RESUMEN
BACKGROUND: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. METHODS: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. RESULTS: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. CONCLUSIONS: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.
Asunto(s)
Adenosina Monofosfato , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Masculino , Femenino , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Persona de Mediana Edad , Método Doble Ciego , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adenosina Monofosfato/administración & dosificación , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Resultado del Tratamiento , Singapur , Ticagrelor/uso terapéutico , Ticagrelor/administración & dosificaciónRESUMEN
Despite the increasing proportion of female medical and nursing students, there is still a significant under-representation of women working as healthcare providers in interventional cardiology, with very few of them reaching senior leadership, academic positions, or acting principal investigators, as well as actively involved in company advisory boards. In this position paper, we will describe the current status of women working in interventional cardiology across Europe. We will also provide an overview of the most relevant determinants of the under-representation of women at each stage of the interventional cardiology career path and offer practical suggestions for overcoming these challenges.
Asunto(s)
Cardiología , Médicos Mujeres , Humanos , Femenino , Cardiología/educación , Europa (Continente) , Liderazgo , Personal de SaludRESUMEN
BACKGROUND: The mechanisms underlying the increased risk of bleeding that female patients with ST-segment Elevation Myocardial Infarction (STEMI) exhibit, remains unclear. The present report assessed sex-related differences in response to pre-hospital dual antiplatelet therapy (DAPT) initiation in patients with STEMI. METHODS: The COMPARE CRUSH trial randomized patients presenting with STEMI to receive a pre-hospital loading dose of crushed or integral prasugrel tablets in the ambulance. In this substudy, we compared platelet reactivity levels and the occurrence of high platelet reactivity (HPR; defined as platelet reactivity ≥208) between sexes at 4 prespecified time points after DAPT initiation, and evaluated post-PCI bleeding between groups. RESULTS: Out of 633 STEMI patients, 147 (23%) were female. Females compared with males presented with significantly higher levels of platelet reactivity and higher HPR rates at baseline (232 [IQR, 209-256] vs 195 [IQR, 171-220], P < .01, and 76% vs 41%, OR 4.58 [95%CI, 2.52-8.32], P < .01, respectively). Moreover, female sex was identified as the sole independent predictor of HPR at baseline (OR 5.67 [95%CI, 2.56-12.53], P < .01). Following DAPT initiation, levels of platelet reactivity and the incidence of HPR were similar between sexes. Post-PCI bleeding occurred more frequently in females compared with males (10% vs 2%, OR 6.02 [95%CI, 2.61-11.87], P < .01). Female sex was an independent predictor of post-PCI bleeding (OR 3.25 [95%CI, 1.09-9.72], P = .04). CONCLUSIONS: In this contemporary STEMI cohort, female STEMI patients remain at risk of bleeding complications after primary PCI. However, this is not explained by sex-specific differences in the pharmacodynamic response to pre-hospital DAPT initiation.
Asunto(s)
Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Femenino , Humanos , Masculino , Fibrinolíticos/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/uso terapéutico , Infarto del Miocardio con Elevación del ST/terapia , Resultado del TratamientoRESUMEN
The optimal treatment strategy for coronary bifurcation lesions by percutaneous coronary intervention (PCI) is complex and remains a subject of debate. Current guidelines advise a stepwise provisional approach with optional two-stent strategy. However, a two-stent strategy, both upfront and stepwise provisional, is technically demanding. Therefore, there is increasing interest in the use of drug-eluting balloons (DEB) in bifurcation lesions, mainly after a provisional approach with unsatisfactory result of the side branch. Some small pilot studies already showed that the use of DEB in bifurcation lesions is safe and feasible. However, a randomized comparison of this hybrid DEB strategy with a two-stent strategy is currently lacking. TRIAL DESIGN: The Hybrid DEB study is a prospective, multicenter, randomized controlled trial investigating noninferiority of a hybrid DEB approach, using a combination of a drug-eluting stent (DES) in the main vessel and DEB in the side branch, compared to stepwise provisional two-stent strategy in patients with true bifurcation lesions. A total of 500 patients with de novo true coronary bifurcation lesions, treated with a stepwise provisional approach and an unsatisfactory result of the side branch after main vessel stenting (≥ 70% stenosis and/or < thrombolysis in myocardial infarction III flow), will be randomized in a 1:1 ratio to receive either treatment with a DEB or with a DES in the side branch. The primary endpoint is a composite endpoint of the occurrence of all-cause death, periprocedural or spontaneous myocardial infarction and/or target vessel revascularization at the anticipated median 2-year follow-up. CONCLUSION: The Hybrid DEB study will compare in a multicenter, randomized fashion a hybrid DEB approach with a stepwise provisional two-stent strategy in patients with true bifurcation lesions. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT05731687.
Asunto(s)
Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/efectos adversos , Stents Liberadores de Fármacos/efectos adversos , Angioplastia Coronaria con Balón/efectos adversos , Estudios Prospectivos , Angiografía Coronaria/efectos adversos , Stents/efectos adversos , Infarto del Miocardio/etiología , Resultado del Tratamiento , Enfermedad de la Arteria Coronaria/complicacionesRESUMEN
The present research letter reports the 1-year clinical outcomes of the randomized COMPARE CRUSH trial, which allocated STEMI patients at first medical contact in the ambulance to receive either crushed or integral tablets of prasugrel loading dose. This trial aimed to investigate whether early enhanced antiplatelet effect constituted by the crushed potent oral P2Y12 inhibitor prasugrel could lead to improved early myocardial reperfusion and clinical outcomes.
Asunto(s)
Servicios Médicos de Urgencia , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Estudios de Seguimiento , Humanos , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Comprimidos , Resultado del TratamientoRESUMEN
AIMS: The prognostic importance of cardiac procedural myocardial injury and myocardial infarction (MI) in chronic coronary syndrome (CCS) patients undergoing elective percutaneous coronary intervention (PCI) is still debated. METHODS AND RESULTS: We analysed individual data of 9081 patients undergoing elective PCI with normal pre-PCI baseline cardiac troponin (cTn) levels. Multivariate models evaluated the association between post-PCI elevations in cTn and 1-year mortality, while an interval analysis evaluated the impact of the size of the myocardial injury on mortality. Our analysis was performed in the overall population and also according to the type of cTn used [52.0% had high-sensitivity cTn (hs-cTn)]. Procedural myocardial injury, as defined by the Fourth Universal Definition of MI (UDMI) [post-PCI cTn elevation ≥1 × 99th percentile upper reference limit (URL)], occurred in 52.8% of patients and was not associated with 1-year mortality [adj odds ratio (OR), 1.35, 95% confidence interval (CI) (0.84-1.77), P = 0.21]. The association between post-PCI cTn elevation and 1-year mortality was significant starting ≥3 × 99th percentile URL. Major myocardial injury defined by post-PCI ≥5 × 99th percentile URL occurred in 18.2% of patients and was associated with a two-fold increase in the adjusted odds of 1-year mortality [2.29, 95% CI (1.32-3.97), P = 0.004]. In the subset of patients for whom periprocedural evidence of ischaemia was collected (n = 2316), Type 4a MI defined by the Fourth UDMI occurred in 12.7% of patients and was strongly associated with 1-year mortality [adj OR 3.21, 95% CI (1.42-7.27), P = 0.005]. We also present our results according to the type of troponin used (hs-cTn or conventional troponin). CONCLUSION: Our analysis has demonstrated that in CCS patients with normal baseline cTn levels, the post-PCI cTn elevation of ≥5 × 99th percentile URL used to define Type 4a MI is associated with 1-year mortality and could be used to detect 'major' procedural myocardial injury in the absence of procedural complications or evidence of new myocardial ischaemia.
Asunto(s)
Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Intervención Coronaria Percutánea , Biomarcadores , Humanos , Intervención Coronaria Percutánea/efectos adversos , TroponinaRESUMEN
A substantial number of chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI) experience periprocedural myocardial injury or infarction. Accurate diagnosis of these PCI-related complications is required to guide further management given that their occurrence may be associated with increased risk of major adverse cardiac events (MACE). Due to lack of scientific data, the cut-off thresholds of post-PCI cardiac troponin (cTn) elevation used for defining periprocedural myocardial injury and infarction, have been selected based on expert consensus opinions, and their prognostic relevance remains unclear. In this Consensus Document from the ESC Working Group on Cellular Biology of the Heart and European Association of Percutaneous Cardiovascular Interventions (EAPCI), we recommend, whenever possible, the measurement of baseline (pre-PCI) cTn and post-PCI cTn values in all CCS patients undergoing PCI. We confirm the prognostic relevance of the post-PCI cTn elevation >5× 99th percentile URL threshold used to define type 4a myocardial infarction (MI). In the absence of periprocedural angiographic flow-limiting complications or electrocardiogram (ECG) and imaging evidence of new myocardial ischaemia, we propose the same post-PCI cTn cut-off threshold (>5× 99th percentile URL) be used to define prognostically relevant 'major' periprocedural myocardial injury. As both type 4a MI and major periprocedural myocardial injury are strong independent predictors of all-cause mortality at 1 year post-PCI, they may be used as quality metrics and surrogate endpoints for clinical trials. Further research is needed to evaluate treatment strategies for reducing the risk of major periprocedural myocardial injury, type 4a MI, and MACE in CCS patients undergoing PCI.
Asunto(s)
Enfermedad de la Arteria Coronaria , Lesiones Cardíacas , Infarto del Miocardio , Intervención Coronaria Percutánea , Biomarcadores , Consenso , Humanos , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/efectos adversos , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Early treatment with a potent oral platelet P2Y12 inhibitor is recommended in patients presenting with ST-segment-elevation myocardial infarction scheduled to undergo primary percutaneous coronary intervention (pPCI). The impact on coronary reperfusion of crushed P2Y12 inhibitor tablets, which lead to more prompt and potent platelet inhibition, is unknown. METHODS: We conducted a randomized controlled, multicenter trial in the Netherlands, enrolling patients with ST-segment-elevation myocardial infarction scheduled to undergo pPCI. Patients were randomly allocated to receive in the ambulance, before transfer, a 60-mg loading dose of prasugrel either as crushed or integral tablets. The independent primary end points were thrombolysis in myocardial infarction (TIMI) 3 flow in the infarct-related artery at initial coronary angiography, and complete (≥70%) ST-segment resolution 1 hour after pPCI. The safety end points were TIMI major and Bleeding Academic Research Consortium ≥3 bleedings. Secondary end points included platelet reactivity and ischemic outcomes. RESULTS: A total of 727 patients were assigned to either crushed or integral tablets of prasugrel loading dose. The median time from study treatment to wire-crossing during pPCI was 57 (47-70) minutes. The primary end point TIMI 3 flow in the infarct-related artery before pPCI occurred in 31.0% in the crushed group versus 32.7% in the integral group (odds ratio, 0.92 [95% CI, 0.65-1.30], P=0.64). Complete ST-segment resolution 1 hour after pPCI was present in 59.9% in the crushed group versus 57.3% in the integral group (odds ratio, 1.11 [95% CI, 0.78-1.58], P=0.55). Platelet reactivity at the beginning of pPCI, measured as P2Y12 reactivity unit, differed significantly between groups (crushed, 192 [132-245] versus integral, 227 [184-254], P≤0.01). TIMI major and Bleeding Academic Research Consortium ≥3 bleeding occurred in 0% in the crushed group versus 0.8% in the integral group, and in 0.3% in the crushed group versus 1.1% in the integral group, respectively. There were no differences observed between groups regarding ischemic events at 30 days. CONCLUSIONS: Prehospital administration of crushed prasugrel tablets does not improve TIMI 3 flow in the infarct-related artery before pPCI or complete ST-segment resolution 1 h after pPCI in patients presenting with ST-segment-elevation myocardial infarction scheduled for pPCI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296540.
Asunto(s)
Plaquetas/efectos de los fármacos , Servicios Médicos de Urgencia , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Clorhidrato de Prasugrel/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Infarto del Miocardio con Elevación del ST/terapia , Anciano , Ambulancias , Plaquetas/metabolismo , Esquema de Medicación , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Estudios Prospectivos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Infarto del Miocardio con Elevación del ST/diagnóstico , Comprimidos , Factores de Tiempo , Tiempo de Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: Dual antiplatelet therapy constitutes the cornerstone of medical treatment in patients with ST elevation myocardial infarction (STEMI). However, oral antiplatelet agents, such as prasugrel or ticagrelor, are characterized by slow gastrointestinal drug absorption in the acute phase of STEMI, leading to decreased bioavailability and therefore delayed onset of platelet inhibition. Evidence suggests that administration of crushed tablets of the P2Y12 inhibitor prasugrel improves drug absorption and achieves earlier antiplatelet effects in STEMI patients undergoing primary percutaneous coronary intervention (PCI). However, the clinical implications of these pharmacokinetic and pharmacodynamic findings are unknown. HYPOTHESIS: The present study is designed to test the hypothesis that patients presenting with STEMI planned for primary PCI will have improved markers of optimal reperfusion and clinical outcomes by prehospital administration of crushed tablets of prasugrel loading dose. STUDY DESIGN: COMPARE CRUSH (NCT03296540) is a randomized trial in a regionally organized ambulance care setting evaluating the efficacy and safety of pre-hospital loading dose with prasugrel crushed tablets versus integral tablets in approximately 674 patients presenting with STEMI planned for primary PCI. The independent primary endpoints are percentage of patients reaching thrombolysis in myocardial infarction (TIMI) flow grade 3 in the infarct-related artery at initial angiography, or achieving ≥70% ST-segment elevation resolution at 1 hour post-PCI. Secondary clinical endpoints are death, myocardial infarction, revascularization, and stent thrombosis followed up to 1 year. Moreover, the primary safety endpoint is bleeding events assessed at 48 hours. CONCLUSIONS: The COMPARE CRUSH trial will assess whether prehospital administration of loading dose prasugrel in form of crushed tablets - which is expected to provide faster platelet inhibition compared to standard treatment with integral tablets - results in improved reperfusion and clinical outcomes. RCT# NCT03296540.
Asunto(s)
Intervención Coronaria Percutánea , Clorhidrato de Prasugrel/administración & dosificación , Infarto del Miocardio con Elevación del ST/terapia , Administración Oral , Anciano , Angiografía Coronaria , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Periodo Preoperatorio , Infarto del Miocardio con Elevación del ST/diagnóstico , Resultado del TratamientoRESUMEN
Circadian patterns in ST-segment elevation myocardial infarction (STEMI) patients have been previously reported, but little is known about the impact of time dependence of symptom onset on long-term prognosis. Our study population consisted of 11,731 STEMI patients treated by primary percutaneous coronary intervention (PPCI), enrolled in the Singapore Myocardial Infarction Registry (SMIR). Analysis of STEMI incidence trends over the 24-hour period showed the highest rate of symptom onset in the morning, with the peak incidence at 09:00â¯am. Patients with symptom onset in between 00:00â¯am-5:59â¯am showed the highest prevalence of diabetes (Pâ¯=â¯.010) and anterior STEMI (Pâ¯<â¯.001) and had the longest ischemic time (Pâ¯<â¯.001). After adjusting for confounders, we found an association between time of symptom onset of STEMI and rehospitalization for heart failure (HF) at 1 year, with symptom onset between 06:00â¯pm-11:59â¯pm and 00:00â¯am-05:59â¯am having an estimated 30% to 50% higher risk of rehospitalization for HF at 1 year. Moreover, symptom onset remained a predictor of worse prognosis only in the subgroup of patients with symptoms lasting longer than 120 minutes. The results of this study demonstrate for the first time that rehospitalization for HF in STEMI patients treated with PPCI has a dependence on the time of onset of symptoms, with prolonged ischemia time playing a pivotal role. This may be an additional risk factor to identify those who warrant closer monitoring and more rigorous optimization of their treatment at follow-up, to improve their outcomes.
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Electrocardiografía , Insuficiencia Cardíaca/epidemiología , Readmisión del Paciente/tendencias , Sistema de Registros , Infarto del Miocardio con Elevación del ST/diagnóstico , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/epidemiología , Singapur/epidemiología , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
OBJECTIVES: The aim of this observational study was to determine the benefits of the novel, orally delivered P2Y12 -inhibitors (Is) in terms of angiographic endpoints and in relation to the time of the loading dose (LD) administration. BACKGROUND: The goal of ST-elevation myocardial infarction (STEMI) treatment is timely reperfusion. The P2Y12 -Is prasugrel and ticagrelor have improved the angiographic outcome of primary percutaneous coronary intervention (pPCI) and patients' prognosis. However, their onset of action is impaired in STEMI and delayed by their oral administration. METHODS: The 328 eligible patients with STEMI consecutively referred for pPCI were divided into three groups depending on the interval of "P2Y12 -I LD administration-to-balloon time": Group 2 included patients that received P2Y12 -I LD at least 60 min prior to pPCI, Group 1 within 60 min prior to pPCI, and Group 0 at the moment of pPCI. Angiographic, clinical, and biochemical parameters were evaluated. Pre- and post-pPCI TIMI flow grade (TFG) and ST resolution (STR) were used as outcome measures to determine efficacy and optimal timing of pretreatment. RESULTS: Pre-pPCI TFG improved with increasing P2Y12 -I LD administration-to-balloon time; pre-PCI TFG 0/1 was 74.5% in Group 0, 65.5% in Group 1 and 54.9% in Group 2 (P < 0.002). Post-pPCI TFG 3 results also differed significantly between the three groups: 85.2% in Group 0, 88.1% in Group 1, 97.6% in Group 2 (P < 0.013). ST resolution rates were also positively associated with longer pretreatment intervals. CONCLUSIONS: This observational study suggests that the angiographic benefit of P2Y12 -I administration is time-dependent: longer pretreatment improves coronary reperfusion in terms of pre- and post-pPCI TFG and STR.
Asunto(s)
Plaquetas/efectos de los fármacos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Clorhidrato de Prasugrel/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Receptores Purinérgicos P2Y12/efectos de los fármacos , Infarto del Miocardio con Elevación del ST/terapia , Ticagrelor/administración & dosificación , Administración Oral , Anciano , Plaquetas/metabolismo , Angiografía Coronaria , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Receptores Purinérgicos P2Y12/sangre , Medición de Riesgo , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/mortalidad , Ticagrelor/efectos adversos , Factores de Tiempo , Tiempo de Tratamiento , Resultado del TratamientoRESUMEN
Mitochondrial dysfunction plays a central role in myocardial ischemia-reperfusion (I/R) injury. Increased reactive oxygen species production, impaired electron transport chain activity, aberrant mitochondrial dynamics, Ca2+ overload, and opening of the mitochondrial permeability transition pore have been proposed as major contributory factors to mitochondrial dysfunction during myocardial I/R injury. Cardiolipin (CL), a mitochondria-specific phospholipid, plays a pivotal role in multiple mitochondrial bioenergetic processes, including respiration and energy conversion, in mitochondrial morphology and dynamics as well as in several steps of the apoptotic process. Changes in CL levels, species composition, and degree of oxidation may have deleterious consequences for mitochondrial function with important implications in a variety of pathophysiological conditions, including myocardial I/R injury. In this review, we focus on the role played by CL alterations in mitochondrial dysfunction in myocardial I/R injury. Pharmacological strategies to prevent myocardial injury during I/R targeting mitochondrial CL are also examined.
Asunto(s)
Cardiolipinas/metabolismo , Fármacos Cardiovasculares/uso terapéutico , Metabolismo Energético/efectos de los fármacos , Mitocondrias Cardíacas/efectos de los fármacos , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Humanos , Peroxidación de Lípido/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/patología , Dinámicas Mitocondriales/efectos de los fármacos , Proteínas de Transporte de Membrana Mitocondrial/efectos de los fármacos , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Poro de Transición de la Permeabilidad Mitocondrial , Mitofagia/efectos de los fármacos , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/fisiopatología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Patients with small vessel disease (SVD) are at higher risk of adverse events after PCI compared to non-SVD patients. In this subset, the use of bioresorbable vascular scaffolds (BVS) has raised particular concern. OBJECTIVE: We aimed to compare outcomes of Absorb BVS versus a 2nd-generation metallic everolimus-eluting stents (EES) in the SVD setting, by pooling patients from three large, prospective studies. METHODS: Patients with SVD (reference vessel diameter ≤2.75 mm by QCA) and treated with Absorb BVS were identified in the Italian RAI and the MAASSTAD-Absorb registries. EES controls were identified in the COMPARE II Trial. We performed a propensity-score matching using several clinical and angiographic variables. Implantation technique was not object of matching, being device-specific. RESULTS: Out of 4635 enrolled subjects, 1147 belonged to the SVD population. After matching, we obtained 337 pairs of patients. High clinical and angiographic complexity was found in both groups. Predilation and postdilation rates were significantly higher in BVS patients. No differences were found in terms of the device-oriented composite end-point at 1-year (HR = 1.08, 95%CI 0.5-2.3, P = .8) and 2-years (HR = 1.28, 95% CI: 0.68-2.43, P = .5). Notwithstanding, higher incidence of definite/probable stent thrombosis was observed in the BVS group at 1 year (HR 4.7, 95%CI 0.8-31.4, P = .08) and 2-years (HR = 8.34 95%CI 1.1-60.2, P = .04). CONCLUSION: In this propensity-matched analysis pooling SVD patients of three large prospective studies, incidence of composite device-related events was comparable between BVS and EES up to 2 years follow-up. However, higher rates of stent thrombosis were found in the BVS group.
Asunto(s)
Implantes Absorbibles , Fármacos Cardiovasculares/administración & dosificación , Enfermedad de la Arteria Coronaria/cirugía , Stents Liberadores de Fármacos , Everolimus/administración & dosificación , Metales , Intervención Coronaria Percutánea/instrumentación , Anciano , Fármacos Cardiovasculares/efectos adversos , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Trombosis Coronaria/epidemiología , Everolimus/efectos adversos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Puntaje de Propensión , Diseño de Prótesis , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: The incidence of left ventricular (LV) thrombus formation in ST-segment elevation myocardial infarction (STEMI) patients in the current era of primary percutaneous coronary intervention (PCI) is not well established. We performed a meta-analysis to assess the actual incidence and predictors of LV thrombus by cardiovascular magnetic resonance (CMR) in STEMI treated by primary PCI. METHODS: We searched MEDLINE and EMBASE databases up to February 2018. We included all studies published as a full-text article, reporting the incidence of LV thrombus by CMR within 1 month following acute STEMI in patients treated by primary PCI. A binary random-effects model was used to estimate the pooled incidence of LV thrombus. The diagnostic performance of transthoracic echocardiography (TTE) as compared with CMR was pooled to obtain the sensitivity and specificity of TTE with CMR as the gold standard. Embolic and bleeding complications of LV thrombus were also evaluated. RESULTS: Ten studies were included in the meta-analysis. The incidence of LV thrombus by CMR in all-comer STEMI patients (n = 2072) was 6.3% with 96% of LV thrombus occurring in those with anterior STEMI (12.2% incidence). When only anterior STEMI with LVEF< 50% were considered (n = 447), the incidence of LV thrombus was 19.2%. Compared with CMR, the sensitivity of TTE to detect LV thrombus was 29% with a specificity of 98%. The sensitivity of TTE increased to 70% in those with anterior STEMI and reduced LVEF. LV thrombus resolved in 88% of cases by 3 to 6 months. After 1-2 years follow-up, the embolic complication rate was similar at 1.5% (P = 0.25) but the bleeding complication rate was significantly higher (8.8% versus 0.5%, P < 0.001) in the LV thrombus group on triple therapy when compared to the no LV thrombus group on dual antiplatelet therapy. CONCLUSION: In the primary PCI era, CMR detection of an LV thrombus post-STEMI remains high with incidence of nearly 20% in anterior STEMI with depressed LVEF. Patients with LV thrombus treated by triple therapy had similar embolic complications but higher bleeding complications than those with no LV thrombus treated with dual antiplatelet therapy. A 3 month follow-up CMR scan to guide anticoagulation duration might help mitigate bleeding risk.
Asunto(s)
Cardiopatías/diagnóstico por imagen , Imagen por Resonancia Magnética , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio con Elevación del ST/cirugía , Trombosis/diagnóstico por imagen , Adulto , Anciano , Quimioterapia Combinada , Femenino , Cardiopatías/epidemiología , Cardiopatías/fisiopatología , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Valor Predictivo de las Pruebas , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/epidemiología , Infarto del Miocardio con Elevación del ST/fisiopatología , Trombosis/epidemiología , Trombosis/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
Aging is a biological process characterized by progressive decline in physiological functions, increased oxidative stress, reduced capacity to respond to stresses, and increased risk of contracting age-associated disorders. Mitochondria are referred to as the powerhouse of the cell through their role in the oxidative phosphorylation to generate ATP. These organelles contribute to the aging process, mainly through impairment of electron transport chain activity, opening of the mitochondrial permeability transition pore and increased oxidative stress. These events lead to damage to proteins, lipids and mitochondrial DNA. Cardiolipin, a phospholipid of the inner mitochondrial membrane, plays a pivotal role in several mitochondrial bioenergetic processes as well as in mitochondrial-dependent steps of apoptosis and in mitochondrial membrane stability and dynamics. Cardiolipin alterations are associated with mitochondrial bienergetics decline in multiple tissues in a variety of physiopathological conditions, as well as in the aging process. Melatonin, the major product of the pineal gland, is considered an effective protector of mitochondrial bioenergetic function. Melatonin preserves mitochondrial function by preventing cardiolipin oxidation and this may explain, at least in part, the protective role of this compound in mitochondrial physiopathology and aging. Here, mechanisms through which melatonin exerts its protective role against mitochondrial dysfunction associated with aging and age-associated disorders are discussed.
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Envejecimiento/efectos de los fármacos , Antioxidantes/farmacología , Metabolismo Energético/efectos de los fármacos , Melatonina/farmacología , Mitocondrias/metabolismo , Enfermedades Mitocondriales/prevención & control , Envejecimiento/fisiología , Animales , Humanos , Mitocondrias/efectos de los fármacosRESUMEN
Cardiolipin is a unique phospholipid which is almost exclusively located in the inner mitochondrial membrane where it is biosynthesized. Considerable progress has recently been made in understanding the role of cardiolipin in mitochondrial function and bioenergetics. This phospholipid is associated with membranes designed to generate an electrochemical gradient that is used to produce ATP, such as bacterial plasma membranes and inner mitochondrial membrane. This ubiquitous and intimate association between cardiolipin and energy transducing membranes indicates an important role for cardiolipin in mitochondrial bioenergetic processes. Cardiolipin has been shown to interact with a number of proteins, including the respiratory chain complexes and substrate carrier proteins. Over the past decade, the significance of cardiolipin in the organization of components of the electron transport chain into higher order assemblies, termed respiratory supercomplexes, has been established. Moreover, cardiolipin is involved in different stages of the mitochondrial apoptotic process, as well as in mitochondrial membrane stability and dynamics. This review discusses the current understanding of the functional role that cardiolipin plays in several reactions and processes involved in mitochondrial bioenergetics. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components.
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Cardiolipinas/metabolismo , Metabolismo Energético , Mitocondrias/metabolismo , Membranas Mitocondriales/metabolismo , Animales , Apoptosis , Transporte de Electrón , Proteínas del Complejo de Cadena de Transporte de Electrón/metabolismo , Humanos , Modelos BiológicosRESUMEN
Mitochondria are the powerhouse of the eukaryotic cell through their use of oxidative phosphorylation to generate ATP. Mitochondrial dysfunction is considered an important contributing factor in a variety of physiopathological situations such as aging, heart ischemia/reperfusion injury, diabetes and several neurodegenerative and cardiovascular diseases, as well as in cell death. Increased formation of reactive oxygen species, altered respiratory chain complexes activity and opening of the mitochondrial permeability transition pore have been suggested as possible factors responsible for impaired mitochondrial function. Therefore, preventing mitochondrial dysfunction could be an effective therapeutic strategy against cellular degenerative processes. Cardiolipin is a unique phospholipid located at the level of inner mitochondrial membrane where it plays an important role in mitochondrial bioenergetics, as well as in cell death. Cardiolipin abnormalities have been associated with mitochondrial dysfunction in a variety of pathological conditions and aging. Melatonin, the major secretory product of the pineal gland, is a well-known antioxidant agent and thus an effective protector of mitochondrial bioenergetic function. Melatonin was reported to prevent mitochondrial dysfunction from oxidative damage by preserving cardiolipin integrity, and this may explain, at least in part, the beneficial effect of this compound in mitochondrial physiopathology. In this article, mechanisms through which melatonin exerts its protective role in mitochondrial dysfunction and related disorders are reviewed.
Asunto(s)
Antioxidantes/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Melatonina/uso terapéutico , Mitocondrias/efectos de los fármacos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Animales , Antioxidantes/administración & dosificación , Cardiolipinas/metabolismo , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatología , Humanos , Melatonina/administración & dosificación , Mitocondrias/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: It has been suggested that coronary microvascular function decreases with age, irrespective of the presence of epicardial atherosclerosis. AIMS: Our aim is to quantitatively investigate the effects of age on microvascular function in patients with normal coronary arteries. METHODS: In 314 patients with angina with no obstructive coronary artery disease (ANOCA), microcirculatory function was tested using the continuous thermodilution method. In 305 patients, the association between age and both resting and hyperaemic myocardial blood flow (Q), microvascular resistance (Rµ), absolute coronary flow reserve (CFR) and microvascular resistance reserve (MRR) was assessed. In addition, patients were divided into 3 groups to test for differences based on age quartiles (≤52 years [24.9%], 53-64 years [49.2%], ≥65 years [25.9%]). RESULTS: The mean age was 59±9 years with a range from 22 to 79 years. The mean resting Q (Qrest) was not different in the 3 age groups (88±34 mL/min, 82±29 mL/min, and 86±38 mL/min, R2=0.001; p=0.62). A trend towards a decreasing mean hyperaemic Q (Qmax) was observed with increasing age (223±79 mL/min, 209±84 mL/min, 200±80 mL/min, R2=0.010; p=0.083). The mean resting Rµ (Rµ,rest) were 1,204±460 Wood units (WU), 1,260±411 WU, and 1,289±455 WU (p=0.23). The mean hyperaemic Rµ (Rµ,hyp) increased significantly with advancing age (429±149 WU, 464±164 WU, 503±162 WU, R2=0.026; p=0.005). Consequently, MRR decreased with age (3.2±1.2, 3.1±1.0, 2.9±0.9; p=0.038). This trend was present in both the patients with (n=121) and without (n=184) coronary microvascular dysfunction (CMD). CONCLUSIONS: There is an age-dependent physiological increase in minimal microvascular resistance and decrease in microvascular function, which is represented by a decreased MRR and is independent of atherosclerosis. The age-dependent decrease in MRR was present in both patients with and without CMD and was most evident in patients with smooth coronary arteries.