Acute myocardial infarction and ischaemic stroke: differences and similarities in reperfusion therapies-a review.

Acute ST-elevation myocardial infarction (STEMI) and acute ischaemic stroke (AIS) share a number of similarities. However, important differences in pathophysiology demand a disease-tailored approach. In both conditions, fast treatment plays a crucial role as ischaemia and eventually infarction develop rapidly. Furthermore, in both fields, the introduction of fibrinolytic treatments historically preceded the implementation of endovascular techniques. However, in contrast to STEMI, only a minority of AIS patients will eventually be considered eligible for reperfusion treatment. Non-invasive cerebral imaging always precedes cerebral angiography and thrombectomy, whereas coronary angiography is not routinely preceded by non-invasive cardiac imaging in patients with STEMI. In the late or unknown time window, the presence of specific patterns on brain imaging may help identify AIS patients who benefit most from reperfusion treatment. For STEMI, a uniform time window for reperfusion up to 12 h after symptom onset, based on old placebo-controlled trials, is still recommended in guidelines and generally applied. Bridging fibrinolysis preceding endovascular treatment still remains the mainstay of reperfusion treatment in AIS, while primary percutaneous coronary intervention is the strategy of choice in STEMI. Shortening ischaemic times by fine-tuning collaboration networks between ambulances, community hospitals, and tertiary care hospitals, optimizing bridging fibrinolysis, and reducing ischaemia-reperfusion injury are important topics for further research. The aim of this review is to provide insights into the common as well as diverging pathophysiology behind current reperfusion strategies and to explore new ways to enhance their clinical benefit.

Ex vivo evaluation of the biventricular cardiac function for donation after circulatory death model: An experimental study.

Few reports on a biventricular working heart model with ex vivo perfusion exist owing to the complexity of establishing a circuit. Hence, we investigated it for donation after circulatory death. The heart in six juvenile pigs (~20 kg) was arrested by asphyxiation. After 30 minutes of global ischemia, the heart was harvested, reperfused with normoxemic blood cardioplegia for 20 minutes, and subsequently perfused with hyperxemic blood. After 70 minutes of controlled reperfusion, the system was switched to the biventricular working mode. Cardiac function was assessed before anoxia and during the biventricular mode. Left and right ventricular functions worsened during the biventricular mode, as compared to those before anoxia (dP/dtmax , 673 ± 120 vs. 283 ± 95 and 251 ± 35 vs. 141 ± 21 mm Hg/s, respectively; P < .001). Systemic (resistance/100 g net heart weight) and pulmonary vascular resistance indexes during the biventricular mode were similar to those before anoxia (829 ± 262 vs. 759 ± 359, P = .707, and 167 ± 57 vs. 158 ± 83 dynes·sec·cm-5 - l-100-g net heart weight, P = .859, respectively). The biventricular working heart model with ex vivo perfusion was feasible, exhibited stable hemodynamics, and has the potential to be a powerful tool for direct cardiac function assessment.

Unloading the Left Ventricle Before Reperfusion in Patients With Anterior ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: In ST-segment-elevation myocardial infarction (STEMI), infarct size correlates directly with heart failure and mortality. Preclinical testing has shown that, in comparison with reperfusion alone, mechanically unloading the left ventricle (LV) before reperfusion reduces infarct size and that 30 minutes of unloading activates a cardioprotective program that limits reperfusion injury. The DTU-STEMI pilot trial (Door-To-Unload in STEMI Pilot Trial) represents the first exploratory study testing whether LV unloading and delayed reperfusion in patients with STEMI without cardiogenic shock is safe and feasible. METHODS: In a multicenter, prospective, randomized exploratory safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events at 30 days. Efficacy parameters included the assessment of infarct size by using cardiac magnetic resonance imaging. RESULTS: All patients completed the U-IR (n=25) or U-DR (n=25) protocols with respective mean door-to-balloon times of 72 versus 97 minutes. Major adverse cardiovascular and cerebrovascular event rates were not statistically different between the U-IR versus U-DR groups (8% versus 12%, respectively, P=0.99). In comparison with the U-IR group, delaying reperfusion in the U-DR group did not affect 30-day mean infarct size measured as a percentage of LV mass (15±12% versus 13±11%, U-IR versus U-DR, P=0.53). CONCLUSIONS: We report that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is feasible within a relatively short time period in anterior STEMI. The DTU-STEMI pilot trial did not identify prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion. An appropriately powered pivotal trial comparing LV unloading before reperfusion to the current standard of care is required. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03000270.

Kinetics Analysis of Circulating MicroRNAs Unveils Markers of Failed Myocardial Reperfusion.

BACKGROUND: Failed myocardial reperfusion occurs in approximately 50% of patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). It manifests as microvascular obstruction (MVO) on cardiac magnetic resonance (CMR) imaging. Although prognostically important, MVO is not routinely screened for. Our aim was to investigate the kinetics of circulating short noncoding ribonucleic acids [microRNAs (miRNAs)] following PPCI and their association with MVO in STEMI patients. METHODS: Screening of 2083 miRNAs in plasma from STEMI patients with (n = 6) and without (n = 6) MVO was performed by next-generation sequencing. Two candidate miRNAs were selected and quantified at 13 time points within 3 h postreperfusion in 20 STEMI patients by reverse transcription and quantitative PCR. Subsequently, these 2 miRNAs were measured in a "validation" STEMI cohort (n = 50) that had CMR imaging performed at baseline and 3 months post-PPCI to evaluate their association with MVO. RESULTS: miR-1 and miR-133b were rapidly released following PPCI in a monophasic or biphasic pattern. Both miRNAs were enriched in circulating microparticles. A second miR-1 peak (90-180 min postreperfusion) seemed to be associated with a higher index of microvascular resistance. In addition, miR-1 and miR-133b levels at 90 min post-PPCI were approximately 3-fold (P = 0.001) and 4.4-fold (P = 0.008) higher in patients with MVO, respectively. Finally, miR-1 was significantly increased in a subgroup of patients with worse left ventricular (LV) functional recovery 3 months post-PPCI. CONCLUSIONS: miR-1 and miR-133b levels increase within 3 h of PPCI. They are positively associated with MVO and worse LV functional recovery post-PPCI.

Postconditioning with Nitrates Protects Against Myocardial Reperfusion Injury: A New Use for an Old Pharmacological Agent.

Early reperfusion remains the key therapy to salvage viable myocardium and must be applied as soon as possible following an acute myocardial infarction (AMI) to attenuate the ischemic insult. However, reperfusion injury may develop following reintroduction of blood and oxygen to vulnerable myocytes, which results in more severe cell death than in the preceding ischemic episode. Ischemic postconditioning (I-PostC) provides a cardioprotective effect in combination with pharmacological agents. Although nitrates have been tested in many experimental and clinical studies of acute AMI to evaluate the cardioprotective effect, few investigations have been focused on nitrates postconditioning in patients undergoing percutaneous coronary intervention (PCI). This review presents the manifestations of myocardial reperfusion injury (RI) and potential mechanisms underlying it, and provides the mechanisms involved in the cardioprotection of I-PostC. We also present a new therapeutic approach to attenuate RI by use of an 'old' agent - nitrates - in AMI patients.

Analysis of situation of acute coronary syndrome based on the date of the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project: single-centre observational study.

BACKGROUND: We are currently faced with an increasing burden of cardiovascular disease in China and the inadequacy of the application of guidelines in clinical practice. In the past decade, China has been strengthening the healthcare system, but it still lacked a national performance measurement system and an appropriate quality improvement strategy. Therefore, in order to improve the implementation of guideline recommendations in clinical practice, China has learnt from the successful experience of Get With The Guidelines project in 2014. Under the guidance of the Medical and Health Hospital of the National Health and Family Planning Commission, the Chinese Society of Cardiology and the American Heart Association jointly launched the Improving Care for Cardiovascular Disease in China (CCC) project. The project team provided an analysis report on the completion of key medical quality evaluation indicators of each hospital every month, supplied guidance through education, training, experience exchange and on-site investigation for problems, and certified hospitals with outstanding performance and obvious progress. The circle pattern, including evaluation, training, improvement and re-evaluation, will boost the guidelines compliance on clinical practice in China and improve the quality of medical services. METHODS: This study was conducted in a centre of the Third Xiangya Hospital of Central South University. It included patients with ACS from December 2009 to December 2011 (n=225), patients with ACS in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project coming from the Third Xiangya Hospital of Central South University (n=665), 12 hospitals in Hunan Province (n=4333) and 150 hospitals in China (n=63 641) from November 2014 to April 2017. It assessed the situation of drug therapy, hospitalisation day, mortality during hospitalisation, median of door-to-needle (D-to-N) time and median of door-to-balloon (D-to-B) time of patients with ST-segment elevation myocardial infarction (STEMI), the proportion of D-to-N within 30 min and D-to-B within 90 min, and the proportion of reperfusion therapy. Patients with ACS from the centre from November 2014 to April 2017 were divided into five groups (every 6 months as a group according to time). The study observed change trends in all the above-mentioned indexes. RESULTS: Compared with before participating in the CCC project, there were increases after participating in the CCC project in the drug usage rates of aspirin, P2Y12 inhibitor (clopidogrel or ticagrelor), ß-blocker, statin and angiotensin converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB). Hospitalisation day and mortality during hospitalisation were shortened. D-to-N and D-to-B times of patients with STEMI were shorter. Compared with Hunan Province and China, the drug usage rates were higher; hospitalisation day and D-to-N time were shorter; D-to-B time was longer; and the proportion of reperfusion therapy was higher. The trend of drug usage rates was on the rise. There was no significant change in the hospitalisation day and D-to-N and D-to-B times. The mortality during hospitalisation showed a downward trend. The proportion of D-to-N within 90 min and reperfusion therapy showed upward trends. CONCLUSION: Quality of care for patients with ACS improved over time in the CCC project, including taking medicine following the guidelines, increased use of reperfusion therapy and faster time to treatment. Although overall mortality has improved, we also should attach importance to high-risk patients. The influence of the CCC project, which is based on guidelines on prognosis of ACS in the centre, presents an important clinical implication that it is necessary to enhance adherence to the guidelines in the treatment of ACS.

Towards medicine of excellence in Mexico: the "Código Infarto" protocol, a view from the perspective of translational bioethics.

INTRODUCTION: Mexico is the country with the highest mortality due to ST-elevation acute myocardial infarction (STEMI), and the IMSS has therefore developed the protocol of care for emergency departments called Código Infarto (Infarction Code). In this article, aspects of translational medicine are discussed with a bioethical and comprehensive perspective. OBJECTIVE: To analyze the Código Infarto protocol from the perspective of translational bioethics. METHOD: A problem-centered approach was carried out through reflective equilibrium (or Rawls' method), as well as by applying the integral method for ethical discernment. RESULTS: The protocol of care for emergency services Código Infarto is governed by evidence-based medicine and value-based medicine; it is guided by a principle of integrity that considers six dimensions of quality for the care of patients with STEMI. CONCLUSION: The protocol overcomes some adverse social determinants that affect STEMI medical care, reduces mortality and global economic disease burden, and develops medicine of excellence with high social reach.

INTRODUCCIÓN: México es el país con mayor mortalidad por infarto agudo de miocardio con elevación del segmento ST (IAM CEST), por lo que el Instituto Mexicano del Seguro Social desarrolló el protocolo de atención para los servicios de urgencias denominado Código Infarto. En este artículo se discuten aspectos de la medicina traslacional con una perspectiva bioética e integral. OBJETIVO: Analizar el protocolo Código Infarto desde la perspectiva de la bioética traslacional. MÉTODO: Se realizó una aproximación centrada en el problema a través del equilibrio reflexivo, así como la aplicación del método integral para el discernimiento ético. RESULTADOS: El protocolo de atención para los servicios de urgencias Código Infarto se rige por la medicina basada en la evidencia y la medicina basada en valores; se orienta por el principio de integridad que considera las seis dimensiones de la calidad para la atención de pacientes con IAM CEST. CONCLUSIÓN: El protocolo supera algunos determinantes sociales adversos que afectan la atención médica del IAM CEST, disminuye la mortalidad, la carga económica global de la enfermedad y desarrolla una medicina de excelencia de alto alcance social.

Interinstitutional clinical practice guidelines for the treatment of acute myocardial infarction.

INTRODUCTION: Mexico has the highest 30-day mortality due to acute myocardial infarction (AMI), which constitutes one of the main causes of mortality in the country: 28 % versus 7.5 % on average for the Organization for Economic Co-operation and Development member countries. 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-segment 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. 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.

Effect of Ischemia Duration and Protective Interventions on the Temporal Dynamics of Tissue Composition After Myocardial Infarction.

RATIONALE: The impact of cardioprotective strategies and ischemia duration on postischemia/reperfusion (I/R) myocardial tissue composition (edema, myocardium at risk, infarct size, salvage, intramyocardial hemorrhage, and microvascular obstruction) is not well understood. OBJECTIVE: To study the effect of ischemia duration and protective interventions on the temporal dynamics of myocardial tissue composition in a translational animal model of I/R by the use of state-of-the-art imaging technology. METHODS AND RESULTS: Four 5-pig groups underwent different I/R protocols: 40-minute I/R (prolonged ischemia, controls), 20-minute I/R (short-duration ischemia), prolonged ischemia preceded by preconditioning, or prolonged ischemia followed by postconditioning. Serial cardiac magnetic resonance (CMR)-based tissue characterization was done in all pigs at baseline and at 120 minutes, day 1, day 4, and day 7 after I/R. Reference myocardium at risk was assessed by multidetector computed tomography during the index coronary occlusion. After the final CMR, hearts were excised and processed for water content quantification and histology. Five additional healthy pigs were euthanized after baseline CMR as reference. Edema formation followed a bimodal pattern in all 40-minute I/R pigs, regardless of cardioprotective strategy and the degree of intramyocardial hemorrhage or microvascular obstruction. The hyperacute edematous wave was ameliorated only in pigs showing cardioprotection (ie, those undergoing short-duration ischemia or preconditioning). In all groups, CMR-measured edema was barely detectable at 24 hours postreperfusion. The deferred healing-related edematous wave was blunted or absent in pigs undergoing preconditioning or short-duration ischemia, respectively. CMR-measured infarct size declined progressively after reperfusion in all groups. CMR-measured myocardial salvage, and the extent of intramyocardial hemorrhage and microvascular obstruction varied dramatically according to CMR timing, ischemia duration, and cardioprotective strategy. CONCLUSIONS: Cardioprotective therapies, duration of index ischemia, and the interplay between these greatly influence temporal dynamics and extent of tissue composition changes after I/R. Consequently, imaging techniques and protocols for assessing edema, myocardium at risk, infarct size, salvage, intramyocardial hemorrhage, and microvascular obstruction should be standardized accordingly.

Critical Issues for the Translation of Cardioprotection.

The translation from numerous successful animal experiments on cardioprotection beyond that by reperfusion to clinical practice has to date been disappointing. Animal experiments often use reductionist approaches and are mostly performed in young and healthy animals which lack the risk factors, comorbidities, and comedications which are characteristics of patients suffering an acute myocardial infarction or undergoing cardiovascular surgery. Conceptually, it is still unclear by how much the time window for successful reperfusion is extended by preconditioning, and how long the duration of ischemia can be so that adjunct cardioprotection by postconditioning at reperfusion still protects. Experimental studies addressing long-term effects of adjunct cardioprotection beyond infarct size reduction, that is, on repair, remodeling, and mortality, are lacking. Technically, reproducibility and robustness of experimental studies are often limited. Grave faults in design and conduct of clinical trials have also substantially contributed to the failure of translation of cardioprotection to clinical practice. Cardiovascular surgery with ischemic cardioplegic arrest is only a surrogate of acute myocardial infarction and confounded by the choice of anesthesia, hypothermia, cardioplegia, and traumatic myocardial injury. Trials in patients with acute myocardial infarction have been performed on agents/interventions with no or inconsistent previous animal data and in patients who had either some reperfusion already at admission or were reperfused too late to expect any myocardial salvage. Of greatest concern is the lack of adequate phase II dosing and timing studies when rushing from promising proof-of-concept trials with surrogate end points such as infarct size to larger clinical outcome trials. Future trials must focus on interventions/agents with robust preclinical evidence, have solid phase II dosing and timing data, and recruit patients who have truly a chance to benefit from adjunct cardioprotection.

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.

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.

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.

Clinical impact of direct stenting and interaction with thrombus aspiration in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: Thrombectomy Trialists Collaboration.

Aims: Preliminary studies suggest that direct stenting (DS) during percutaneous coronary intervention (PCI) may reduce microvascular obstruction and improve clinical outcome. Thrombus aspiration may facilitate DS. We assessed the impact of DS on clinical outcome and myocardial reperfusion and its interaction with thrombus aspiration among ST-segment elevation myocardial infarction (STEMI) patients undergoing PCI. Methods and results: Patient-level data from the three largest randomized trials on routine manual thrombus aspiration vs. PCI only were merged. A 1:1 propensity matched population was created to compare DS and conventional stenting. Synergy between DS and thrombus aspiration was assessed with interaction P-values in the final models. In the unmatched population (n = 17 329), 32% underwent DS and 68% underwent conventional stenting. Direct stenting rates were higher in patients randomized to thrombus aspiration as compared with PCI only (41% vs. 22%; P < 0.001). Patients undergoing DS required less contrast (162 mL vs. 172 mL; P < 0.001) and had shorter fluoroscopy time (11.1 min vs. 13.3 min; P < 0.001). After propensity matching (n = 10 944), no significant differences were seen between DS and conventional stenting with respect to 30-day cardiovascular death [1.7% vs. 1.9%; hazard ratio 0.88, 95% confidence interval (CI) 0.55-1.41; P = 0.60; Pinteraction = 0.96) and 30-day stroke or transient ischaemic attack (0.6% vs. 0.4%; odds ratio 1.02; 95% CI 0.14-7.54; P = 0.99; Pinteraction = 0.81). One-year results were similar. No significant differences were seen in electrocardiographic and angiographic myocardial reperfusion measures. Conclusion: Direct stenting rates were higher in patients randomized to thrombus aspiration. Clinical outcomes and myocardial reperfusion measures did not differ significantly between DS and conventional stenting and there was no interaction with thrombus aspiration.

No time to delay reperfusion: A cross-sectional study of primary percutaneous coronary intervention times.

AIMS AND OBJECTIVES: To establish and report cross-sectional data of reperfusion times for emergency primary percutaneous coronary interventions (PPCI) and to examine factors associated with times to reperfusion. BACKGROUND: Rapid coronary reperfusion can salvage myocardial tissue, preserve left ventricular function and reduce mortality. PPCI is the gold standard of management. Researchers have reported on international median reperfusion times, but this is the first Irish study to do so. METHODS: This observational, prospective, cross-sectional study included patients diagnosed with ST-segment elevation myocardial infarction (STEMI) and admitted for emergency PPCI. Descriptive and inferential statistics were used. The study was ethically approved. We adopted the STROBE guidelines. RESULTS: All patients (N = 133) who met the inclusion criteria were included initially. Of these, 105 (79%) were diagnosed with STEMI and received emergency PPCI. The majority of STEMIs were diagnosed by paramedics and most (67%) were reperfused within 120 min, with a median time of 96 min. The results suggested that younger patients achieved timelier PPCI and source of referral was also significant in that more of those transferred directly to the coronary catheterisation laboratory achieved reperfusion within 120 min, compared with those who presented to the emergency department. CONCLUSION: A timely reperfusion service is achieved for the majority. Attention is needed in respect of the ageing and those admitted directly to the emergency departments with STEMI. RELEVANCE TO CLINICAL PRACTICE: Further international research is recommended to compare current reperfusion times against guidelines and to identify areas for improvement. Clinicians should be mindful of the importance of rapid reperfusion and the implications of its delay for patients with STEMI. Those presenting to emergency departments with chest pain should be prioritised.

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.

A novel adenylyl cyclase type 5 inhibitor that reduces myocardial infarct size even when administered after coronary artery reperfusion.

We developed a novel adenylyl cyclase type 5 (AC5) inhibitor, C90, that reduces myocardial infarct size even when administered after coronary reperfusion. This is key, since it is not practical to administer a drug to a patient with myocardial infarction before revascularization, and is one reason why so many prior drugs, which reduced infarct in experimental animals, failed in clinical trials. C90 is the most potent AC5 inhibitor, as exhibited by its IC50 value for AC5 inhibition, which was 5 times lower than the next most potent AC5 inhibitor. C90 reduced cAMP in response to forskolin in wild type mice by 42%, but no longer reduced cAMP in response to forskolin in mice with disruption of AC5, indicating that the mechanism of C90 was specific for AC5 inhibition. Compared with vehicle treatment, C90 reduced infarct size by 64% at a dose of 0.6 mg/kg. Thus, C90 is a novel, selective and potent AC5 inhibitor that reduces infarct size, when delivered after coronary artery reperfusion, rendering it potentially clinically useful. It also reduces beta-adrenergic receptor signaling, which will provide additional benefit to patients with coronary artery disease or heart failure.

Is Cardioprotection Dead?

For >4 decades, the holy grail in the treatment of acute myocardial infarction has been the mitigation of lethal injury. Despite promising initial results and decades of investigation by the cardiology research community, the only treatment with proven efficacy is early reperfusion of the occluded coronary artery. The remarkable record of failure has led us and others to wonder if cardioprotection is dead. The path to translation, like the ascent to Everest, is certainly littered with corpses. We do, however, highlight a therapeutic principle that provides a glimmer of hope: cellular postconditioning. Administration of cardiosphere-derived cells after reperfusion limits infarct size measured acutely, while providing long-term structural and functional benefits. The recognition that cell therapy may be cardioprotective, and not just regenerative, merits further exploration before we abandon the pursuit entirely.

Comparative efficacy and safety of reperfusion therapy with fibrinolytic agents in patients with ST-segment elevation myocardial infarction: a systematic review and network meta-analysis.

BACKGROUND: Fibrinolytic therapy offers an alternative to mechanical reperfusion for ST-segment elevation myocardial infarction (STEMI) in settings where health-care resources are scarce. Comprehensive evidence comparing different agents is still unavailable. In this study, we examined the effects of various fibrinolytic drugs on clinical outcomes. METHODS: We did a network meta-analysis based on a systematic review of randomised controlled trials comparing fibrinolytic drugs in patients with STEMI. Several databases were searched from inception up to Feb 28, 2017. We included only randomised controlled trials that compared fibrinolytic agents as a reperfusion therapy in adult patients with STEMI, whether given alone or in combination with adjunctive antithrombotic therapy, against other fibrinolytic agents, a placebo, or no treatment. Only trials investigating agents with an approved indication of reperfusion therapy in STEMI (streptokinase, tenecteplase, alteplase, and reteplase) were included. The primary efficacy outcome was all-cause mortality within 30-35 days and the primary safety outcome was major bleeding. This study is registered with PROSPERO (CRD42016042131). FINDINGS: A total of 40 eligible studies involving 128 071 patients treated with 12 different fibrinolytic regimens were assessed. Compared with accelerated infusion of alteplase with parenteral anticoagulants as background therapy, streptokinase and non-accelerated infusion of alteplase were significantly associated with an increased risk of all-cause mortality (risk ratio [RR] 1·14 [95% CI 1·05-1·24] for streptokinase plus parenteral anticoagulants; RR 1·26 [1·10-1·45] for non-accelerated alteplase plus parenteral anticoagulants). No significant difference in mortality risk was recorded between accelerated infusion of alteplase, tenecteplase, and reteplase with parenteral anticoagulants as background therapy. For major bleeding, a tenecteplase-based regimen tended to be associated with lower risk of bleeding compared with other regimens (RR 0·79 [95% CI 0·63-1·00]). The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy increased the risk of major bleeding by 1·27-8·82-times compared with accelerated infusion alteplase plus parenteral anticoagulants (RR 1·47 [95% CI 1·10-1·98] for tenecteplase plus parenteral anticoagulants plus glycoprotein inhibitors; RR 1·88 [1·24-2·86] for reteplase plus parenteral anticoagulants plus glycoprotein inhibitors). INTERPRETATION: Significant differences exist among various fibrinolytic regimens as reperfusion therapy in STEMI and alteplase (accelerated infusion), tenecteplase, and reteplase should be considered over streptokinase and non-accelerated infusion of alteplase. The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy should be discouraged. FUNDING: None.

Acute myocardial infarction.

Acute myocardial infarction has traditionally been divided into ST elevation or non-ST elevation myocardial infarction; however, therapies are similar between the two, and the overall management of acute myocardial infarction can be reviewed for simplicity. Acute myocardial infarction remains a leading cause of morbidity and mortality worldwide, despite substantial improvements in prognosis over the past decade. The progress is a result of several major trends, including improvements in risk stratification, more widespread use of an invasive strategy, implementation of care delivery systems prioritising immediate revascularisation through percutaneous coronary intervention (or fibrinolysis), advances in antiplatelet agents and anticoagulants, and greater use of secondary prevention strategies such as statins. This seminar discusses the important topics of the pathophysiology, epidemiological trends, and modern management of acute myocardial infarction, focusing on the recent advances in reperfusion strategies and pharmacological treatment approaches.