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1.
Eur Heart J Case Rep ; 7(9): ytad444, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37719005

RESUMO

Background: The evaluation of a three-dimensional structure with a two-dimensional imaging technique makes intracoronary diagnostic techniques essential, especially in the setting of acute myocardial infarction (AMI) when no apparent coronary lesions are detected. Expert consensus recommend their use in certain scenarios such as angiographically ambiguous disease and identification of the culprit lesion. Although both intravascular ultrasound and optical coherence tomography (OCT) allow the characterization of the atherosclerotic plaque and assess the immediate and long-term results of stent implantation, they have their own benefits and limitations that make them ideal for different types of coronary lesions. Case summary: We present the case of a lateral ST-elevation myocardial infarction with no evident coronary lesions in angiography, in which OCT not only allowed us to confirm a diagonal branch occlusion, but it also became crucial to locate the occlusion point and to guide the procedure, allowing complete revascularization of the culprit lesion that otherwise could have been missed. Discussion: To know the actual limitations of conventional coronary angiography to adequately assess coronary disease, intracoronary diagnostic techniques are key to evaluate the underlying mechanisms of the event, especially in the setting of AMI when no clear culprit lesion has been identified. They can be of great value to locate and revascularize acute occlusions that could go unnoticed on the angiogram, guiding the revascularization and stent implantation and, therefore, preventing myocardial injury that could become irreversible when coronary disease is not treated promptly.

2.
Cell Death Differ ; 29(1): 105-117, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34363019

RESUMO

The cell division cycle 25A (CDC25A) phosphatase is a key regulator of cell cycle progression that acts on the phosphorylation status of Cyclin-Cyclin-dependent kinase complexes, with an emergent role in the DNA damage response and cell survival control. The regulation of CDC25A activity and its protein level is essential to control the cell cycle and maintain genomic integrity. Here we describe a novel ubiquitin/proteasome-mediated pathway negatively regulating CDC25A stability, dependent on its phosphorylation by the serine/threonine kinase DYRK2. DYRK2 phosphorylates CDC25A on at least 7 residues, resulting in its degradation independent of the known CDC25A E3 ubiquitin ligases. CDC25A in turn is able to control the phosphorylation of DYRK2 at several residues outside from its activation loop, thus affecting DYRK2 localization and activity. An inverse correlation between DYRK2 and CDC25A protein amounts was observed during cell cycle progression and in response to DNA damage, with CDC25A accumulation responding to the manipulation of DYRK2 levels or activity in either physiological scenario. Functional data show that the pro-survival activity of CDC25A and the pro-apoptotic activity of DYRK2 could be partly explained by the mutual regulation between both proteins. Moreover, DYRK2 modulation of CDC25A expression and/or activity contributes to the DYRK2 role in cell cycle regulation. Altogether, we provide evidence suggesting that DYRK2 and CDC25A mutually control their activity and stability by a feedback regulatory loop, with a relevant effect on the genotoxic stress pathway, apoptosis, and cell cycle regulation.


Assuntos
Proteínas Serina-Treonina Quinases , Fosfatases cdc25 , Ciclo Celular , Dano ao DNA , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Fosfatases cdc25/genética , Fosfatases cdc25/metabolismo
3.
Cardiovasc Revasc Med ; 42: 114-120, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35151602

RESUMO

BACKGROUND: TiNO-coated BAS have demonstrated competitive outcomes compared to drug-eluting stents (DES). These devices allow short antiplatelet regimens and may be a good option for the growing elderly population undergoing percutaneous coronary intervention (PCI). METHODS: Multicenter observational trial in routine clinical practice. A propensity-score matched analysis compared a prospective cohort of patients ≥ 75 years undergoing PCI with BAS, with a contemporary and retrospective cohort treated with last-generation DES. The co-primary endpoints of the study were the Target-Lesion-Failure (Cardiac death, non-fatal myocardial infarction, or target lesion revascularization) and Major Adverse Cardiovascular Events (total death, non-fatal myocardial infarction, stroke, or new revascularization) at 1 year. RESULTS: Whole population included 1000 patients, and 326 patients in each group were matched for analysis. No differences in primary endpoints were found: TLF 10.4% vs. 11% (HR 0.96 (Confidence Interval 95%, 0.36-1.7; p = 0.87)) and MACE 16.3% vs. 17.2% (HR 0.98 (Confidence Interval 95%; 0.3-1.5, p = 0.93)). Patients treated with BAS received shorter antiplatelets regimens (dual antiplatelet therapy at 1 year, 25.7% vs. 70.6%, p = 0.0001), and they presented lower incidence of bleeding (3.7% vs. 11.7%, HR 0.3 (IC 95% 0.16-0.6, p = 0.001)). CONCLUSION: In this real-life registry of patients ≥ 75 years, BAS were similar to the latest-generation DES in terms of efficacy and reduced the duration of the antithrombotic therapy, lowering bleeding events.


Assuntos
Stents Farmacológicos , Infarto do Miocárdio , Intervenção Coronária Percutânea , Idoso , Stents Farmacológicos/efeitos adversos , Humanos , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Stents/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
4.
Circ Cardiovasc Interv ; 15(11): 861-871, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36111801

RESUMO

BACKGROUND: There is little information available on agreement between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) in left main coronary artery (LMCA) intermediate stenosis. Besides, several meta-analyses support the use of FFR to guide LMCA revascularization, but limited information is available on iFR in this setting. Our aims were to establish the concordance between FFR and iFR in intermediate LMCA lesions, to evaluate with intravascular ultrasound (IVUS) in cases of FFR/iFR discordance, and to prospectively validate the safety of deferring revascularization based on a hybrid decision-making strategy combining iFR and IVUS. METHODS: Prospective, observational, multicenter registry with 300 consecutive patients with intermediate LMCA stenosis who underwent FFR and iFR and, in case of discordance, IVUS and minimal lumen area measurements. Primary clinical end point was a composite of cardiovascular death, LMCA lesion-related nonfatal myocardial infarction, or unplanned LMCA revascularization. RESULTS: FFR and iFR had an agreement of 80% (both positive in 67 and both negative in 167 patients); in case of disagreement (31 FFR+/iFR- and 29 FFR-/iFR+) minimal lumen area was ≥6 mm2 in 8.7% of patients with FFR+ and 14.6% with iFR+. Among the 300 patients, 105 (35%) underwent revascularization and 181 (60%) were deferred according to iFR and IVUS. At a median follow-up of 20 months, major adverse cardiac events incidence was 8.3% in the defer group and 13.3% in the revascularization group (hazard ratio, 0.71 [95% CI 0.30-1.72]; P=0.45). CONCLUSIONS: In patients with intermediate LMCA stenosis, a physiology-guided treatment decision is feasible either with FFR or iFR with moderate concordance between both indices. In case of disagreement, the use of IVUS may be useful to indicate revascularization. Deferral of revascularization based on iFR appears to be safe in terms of major adverse cardiac events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03767621.


Assuntos
Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Humanos , Prognóstico , Angiografia Coronária , Estudos Prospectivos , Constrição Patológica , Resultado do Tratamento , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/terapia , Vasos Coronários/diagnóstico por imagem , Índice de Gravidade de Doença , Ultrassonografia de Intervenção , Valor Preditivo dos Testes , Cateterismo Cardíaco
5.
PLoS One ; 16(4): e0245898, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33798205

RESUMO

BACKGROUND: We aimed to compare the performance of the recent CASTLE score to J-CTO, CL and PROGRESS CTO scores in a comprehensive database of percutaneous coronary intervention of chronic total occlusion procedures. METHODS: Scores were calculated using raw data from 1,342 chronic total occlusion procedures included in REBECO Registry that includes learning and expert operators. Calibration, discrimination and reclassification were evaluated and compared. RESULTS: Mean score values were: CASTLE 1.60±1.10, J-CTO 2.15±1.24, PROGRESS 1.68±0.94 and CL 2.52±1.52 points. The overall percutaneous coronary intervention success rate was 77.8%. Calibration was good for CASTLE and CL, but not for J-CTO or PROGRESS scores. Discrimination: the area under the curve (AUC) of CASTLE (0.633) was significantly higher than PROGRESS (0.557) and similar to J-CTO (0.628) and CL (0.652). Reclassification: CASTLE, as assessed by integrated discrimination improvement, was superior to PROGRESS (integrated discrimination improvement +0.036, p<0.001), similar to J-CTO and slightly inferior to CL score (- 0.011, p = 0.004). Regarding net reclassification improvement, CASTLE reclassified better than PROGRESS (overall continuous net reclassification improvement 0.379, p<0.001) in roughly 20% of cases. CONCLUSION: Procedural percutaneous coronary intervention difficulty is not consistently depicted by available chronic total occlusion scores and is influenced by the characteristics of each chronic total occlusion cohort. In our study population, including expert and learning operators, the CASTLE score had slightly better overall performance along with CL score. However, we found only intermediate performance in the c-statistic predicting chronic total occlusion success among all scores.


Assuntos
Oclusão Coronária/cirurgia , Intervenção Coronária Percutânea , Idoso , Área Sob a Curva , Oclusão Coronária/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
6.
EuroIntervention ; 14(16): 1668-1675, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30418157

RESUMO

AIMS: We sought to compare the effects of intracoronary administration of a fibrinolytic drug (tenecteplase) to those of a glycoprotein IIb/IIIa inhibitor (abciximab) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). METHODS AND RESULTS: In this pilot trial, 76 patients (59 male) with anterior STEMI were randomised to intracoronary infusion of reduced-dose tenecteplase or abciximab during PPCI. Angiography was repeated at 48 hours to assess corrected TIMI frame count (cTFC) and TIMI myocardial perfusion grade (TMPG). The primary endpoint was infarct size as assessed by cardiac MRI. The abciximab group showed lower cTFC (median 14.1 [IQR 9.4-17.1]) than the tenecteplase group (18.2 [10.0-28.2]) (p=0.02), and the proportion of patients with TMPG grade 2/3 was higher in the abciximab group (90.3% vs. 67.7%; p=0.03). Major cardiac and cerebrovascular event rates did not differ; however, notably, 2/38 patients in the tenecteplase group experienced subacute stent thrombosis. At four months, there were no significant differences in infarct size between the tenecteplase and abciximab groups (17.0 g [9.6-27.5] vs. 21.1 g [11.3-35.0], p=0.33). CONCLUSIONS: Intracoronary administration of tenecteplase did not reduce infarct size compared to abciximab in STEMI patients undergoing PPCI. Tenecteplase exhibited poorer myocardial reperfusion and might be associated with increased subacute stent thrombosis.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Abciximab , Anticorpos Monoclonais , Angiografia Coronária , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas , Masculino , Inibidores da Agregação Plaquetária , Tenecteplase , Resultado do Tratamento
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