessed blood pressure, plasma inflammatory cytokines, lactate, B-type natriuretic peptide, and survival in mouse models of endotoxemia or polymicrobial infection (cecal ligation and puncture, [ CLP ]) of moderate and high severity. We observed that myocardial strain and cardiac output were consistently impaired early in both sepsis models. Suppression of cardiac output was associated with systolic dysfunction in endotoxemia or combined systolic dysfunction and reduced preload in the CLP model. We found that cardiac output at 2 hours post- CLP is a negative prognostic indicator with high sensitivity and specificity that predicts mortality at 48 hours. Using a known antibiotic (ertapenem) treatment, we confirmed that this approach can document recovery. Conclusions We propose a non-invasive approach for assessment of cardiac function in sepsis and myocardial strain and strain rate as preferable measures for monitoring cardiovascular function in sepsis mouse models. We further show that the magnitude of cardiac output suppression 2 hours post- CLP can be used to predict mortality.

8.
Clin Res Cardiol ; 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30972479

RESUMO

BACKGROUND: Accurate assessment of the aortic annulus is crucial for successful transcatheter aortic valve replacement (TAVR), in particular to prevent paravalvular regurgitation (PVR). We compared aortic annular sizing using multidetector computed tomography (MDCT) and three-dimensional transoesophageal echocardiography (3-D TEE) to determine the predictive value of MDCT. METHODS AND RESULTS: All patients admitted for transfemoral TAVR [n = 227; 48.9% balloon expandable (Edwards Sapien 3); 51.1% self-expandable (Core Valve, Evolut R)] at our institution from January 2015 until December 2016 were analysed retrospectively. Aortic annular parameters were obtained either by MDCT or 3-D TEE. Additionally, we included a cohort of patients (n = 27) assessed by both MDCT and 3D TEE between October 2017 and April 2018 to enable intra-individual comparison of the two methods. Indications for TAVR were severe degenerative aortic stenosis (AS; 94.7%) or re-stenosis after surgical AVR (5.3%). 74.4% were classified as high-gradient AS. The mean age was 80 (37-94) years and 75.8% presented with NYHA III/IV. STS risk of mortality was intermediate (3.5 ± 2.3). MDCT and 3-D TEE were performed in 116 and 111 patients for aortic annulus sizing, respectively. Significantly larger implants were chosen in the CT group irrespective of prosthesis type or post-dilatation. Follow-up (median at 79 days) revealed significantly less PVR in the MDCT compared to 3-D TEE group (absence of PVR in 59.3% and 40.7%, p = 0.016), without differences in mortality. Patients without PVR or mild PVR had a better clinical performance according to NYHA class (p = 0.016). CONCLUSION: MDCT is superior to 3-D TEE in terms of sizing accuracy and clinical outcomes. Reduction of PVR after TAVR with MDCT is likely due to valve annulus undersizing by TEE.

9.
Expert Rev Med Devices ; 16(5): 429-435, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30999776

RESUMO

OBJECTIVES: To report long-term safety and efficacy of combined percutaneous LAA and PFO/ASD closure. METHODS: A retrospective study of 370 consecutive patients undergoing LAAC procedures using the Watchman (WM) device. Data were compared between 330 cases only with LAAC procedure (Group I) and 25/5 (PFO/ASD) cases with sequential procedures of LAAC and PFO/ASD closure (Group II). RESULTS: Compared to Group I, Group II had more males (86.7% vs. 65.8%, p < 0.05) and a higher rate of stroke (33.3% vs. 10.6%, p < 0.01), but there were no statistical differences in the remaining patient characteristics. During the follow-up period, there were no significant differences between the two groups in embolism events (6.1% vs. 0%, p = 0.39), device related thrombus (5.8% vs 3.3%, p = 1.0), major bleeding (9.4% vs. 6.7%, p = 1.0) and cardiac death (3.6% vs. 0%, p = 0.61). The observed rate of all thromboembolic events by Kaplan-Meier analysis was decreased by 39.9% and 100% and the observed annual rate of bleeding was reduced by 32.9% and 57.6% in Group I and Group II, respectively. CONCLUSIONS: LAAC combined with PFO/ASD closure might be an ideal choice to prevent stroke and other thrombotic complications in patients with both NVAF and PFO/ASD.


Assuntos
Procedimentos Cirúrgicos Cardiovasculares , Forame Oval Patente/cirurgia , Comunicação Interatrial/cirurgia , Idoso , Feminino , Seguimentos , Forame Oval Patente/complicações , Comunicação Interatrial/complicações , Humanos , Estimativa de Kaplan-Meier , Masculino , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento
10.
Clin Res Cardiol ; 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30949753

RESUMO

IMPORTANCE: A more precise identification of patients at "high cardiovascular risk" is preeminent in cardiovascular risk stratification. OBJECTIVE: To investigate the relationships between markers of cholesterol homeostasis, cardiovascular events and all-cause mortality. DESIGN, SETTING AND PARTICIPANTS: We quantified markers of cholesterol homeostasis by gas chromatography-mass spectrometry in 377 subjects with suspected coronary artery disease, who were not on lipid-lowering drugs at baseline. All patients were followed for occurrence of cardiovascular events and mortality over a period of 4.9 +/- 1.7 years. The standardized mortality ratio (SMR) was calculated as the ratio of the observed and the expected deaths based on the death rates of the Regional Databases Germany, and Poisson regression (rate ratio, RR) was used to compare subgroups. The SMR and RR were standardized for sex, age category and calendar period. In addition, Cox regression (Hazard ratio, HR) was used to determine the effect of co-variables on (cardiovascular) mortality within the cohort. MAIN OUTCOMES: Cardiovascular events, cardiovascular mortality and all-cause mortality. RESULTS: A total of 42 deaths were observed in 1818 person-years corresponding with an SMR of 0.99 (95% CI 0.71-1.33; p = 0.556). A fatal cardiovascular event occurred in 26 patients. Lower levels of lathosterol were associated with increased cardiovascular mortality (HR 1.59; 95% CI: 1.16-2.17; p = 0.004) and excess all-cause mortality (HR 1.41; 95% CI: 1.09-1.85; p = 0.011). Lower lathosterol tertile compared to the adjacent higher tertile was associated with 1.6 times higher all-cause mortality risk (RR 1.60; 95% CI 1.07-2.40; p for trend = 0.022). This corresponded with a 2.3 times higher mortality risk of a lathosterol-LDL ratio equal to or below the median (RR 2.29; 95% CI 1.19-4.43; p = 0.013). None of the other cholesterol homeostasis markers were associated with cardiovascular and all-cause mortality. CONCLUSIONS: In patients not on lipid-lowering agents, low serum lathosterol correlated with increased risk of cardiovascular events and excess all-cause mortality.

11.
J Card Fail ; 25(5): 380-400, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30877038

RESUMO

Dietary guidance for patients with heart failure (HF) has traditionally focused on sodium and fluid intake restriction, but dietary quality is frequently poor in patients with HF and may contribute to morbidity and mortality. Restrictive diets can lead to inadequate intake of macronutrients and micronutrients by patients with HF, with the potential for deficiencies of calcium, magnesium, zinc, iron, thiamine, vitamins D, E, and K, and folate. Although inadequate intake and low plasma levels of micronutrients have been associated with adverse clinical outcomes, evidence supporting therapeutic repletion is limited. Intravenous iron, thiamine, and coenzyme Q10 have the most clinical trial data for supplementation. There is also limited evidence supporting protein intake goals. Obesity is a risk factor for incident HF, and weight loss is an established approach for preventing HF, with a role for bariatric surgery in patients with severe obesity. However weight loss for patients with existing HF and obesity is a more controversial topic owing to an obesity survival paradox. Dietary interventions and pharmacologic weight loss therapies are understudied in HF populations. There are also limited data for optimal strategies to identify and address cachexia and sarcopenia in patients with HF, with at least 10%-20% of patients with ambulatory systolic HF developing clinically significant wasting. Gaps in our knowledge about nutrition status in patients with HF are outlined in this Statement, and strategies to address the most clinically relevant questions are proposed.

12.
Circulation ; 139(24): 2765-2777, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-30909726

RESUMO

BACKGROUND: Metabolic remodeling in heart failure contributes to dysfunctional lipid trafficking and lipotoxicity. Acyl coenzyme A synthetase-1 (ACSL1) facilitates long-chain fatty acid (LCFA) uptake and activation with coenzyme A (CoA), mediating the fate of LCFA. The authors tested whether cardiac ACSL1 overexpression aids LCFA oxidation and reduces lipotoxicity under pathological stress of transverse aortic constriction (TAC). METHODS: Mice with cardiac restricted ACSL1 overexpression (MHC-ACSL1) underwent TAC or sham surgery followed by serial in vivo echocardiography for 14 weeks. At the decompensated stage of hypertrophy, isolated hearts were perfused with 13C LCFA during dynamic-mode 13C nuclear magnetic resonance followed by in vitro nuclear magnetic resonance and mass spectrometry analysis to assess intramyocardial lipid trafficking. In parallel, acyl CoA was measured in tissue obtained from heart failure patients pre- and postleft ventricular device implantation plus matched controls. RESULTS: TAC-induced cardiac hypertrophy and dysfunction was mitigated in MHC-ACSL1 hearts compared with nontransgenic hearts. At 14 weeks, TAC increased heart weight to tibia length by 46% in nontransgenic mice, but only 26% in MHC-ACSL1 mice, whereas ACSL1 mice retained greater ejection fraction (ACSL1 TAC: 65.8±7.5%; nontransgenic TAC: 45.9±7.3) and improvement in diastolic E/E'. Functional improvements were mediated by ACSL1 changes to cardiac LCFA trafficking. ACSL1 accelerated LCFA uptake, preventing C16 acyl CoA loss post-TAC. Long-chain acyl CoA was similarly reduced in human failing myocardium and restored to control levels by mechanical unloading. ACSL1 trafficked LCFA into ceramides without normalizing the reduced triglyceride storage in TAC. ACSL1 prevented de novo synthesis of cardiotoxic C16- and C24-, and C24:1 ceramides and increased potentially cardioprotective C20- and C22-ceramides post-TAC. ACLS1 overexpression activated AMP activated protein kinase at baseline, but during TAC, prevented the reduced LCFA oxidation in hypertrophic hearts and normalized energy state (phosphocreatine:ATP) and consequently, AMP activated protein kinase activation. CONCLUSIONS: This is the first demonstration of reduced acyl CoA in failing hearts of humans and mice, and suggests possible mechanisms for maintaining mitochondrial oxidative energy metabolism by restoring long-chain acyl CoA through ASCL1 activation and mechanical unloading. By mitigating cardiac lipotoxicity, via redirected LCFA trafficking to ceramides, and restoring acyl CoA, ACSL1 delayed progressive cardiac remodeling and failure.

13.
J Heart Lung Transplant ; 38(4): 396-405, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30559034

RESUMO

BACKGROUND: Elevated blood pressure (BP) has been linked to adverse events during left ventricular assist device support. In this study we investigated the association between outpatient BP and stroke or suspected pump thrombosis among HeartMate II (HMII) recipients. METHODS: We retrospectively studied 220 HMII patients. Serial outpatient BP measurements were averaged. Patients were categorized by: (1) mean arterial pressure (MAP), high (>90 mm Hg) vs intermediate (80 mm Hg ≤ MAP ≤ 90 mm Hg) vs low (<80 mm Hg); (2) systolic BP (SBP), high (≥101 mm Hg, median) vs low; and (3) pulse pressure (PP), high (≥22 mm Hg, median) vs low. To assess visit-to-visit BP variability, patients were divided in quartiles of standard deviation of MAP and SBP. The primary end-point was the composite of stroke or suspected pump thrombosis. RESULTS: The risk for the primary end-point was increased in the high MAP group (adjusted hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.49 to 5.05, vs intermediate MAP; and 6.73, 1.9 to 23.9, vs low MAP). MAP had higher predictive value for the primary end-point compared with SBP (p = 0.05). Patients with high SBP had a higher rate of stroke (HR 2.8, 95% CI 1.09 to 7.17, vs low SBP). The combination of high SBP and low PP was associated with the highest risk for stroke. The lowest quartile of visit-to-visit MAP variability was associated with the highest risk for the primary end-point. CONCLUSIONS: Elevated outpatient BP is associated with increased risk for stroke or suspected pump thrombosis in HMII recipients. Reduced PP and low visit-to-visit BP variability may confer additional risk.

14.
Circulation ; 139(10): 1249-1258, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30586755

RESUMO

BACKGROUND: Percutaneous mechanical circulatory support devices are increasingly used in acute myocardial infarction complicated by cardiogenic shock (AMI-CS), despite limited evidence for their effectiveness. The aim of this study was to evaluate outcomes associated with use of the Impella device compared with intra-aortic balloon pump (IABP) and medical treatment in patients with AMI-CS. METHODS: Data of patients with AMI-CS treated with the Impella device at European tertiary care hospitals were collected retrospectively. All patients underwent early revascularization and received optimal medical treatment. Using IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) trial inclusion and exclusion criteria, 372 patients were identified and included in this analysis. These patients were matched to 600 patients from the IABP-SHOCK II trial. The following baseline criteria were used as matching parameters: age, sex, mechanical ventilation, ejection fraction, prior cardiopulmonary resuscitation, and lactate. Primary end point was 30-day all-cause mortality. RESULTS: In total, 237 patients treated with an Impella could be matched to 237 patients from the IABP-SHOCK II trial. Baseline parameters were similarly distributed after matching. There was no significant difference in 30-day all-cause mortality (48.5% versus 46.4%, P=0.64). Severe or life-threatening bleeding (8.5% versus 3.0%, P<0.01) and peripheral vascular complications (9.8% versus 3.8%, P=0.01) occurred significantly more often in the Impella group. Limiting the analysis to IABP-treated patients as a control group did not change the results. CONCLUSIONS: In this retrospective analysis of patients with AMI-CS, the use of an Impella device was not associated with lower 30-day mortality compared with matched patients from the IABP-SHOCK II trial treated with an IABP or medical therapy. To further evaluate this, a large randomized trial is warranted to determine the effect of the Impella device on outcome in patients with AMI-CS. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03313687.

15.
Heart Vessels ; 34(6): 976-983, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30535754

RESUMO

Peripheral arterial disease (PAD) is one of the most common manifestations of systemic atherosclerosis. The prevalence of unrecognized PAD is high, leading to a lack of opportunity to detect subjects at a high risk for cardiovascular events. Inflammatory processes play an important role in the disease initiation as well as in the disease progression. Vascular cell adhesion molecule 1 (VCAM-1), a biomarker of endothelial dysfunction, appears to be an important mediator in inflammatory processes. Therefore, we hypothesized that in patients with PAD, circulating VCAM-1 might be elevated due to its function in mediating adhesion of immune cells to the vascular endothelium in the process of endothelial dysfunction and inflammation, and, therefore, applicable as a diagnostic biomarker. A total of 126 non-consecutive patients were enrolled in this study, of whom 51 patients had typical clinical manifestations of PAD and as controls 75 patients with no history of PAD or cardiovascular disease. All serum samples were obtained either during hospitalization or during out-patient visits and analyzed for VCAM-1 by the ELISA. Compared with controls, median levels of VCAM-1 were significantly elevated in patients suffering from PAD (953 vs. 1352 pg/ml; p < 0.001). Furthermore, VCAM-1 appeared to be highly discriminative for the detection of PAD (AUC = 0.76; CI 0.67-0.83). We could not observe dynamics related to increasing disease stages according to Rutherford classes in patients with apparent PAD. VCAM-1 was shown to be a potential discriminator and biomarker for the severity of systemic atherosclerosis. In a logistic regression analysis, VCAM-1 was robustly associated with the diagnosis of PAD, even after correction for clinically relevant cofounders (namely age, arterial hypertension, diabetes and LDL levels). Thusly, VCAM-1 might serve as a biomarker for PAD screening and detection.

16.
Intensive Care Med ; 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30478622

RESUMO

PURPOSE: Changes of lactate concentration over time were reported to be associated with survival in septic patients. We aimed to evaluate delta-lactate (ΔLac) 24 h after admission (Δ24Lac) to an intensive care unit (ICU) in critically ill patients for short- and long-term prognostic relevance. METHODS: In total, 26,285 lactate measurements of 2191 patients admitted to a German ICU were analyzed. Inclusion criterion was a lactate concentration at admission above 2.0 mmol/L. Maximum lactate concentrations of day 1 and day 2 were used to calculate Δ24Lac. Follow-up of patients was performed retrospectively. Association of Δ24Lac and both in-hospital and long-term mortality were investigated. An optimal cut-off was calculated by means of the Youden index. RESULTS: Patients with lower Δ24Lac were of similar age, but clinically sicker. As continuous variable, higher Δ24Lac was associated with decreased in-hospital mortality (per 1% Δ24Lac; HR 0.987 95%CI 0.985-0.990; p < 0.001) and an optimal Δ24Lac cut-off was calculated at 19%. Δ24Lac ≤ 19% was associated with both increased in-hospital (15% vs 43%; OR 4.11; 95%CI 3.23-5.21; p < 0.001) and long-term mortality (HR 1.54 95%CI 1.28-1.87; p < 0.001), even after correction for APACHE II, need for catecholamines and intubation. We matched 256 patients with Δ24Lac ≤ 19% to case-controls > 19% corrected for APACHE II scores, baseline lactate level and sex: Δ24Lac ≤ 19% remained associated with lower in-hospital and long-term survival. CONCLUSIONS: Lower Δ24Lac was robustly associated with adverse outcome in critically ill patients, even after correction for confounders. Δ24Lac might constitute an independent, easily available and important parameter for risk stratification in the critically ill.

18.
PLoS One ; 13(10): e0204235, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30332417

RESUMO

INTRODUCTION: Amyloidosis is caused by dysregulation of protein folding resulting in systemic or organ specific amyloid aggregation. When affecting the heart, amyloidosis can cause severe heart failure, which is associated with a high morbidity and mortality. Different subtypes of cardiac amyloidosis exist e.g. transthyretin cardiac amyloidosis and senile cardiac amyloidosis. Today, diagnostics is primarily based on cardiac biopsies and no clinically used circulating blood-based biomarkers existing. Therefore, our aim was to identify circulating microRNAs in patients with different forms of amyloidosis. METHODS: Blood was collected from healthy subjects (n = 10), patients with reduced ejection fraction (EF < 35%; n = 10), patients affected by transthyretin cardiac amyloidosis (n = 13) as well as senile cardiac amyloidosis (n = 11). After performing TaqMan array profiling, promising candidates, in particular miR-99a-5p, miR-122-5p, miR-27a-3p, miR-221-3p, miR-1180-3p, miR-155-5p, miR-339-3p, miR-574-3p, miR-342-3p and miR-329-3p were validated via quantitative real time PCR. RESULTS: The validation experiments revealed a significant upregulation of miR-339-3p in patients affected with senile cardiac amyloidosis compared to controls. This corresponded to the array profiling results. In contrast, there was no deregulation in the other patient groups. CONCLUSION: MiR-339-3p was increased in blood of patients with senile cardiac amyloidosis. Therefore, miR-339-3p is a potential candidate as biomarker for senile cardiac amyloidosis in future studies. Larger patient cohorts should be investigated.

19.
Int J Cardiol Heart Vasc ; 21: 50-55, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30302369

RESUMO

Background: We sought to evaluate a temperature-guided approach of cryoballoon (CB) ablation without visualization of real-time recordings. Methods and results: We analysed 166 patients (34.9% female, 60 ±â€¯11 years) with paroxysmal or short-term persistent atrial fibrillation (AF). Comorbidities included diabetes mellitus (n = 28), coronary artery disease (n = 24), hypertension (n = 122), previous stroke or TIA > 3 months (n = 12). Cryoablation of the pulmonary veins (PV) was performed using first-generation (n = 78) and second-generation CB (n = 88). Two 5-minute freezes were performed for the first-generation and two 4-minute freezes for the second-generation CB with the intention to achieve a temperature drop below -40 °C. At 12-month follow-up, we observed overall freedom from AF in 92 patients (56.6%, mean time to AF recurrence 3.4 ±â€¯2.9 months). There was a significant difference in freedom from AF between first-generation CB (45%) and second-generation CB (67%; p < 0.005). Complications were groin hematoma (4.8%) and phrenic nerve palsy (PVP) (2.4%). PVP disappeared after 12 months in all patients. Three patients developed cardiac tamponade (1.8%) that resolved without further sequelae after pericardiocentesis. Multivariate analysis revealed that only the achieved temperature in the right inferior PV (RIPV) was a predictor of long-term freedom from AF (OR 0.9; p = 0.014). Female gender was a predictor of AF recurrence (OR 6.1; p = 0.022). Conclusion: Temperature-guided CB ablation without real-time recordings is feasible and safe without reducing the efficacy if second-generation CB is used. Deep nadir temperatures especially in the RIPV are necessary for long term-success.

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