A intervenção precoce do paciente com síndrome coronariana aguda e sua implicação na redução da morbimortalidade cardiovascular / The early intervention of acute coronary disease and its implication in the reduction of cardiovascular morbimortality

Introdução. O infarto agudo do miocárdio apresenta significativas taxas de morbimortalidade. A reperfusão precoce por angioplastia primária é a intervenção que reduz a mortalidade e as complicações, e deve ser iniciada em até 12 horas, a fim de impedir a perda muscular irreversível. O tempo entre chegada do paciente ao hospital e a abertura da artéria acometida, tempo porta-balão, determina a morbimortalidade do paciente. Objetivo. Esse estudo busca analisar o potencial benefício do tratamento da reperfusão coronariana precoce, os fatores de risco, as possíveis complicações e o Killip em pacientes que sofreram infarto agudo do miocárdio relacionando-os a sua morbimortalidade. Materiais e métodos. Estudo observacional transversal realizado por meio de coleta de dados dos prontuários dos pacientes submetidos a angioplastia primária de um hospital privado. Resultados. A hipertensão arterial sistêmica foi a variável mais prevalente (75%), e que houve predomínio no sexo masculino (71%) e associação com a progressão da idade. 61% dos pacientes apresentaram um tempo porta balão menor que 90 minutos. Houve significância estatística entre o tempo porta balão e a evolução do Killip, evidenciando um tempo porta-balão maior que 90 minutos na maioria dos pacientes que obtiveram aumento da pontuação do Killip. Conclusão. A precocidade da intervenção no paciente com IAM impacta na morbimortalidade, visto que o tempo porta balão está diretamente associado a evolução da do Killip. Logo, deve-se identificar os fatores que interferem no atendimento, a fim de proporcionar uma intervenção otimizada. (AU)

Introduction. Acute myocardial infarction has significant rates of morbidity and mortality. Early reperfusion by primary angioplasty is the intervention that reduces mortality and complications, and should be started within 12 hours in order to prevent irreversible muscle loss. The time between the patient's arrival at the hospital and the opening of the affected artery, door-to-balloon time, determines the patient's morbidity and mortality. Objective. The proposition of this study is to analyze the potential benefits of early coronary reperfusion, associated with the risk factors, possible complications, and the Killip score in patients whit acute myocardial infarction (AMI) and the relation of those factors with the morbidity and mortality. Materials and methods. This is a transversal observational study and uses data collected of medical records of patients subjected to primary angioplasty in a private hospital. Results. Systemic arterial hypertension was the most prevalent one (75%), it was more common in males (71%) and associated with a higher age. In 61% of the patients port-balloon time was less than 90 minutes. There was statistical significance between port-balloon time and Killip score evaluation, that showed a higher score in patient with a port-balloon time that exceeded 90 minutes. Conclusion. Early intervention in patients with AMI impacts morbimortality, once that the port-balloon time is directly associated with the Killip score results. Therefore, all factors that can lead to a delay in their care of those patients should be identified with the objective of optimize the intervention. (AU)

Rapidly growing cardiac mass: a rare case of left atrial intramural hematoma complicating coronary artery stenting.

Formation of an intramural left atrial hematoma (ILAH) is a rare complication of coronary artery stenting. Rapid diagnosis with noninvasive multimodality imaging can potentially be lifesaving. We report a case of ILAH that resulted in left ventricular inflow obstruction and pericardial tamponade in a 55-year-old male who presented with hemodynamic instability and worsening dyspnea three weeks after seemingly uncomplicated left circumflex artery stenting. We demonstrate features on transthoracic echocardiography with contrast and cardiac computed tomography that were used for diagnosis and management.

Mechanical Pre-Conditioning With Acute Circulatory Support Before Reperfusion Limits Infarct Size in Acute Myocardial Infarction.

OBJECTIVES: This study tested the hypothesis that first reducing myocardial work by unloading the left ventricle (LV) with a novel intracorporeal axial flow catheter while delaying coronary reperfusion activates a myocardial protection program and reduces infarct size. BACKGROUND: Ischemic heart disease is a major cause of morbidity and mortality worldwide. Primary myocardial reperfusion remains the gold standard for the treatment of an acute myocardial infarction (AMI); however, ischemia-reperfusion injury contributes to residual myocardial damage and subsequent heart failure. Stromal cell-derived factor (SDF)-1α is a chemokine that activates cardioprotective signaling via Akt, extracellular regulated kinase, and glycogen synthase kinase-3ß. METHODS: AMI was induced by occlusion of the left anterior descending artery (LAD) via angioplasty for 90 min in 50-kg male Yorkshire swine (n = 5/group). In the primary reperfusion (1° Reperfusion) group, the LAD was reperfused for 120 min. In the primary unloading (1° Unloading) group, after 90 min of ischemia the axial flow pump was activated and the LAD left occluded for an additional 60 min, followed by 120 min of reperfusion. Myocardial infarct size and kinase activity were quantified. RESULTS: Compared with 1° Reperfusion, 1° Unloading reduced LV wall stress and increased myocardial levels of SDF-1α, CXCR4, and phosphorylated Akt, extracellular regulated kinase, and glycogen synthase kinase-3ß in the infarct zone. 1° Unloading increased antiapoptotic signaling and reduced myocardial infarct size by 43% compared with 1° Reperfusion (73 ± 13% vs. 42 ± 8%; p = 0.005). Myocardial levels of SDF-1 correlated inversely with infarct size (R = 0.89; p < 0.01). CONCLUSIONS: Compared with the contemporary strategy of primary reperfusion, mechanically conditioning the myocardium using a novel axial flow catheter while delaying coronary reperfusion decreases LV wall stress and activates a myocardial protection program that up-regulates SDF-1α/CXCR4 expression, increases cardioprotective signaling, reduces apoptosis, and limits myocardial damage in AMI.

Diferencias según sexo en el tratamiento y la evolución de pacientes con síndrome coronario agudo / Gender differences in the treatment and outcome of patients with acuite coronary syndrome

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Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.

BACKGROUND: The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation. METHODS: We did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712. FINDINGS: Between June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events. INTERPRETATION: Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study. FUNDING: TransMedics.

An experimental model of myocardial infarction and controlled reperfusion using a miniaturized cardiopulmonary bypass in rats.

OBJECTIVES: Different revascularization strategies for patients with acute myocardial infarction (AMI) exist. It remains unclear whether ventricular unloading using cardiopulmonary bypass (CPB) or extracorporeal life support (ECLS) has an impact on early postischaemic ventricular function. Here, we report on the results of an approach using a miniaturized CPB in a well-established animal model of AMI. METHODS: In a randomized fashion, 30 male Wistar rats were assigned to temporary left anterior descending (LAD) ligation (30 min) followed by 180 min of reperfusion either with or without 60 min of CPB (70 ml/min, 36°C). The CPB circuit consisted of a venous reservoir, a peristaltic roller pump and a membrane oxygenator with heat exchanger. Cardiac function was measured at 60 and 120 min after reperfusion (F60, F120) using a conductance catheter. RESULTS: The mortality rate was 37% (11/30). Thus, 19 animals could be included into the analysis (8 CPB). The mean cardiac output did not differ between the groups at F60 [63 ± 29 vs 54 ± 25 ml/min (CPB), P = 0.56] and F120 [73 ± 27 vs 53 ± 24 ml/min (CPB), P = 0.21]. During reperfusion, the mean left ventricular ejection fraction (LVEF) was stable in both the control (F60 37 ± 5% vs F120 33 ± 8%, P = 0.42) and the CPB groups (F60 52 ± 11% vs F120 51 ± 13%, P = 0.71). CPB animals had a significantly better LVEF after reperfusion (F60 P = 0.007, F120 P = 0.01). CONCLUSIONS: In this animal model of AMI, the establishment of CPB resulted in a significantly better LVEF in comparison with conventional reperfusion only. This beneficial effect may have an impact on revascularization strategies and timing in patients presenting with AMI in the future.

El uso del acceso radial en la angioplastia primaria: resultados en 1.029 pacientes consecutivos y análisis en subgrupos desfavorables / Use of the radial approach in primary angioplasty: results in 1029 consecutive patients and analyses in unfavorable subgroups

INTRODUCCIÓN Y OBJETIVO:S: El acceso radial reduce las complicaciones vasculares tras la angioplastia primaria. El objetivo es examinar la factibilidad del acceso radial sistemático en la angioplastia primaria y evaluar cómo afecta a los subgrupos menos favorables. MÉTODOS: Se ha analizado a 1.029 pacientes consecutivos con síndrome coronario agudo con elevación del segmento ST tratados con angioplastia primaria. RESULTADOS: En el 93,1% de los pacientes, el acceso radial ha sido el acceso primario. La tasa de éxito de angioplastia primaria fue del 95,9%, y el 87,6% de los pacientes estaban libres de eventos clínicos a los 30 días del procedimiento. La tasa de cruce vascular fue del 3,0%, estable durante el periodo estudiado. La edad mayor de 75 años (odds ratio = 2,50; intervalo de confianza del 95%, 1,09-5,71; p = 0,03) y la historia de cardiopatía isquémica previa (odds ratio = 2,65, intervalo de confianza del 95%, 1,12-6,24; p = 0,02) fueron predictores de necesidad de cruce. En las mujeres y los mayores de 75 años, el uso del acceso femoral primario fue mayor. Sin embargo, en este subgrupo de pacientes el acceso radial no afectó a los tiempos de reperfusión ni al éxito de la angioplastia, aunque sí se observó una mayor tasa de cruce (el 10,9 frente al 2,6%; p = 0,006). En los pacientes en shock cardiogénico, el acceso radial se utilizó en el 51,5% de los casos, con tiempos de reperfusión y tasas de éxito de la angioplastia similares a los del acceso femoral, aunque con mayor necesidad de cruce. CONCLUSIONES: El acceso radial se puede utilizar de manera segura y eficaz en la mayoría de las angioplastias primarias. En mujeres de edad avanzada y en pacientes en shock, aumenta la necesidad de cruce sin penalizar los tiempos de reperfusión

INTRODUCTION AND OBJECTIVES: The transradial approach is associated with a reduction in vascular access-related complications after primary percutaneous coronary interventions. The purpose of this study was to examine the feasibility of the routine use of transradial access in primary angioplasty and to evaluate how it affects subgroups with less favorable characteristics. METHODS: We analyzed 1029 consecutive patients with an ST-segment elevation acute coronary syndrome treated with primary angioplasty. RESULTS: Transradial access was the primary approach in 93.1% of the patients. The success rate of primary angioplasty was 95.9%, and 87.6% of the patients were event-free 30 days after the procedure. Crossover was required in 3.0% of the patients with primary transradial access, and this rate remained stable over the years. Predictors of the need for crossover were age older than 75 years (odds ratio=2.50, 95% confidence interval, 1.09-5.71; P=.03) and a history of ischemic heart disease (odds ratio=2.65; 95% confidence interval, 1.12-6.24; P=.02). Primary transfemoral access use was higher in women older than 75 years. Use of the transradial approach in this subgroup did not affect reperfusion time or the success of angioplasty, although there was a greater need for crossover (10.9% vs 2.6%; P=.006). Among patients in cardiogenic shock, the transradial approach was used in 51.5%; reperfusion times and angioplasty success rates were similar to those obtained with transfemoral access, but there was a greater need for crossover. CONCLUSIONS: Transradial access can be used safely and effectively in most primary angioplasty procedures. In older women and in patients in cardiogenic shock, there is a higher crossover requirement, with no detriment to reperfusion time

Mortalidad intrahospitalaria por infarto agudo de miocardio. Relevancia del tipo de hospital y la atención dispensada. Estudio RECALCAR / In-hospital mortality due to acute myocardial infarction. Relevance of type of hospital and care provided. RECALCAR study

Introducción y objetivos. Investigar la relación entre mortalidad intrahospitalaria por infarto agudo de miocardio y tipología del hospital, servicio de alta y tratamiento dispensado. Métodos. Análisis retrospectivo de 100.993 altas por infarto en los hospitales del Sistema Nacional de Salud. La mortalidad se ajustó por riesgo utilizando los modelos del Institute of Clinical Evaluative Sciences (Canadá) y de los Centers for Medicare & Medicaid Services (Estados Unidos). Resultados. Las características de los hospitales son relevantes para explicar la variación de la probabilidad individual de morir por infarto (odds ratio mediana = 1,3561). La mortalidad intrahospitalaria ajustada por riesgo fue significativamente menor en los hospitales de los clusters 3 y 4 (500 a 1.000 camas y complejidad mediana-alta) que en hospitales de menos de 200 camas. El cluster 5 (más de 1.000 camas), que es muy heterogéneo, tenía mayor mortalidad que los clusters 3 y 4. Las diferencias de la mortalidad ajustada entre el grupo con mejores y peores resultados fueron del 6,74% (cluster 4) y el 8,49% (cluster 1) (p < 0,001). La mortalidad también fue menor cuando el servicio de cardiología se encargó del alta, así como cuando se practicó angioplastia. Conclusiones. Las características del hospital, ser atendido por un servicio de cardiología y el intervencionismo coronario se asocian con la supervivencia intrahospitalaria del paciente con infarto. Se recomienda la creación de redes asistenciales en el Sistema Nacional de Salud que favorezcan el intervencionismo coronario y la participación de los servicios de cardiología en el manejo de pacientes con infarto agudo de miocardio (AU)

Introduction and objectives. To investigate the relationship between in-hospital mortality due to acute myocardial infarction and type of hospital, discharge service, and treatment provided. Methods. Retrospective analysis of 100 993 hospital discharges with a principal diagnosis of myocardial infarction in hospitals of the Spanish National Health Service. In-hospital mortality was adjusted for risk following the models of the Institute for Clinical Evaluative Sciences (Canada) and the Centers for Medicare & Medicaid Services (United States). Results. Hospital characteristics are relevant to explain the variation in the individual probability of dying from myocardial infarction (median odds ratio: 1.3561). The risk-adjusted in-hospital mortality in cluster 3 and especially in cluster 4 hospitals (500 beds to 1000 beds and medium-high complexity) was significantly lower than in hospitals with less than 200 beds. Cluster 5 (more than 1000 beds), which includes a diverse group of hospitals, had a higher mortality rate than clusters 3 and 4. The adjusted mortality in the groups with the best and worst outcomes was 6.74% (cluster 4) and 8.49% (cluster 1), respectively. Mortality was also lower when the cardiology unit was responsible for the discharge or when angioplasty had been performed. Conclusions. The typology of the hospital, treatment in a cardiology unit, and percutaneous coronary intervention are significantly associated with the survival of a patient hospitalized for myocardial infarction. We recommend that the Spanish National Health Service establish health care networks that favor percutaneous coronary intervention and the participation of cardiology units in the management of patients with acute myocardial infarction (AU)

Development of a new selective coronary perfusion cannula.

The two most common types of coronary perfusion cannulae currently being used are the "balloon type", with a balloon at the tip, and the "fenestrated type", which has holes along the side near the tip. However, on occasion an unusually high perfusion pressure or a considerable amount of leakage is encountered during infusion of the cardioplegic solution. We have examined the properties of a newly developed Kochi Medical School (KMS)-type cannula and compared these to the properties of the balloon-type and fenestrated-type cannulae in an ex vivo experimental model that contains ostia of 4, 3, or 2 mm in diameter. Ejected flow velocity, circuit pressure, and the amount of leakage were measured at an infusion rate of 100 and 200 mL/min, with the latter two parameters measured under the counterpressure of 0 and 50 cmH2O to examine the influence of coronary vascular resistance. Without counterpressure, the balloon type presented with the highest flow velocity (263 cm/s at 200 mL/min) and perfusion pressure (64 mmHg at 200 mL/min) but without leakage. The fenestrated type yielded a considerable amount of leakage (40 % at an ostium size of 2 mm). The KMS type showed a lower flow velocity and circuit pressure with less leakage. Under 50 cmH2O counterpressure, however, only the KMS-type cannula could inject the water to any ostium size at both flow rates. These results suggest that the concept of the KMS-type cannula may be advantageous to achieving a secure infusion to a diseased coronary ostium.

Resultados tras 6 años de funcionamiento de la red asistencial de reperfusión coronaria de pacientes con infarto agudo de miocardio en la Comunidad de Galicia-Área Sur (PROGALIAM Sur) / Results after 6 years of the health care network for coronary reperfusion in patients with acute myocardial infarction in the southern area of Galicia (PROGALIAM-South)

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Contemporary pharmacological reperfusion in ST elevation myocardial infarction.

PURPOSE OF REVIEW: Fibrinolysis remains a key therapeutic alternative mode of reperfusion in patients with ST segment elevation myocardial infarction (STEMI). Its venerability relates to the wealth of clinical efficacy evidence, ease of administration, and broad applicability to the large number of patients who cannot receive mechanical reperfusion within a reasonable period of time. This review focuses on recent data that will further enhance the clinician's ability to deliver a pharmacological reperfusion strategy to this patient population. RECENT FINDINGS: Combined data from clinical trials as well as registry data support implementation of the guideline endorsed pharmacoinvasive strategy for patients unable to achieve rapid primary percutaneous coronary intervention. The most appropriate mode of reperfusion remains dependent upon the time from symptom onset to presentation as well as perceived delay to initiation of mechanical reperfusion therapy, and one strategy does not fit all patients at all times. Additional information is required in the growing population of elderly patients with STEMI to identify the most appropriate approach to reperfusion in this high-risk population. SUMMARY: Despite extensive investigation concerning the optimal management of STEMI over the last three decades, significant knowledge gaps exist and the efficient application of current evidence to clinical practice remains elusive.

Development of the orpheus perfusion simulator for use in high-fidelity extracorporeal membrane oxygenation simulation.

Despite its life-sustaining potential, extracorporeal membrane oxygenation (ECMO) remains a complex treatment modality for which close teamwork is imperative with a high risk of adverse events leading to significant morbidity and mortality. The provision of adequate training and continuing education is key in mitigating these risks. Traditional training for ECMO has relied predominantly on didactic education and hands-on water drills. These methods may overemphasize cognitive skills while underemphasizing technical skills and completely ignoring team and human factor skills. These water drills are often static, lacking the time pressure, typical alarms, and a sense of urgency inherent to actual critical ECMO scenarios. Simulation-based training provides an opportunity for staff to develop and maintain technical proficiency in high-risk, infrequent events without fear of harming patients. In addition, it provides opportunities for interdisciplinary training and improved communication and teamwork among team members (1). Although simulation has become widely accepted for training of practitioners from many disciplines, there are currently, to our knowledge, no commercially available dedicated high-fidelity ECMO simulators. Our article describes the modification of the Orpheus Perfusion Simulator and its incorporation into a fully immersive, high-fidelity, point-of-care ECMO simulation model.

Hospital process intervals, not EMS time intervals, are the most important predictors of rapid reperfusion in EMS Patients with ST-segment elevation myocardial infarction.

OBJECTIVE: To assess the relationship of emergency medical services (EMS) intervals and internal hospital intervals to the rapid reperfusion of patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We performed a secondary analysis of a prospectively collected database of STEMI patients transported to a large academic community hospital between January 1, 2004, and December 31, 2009. EMS and hospital data intervals included EMS scene time, transport time, hospital arrival to myocardial infarction (MI) team activation (D2Page), page to catheterization laboratory arrival (P2Lab), and catheterization laboratory arrival to reperfusion (L2B). We used two outcomes: EMS scene arrival to reperfusion (S2B) ≤90 minutes and hospital arrival to reperfusion (D2B) ≤90 minutes. Means and proportions are reported. Pearson chi-square and multivariate regression were used for analysis. RESULTS: During the study period, we included 313 EMS-transported STEMI patients with 298 (95.2%) MI team activations. Of these STEMI patients, 295 (94.2%) were taken to the cardiac catheterization laboratory and 244 (78.0%) underwent percutaneous coronary intervention (PCI). For the patients who underwent PCI, 127 (52.5%) had prehospital EMS activation, 202 (82.8%) had D2B ≤90 minutes, and 72 (39%) had S2B ≤90 minutes. In a multivariate analysis, hospital processes EMS activation (OR 7.1, 95% CI 2.7, 18.4], Page to Lab [6.7, 95% CI 2.3, 19.2] and Lab arrival to Reperfusion [18.5, 95% CI 6.1, 55.6]) were the most important predictors of Scene to Balloon ≤ 90 minutes. EMS scene and transport intervals also had a modest association with rapid reperfusion (OR 0.85, 95% CI 0.78, 0.93 and OR 0.89, 95% CI 0.83, 0.95, respectively). In a secondary analysis, Hospital processes (Door to Page [OR 44.8, 95% CI 8.6, 234.4], Page 2 Lab [OR 5.4, 95% CI 1.9, 15.3], and Lab arrival to Reperfusion [OR 14.6 95% CI 2.5, 84.3]), but not EMS scene and transport intervals were the most important predictors D2B ≤90 minutes. CONCLUSIONS: In our study, hospital process intervals (EMS activation, door to page, page to laboratory, and laboratory to reperfusion) are key covariates of rapid reperfusion for EMS STEMI patients and should be used when assessing STEMI care.

Validation of minimal luminal area measured by intravascular ultrasound for assessment of functionally significant coronary stenosis comparison with myocardial perfusion imaging.

OBJECTIVES: This study sought to evaluate the ability of minimal luminal area (MLA) measured by intravascular ultrasound (IVUS) to assess the functional significance of coronary artery disease. BACKGROUND: The use of IVUS to determine the functional significance of coronary artery lesions remains a matter for debate. METHODS: From our prospective IVUS imaging database, between July 2009 and April 2010, 170 coronary lesions in 150 patients who underwent stress myocardial single-photon emission computed tomography (SPECT) performed within 1 month of IVUS evaluation were identified and analyzed. MLA and other parameters were measured by IVUS and compared with the results of myocardial SPECT. RESULTS: Overall, 45 lesions had positive SPECT, and 125 lesions had negative SPECT. The MLA of lesions with positive SPECT was smaller than the MLA of those with negative SPECT (1.7 ± 0.5 mm² vs. 2.3 ± 1.1 mm², p < 0.001). By logistic regression analysis, MLA (odds ratio: 3.1 by decrease of 1 mm², 95% confidence interval [CI]: 1.75 to 5.5, p < 0.01) was an independent predictor of the positive SPECT. Using receiver-operator characteristic curve analysis, the best cutoff value of MLA was ≤ 2.1 mm² with an 86.7% sensitivity, a 50.4% specificity, a 38.6% positive predictive value, and a 91.3% negative predictive value versus lesions with a positive SPECT (area under the curve: 0.690, 95% CI: 0.615 to 0.759, p < 0.01). CONCLUSIONS: The best cutoff value of MLA measured by IVUS to predict myocardial ischemia was 2.1 mm². The IVUS-measured MLA appeared to play a limited role in detecting functionally significant lesions assessed by myocardial SPECT.

Comparison of titanium-nitride-oxide-coated stents with zotarolimus-eluting stents for coronary revascularization a randomized controlled trial.

OBJECTIVES: This study sought to compare the efficacy of passive stent coating with titanium-nitride-oxide (TiNO) with drug-eluting stents releasing zotarolimus (ZES) (Endeavor, Medtronic, Minneapolis, Minnesota). BACKGROUND: Stent coating with TiNO has been shown to reduce restenosis compared with bare-metal stents in experimental and clinical studies. METHODS: In an assessor-blind noninferiority study, 302 patients undergoing percutaneous coronary intervention were randomized to treatment with TiNO or ZES. The primary endpoint was in-stent late loss at 6 to 8 months, and analysis was by intention to treat. RESULTS: Both groups were well balanced with respect to baseline clinical and angiographic characteristics. The TiNO group failed to reach the pre-specified noninferiority margin for the primary endpoint (in-stent late loss: 0.64 ± 0.61 mm vs. 0.47 ± 0.48 mm, difference: 0.16, upper 1-sided 95% confidence interval [CI]: 0.26; p(noninferiority) = 0.54), and subsequent superiority testing was in favor of ZES (p(superiority) = 0.02). In-segment binary restenosis was lower with ZES (11.1%) than with TiNO (20.5%; p(superiority) = 0.04). A stratified analysis of the primary endpoint found particularly pronounced differences between stents among diabetic versus nondiabetic patients (0.90 ± 0.69 mm vs. 0.39 ± 0.38 mm; p(interaction) = 0.04). Clinical outcomes showed a similar rate of death (0.7% vs. 0.7%; p = 1.00), myocardial infarction (5.3% vs. 6.7%; p = 0.60), and major adverse cardiac events (21.1% vs. 18.0%, hazard ratio: 1.19, 95% CI: 0.71 to 2.00; p = 0.50) at 1 year. There were no differences in rates of definite or probable stent thrombosis (0.7% vs. 0%; p = 0.51) at 1 year. CONCLUSIONS: Compared with TiNO, ZES was superior with regard to late loss and binary restenosis. The concept of passive stent coating with TiNO remains inferior to drug-eluting stent technology in reducing restenosis. ([TIDE] Randomized Trial Comparing Titan Stent With Zotarolimus-Eluting Stent: NCT00492908).

Use of a hanging weight system for coronary artery occlusion in mice.

Murine studies of acute injury are an area of intense investigation, as knockout mice for different genes are becoming increasingly available. Cardioprotection by ischemic preconditioning (IP) remains an area of intense investigation. To further elucidate its molecular basis, the use of knockout mouse studies is particularly important. Despite the fact that previous studies have already successfully performed cardiac ischemia and reperfusion in mice, this model is technically very challenging. Particularly, visual identification of the coronary artery, placement of the suture around the vessel and coronary occlusion by tying off the vessel with a supported knot is technically difficult. In addition, re-opening the knot for intermittent reperfusion of the coronary artery during IP without causing surgical trauma adds additional challenge. Moreover, if the knot is not tied down strong enough, inadvertent reperfusion due to imperfect occlusion of the coronary may affect the results. In fact, this can easily occur due to the movement of the beating heart. Based on potential problems associated with using a knotted coronary occlusion system, we adopted a previously published model of chronic cardiomyopathy based on a hanging weight system for intermittent coronary artery occlusion during IP. In fact, coronary artery occlusion can thus be achieved without having to occlude the coronary by a knot. Moreover, reperfusion of the vessel can be easily achieved by supporting the hanging weights which are in a remote localization from cardiac tissues. We tested this system systematically, including variation of ischemia and reperfusion times, preconditioning regiments, body temperature and genetic backgrounds. In addition to infarct staining, we tested cardiac troponin I (cTnI) as a marker of myocardial infarction in this model. In fact, plasma levels of cTnI correlated with infarct sizes (R2=0.8). Finally, we could show in several studies that this technique yields highly reproducible infarct sizes during murine IP and myocardial infarction. Therefore, this technique may be helpful for researchers who pursue molecular mechanisms involved in cardioprotection by IP using a genetic approach in mice with targeted gene deletion. Further studies on cardiac IP using transgenic mice may consider this technique.

The in-situ pig heart with regional ischemia/reperfusion - ready for translation.

The pig heart in situ with regional myocardial ischemia and reperfusion is of unique translational value. Cardiac size, heart rate and blood pressure are similar to those in humans. The temporal and spatial development of myocardial infarction resembles that seen in humans. Technically, the pig heart permits precise control of coronary blood flow during ischemia and reperfusion, includes an intra-individual remote control zone for comparison, and permits the sequential sampling of microdialysates and biopsies for further biochemical, molecular and morphological analyses. Conceptually, all cardioprotective phenomena, including hibernation, ischemic preconditioning, ischemic postconditioning, and remote conditioning, have been demonstrated in pig hearts. The cardioprotective signalling is in part similar, but in part also different from that in rodent hearts.