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2.
J Am Heart Assoc ; 9(20): e017434, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33032485

RESUMO

Background Efficacy data on drug-eluting stents (DES) versus bare-metal stents (BMS) in saphenous vein grafts are controversial. We aimed to compare DES with BMS among patients undergoing saphenous vein grafts intervention regarding long-term outcome. Methods and Results In this multinational trial, patients were randomized to paclitaxel-eluting or BMS. The primary end point was major adverse cardiac events (cardiac death, nonfatal myocardial infarction, and target-vessel revascularization at 1 year. Secondary end points included major adverse cardiac events and its individual components at 5-year follow-up. One hundred seventy-three patients were included in the trial (89 DES versus 84 BMS). One-year major adverse cardiac event rates were lower in DES compared with BMS (2.2% versus 16.0%, hazard ratio, 0.14; 95% CI, 0.03-0.64, P=0.01), which was mainly driven by a reduction of subsequent myocardial infarctions and need for target-vessel revascularization. Five-year major adverse cardiac event rates remained lower in the DES compared with the BMS arm (35.5% versus 56.1%, hazard ratio, 0.40; 95% CI, 0.23-0.68, P<0.001). A landmark-analysis from 1 to 5 years revealed a persistent benefit of DES over BMS (hazard ratio, 0.33; 95% CI, 0.13-0.74, P=0.007) in terms of target-vessel revascularization. More patients in the BMS group underwent multiple target-vessel revascularization procedures throughout the study period compared with the DES group (DES 1.1% [n=1] versus BMS 9.5% [n=8], P=0.013). Enrollment was stopped before the target sample size of 240 patients was reached. Conclusions In this randomized controlled trial with prospective long-term follow-up of up to 5 years, DES showed a better efficacy than BMS with sustained benefits over time. DES may be the preferred strategy in this patient population. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00595647.

3.
Surg Endosc ; 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32648038

RESUMO

INTRODUCTION: Endoscopic full-thickness resection (eFTR) using the full-thickness resection device (FTRD®) is a novel minimally invasive procedure that allows the resection of various lesions in the gastrointestinal tract including the colorectum. Real-world data outside of published studies are limited. The aim of this study was a detailed analysis of the outcomes of colonoscopic eFTR in different hospitals from different care levels in correlation with the number of endoscopists performing eFTR. MATERIAL AND METHODS: In this case series, the data of all patients who underwent eFTR between November 2014 and June 2019 (performed by a total of 22 endoscopists) in 7 hospitals were analyzed retrospectively regarding rates of technical success, R0 resection, and procedure-related complications. RESULTS: Colonoscopic eFTR was performed in 229 patients (64.6% men; average age 69.3 ± 10.3 years) mainly on the basis of the following indication: 69.9% difficult adenomas, 21.0% gastrointestinal adenocarcinomas, and 7.9% subepithelial tumors. The average size of the lesions was 16.3 mm. Technical success rate of eFTR was achieved in 83.8% (binominal confidence interval 78.4-88.4%). Overall, histologically complete resection (R0) was achieved in 77.2% (CI 69.8-83.6%) while histologically proven full-wall excidate was confirmed in 90.0% (CI 85.1-93.7%). Of the resectates obtained (n = 210), 190 were resected en bloc (90.5%). We did not observe a clear improvement of technical success and R0 resection rate over time by the performing endoscopists. Altogether, procedure-related complications were observed in 17.5% (mostly moderate) including 2 cases of acute gangrenous appendicitis requiring operation. DISCUSSION: In this pooled analysis, eFTR represents a feasible, effective, and safe minimally invasive endoscopic technique.

4.
Lancet Infect Dis ; 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32598869

RESUMO

BACKGROUND: In 1994, prevalence and incidence of epilepsy were high in the Itwara onchocerciasis focus (western Uganda), and cases of nodding and Nakalanga syndrome were documented. Onchocerciasis transmission was interrupted successfully in 2001. 17 years later, we re-investigated the epilepsy burden in this area. METHODS: From Dec 11 to Dec 15, 2018, a door-to-door survey was done in the three villages (Kabende Centre, Masongora South, and Rwesenene) with the highest epilepsy rates in 1994 to identify people with suspected epilepsy. Epilepsy diagnoses were confirmed by an interview and physical examination by a study clinician. The prevalence and incidence of epilepsy were measured using methods consistent with those used in 1994. Results from 2018 were compared with those from 1994. FINDINGS: The overall crude prevalence of epilepsy in the study villages decreased from 3·0% (35 of 1169) in 1994 to 1·2% (27 of 2325) in 2018 (p=0·0002), with a concomitant decrease in the proportion of people with epilepsy with unknown cause (p=0·037). Between 1994 and 2018, the overall incidence of epilepsy decreased from 418 cases per 100 000 person-years (95% CI 265-626) to 73 new cases per 100 000 person-years (32-114; p<0·0001); this reduction was more pronounced for cases having the first seizure between ages 3 years and 18 years (p<0·0001). No new case of nodding or Nakalanga syndromes had occurred since the interruption of onchocerciasis transmission. INTERPRETATION: Our findings support the existence of a negative association between onchocerciasis elimination and epilepsy burden in previously hyperendemic areas. Therefore, onchocerciasis elimination efforts should be intensified in endemic regions with a high prevalence of epilepsy, which might reduce the burden of epilepsy. FUNDING: Flemish University Development Cooperation and the European Research Council.

6.
Eur Heart J ; 41(34): 3255-3268, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32484517

RESUMO

AIMS: Takotsubo syndrome (TTS) is an acute heart failure syndrome, which shares many features with acute coronary syndrome (ACS). Although TTS was initially described with angiographically normal coronary arteries, smaller studies recently indicated a potential coexistence of coronary artery disease (CAD) in TTS patients. This study aimed to determine the coexistence, features, and prognostic role of CAD in a large cohort of patients with TTS. METHODS AND RESULTS: Coronary anatomy and CAD were studied in patients diagnosed with TTS. Inclusion criteria were compliance with the International Takotsubo Diagnostic Criteria for TTS, and availability of original coronary angiographies with ventriculography performed during the acute phase. Exclusion criteria were missing views, poor quality of angiography loops, and angiography without ventriculography. A total of 1016 TTS patients were studied. Of those, 23.0% had obstructive CAD, 41.2% had non-obstructive CAD, and 35.7% had angiographically normal coronary arteries. A total of 47 patients (4.6%) underwent percutaneous coronary intervention, and 3 patients had acute and 8 had chronic coronary artery occlusion concomitant with TTS, respectively. The presence of CAD was associated with increased incidence of shock, ventilation, and death from any cause. After adjusting for confounders, the presence of obstructive CAD was associated with mortality at 30 days. Takotsubo syndrome patients with obstructive CAD were at comparable risk for shock and death and nearly at twice the risk for ventilation compared to an age- and sex-matched ACS cohort. CONCLUSIONS: Coronary artery disease frequently coexists in TTS patients, presents with the whole spectrum of coronary pathology including acute coronary occlusion, and is associated with adverse outcome. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01947621.

7.
J Am Coll Cardiol ; 75(16): 1869-1877, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32327096

RESUMO

BACKGROUND: Takotsubo syndrome (TTS) occurs predominantly in post-menopausal women but is also found in younger patients. OBJECTIVES: This study aimed to investigate age-related differences in TTS. METHODS: Patients diagnosed with TTS and enrolled in the International Takotsubo Registry between January 2011 and February 2017 were included in this analysis and were stratified by age (younger: ≤50 years, middle-age: 51 to 74 years, elderly: ≥75 years). Baseline characteristics, hospital course, as well as short- and long-term mortality were compared among groups. RESULTS: Of 2,098 TTS patients, 242 (11.5%) patients were ≤50 years of age, 1,194 (56.9%) were 51 to 74 years of age, and 662 (31.6%) were ≥75 years of age. Younger patients were more often men (12.4% vs. 10.9% vs. 6.3%; p = 0.002) and had an increased prevalence of acute neurological (16.3% vs. 8.4% vs. 8.8%; p = 0.001) or psychiatric disorders (14.1% vs. 10.3% vs. 5.6%; p < 0.001) compared with middle-aged and elderly TTS patients. Furthermore, younger patients had more often cardiogenic shock (15.3% vs. 9.1% vs. 8.1%; p = 0.004) and had a numerically higher in-hospital mortality (6.6% vs. 3.6% vs. 5.1%; p = 0.07). At multivariable analysis, younger (odds ratio: 1.60; 95% confidence interval: 0.86 to 3.01; p = 0.14) and older age (odds ratio: 1.09; 95% confidence interval: 0.66 to 1.80; p = 0.75) were not independently associated with in-hospital mortality using the middle-aged group as a reference. There were no differences in 60-day mortality rates among groups. CONCLUSIONS: A substantial proportion of TTS patients are younger than 50 years of age. TTS is associated with severe complications requiring intensive care, particularly in younger patients.

8.
JACC Cardiovasc Interv ; 13(7): 833-842, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32171721

RESUMO

OBJECTIVES: This study sought to determine the efficacy profile and safety of recombinant human C1 esterase inhibitor (rhC1INH) in the prevention of contrast-associated acute kidney injury after elective coronary angiography. BACKGROUND: Contrast-associated acute kidney injury is caused by tubular cytotoxicity and ischemia/reperfusion injury. rhC1INH is effective in reducing renal ischemia/reperfusion injury in experimental models. METHODS: In this placebo-controlled, double-blind, single-center trial 77 patients with chronic kidney disease were randomized to receive 50 IU/kg rhC1INH before and 4 h after elective coronary angiography or placebo. The primary outcome was the peak change of urinary neutrophil gelatinase-associated lipocalin within 48 h, a surrogate marker of kidney injury. RESULTS: Median peak change of urinary neutrophil gelatinase-associated lipocalin was lower in the rhC1INH group (4.7 ng/ml vs. 22.5 ng/ml; p = 0.038) in the per-protocol population but not in the modified intention-to-treat analysis, and in patients with percutaneous coronary interventions (median, 1.8 ng/ml vs. 26.2 ng/ml; p = 0.039 corresponding to a median proportion peak change of 11% vs. 205%; p = 0.002). The incidence of a cystatin C increase ≥10% within 24 h was lower in the rhC1INH group (16% vs. 33%; p = 0.045), whereas the frequency of contrast-associated acute kidney injury was comparable. Adverse events during a 3-month follow-up were similarly distributed. CONCLUSIONS: Administration of rhC1INH before coronary angiography may attenuate renal injury as reflected by urinary neutrophil gelatinase-associated lipocalin and cystatin C. The safety profile of rhC1INH was favorable in a patient population with multiple comorbidities. (Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy in High-risk Subjects [PROTECT]; NCT02869347).

9.
J Am Heart Assoc ; 9(5): e014446, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32089049

RESUMO

Background Left bundle branch block (LBBB) is common after transcatheter aortic valve implantation (TAVI) and is an indicator of subsequent high-grade atrioventricular block (HAVB). No standardized protocol is available to identify LBBB patients at risk for HAVB. The aim of the current study was to evaluate the safety and efficacy of an electrophysiology study tailored strategy in patients with LBBB after TAVI. Methods and Results We prospectively analyzed consecutive patients with LBBB after TAVI. An electrophysiology study was performed to measure the HV-interval the day following TAVI. In patients with normal His-ventricular (HV)-interval ≤55 ms, a loop recorder was implanted (ILR-group), whereas pacemaker implantation was performed in patients with prolonged HV-interval >55 ms (PM-group). The primary end point was occurrence of HAVB during a follow-up of 12 months. Secondary end points were symptoms, hospitalizations, adverse events because of device implantation or electrophysiology study, and death. Of 373 patients screened after TAVI, 56 patients (82±6 years, 41% male) with LBBB were included. HAVB occurred in 4 of 41 patients (10%) in the ILR-group and in 8 of 15 patients (53%) in the PM-group (P<0.001). We did not identify other predictors for HAVB than the HV interval. The negative predictive value for the cut-off of HV 55 ms to detect HAVB was 90%. No HAVB-related syncope occurred in the 2 groups. Conclusions An electrophysiology study tailored strategy to LBBB after TAVI with a cut-off of HV >55 ms is a feasible and safe approach to stratify patients with regard to developing HAVB during a follow-up of 12 months.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31990323

RESUMO

AIMS: We assessed morphological features of near-infrared spectroscopy (NIRS)-detected lipid-rich plaques (LRPs) by using optical coherence tomography (OCT) and intravascular ultrasound (IVUS). METHODS AND RESULTS: IVUS-NIRS and OCT were performed in the two non-infarct-related arteries (non-IRAs) in patients undergoing percutaneous coronary intervention for treatment of an acute coronary syndrome. A lesion was defined as the 4 mm segment with the maximum amount of lipid core burden index (maxLCBI4mm) of each LRP detected by NIRS. We divided the lesions into three groups based on the maxLCBI4mm value: <250, 250-399, and ≥400. OCT analysis and IVUS analysis were performed blinded for NIRS. We measured fibrous cap thickness (FCT) by using a semi-automated method. A total of 104 patients underwent multimodality imaging of 209 non-IRAs. NIRS detected 299 LRPs. Of those, 41% showed a maxLCBI4mm <250, 39% a maxLCBI4mm 251-399, and 19% a maxLCBI4mm ≥400. LRPs with a maxLCBI4mm ≥400, as compared with LRPs with a maxLCBI4mm 250-399 and <250, were more frequently thin-cap fibroatheroma (TCFA) (42.1% vs. 5.1% and 0.8%; P < 0.001) with a smaller minimum FCT (80 µm vs. 110 µm and 120 µm; P < 0.001); a higher IVUS-derived percent atheroma volume (53% vs. 53% and 44%; P < 0.001) and a higher remodelling index (1.08 vs. 1.02 and 1.01; P < 0.001). MaxLCBI4mm correlated with OCT-derived FCT (r = 0.404; P < 0.001) and was the best predictor for TCFA with an optimal cut-off value of 401 (area under the curve = 0.882; P < 0.001). CONCLUSION: LRPs with increasing maxLCBI4mm exhibit OCT and IVUS features of presumed plaque vulnerability including TCFA morphology, increased plaque burden, and positive remodelling.

11.
Ann Intern Med ; 172(3): 175-185, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31905377

RESUMO

Background: The optimal noninvasive method for surveillance in symptomatic patients with stable coronary artery disease (CAD) is unknown. Objective: To apply a novel approach using very low concentrations of high-sensitivity cardiac troponin I (hs-cTnI) for exclusion of inducible myocardial ischemia in symptomatic patients with CAD. Design: Prospective diagnostic cohort study. (ClinicalTrials.gov: NCT01838148). Setting: University hospital. Patients: 1896 consecutive patients with CAD referred with symptoms possibly related to inducible myocardial ischemia. Measurements: Presence of inducible myocardial ischemia was adjudicated using myocardial perfusion imaging with single-photon emission computed tomography, as well as coronary angiography and fractional flow reserve measurements where available. Staff blinded to adjudication measured circulating hs-cTn concentrations. An hs-cTnI cutoff of 2.5 ng/L, derived previously in mostly asymptomatic patients with CAD, was assessed. Predefined target performance criteria were at least 90% negative predictive value (NPV) and at least 90% sensitivity for exclusion of inducible myocardial ischemia. Sensitivity analyses were based on measurements with an hs-cTnT assay and an alternative hs-cTnI assay with even higher analytic sensitivity (limit of detection, 0.1 ng/L). Results: Overall, 865 patients (46%) had inducible myocardial ischemia. The hs-cTnI cutoff of 2.5 ng/L provided an NPV of 70% (95% CI, 64% to 75%) and a sensitivity of 90% (CI, 88% to 92%) for exclusion of inducible myocardial ischemia. No hs-cTnI cutoff reached both performance characteristics predefined as targets. Similarly, using the alternative assays for hs-cTnI or hs-cTnT, no cutoff achieved the target performance: hs-cTnT concentrations less than 5 ng/L yielded an NPV of 66% (CI, 59% to 72%), and hs-cTnI concentrations less than 2 ng/L yielded an NPV of 68% (CI, 62% to 74%). Limitation: Data were generated in a large single-center diagnostic study using central adjudication. Conclusion: In symptomatic patients with CAD, very low hs-cTn concentrations, including hs-cTnI concentrations less than 2.5 ng/L, do not generally allow users to safely exclude inducible myocardial ischemia. Primary Funding Source: European Union, Swiss National Science Foundation, Kommission für Technologie und Innovation (Innosuisse), Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel, University Hospital Basel, Roche, Abbott, and Singulex.


Assuntos
Doença da Artéria Coronariana/sangue , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico , Troponina I/sangue , Troponina T/sangue , Idoso , Biomarcadores/sangue , Estudos de Coortes , Angiografia Coronária , Feminino , Reserva Fracionada de Fluxo Miocárdico , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio , Valor Preditivo dos Testes , Tomografia Computadorizada de Emissão de Fóton Único
12.
Clin Res Cardiol ; 109(9): 1114-1124, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31993736

RESUMO

BACKGROUND: The randomized BASKET-SMALL 2 trial showed non-inferiority for treatment with drug-coated balloon (DCB) compared with drug-eluting stents (DES) in patients undergoing percutaneous coronary intervention (PCI) for de novo lesions in small coronary arteries regarding clinical endpoints at 1 year. In this predefined substudy, we investigated the angiographic findings in patients undergoing a clinically indicated follow-up angiography during the study phase. METHODS: Eight-hundred and eighty-three patients underwent PCI with either DES or DCB in a culprit vessel < 3 mm in diameter for stable coronary artery disease or acute coronary syndrome. Event-driven re-angiographies and the corresponding images at baseline were analyzed for angiographic endpoints. RESULTS: One-hundred and eleven patients (117 lesions, 66 DES versus 51 DCB) presented for an unscheduled re-angiography at median 5.7 months after the index procedure. At baseline, mean reference vessel diameter was 2.05 mm and the residual in-segment stenosis after the index procedure was less in DES compared to DCB (23.7% vs 33.8%, p = 0.001). At follow-up angiography, diameter stenosis in the DES group (29.0%) was still somewhat smaller than after DCB angioplasty (35.8%) when adjusting for time since PCI (p = 0.047), whereas lumen loss (LL) did not differ between the two treatment arms (LL-DES 0.06 mm vs LL-DCB 0.10 mm, p = 0.20). Eight patients following DES implantation presented with a complete occlusion of the target lesion compared to no occlusion in the DCB group (p = 0.009). CONCLUSIONS: The clinically indicated follow-up angiography within 1 year showed no difference in LL. Complete thrombotic vessel occlusions were found only in the DES group. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov ; number, NCT01574534.

13.
Expert Opin Drug Deliv ; 17(2): 201-211, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31918593

RESUMO

Introduction: Newer-generation drug-eluting stents (DES) are the standard of care for the treatment of symptomatic coronary artery disease. However, their efficacy is limited by in-stent restenosis and stent thrombosis. Drug-coated balloons (DCB) are a treatment option for in-stent-restenosis and for certain clinical and anatomical situations in de novo diseases such as small coronary arteries, bifurcation lesions, and high bleeding risk situations.Areas covered: This review summarizes the current clinical status of DCB angioplasty in coronary artery disease.Expert opinion: DCB deliver an anti-proliferative drug into the vessel wall without implanting a stent and are a promising and technique in the treatment of coronary artery disease. Several studies and meta-analysis have demonstrated the safety and efficacy of DCB angioplasty for several indications such as in-stent restenosis, small-vessel disease, and high bleeding risk. Due to absent short- and long-term complications of stent implantation and a short dual antiplatelet therapy duration, DCB angioplasty has the potential to achieve a clear role in the interventional field in clinical settings with a comparable or even a superior efficacy in comparison with DES use.

14.
Eur Heart J Qual Care Clin Outcomes ; 6(1): 81-88, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31228186

RESUMO

AIMS: The biodegradable polymer drug-eluting stents (BP-DES) offer controlled drug elution and complete degradation of the polymer over time, eventually lowering the risk for chronic inflammation and neoatherosclerosis, which can be particularly helpful in patients with diabetes. While BP-DES and durable polymer drug-eluting stents (DP-DES) have demonstrated comparable efficacy in all-comers population, their efficacy and safety in patients with diabetes remains uncertain. METHODS AND RESULTS: Electronic databases were systematically searched for randomized controlled trials (RCTs) comparing BP-DES with contemporary DP-DES in patients with diabetes. Study investigators were contacted to obtain additional data. The primary outcome was efficacy in terms of target-vessel revascularization (TVR) and target-lesion revascularization (TLR). We also evaluated the following safety outcomes separately: all-cause mortality, cardiac mortality, myocardial infarction (MI), and definite or probable stent thrombosis. Eleven RCTs including 5190 diabetic patients were included. At the longest available follow-up (mean 2.7 years), there was no significant difference in TLR [relative risk (RR): 1.02, 95% confidence interval (CI): 0.85-1.24; P = 0.80] or TVR (RR: 1.04, 95% CI: 0.81-1.34; P = 0.76). Safety outcomes of all-cause mortality, cardiac mortality, and MI were similar between the two groups. Stent thrombosis rates were also similar between BP-DES and DP-DES groups (1.66% vs. 1.83%; RR: 0.84, 95% CI: 0.54-1.31; P = 0.45). The heterogeneity was low and fixed-effect model yielded similar results. Meta-regression analysis showed no relationship between insulin requiring diabetes and difference in TLR or stent thrombosis between BP-DES and DP-DES. CONCLUSION: Overall, BP-DESs have similar safety and efficacy profiles compared to contemporary DP-DES in patients with diabetes.

15.
Arterioscler Thromb Vasc Biol ; 40(1): 279-287, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31766870

RESUMO

OBJECTIVE: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×103 cells/µL emerged as independent predictors for thrombus formation or embolism. CONCLUSIONS: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.


Assuntos
Embolia/etiologia , Sistema de Registros , Medição de Risco/métodos , Cardiomiopatia de Takotsubo/complicações , Trombose/etiologia , Idoso , Austrália/epidemiologia , Angiografia Coronária , Eletrocardiografia , Embolia/diagnóstico , Embolia/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Cardiopatias/etiologia , Ventrículos do Coração , Humanos , Incidência , Imagem Cinética por Ressonância Magnética , Masculino , Ventriculografia com Radionuclídeos , Fatores de Risco , Taxa de Sobrevida/tendências , Cardiomiopatia de Takotsubo/diagnóstico , Trombose/diagnóstico , Trombose/epidemiologia , Fatores de Tempo , Estados Unidos/epidemiologia
16.
Eur J Heart Fail ; 22(2): 330-337, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31863563

RESUMO

AIMS: The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS). METHODS AND RESULTS: Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50-3.04, P = 0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78-1.58, P = 0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting. CONCLUSION: In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621.

17.
Nat Struct Mol Biol ; 26(12): 1141-1150, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31792453

RESUMO

The small heat shock protein αA-crystallin is a molecular chaperone important for the optical properties of the vertebrate eye lens. It forms heterogeneous oligomeric ensembles. We determined the structures of human αA-crystallin oligomers by combining cryo-electron microscopy, cross-linking/mass spectrometry, NMR spectroscopy and molecular modeling. The different oligomers can be interconverted by the addition or subtraction of tetramers, leading to mainly 12-, 16- and 20-meric assemblies in which interactions between N-terminal regions are important. Cross-dimer domain-swapping of the C-terminal region is a determinant of αA-crystallin heterogeneity. Human αA-crystallin contains two cysteines, which can form an intramolecular disulfide in vivo. Oxidation in vitro requires conformational changes and oligomer dissociation. The oxidized oligomers, which are larger than reduced αA-crystallin and destabilized against unfolding, are active chaperones and can transfer the disulfide to destabilized substrate proteins. The insight into the structure and function of αA-crystallin provides a basis for understanding its role in the eye lens.


Assuntos
Cadeia A de alfa-Cristalina/química , Microscopia Crioeletrônica , Humanos , Cristalino/química , Modelos Moleculares , Oxirredução , Conformação Proteica , Multimerização Proteica , Desdobramento de Proteína , Cadeia A de alfa-Cristalina/ultraestrutura
18.
J Am Heart Assoc ; 8(22): e013607, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31696762

RESUMO

Background The choice of optimal drug-eluting stent therapy for patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention remains uncertain. We aimed to assess the long-term clinical outcomes after percutaneous coronary intervention with biodegradable polymer sirolimus-eluting stents (BP-SES) versus durable polymer everolimus-eluting stents (DP-EES) in patients with DM. Methods and Results In a prespecified subgroup analysis of the BIOSCIENCE (Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularization) trial (NCT01443104), patients randomly assigned to ultrathin-strut BP-SES or thin-strut DP-EES were stratified according to diabetic status. The primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization, at 5 years. Among 2119 patients, 486 (22.9%) presented with DM. Compared with individuals without DM, patients with DM were older and had a greater baseline cardiac risk profile. In patients with DM, target lesion failure at 5 years occurred in 74 patients (cumulative incidence, 31.0%) treated with BP-SES and 57 patients (25.8%) treated with DP-EES (risk ratio, 1.23; 95% CI, 0.87-1.73 [P=0.24]). In individuals without DM, target lesion failure at 5 years occurred in 124 patients (16.8%) treated with BP-SES and 132 patients (16.8%) treated with DP-EES (risk ratio, 0.98; 95% CI, 0.77-1.26 [P=0.90; P for interaction=0.31]). Cumulative 5-year incidence rates of cardiac death, target vessel myocardial infarction, clinically indicated target lesion revascularization, and definite stent thrombosis were similar among patients with DM treated with BP-SES or DP-EES. There was no interaction between diabetic status and treatment effect of BP-SES versus DP-EES. Conclusions In a prespecified subgroup analysis of the BIOSCIENCE trial, we found no difference in clinical outcomes throughout 5 years between patients with DM treated with ultrathin-strut BP-SES or thin-strut DP-EES. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01443104.

19.
J Am Heart Assoc ; 8(21): e011194, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31672100

RESUMO

Background Left ventricular (LV) recovery in takotsubo syndrome (TTS) occurs over a wide-ranging interval, varying from hours to weeks. We sought to investigate the clinical predictors and prognostic impact of recovery time for TTS patients. Methods and Results TTS patients from the International Takotsubo Registry were included in this study. Cut-off for early LV recovery was determined to be 10 days after the acute event. Multivariable logistic regression was used to assess factors associated with the absence of early recovery. In-hospital outcomes and 1-year mortality were compared for patients with versus without early recovery. We analyzed 406 patients with comprehensive and serial imaging data regarding time to recovery. Of these, 191 (47.0%) had early LV recovery and 215 (53.0%) demonstrated late LV improvement. Patients without early recovery were more often male (12.6% versus 5.2%; P=0.011) and presented more frequently with typical TTS (76.3% versus 67.0%, P=0.040). Cardiac and inflammatory markers were higher in patients without early recovery than in those with early recovery. Patients without early recovery showed unfavorable 1-year outcome compared with patients with early recovery (P=0.003). On multiple logistic regression, male sex, LV ejection fraction <45%, and acute neurologic disorders were associated with the absence of early recovery. Conclusions TTS patients without early LV recovery have different clinical characteristics and less favorable 1-year outcome compared with patients with early recovery. The factors associated with the absence of early recovery included male sex, reduced LV ejection fraction, and acute neurologic events. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

20.
BMC Cardiovasc Disord ; 19(1): 226, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619181

RESUMO

BACKGROUND: The new generation thinner-strut silicon carbide (SiC) coated cobalt chromium (CoCr) bare-metal stents (BMS) are designed to accelerate rapid endothelialisation and reduce thrombogenicity when implanted in coronary arteries. However, smaller studies suggest higher rates of symptomatic restenosis in patients receiving the newer generation BMS. We investigated the efficacy of a newer generation ultrathin strut silicon-carbide coated cobalt-chromium (CoCr) BMS (SCC-BMS) as compared to an older thin-strut uncoated CoCr BMS (UC-BMS) in patients presenting with coronary artery disease requiring stenting of large vessels (≥3.0 mm). METHODS: All patients randomized to SCC- (n = 761) or UC-BMS (n = 765) in the two BASKET-PROVE trials were included. Design, patients, interventions and follow-up were similar between trials except differing regimens of dual antiplatelet therapy. The primary endpoint was clinically driven target-vessel revascularization within 24 months. Safety endpoints of cardiac death, non-fatal myocardial infarction (MI), and definite/probable stent thrombosis (ST) were also assessed. We used inverse probability weighted proportional hazards Cox regressions adjusting for known confounders. RESULTS: Demographics, clinical presentation, and risk factors were comparable between the groups, but patients receiving SCC-BMS underwent less complex procedures. The risk for clinically driven TVR was increased om the SCC-BMS group compared to the UC-BMS group (cumulative incidence, 10.6% vs. 8.4%; adjusted relative hazard [HR], 1.49 [95% CI, 1.05-2.10]). No differences in safety endpoints were detected, cardiac death (1.6% vs. 2.8%; HR, 0.62 [CI, 0.30-1.27]), non-fatal MI (3.2% vs. 2.5%; HR, 1.56 [CI, 0.83-2.91]), and definite/probable ST (0.8% vs. 1.1%; HR, 1.17 [CI, 0.39-3.50]). Differences in strut thickness between the two stents did not explain the association between stent type and clinically driven TVR. CONCLUSIONS: In patients requiring stenting of large coronary arteries, use of the newer generation SCC-BMS was associated with a higher risk of clinically driven repeat revascularization compared to the UC-BMS with no signs of an offsetting safety benefit.

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