Reperfusion Strategies in Acute Myocardial Infarction: State of the Art

Abstract ST elevation myocardial infarction (STEMI) is a highly prevalent condition worldwide. Reperfusion therapy is strongly associated with the prognosis of STEMI and must be performed with a high standard of quality and without delay. A systematic review of different reperfusion strategies for STEMI was conducted, including randomized controlled trials that included major cardiovascular events (MACE), and systematic reviews in the last 5 years through the PRISMA ( Preferred Reporting Items for Systematic Reviews and Meta-Analysis) methodology. The research was done in the PubMed and Cochrane Central Register of Controlled Trials databases, in addition to a few manual searches. After the exclusion criteria were applied, 90 articles were selected for this review. Despite the reestablishment of IRA patency in PCI for STEMI, microvascular lesions occur in a significant proportion of these patients, which can compromise ventricular function and clinical course. Several therapeutic strategies - intracoronary administration of nicorandil, nitrates, melatonin, antioxidant drugs (quercetin, glutathione), anti-inflammatory substances (tocilizumab [an inhibitor of interleukin 6], inclacumab, P-selectin inhibitor), immunosuppressants (cyclosporine), erythropoietin and ischemic pre- and post-conditioning and stem cell therapy - have been tested to reduce reperfusion injury, ventricular remodeling and serious cardiovascular events, with heterogeneous results: These therapies need confirmation in larger studies to be implemented in clinical practice

Guía práctica interinstitucional para el tratamiento del infarto agudo de miocardio / Interinstitutional clinical practice guidelines for the treatment of acute myocardial infarction

Resumen Introducción: México tiene la mortalidad más alta a 30 días por infarto agudo de miocardio (IAM), el cual constituye una de las principales causas de mortalidad en el país: 28 % versus 7.5 % del promedio de los países de la Organización para la Cooperación y el Desarrollo Económicos. Objetivo: Establecer las rutas críticas y las estrategias farmacológicas esenciales interinstitucionales para la atención de los pacientes con IAM en México, independientemente de su condición socioeconómica. Método: Se reunió a un grupo de expertos en diagnóstico y tratamiento de IAM, representantes de las principales instituciones públicas de salud de México, así como las sociedades cardiológicas mexicanas, Cruz Roja Mexicana y representantes de la Sociedad Española de Cardiología, con la finalidad de optimizar las estrategias con base en la mejor evidencia existente. Resultados: Se diseñó una guía de práctica clínica interinstitucional para el diagnóstico temprano y tratamiento oportuno del IAM con elevación del segmento ST, siguiendo el horizonte clínico de la enfermedad, con la propuesta de algoritmos que mejoren el pronóstico de los pacientes que acuden por IAM a los servicios de urgencias. Conclusión: Con la presente guía práctica, el grupo de expertos propone universalizar el diagnóstico y tratamiento en el IAM, independientemente de la condición socioeconómica del paciente.

Abstract Introduction: Mexico has the highest 30-day acute myocardial infarction (AMI) mortality rate: 28% versus 7.5% on average for the OECD countries, and it constitutes one of the main causes of mortality in the country. Objective: To establish critical pathways and essential interinstitutional pharmacological strategies for the care of patients with AMI in Mexico, regardless of their socioeconomic status. Method: A group of experts in AMI diagnosis and treatment, representatives of the main public health institutions in Mexico, as well as the Mexican cardiology societies, the Mexican Red Cross and representatives of the Spanish Society of Cardiology, were brought together in order to optimize strategies based on the best existing evidence. Results: An interinstitutional clinical practice guideline was designed for early diagnosis and timely treatment of AMI with ST elevation, following the clinical horizon of the disease, with the proposal of algorithms that improve the prognosis of patients who attend the emergency services due to an AMI. Conclusion: With these clinical practice guidelines, the group of experts proposes to universalize AMI diagnosis and treatment, regardless of patient socioeconomic status.

Dexmedetomidine pretreatment attenuates myocardial ischemia reperfusion induced acute kidney injury and endoplasmic reticulum stress in human and rat.

BACKGROUND: Patients undergoing cardiopulmonary bypass (CPB) often develop acute kidney injury (AKI) caused by myocardial ischemia reperfusion (MI/R), and this renal injury can be resolved notably by dexmedetomidine. Endoplasmic reticulum (ER) stress was reported to get involved in organ injury including AKI. OBJECTIVES: The current study aimed to address the correlation between MI/R induced AKI with ER stress and to assess the effects of dexmedetomidine pretreatment on AKI protection. METHOD: Patients selected for heart valve replacement surgery were randomly assigned to NS group (pre-anesthesia with 0.9% NaCl) and DEX group (pre-anesthesia with dexmedetomidine). Rat MI/R model was induced by occluding coronary artery for 30 min followed by 48-hour reperfusion. Rats were randomized into Sham (0.9% NaCl), I/R (MI/R + 0.9% NaCl) and I/R + DEX (MI/R + dexmedetomidine). Organ function and ER stress condition were evaluated by blood chemistry, pathology, and molecular test. RESULTS: Clinical data indicated dexmedetomidine pretreatment attenuated AKI and oxidative stress as well as postischemic myocardial injury in patients. Accordingly animal results suggested dexmedetomidine reduced cellular injury and improved postischemic myocardial and renal function. Dexmedetomidine also reduced myocardial and renal cells apoptosis and down-regulated ER stress. CONCLUSIONS: These results suggested that dexmedetomidine pretreatment attenuates MI/R injury-induced AKI by relieving the ER stress.

Impacto de la contingencia sanitaria por COVID-19 en las estrategias de reperfusión del síndrome coronario agudo / Impact of COVID-19 on reperfusion strategies for acute coronary syndromes

Resumen Las terapias de reperfusión, tales como intervención coronaria y fibrinólisis, son las principales medidas de atención en pacientes con síndromes coronarios agudos. La angioplastia primaria se considera el estándar de oro, sin embargo, en pacientes con infección por coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2), la estrategia de reperfusión más recomendada es la terapia fibrinolítica, debido al menor tiempo requerido para realizarla y menor exposición al agente infeccioso. Esta pandemia representa una problemática de contagio en el personal de salud, ya que los casos van en aumento a nivel mundial, por lo cual es importante conocer las medidas que se deben seguir a fin de evitar la enfermedad por coronavirus 2019 (COVID-19).

Abstract Reperfusion therapy is a measure of care in patients with ST-elevation myocardial infarction (STEMI), which should be performed once we have the diagnosis. Percutaneous coronary intervention is considered the gold standard, however in patients with SARS-CoV-2 infection, the reperfusion strategy is more focused on fibrinolytic therapy due to the shorter time required to perform and less exposure. This pandemic represents a contact problem in health personnel, since cases are increasing worldwide, so it is important to know the measures that must be followed to avoid coronavirus disease (COVID-19).

Desfechos clínicos de pacientes após uso de terapia fibrinolítica pré-hospitalar: revisão sistemática / Resultados clínicos de pacientes después del uso de terapia fibrinolítica prehospitalaria: revisión sistemática / Clinical outcomes of patients after using prehospital fibrinolytic therapy: a systematic review

Resumo Objetivo: Comparar desfechos clínicos de óbito, reinfarto e Acidente Vascular Encefálico (AVE) em estudos primários que avaliaram o uso da Terapia Fibrinolítica (TF) em relação à Intervenção Coronariana Percutânea Primária (ICPP) para reperfusão miocárdica em pacientes com Infarto Agudo do Miocárdio com supradesnivelamento do segmento ST (IAMCST) no atendimento pré-hospitalar. Método: Revisão sistemática de literatura com busca realizada nas bases de dados CINAHL, MEDLINE, PUBMED, Science Direct, SCOPUS e Web of Science no período de outubro a dezembro de 2017. Foram incluídos Ensaios Clínicos Randomizados, disponíveis na íntegra, em qualquer idioma, sem recorte temporal. A avaliação da elegibilidade foi realizada em duas etapas e aplicada a Escala de Jadad para avaliação metodológica dos estudos encontrados. Resultados: Foram incluídos cinco Ensaios Clínicos Randomizados. A TF pré-hospitalar apresentou taxas de mortalidade em 30 dias após a intervenção semelhantes à ICPP, enquanto que em cinco anos foram encontrados valores menores para a TF. O tratamento instituído em um período menor que duas horas dos sintomas iniciais apresentou associação com a diminuição da mortalidade quando foi utilizada a TF. O reinfarto não-fatal, acidente vascular encefálico e a hemorragia intracraniana foram maiores quando utilizada a TF, enquanto que o choque cardiogênico apresentou menor frequência. Conclusão: A TF foi mais eficaz no tratamento pré-hospitalar para a redução dos óbitos após cinco anos, entretanto, o reinfarto e o AVE ocorreram de forma semelhante na amostra analisada. O fator tempo reduziu os desfechos clínicos, principalmente quando a terapia implementada ocorreu em até duas horas após a ocorrência do IAMCST. Assim, apesar das intervenções terem apresentado desfechos semelhantes, entretanto, a TF pode representar um tratamento viável em locais onde a ICPP não pode ser alcançada em tempo hábil.

Resumen Objetivo: Comparar resultados clínicos de fallecimiento, reinfarto y accidente vascular encefálico (AVE) en estudios primarios que analizaron el uso de la terapia fibrinolítica (TF) respecto a la intervención coronaria percutánea primaria (ICPP) para reperfusión miocárdica en pacientes con infarto agudo de miocardio con supradesnivel del segmento ST (IAMCST) en la atención prehospitalaria. Método: Revisión sistemática de literatura con búsqueda realizada en las bases de datos CINAHL, MEDLINE, PUBMED, Science Direct, SCOPUS y Web of Science en el período de octubre a diciembre de 2017. Se incluyeron ensayos clínicos aleatorizados, con texto completo disponible, en cualquier idioma, sin recorte temporal. El análisis de elegibilidad se realizó en dos etapas y se aplicó la escala de Jadad para una evaluación metodológica de los estudios encontrados. Resultados: Se incluyeron cinco ensayos clínicos aleatorizados. La TF prehospitalaria presentó índices de mortalidad 30 días después de la intervención semejantes a la ICPP, mientras que en cinco años se encontraron valores menores en la TF. El tratamiento aplicado en un período menor a dos horas desde los síntomas iniciales presentó una relación con la reducción de la mortalidad cuando se utilizó la TF. Los reinfartos no fatales, los accidentes vasculares encefálicos y las hemorragias intracerebrales fueron mayores cuando se utilizó la TF, mientras que los choques cardiogénicos presentaron menor frecuencia. Conclusión: La TF fue más eficaz en el tratamiento prehospitalario para reducir los fallecimientos después de cinco años, sin embargo, los reinfartos y los AVE ocurrieron de forma semejante en la muestra analizada. El factor tiempo redujo los resultados clínicos, principalmente cuando la terapia implementada ocurrió hasta dos horas después del episodio del IAMCST. De esta forma, a pesar de que las intervenciones presentaron resultados semejantes, la TF puede representar un tratamiento viable en lugares donde la ICPP no puede realizarse a tiempo.

Abstract Objective: To compare clinical outcomes of death, reinfarction, and stroke in primary studies assessing Fibrinolytic Therapy (FT) use in relation to Primary Percutaneous Coronary Intervention (PPCI) for myocardial reperfusion in patients with ST-Elevation Myocardial Infarction (STEMI) in prehospital care. Method: A systematic literature review conducted in the CINAHL, MEDLINE, PUBMED, Science Direct, SCOPUS, and Web of Science databases from October to December 2017. Randomized Clinical Trials, available in full, in any language, without temporal clipping were included. The eligibility assessment was carried out in two stages and applied to the Jadad Scale for methodological assessment of the studies found. Results: Five Randomized Clinical Trials were included. Prehospital FT presented mortality rates at 30 days after the intervention similar to PPCI, while in five years lower values were found for FT. The treatment instituted in a period of less than two hours of the initial symptoms was associated with the decrease in mortality when FT was used. Non-fatal reinfarction, stroke and intracranial hemorrhage were higher when FT was used, while cardiogenic shock showed lower frequency. Conclusion: FT was more effective in prehospital treatment to reduce deaths after five years, however, reinfarction and stroke occurred similarly in the sample analyzed. The time factor reduced clinical outcomes, especially when the implemented therapy occurred within two hours after the occurrence of STEMI. Thus, although the interventions presented similar outcomes. However, FT may represent a viable treatment in places where PPCI cannot be achieved in a timely manner.

Frequency and factors related to not receiving acute reperfusion therapy in patients with ST elevation myocardial infarction; a single specialty cardiac center.

OBJECTIVE: To determine the frequency of no reperfusion therapy, its reasons, hospital management and intermediate-term outcome s of ST- elevation my ocardial in farction patients . METHODS: The retrospective ambi-directional observational study was conducted at Tabba Heart Institute, Karachi, and comprised record of ST-elevation myocardial infarction patients without immediate reperfusion therapy with symptom onset time of 12 hours who presented between January 2013 and December 2017. Prospective follow-up of all patients was performed till June 2018. Coronary angiography, non-invasive stress tests, medications and late revascularisation were explored. Predictors of hospital mortality and major adverse cardiovascular events at follow-up were analysed. Data was analysed using SPSS 19. RESULTS: Of the 1977 records evaluated, 218(11%) patients of mean age 60.3±12.4 years did not receive immediate reperfusion therapy. Coronary angiography was done in 163(74.7%) patients of whom 45(27.6%) were taken for immediate procedure. Besides, 26 (11.9%) patients died during hospital stay. Predictors of hospital mortality were no revascularisation (odds ratio: 24.1, 95% confidence interval: 1.3-500), cardiogenic shock (odds ratio: 65, 95% confidence interval: 5.7-745) and tachycardia (odds ratio: 17, 95% confidence interval: 1.2-254.5) at presentation. Predictor of major adverse cardiovascular events was guideline-directed medical therapy (hazard ratio 2.6, 95% confidence interval: 1.16-6.2) at discharge, while revascularisation was not a significant predictor (p>0.05). CONCLUSION: A huge number of salvageable ST-elevation myocardial infarction patients failed to receive reperfusion therapy. There is a huge potential of improvement in ST-elevation myocardial infarction care in terms of increasing community awareness, prompt reperfusion therapy and usage of optimal medical therapy.

Role of Phosphorylated AMP-Activated Protein Kinase (AMPK) in Myocardial Insulin Resistance After Myocardial Ischemia-Reperfusion During Cardiopulmonary Bypass Surgery in Dogs.

BACKGROUND The aim of this study was to determine the role of AMP-activated protein kinase (AMPK) in myocardial insulin resistance after myocardial ischemia-reperfusion during cardiopulmonary bypass surgery in dogs. MATERIAL AND METHODS Twenty-four mongrel dogs were randomly assigned to 4 groups. The control group did not undergo aortic cross-clamping; the model group underwent 60 mins of aortic cross-clamping with 150 ml cardioplegic solution. The treatment group, the inhibition group respectively with 0.11mg/kg AICAR (AMPK agonist) in 150 ml cardioplegic solution and 0.11mg/kg Compound C (AMPK inhibitor) in 150 ml cardioplegic solution. The blood flow was determined and left ventricular myocardial tissue were taken at pre-bypass, 15, 60, and 90 min after aorta declamping, respectively. Expression of AMPK mRNA, p-AMPK and GLUT-4 proteins was determined by RT-PCR, IHC and WB. RESULTS Compared with the control group, receiving 60 min ischemia at 15 min after reperfusion, Myocardial Glucose Extraction Ratio were significantly decreased in the other 3 groups, it was significantly decreased from 20.0% to 1.2% at 60 min of reperfusion, and recovered to 6.1% after 90 min reperfusion in model group, while recovered to 4.1%, 12.0% after 90 min reperfusion respectively exposed to Compound C and AICAR. The expressions of p-AMPK, GLUT-4 protein and AMPK mRNA in myocardium were decreased in different experiment groups, but these changes occurred to a lesser extent in the treatment group. CONCLUSIONS The inability of GLUT-4 expression induced by the decreases in p-AMPK protein expression that may be one of the reasons for myocardial insulin resistance.

Implementation of an Acute Coronary Syndrome Simulation Training Strategy for Emergency Healthcare Professionals

The knowledge on the management of patients with acute coronary syndrome (ACS) is essential to reduce the gap between evidence and practice. Objective: To describe a simulation training strategy for emergency healthcare professionals and provide preliminary data on knowledge acquisition, learners' confidence and prescription of medications after training. Methods: The training was part of the implementation of two myocardial infarction systems of care. It comprehended lectures and simulation-based learning using high and low-fidelity mannequins and actors. It was tested in two phases: the first one in Belo Horizonte and the second one in Montes Claros, both in the state of Minas Gerais. A test was applied before and after training to assess knowledge acquisition. Confidence to perform thrombolysis in ST-elevation myocardial infarction (STEMI) patients was assessed using a questionnaire, and the impact on medication prescription analyzed STEMI patients admitted to hospitals in Montes Claros. Results: In the first phase, 156 professionals answered both tests: 70% of them improved their results and the median number of right answers increased (6, interquartile range [IQR] 5-7; vs 7 ([IQR] 6-9; p < 0.05). In the second phase, 242 professionals answered both tests: 58% of the physicians and 83% of the nurses obtained better test scores. Participants referred a positive impact on their clinical practice, 95% reported feeling very secure when perform fibrinolysis after the training, and there was also an impact on medication prescription. Conclusions: There was an impact on the learners' knowledge acquisition and confidence using our two-phase training model, with evidence of impact on performance

Effects of Sevoflurane Pretreatment on Myocardial Ischemia-Reperfusion Injury Through the Akt/Hypoxia-Inducible Factor 1-alpha (HIF-1α)/Vascular Endothelial Growth Factor (VEGF) Signaling Pathway.

BACKGROUND The aim of this study was to investigate the effects of sevoflurane (SEV) on myocardial ischemia/reperfusion (I/R) injury in rats and its mechanism. MATERIAL AND METHODS Sixty male Sprague-Dawley rats were randomly divided into 3 groups: Sham group (n=20), I/R group (n=20) and I/R+SEV group (n=20). The I/R model was established by ligating and recanalizing the left anterior descending coronary artery (LAD). Triphenyl tetrazolium chloride (TTC) test and echocardiography (ECG) were used for analysis. Hematoxylin and eosin (H&E) staining was applied to detect the morphological changes. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was conducted to detect the apoptosis levels. The expression level of superoxide dismutase 2 (SOD2) was measured. Finally, the effect of SEV on the protein kinase B (Akt)/hypoxia-inducible factor 1-alpha (HIF-1alpha)/vascular endothelial growth factor (VEGF) signaling pathway was detected via western blotting. RESULTS SEV could significantly improve I/R-induced cardiac insufficiency, inhibit cardiac infarction, and as well as reduce the infarction area from 53.21±2.11% to 32.33±3.49% (P<0.05). Compared with rats in I/R group, the cardiac myofilament was better in alignment, degradation and necrosis were milder, and cell edema was notably reduced in the I/R+SEV group. Thus, SEV could significantly reverse the decreased expression of SOD2 caused by I/R and reduce oxidative stress in the heart (P<0.05). According to the western blotting results, SEV was capable of obviously activating the expressions of phosphorylated-Akt (p-Akt), HIF-1alpha, and VEGF. CONCLUSIONS SEV can significantly improve myocardial injury caused by I/R in rats, and its mechanism might be related to the activation of the Akt/HIF-1alpha/VEGF signaling pathway.

Reperfusión fármaco-invasiva en el manejo del infarto agudo de miocardio en Chile: un llamado a la acción / Pharmaco-invasive reperfusion in acute myocardial infarction in Chile: a call for action

Resumen En Chile, se han logrado avances importantes en el manejo del Infarto Agudo de Miocardio (IAM) con elevación del segmento ST (IAMCEST). Debido a la mejoría en el diagnóstico precoz y tratamiento, particularmente, con el incremento de la Angioplastía Primaria (APP), hoy están dadas las condiciones para seguir progresando por la vía de la combinación de estrategias de reperfusión y la creación de Redes de Manejo del IAM. El siguiente artículo revisa la evidencia que justifica impulsar dicho avance y se esbozan posibles caminos para lograrlo.

Abstract In Chile, important advances have been made in the management of Acute Myocardial Infarction (MI) with ST segment elevation (STEMI). Due to the progress in early diagnosis and treatment, particularly with the increase in Primary Angioplasty (Primary PCI), nowadays there are conditions to improve early management through the combination of reperfusion strategies and the implementation of MI reperfusion networks. The present article reviews the evidence justifying the promotion of this strategy and outlines possible actions to achieve it.

Mitochondrial integrity during early reperfusion in an isolated rat heart model of donation after circulatory death-consequences of ischemic duration.

BACKGROUND: Cardioprotection and graft evaluation after ischemia-reperfusion (IR) are essential in facilitating heart transplantation with donation after circulatory death. Given the key role of mitochondria in IR, we aimed to investigate the tolerance of cardiac mitochondria to warm, global ischemia and to determine the predictive value of early reperfusion mitochondria-related parameters for post-ischemic cardiac recovery. METHODS: Isolated, working rat hearts underwent 0, 21, 24, 27, 30, or 33 minutes of warm, global ischemia, followed by 60 minutes of reperfusion. Functional recovery (developed pressure × heart rate) was determined at 60 minutes of reperfusion, whereas mitochondrial integrity was measured at 10 minutes of reperfusion. RESULTS: Functional recovery at 60 minutes of reperfusion decreased with ≥ 27 minutes of ischemia vs no ischemia (n = 7-8/group; p < 0.01). Cytochrome c, succinate release, and mitochondrial Ca2+ content increased with ≥ 27 minutes of ischemia vs no ischemia (p < 0.05). Ischemia at ≥ 21 minutes decreased mitochondrial coupling, adenosine 5'-triphosphate content, mitochondrial Ca2+ retention capacity, and increased oxidative damage vs no ischemia (p < 0.05). Reactive oxygen species (ROS) from reverse electron transfer increased with 21 and 27 minutes of ischemia vs no ischemia and 33 minutes of ischemia (p < 0.05), whereas ROS from forward electron transfer increased only with 33 minutes of ischemia vs no ischemia (p < 0.05). Mitochondrial coupling and adenosine 5'-triphosphate content correlated positively and cytochrome c, succinate, oxidative damage, and mitochondrial Ca2+ content correlated negatively with cardiac functional recovery (p < 0.05). CONCLUSIONS: Mitochondrial dysfunction occurs with shorter periods of ischemia than cardiac dysfunction. Mitochondrial coupling, ROS emission from reverse electron transfer, and calcium retention are particularly sensitive to early reperfusion injury, reflecting potential targets for cardioprotection. Indicators of mitochondrial integrity may be of aid in evaluating suitability of donation after circulatory death grafts for transplantation.

Prolonged Tpeak-Tend interval is associated with ventricular fibrillation during reperfusion in ST-elevation myocardial infarction.

AIM: Ventricular fibrillation (VF) during reperfusion in ST-elevation myocardial infarction (STEMI) is associated with increased in-hospital mortality. Dispersion of ventricular repolarization contributes to ventricular vulnerability during ischemia. Tpeak-Tend interval was proposed as a ventricular repolarization dispersion marker, however its value for prediction of reperfusion VF remains uncertain. We aimed to assess whether Tpeak-Tend before PCI in STEMI is associated with reperfusion VF. METHODS: STEMI patients admitted for primary PCI were retrospectively assessed for VF during reperfusion. Pre-PCI ECGs recorded in 40 patients with reperfusion VF (rVF group; age 65 ±â€¯13 years, 80% male) were compared with 374 consecutive patients without reperfusion arrhythmias (No-rVF group; age 67 ±â€¯12 years; 68% male). Digital ECGs were automatically processed and Tpeak-Tend interval computed on a per-lead basis. The global Tpeak-Tend was calculated between the earliest Tpeak and the latest Tend in any lead, and tested for association with reperfusion VF using logistic regression analysis. RESULTS: The leftward shift of Tpeak toward QRS complex in ischemic leads resulted in Tpeak-Tend prolongation. Global Tpeak-Tend in rVF group was higher than in No-rVF group (142 ±â€¯24 vs 130 ±â€¯27 ms; p = 0.007). Global Tpeak-Tend ≥ 131 ms predicted reperfusion VF (OR = 3.41; 95% CI 1.66-7.04; p = 0.001) and remained a significant predictor of reperfusion VF in multivariable analysis. CONCLUSION: Tpeak-Tend interval before PCI in STEMI was an independent predictor of reperfusion VF. Our findings warrants further research aimed at prospective validation of Tpeak-Tend as a marker of periprocedural arrhythmic risk.

Challenges and unanswered questions in STEMI management.

The management of ST-segment elevation myocardial infarction (STEMI) has evolved significantly over the last decades. STEMI treatment includes reperfusion therapy, ideally by primary percutaneous coronary intervention (pPCI), modern antithrombotic therapy and secondary prevention measures. Even though many areas in the management of STEMI are well studied and analyzed in the guidelines, there are still challenges and unanswered questions on how to improve outcomes. This review aims to offer an insight in areas that need to be explored.

Regional QT Interval Dispersion as an Early Predictor of Reperfusion in Patients with Acute Myocardial Infarction after Fibrinolytic Therapy / A Dispersão do Intervalo QT Regional como Preditor Precoce de Reperfusão em Pacientes com Infarto Agudo do Miocárdio Pós-terapia Fibrinolítica

Abstract Background: Patients with ST-elevation acute myocardial infarction attending primary care centers, treated with pharmaco-invasive strategy, are submitted to coronary angiography within 2-24 hours of fibrinolytic treatment. In this context, the knowledge about biomarkers of reperfusion, such as 50% ST-segment resolution is crucial. Objective: To evaluate the performance of QT interval dispersion in addition to other classical criteria, as an early marker of reperfusion after thrombolytic therapy. Methods: Observational study including 104 patients treated with tenecteplase (TNK), referred for a tertiary hospital. Electrocardiographic analysis consisted of measurements of the QT interval and QT dispersion in the 12 leads or in the ST-segment elevation area prior to and 60 minutes after TNK administration. All patients underwent angiography, with determination of TIMI flow and Blush grade in the culprit artery. P-values < 0.05 were considered statistically significant. Results: We found an increase in regional dispersion of the QT interval, corrected for heart rate (regional QTcD) 60 minutes after thrombolysis (p = 0.06) in anterior wall infarction in patients with TIMI flow 3 and Blush grade 3 [T3B3(+)]. When regional QTcD was added to the electrocardiographic criteria for reperfusion (i.e., > 50% ST-segment resolution), the area under the curve increased to 0.87 [(0.78-0.96). 95% IC. p < 0.001] in patients with coronary flow of T3B3(+). In patients with ST-segment resolution >50% and regional QTcD > 13 ms, we found a 93% sensitivity and 71% specificity for reperfusion in T3B3(+), and 6% of patients with successful reperfusion were reclassified. Conclusion: Our data suggest that regional QTcD is a promising non-invasive instrument for detection of reperfusion in the culprit artery 60 minutes after thrombolysis.

Resumo Fundamento: Pacientes com infarto do miocárdico com elevação do segmento-ST atendidos em centros de atendimento primário e tratados de acordo com a estratégia fármaco-invasiva são submetidos à fibrinólise seguida de coronariografia em período de 2-24h. Neste cenário, o conhecimento de marcadores de reperfusão como a redução em 50% do segmento-ST é fundamental. Objetivo: Analisar o desempenho da dispersão do intervalo QT em adição aos critérios clássicos, como marcador precoce de reperfusão pós-terapia trombolítica. Métodos: Estudo observacional com a inclusão de 104 pacientes tratados com tenecteplase (TNKase) e referenciados a hospital de atendimento terciário. A análise dos eletrocardiogramas (ECG) consistiu em mensuração do intervalo QT e sua dispersão nas 12 derivações, e também apenas na região com supradesnivelamento-ST antes e 60min pós-TNKase. A angiografia foi realizada em todos os pacientes com obtenção do fluxo TIMI e Blush da artéria culpada. Foram considerados significantes valores de p < 0,05. Resultados: Observamos aumento da dispersão do intervalo QT, corrigido pela frequência cardíaca, regional (dQTcR) 60min pós-lise (p = 0,006) em infartos de parede anterior nos casos com fluxo TIMI 3 e Blush 3 [T3B3(+)]. Adicionando a dQTcR ao critério ECG (redução do ST > 50%) de reperfusão, a área sob a curva aumentou para 0,87 [(0,78-0,96), IC95%, p < 0,001] em pacientes com fluxo coronário T3B3(+). Nos pacientes com critério de ECG para reperfusão e dQTcR > 13 ms a sensibilidade e especificidade foram 93% e 71%, respectivamente, para reperfusão em T3B3(+), possibilitando reclassificar 6% dos pacientes com sucesso de reperfusão. Conclusão: Os dados sugerem a dQTcR como instrumento promissor na identificação não invasiva de reperfusão na artéria coronária culpada, 60min pós-trombólise.

Alteração letrocardiográfica incomum por oclusão de coronária descendente anterior: padrão "De Winter" / Uncommon ECG abnormality due to proximal occlusion of lad coronary artery: De Winter pattern

O eletrocardiograma (ECG) é fundamental na avaliação dos pacientes com síndrome coronariana aguda (SCA), pois possibilita a identificação precoce dos pacientes com sinais de oclusão coronariana (infarto agudo do miocárdio com supradesnivelamento do segmento ST - IAMCSSST), que se beneficiam com estratégias de reperfusão miocárdica de emergência. Os casos de SCA sem supradesnivelamento de segmento ST pressupõem ausência de oclusão coronariana, e o ECG pode mostrar sinais de isquemia como inversão simétrica de ondas T, infradesnivelamento de segmento ST, ou mesmo ser normal em até 15% dos casos. No entanto, recentemente foi descrito um padrão eletrocardiográfico raro, conhecido como padrão "De Winter", relacionado à oclusão coronariana aguda da artéria descendente anterior (ADA) em seu terço proximal, na ausência de supradesnivelamento de segmento ST. Este é o relato de um paciente jovem, do sexo masculino, com quadro clínico anginoso típico, menos de uma hora depois de angioplastia eletiva da ADA, que apresentou padrão "De Winter" no ECG e teve confirmada trombose aguda de stent. O reconhecimento desse padrão eletrocardiográfico incomum é fundamental para garantir terapia de reperfusão coronariana emergencial em casos de síndrome coronariana aguda

he electrocardiogram (ECG) is a crucial tool in the evaluation of patients with acute coronary syndrome (ACS), since it allows the early identification of patients with signs of coronary occlusion (ST-elevation myocardial infarction ­ STEMI), who benefit from emergency myocardial reperfusion strategies. On the other hand, cases of non-ST-elevation ACS presumably have no coronary occlusion, and the ECG may show signs of ischemia such as symmetrical T-wave inversion, ST-segment depression, or even be normal in up to 15% of cases. However, a rare ECG pattern, known as the "De Winter" pattern, related to an acute occlusion of the Left Anterior Descending (LAD) coronary artery in its proximal third segment, has been recently described without ST-segment elevation. This is a case report of a young male patient with typical chest pain symptoms less than one hour after an elective LAD angioplasty, who presented with "De Winter" pattern on the ECG and had confirmed acute stent thrombosis. The recognition of this unusual electrocardiographic pattern is essential to guarantee emergency coronary reperfusion therapy in cases of acute coronary syndrome

Differential Effects of Normoxic and Hyperoxic Reperfusion on Global Myocardial Ischemia-Reperfusion Injury.

The objectives were to investigate if after hypoxia or ischemia, normoxic reperfusion is associated with less oxidant stress (OS), inflammation, and myocardial injury than hyperoxic reperfusion. In this study, cardiomyocytes (H9c2 cells) were cultured in hypoxia, followed by reoxygenation in normoxia or hyperoxia. Cardiomyocyte OS, inflammation, and apoptosis were measured. In parallel experiments, rabbits were cannulated for cardiopulmonary bypass (CPB). Following cardioplegic arrest and aortic cross-clamp removal, hearts were reperfused under normoxic or hyperoxic conditions. Left ventricular developed pressure and contractility (LV +dP/dt) were recorded, and blood samples and heart tissues were collected for measurement of OS, inflammation, and cardiac injury. Results showed that H9c2 cells exposed to hyperoxic reoxygenation showed significant increases in OS, inflammation, and apoptosis compared to normoxic reoxygenation. Following CPB and 2-hour hyperoxic reperfusion, LV +dP/dt and left ventricular developed pressure were significantly decreased compared with pre-CPB values (to 36 ± 21%, P = 0.002; and 53 ± 20%, P = 0.02, respectively), associated with significant increases in all plasma and tissue biomarkers for OS, inflammation, and myocardial injury. In contrast, LV +dP/dt was relatively well preserved under normoxic reperfusion conditions (to 70 ± 14% after 2-hour reperfusion), and was associated with an attenuated myocardial OS, inflammatory, apoptotic, and injury response compared to the hyperoxia group (eg, cTn-I: 5.9 ± 1.5 vs 20.2 ± 7.6 ng/mL, respectively, P < 0.0001). Overall, in both in vitro and in vivo experiments, normoxic reperfusion/reoxygenation was associated with less robust OS, inflammation, apoptosis, and myocardial injury compared with hyperoxic reperfusion/reoxygenation. These results suggest that hyperoxia should be avoided to minimize myocardial OS, inflammation, and ventricular dysfunction after CPB.

Prophylactic Effect of Amiodarone Infusion on Reperfusion Ventricular Fibrillation After Release of Aortic Cross-Clamp in Patients with Left Ventricular Hypertrophy Undergoing Aortic Valve Replacement: ARandomized Controlled Trial.

OBJECTIVE: To investigate whether prophylactic amiodarone infusion prevents ventricular fibrillation after aortic cross-clamp release and attenuates cytokine production in patients with left ventricular hypertrophy undergoing cardiac surgery. DESIGN: Prospective, randomized controlled trial. SETTING: A public hospital. PARTICIPANTS: The study comprised 68 patients undergoing aortic valve replacement for severe aortic stenosis. INTERVENTIONS: Patients were randomly assigned to receive a 150mg bolus then 30mg/h continuous infusion of amiodarone (amiodarone group) or a 1 mg/kg bolus then 1 mg/kg/h continuous infusion of lidocaine (lidocaine group). The primary outcome was the ventricular fibrillation incidence rate after aortic cross-clamp release. Secondary outcomes included perioperative serum interleukin-6 and tumor necrosis factor-alpha levels. MEASUREMENTS AND MAIN RESULTS: The ventricular fibrillation incidence rate was significantly lower in the amiodarone than in the lidocaine group (20.6% v 50%, relative risk 0.41; 95% confidence interval [CI] 0.20-0.86; p = 0.021). Interleukin-6 levels 1hour after aortic cross-clamp release and at intensive care unit admission were significantly lower in the amiodarone than in the lidocaine group (geometric mean [95% CI] 117.4pg/mL [87.1-158.4] v 339.5pg/mL [210.6-547.2]; p < 0.01 and 211.1pg/mL [162.8-73.6] v 434.1pg/mL [293.7-641.5]; p < 0.01, respectively). Tumor necrosis factor-alpha levels 1hour after aortic cross-clamp release were significantly lower in the amiodarone than in the lidocaine group (geometric mean [95% CI] 1.624pg/mL [1.359-1.940] v 2.283pg/mL [1.910-2.731]; p = 0.02). CONCLUSIONS: Amiodarone prevented reperfusion ventricular fibrillation in patients with left ventricular hypertrophy undergoing aortic valve replacement to a greater extent than did lidocaine. Furthermore, amiodarone inhibited postoperative interleukin-6 and tumor necrosis factor-alpha production.