Estudio de la afectación del ventrículo derecho en el infarto anterior reperfundido

La afectación del ventrículo derecho (VD) en el seno de un infarto agudo de miocardio de localización inferior, es de sobra conocida. Sin embargo, la vascularización de la cara anterior del VD depende de ramas de la arteria descendente anterior (ADA), siendo escasos los trabajos que estudian la afectación del VD que se produce durante un infarto agudo de miocardio de localización anterior. Evaluamos la afectación del VD que se produce tras la oclusión del ADA en un grupo experimental de 9 cerdos, al que le realizamos un modelo de isquemia-reperfusión percutánea mediante el hinchado de un balón de angioplastia en la ADA media durante 90 minutos, y en un grupo de pacientes con un primera infarto agudo de miocardio de localización anterior secundario a la oclusión trombótica de la ADA proximal, y estudiados mediante resonancia magnética cardiaca (RMC). Valoramos el área en riesgo de VD dependiente de la oclusión con balón de la ADA a partir de la infusión intracoronaria de tioflavina-S, Se consideró área en riesgo aquel porcentaje de volumen de miocardio que mostraba tintinó con tioflavina-S. Se valoró el área de necrosis a partir de la incubación de las piezas de corazón porcino en una solución de cloruro de 2-3-5 trifeniltetrazolio, se cualificaron como áreas de necrosis aquel porcentaje de volumen de miocardio que nos mostraba captación por 2-3-5 trifeniltetrazolio. Se cualificó el miocardio salvado como aquel porcentaje que mostraba tintinó con tioflavina-S y captación por 2-3-5 trifeniltetrazolio. En nuestro grupo de pacientes se valoró el área en riesgo a partir del análisis de las secuencias potenciadas en T2 y el área de necrosis mediante el análisis de las secuencias de realce tardío de gadolinio. Se consideró miocardio sacado aquel porcentaje de masa ventricular con hiperintensidad de señal en las secuencias potenciadas en T2 y que nos mostraba realce tardío de gadolinio. Obtuvimos en nuestro grupo experimental que tanto el VD como el ventrículo izquierdo (VI) mostraban tinción por tioflavina-S, es decir ambos ventrículos recibían irrigación por la ADA La cuantificación del área en riesgo fue del 30% del volumen de miocardio derecho y del 62% para VI. El 50% (4 animales) mostraron necrosis en el VD y el 100% en VI, sin embargo la extensión del área de necrosis de VD fue pequeño, el 2% del volumen de miocardio derecho, obteniendo por tanto una extensa área de miocardio salvado en VD. En nuestro grupo de pacientes, el 100% mostraron área de edema, es decir en riesgo tanto en VD como el VI, con un porcentaje del área en riesgo del 34% de la masa ventricular derecha. El 40% (8 pacientes) mostraron necrosis en VD, sin embargo la extensión del área de necrosis fue pequeña, observan también una extensa área de miocardio salvado, superior al 90% del área en riesgo. Concluimos, que tanto en un grupo experimental como en un grupo real de pacientes la oclusión de la ADA ocasiona un área en riesgo en VD, siendo el tamaño de la necrosis resultante pequeña y obteniendo una extensa área de miocardio salvado, lo que corrobora la resistencia a la isquemia del VD, debido fundamentalmente a su bajo consumo de oxígeno y a su extensa red de colaterales.Coronary heart disease is the leading cause of death in the Spanish population, and acute coronary syndromes are actually the main cause of mortality, morbidity and health care costs in Spain. In ischemic heart disease, much attention has been focused on the study and characterization of the left ventricle (LV), and the prognostic implications that LV dysfunction has in these patients, overshadowing the right ventricle (RV) and considering it dispensable for cardiac function and in consequence, it has been partly ignored. The right ventricle’s blood supply varies according to the coronary artery dominance. In a right-dominant system, the right coronary artery (RCA) distributes blood to most of the RV. Its lateral wall is supplied by the marginal branches, whereas the posterior wall and the inferoseptal region are supplied by the posterior descending artery. The anterior wall and the anteroseptal region are usually supplied by branches of the left anterior descending artery (LAD). The RV has besides, an excellent collateral system that originates from the moderator band, receiving blood supply from the first septal perforator branch which arises from the LAD. This feature, along with its low oxygen consumption and its capability to increase oxygen extraction, gives the RV a certain resistance to irreversible ischemia injury. Cardiac magnetic resonance (CMR) represents a non-invasive technique with increasing applications in acute myocardial infarction, and provides us with a wide range of information such as: identification of myocardial oedema (myocardium at risk), location of transmural necrosis, cuantification of infarct size and salvaged myocardium, and also identifying microvascular obstruction in a highly reproducible manner. Actually, is the gold standard technique for the evaluation of cardiac volumes and systolic function of RV. However, the literature that focuses on right ventricular involvement in the setting of an anterior myocardial infarction assessed by CMR is scarce. Our study was performed in an experimental group and in a group of patients with a first anterior ST segment elevation myocardial infarction (STEMI). Experimental Group: The study was approved by the Animal Care and Use Committee of the University of Valencia and it conforms with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85–23, revised 1996). It was performed in nine female domestic pigs employing a percutaneous reversible ischemia technique, after sedation and anesthesia of the animal. A 6-F sheath was introduced into the right femoral artery to measure blood pressure and to access the LAD. An Amplatz left 0.75 guiding catheter and a standard hydrophilic angioplasty wire were also used. Ischaemia was induced by inflating a 2.5 × 10 mm over the wire balloon up to four atmospheres in the mid LAD. Coronary artery occlusion was confirmed by contrast injection and by electrocardiographic ST-segment elevation. After 90 minutes, the LAD balloon was deflated and restoration of normal coronary flow was documented by angiography. After 72 hours, 20 mL of 4% thioflavin-S solution was selectively infused into the mid LAD using the same over the wire balloon. The hearts were then arrested with potassium chloride and excised. The necropsy pieces were incubated in 2% 2,3,5-triphenyltetrazolium chloride solution during 20 minutes at 37ºC. The LAD-perfused area in both, RV and LV, was defined as the percentage of the myocardial volume showing thioflavin-S staining. Infarct size was designated as the percentage of the myocardial volume that failed to stain with 2,3,5-triphenyltetrazolium chloride. The salvaged myocardium was regarded as the percentage of the LAD-perfused area showing 2,3,5-triphenyltetrazolium chloride staining. Group of patients: From January 2008 to December 2012, we prospectively included 106 patients admitted consecutively with a first STEMI, whose repercussion strategy was primary angioplasty and did not show contraindication for CMR. CMR was performed 4 ± 1 and 181 ± 11 days after STEMI. Steady-state free-precession sequences were used for cine and first-pass perfusion imaging, a dark-blood T2-weighted short-tau inversion-recovery turbo-spin echo sequence was applied for determining the area at risk (oedema) and a segmented inversion recovery steady-state free-precession sequence was used for late enhancement imaging. All images were acquired by a phased-array body surface coil during breath-holds and were ECG triggered. The 17-segment model for the LV and the nine-segment model for the RV were applied. In cine images, end-diastolic volume index (mL/m2 ), end-systolic volume index (mL/m2), ejection fraction (%), and left ventricular mass (g/m2) were quantified by manual definition of endocardial and epicardial borders of all short-axis slices. T2-weighted images were used to quantify the area at risk in the RV and LV. Area at risk was defined as the percentage of ventricular mass with signal intensity two standard deviations above the mean signal obtained in the remote non-infarcted myocardium (posterior wall). Increased signal intensity from the blood pool adjacent to the endocardium was excluded. Late enhancement imaging was used to define infarct size in the RV and LV. Infarct size was regarded as the percentage of ventricular mass with signal intensity two standard deviations above the mean signal obtained in the remote non-infarcted myocardium (posterior wall). The salvaged myocardium was regarded as the percentage of the area at risk without late enhancement. For the assessment of the area at risk, area of necrosis and RV systolic function after a first anterior STEMI, 20 patients with an excellent image quality in CMR were included. For the evaluation of the area at risk, area of necrosis and RV systolic function after a first inferior STEMI, 10 patients with an excellent image quality in CMR were included.An experimental model was developed using 9 domestic pigs, and performing a percutaneous model of reversible ischemia based on inflating during 90 minutes an angioplasty balloon in the mid LAD and the subsequent repercussion. During balloon inflation, five pigs developed ventricular fibrillation. Four of them reverted to a stable sinus rhythm after undergoing electrical cardioversion; but one developed a refractory ventricular fibrillation, resulting in asystole and death. None of the animals presented an occlusion or dissection of the LAD after deflation of the angioplasty balloon. Within 72 hours, a new catheterization was performed in order to infuse selectively 20 ml of thioflavin-S to 4% in the LAD, without notable complications. To quantify the area at risk of the right ventricle that depends on the left anterior descending artery. Intracoronary thioflavin-S was the dye used to identify the area at risk, obtaining an excellent staining quality in all cases. Thioflavin-S staining (LAD-perfused area) was detected both in the RV and in the LV in all cases. A large area of the anterior wall of the RV (30 5% of the myocardial volume) was perfused by LAD. In comparison, the LV displayed a significant larger LAD-perfused area (62 15% of the myocardial volume, p< 0.001) comprising all anterior, antero-lateral and antero-septal segments. To quantify the salvaged myocardium and necrosis of the right ventricle resulting from a transient occlusion of the mid left anterior descending artery with the angioplasty balloon. The area of necrosis was evaluated after the incubation of the necropsy pieces in a 2-3-5 triphenyltetrazolium chloride 2% solution at 37ºC during 20 minutes. Areas that showed no staining with 2-3-5 triphenyltetrazolium corresponded to areas of necrosis. The area of necrosis was detected in four cases in the RV (50%) and in eight (100%) in the LV (p= 0.04). A large percentage of salvaged myocardium was observed in the RV; 94 6% of the area supplied by the LAD showed no necrosis after staining with 2-3-5 triphenyltetrazolium, resulting in a very small RV infarction (2 1% of the RV myocardial volume). In comparison, the percentage of salvaged myocardium in the LV was significantly lower (73 11% of the area supplied by the LAD, p<0.001), resulting in a significantly larger infarct size (16 5% of the LV myocardial volume, p<0.001). To determine the area of the right ventricle that is supplied by the right coronary artery. On average, 65 ± 8% of the RV and 30 ± 6% of the LV were supplied by the RCA, showing thioflavin-S staining. This area comprised mainly the inferior and infero-septal segments of the LV, and the inferior and lateral segments of the RV. To analyze right ventricular systolic function by cardiac magnetic resonance in the first week and sixth month after ST segment elevation myocardial infarction, in a consecutive group of patients with a first ST segment elevation myocardial infarction and reperfused by primary angioplasty. In the CMR studies at first week and sixth month after STEMI, we observed a preserved systolic function of the RV at first week CMR (mean RV ejection fraction of 60 8%), which showed a significant improvement at sixth month CMR (62 8%, p=0.03). The patients were categorized in 2 groups according to the location of the infarction: anterior and non-anterior STEMI. We observed no significant differences regarding RV ejection fraction between both groups, neither at first week nor at sixth month CMR (61 ± 9% vs 59 ± 8%, p=0.2 at first week and 63 ± 8% vs 61 ± 8%, p=0.1 at sixth month). When comparing the ejection fraction evolution in both groups, we observed a significant improvement in right ventricular ejection fraction at sixth month in the non-anterior STEMI group (59.8 ± 8% at first week vs 61 ± 8% at sixth month, p=0.022). Patients in the anterior STEMI group showed a similar tendency, although non significant. When classifying our patients according to the reference criteria for RV dysfunction established by Maceira et al. 8 patients (16.7%) with an anterior STEMI and 13 (22.4%) patients with a non-anterior STEMI (p=0.6) showed a depressed RV ejection fraction at first week CMR. This result suggests that patients with a non- anterior STEMI have a tendency of more depressed RV ejection fraction at first week after STEMI. There was a significant decrease in the number of patients with depressed RV ejection fraction in the non-anterior STEMI group at sixth month CMR: first week 13 (22.4%) vs sixth month 4 (6.9%), (p=0.03). The anterior STEMI group showed a similar tendency, although non significant. To assess the area at risk, area of necrosis and the right ventricle systolic function by cardiac magnetic resonance in a group of patients with a first ST segment elevation myocardial infarction due to the thrombotic occlusion of the proximal left anterior descending artery and reperfused by primary angioplasty. All the analysed cases (100%) displayed a certain amount of area at risk in T2-weighted imaging, both in the RV and in the LV. Necrosis (late enhancement) was detected in four cases (40%) in the RV (p<0.001) and in 20 cases (100%) in the LV (p<0.001). A large area of the anterior wall of the RV was at risk (34 ± 13%), owing to a large area of salvaged myocardium (94 ± 10% of the area at risk) and resulting in a small RV infarct size (2 ± 3%). On the other hand, the LV displayed more myocardium at risk (43 ± 12%, p= 0.02). As a consequence of a lesser amount of salvaged myocardium (33 ± 26% of the area at risk, p< 0.001) the resulting infarct size (30 ± 16%, p< 0.001) was larger than in the RV. To assess the area at risk, area of necrosis and right ventricle systolic function by cardiac magnetic resonance in a group of patients with a first ST segment elevation myocardial infarction due to the thrombotic occlusion of the proximal right coronary artery and reperfused by primary angioplasty. All the analysed cases with inferior STEMI (100%) displayed a certain amount of area at risk in T2-weighted imaging, both in the RV and in the LV. The RV exhibited larger area at risk than in the LV (49 ± 9% vs 27 ± 11%, p=0.01). Necrosis (late enhancement) was detected in five cases (50%) in the RV and in 9 cases (90%) in the LV (p<0.001). However, the area of necrosis in the RV (6 ± 5%) was significantly smaller when compared with the area of necrosis in the LV (19± 10%, p=0.01).This was probably the result of the fact that salvaged myocardium was significantly higher in the RV (85 ± 29% of the area at risk) when compared with the LV (28 ± 19%, p=0.01)

Hemorragia alveolar difusa como complicación del síndrome coronario agudo

El tratamiento anticoagulante y antiagregante del síndrome coronario agudo puede derivar en complicaciones hemorrágicas graves. Una complicación que puede pasar desapercibida es la hemorragia alveolar difusa que causa insuficiencia respiratoria aguda y que es potencialmente mortal. Se presentan dos casos del síndrome coronario agudo complicados con la hemorragia alveolar. Se discuten los factores predisponentes, el diagnóstico y el tratamiento de esta entidad

Incidencia de oclusión radial en pacientes sometidos a cateterismo cardiaco

Introduction and Objectives: The radial artery is the access of choice when performing cardiac catheterization, a procedure indicated for the diagnosis and treatment of coronary artery diseases. Despite complications such as vasospasm or arterial occlusion, this access is shown to be the one that offers the lowest number of complications. The aim of this study was to know the incidence of radial occlusion after performing cardiac catheterization in our workplace. The secondary aim was to establish possible relationships between the variables collected in the study and radial occlusion. Material and Methods: Prospective descriptive study, with a sample of 93 consecutive patients from October 2015 to February 2016. The incidence of radial occlusion has been measured 30 days after cardiac catheterization by a modified Allen test and pulsioxymetry. Results: An incidence of radial artery occlusion was observed in 7 patients (7.5%) 30 days after catheterization, and only the presence of dyslipidemia is statistically significant as a protective factor against radial occlusion. Conclusion: The occlusion rate in different studies shows a wide range of results, between 1-30% depending on the studies, and it is therefore difficult to compare our results. It is certainly true that there are results around 1% in our environment with which we should compare ourselves so as to try to reduce this incidence. Dyslipidemia as a protective factor against occlusion is not found in further studies analyzed, so it could be due to chance. In order to know it, it would be necessary to follow up a larger size sample.Introducción y Objetivos: La arteria radial es el acceso de elección en la realización del cateterismo cardiaco, procedimiento indicado para el diagnóstico y tratamiento de enfermedades de las arterias coronarias. A pesar de existir complicaciones como el vasoespasmo o la oclusión arterial, este acceso se presenta como el que ofrece menor número de complicaciones. El objetivo de este estudio fue conocer la incidencia de oclusión radial tras la realización de cateterismo cardiaco en nuestro centro de trabajo. El objetivo secundario fue establecer posibles relaciones entre las variables recogidas en el estudio y la oclusión radial. Material y Métodos: Estudio descriptivo prospectivo, con una muestra de 93 pacientes consecutivos entre octubre de 2015 y febrero de 2016. Se ha medido la incidencia de oclusión radial 30 días poscateterismo cardiaco mediante test de Allen modificado y pulsioximetría. Resultados: Se observó una incidencia de oclusión de arteria radial en 7 pacientes (7,5 %) 30 días poscateterismo y únicamente la presencia de dislipemia resulta estadísticamente significativa como factor protector de oclusión radial. Conclusión: La tasa de oclusión en diferentes estudios se muestra en una amplia horquilla de resultados, entre 1-30% según estudios, por lo que es difícil comparar nuestros resultados. Sí es cierto que existen resultados en torno al 1% en nuestro entorno con los que deberíamos compararnos para intentar reducir esta incidencia. Dislipemia como factor protector de oclusión no se encuentra en más estudios analizados por lo que podría ser debido al azar. Para saberlo sería necesario realizar un seguimiento a una muestra mayor

Plasma neutrophil gelatinase-associated lipocalin and long-term mortality in patients with acute heart failure and normal renal function

Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a renal tubular marker for early renal dysfunction [1]. Recent studies highlighted its role in predicting acute kidney injury (AKI) and clinical outcomes in a wide range of cardiovascular diseases [2], [3], [4] and [5]. However, in heart failure (HF), conflicting results have been reported [4], [5], [6] and [7] and some ambiguities still prevail about the prognostic utility of NGAL beyond standard prognosticators and traditional renal biomarkers. We aimed to evaluate the independent ability of serum NGAL for predicting long-term mortality in patients admitted for acute HF (AHF). We prospectively enrolled 206 patients consecutively admitted for AHF in the Cardiology Department of a third level centre from April 30th 2010 to March 1st 2011. We excluded patients with a diagnosis of pneumonia, sepsis, acute coronary syndrome or end-stage renal failure on dialysis or imminent need of dialysis. Demographic data, medical history, vital signs, 12-lead electrocardiogram, and laboratory data were determined on admission. Left ventricular ejection fraction (LVEF) was assessed by echocardiography during index hospitalization. Treatment was individualized following established guidelines [8]

In-hospital versus after-discharge complete revascularization in patients with ST segment elevation myocardial infarction and multivessel disease. REVIVA-ST trial.

IntroductionComplete revascularization (CR) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD), is associated with a reduction in major adverse cardiovascular events (MACE). However, there is uncertainty about whether nonculprit-lesion revascularization should be performed, during index hospitalization or delayed, especially regarding health care resources utilization. In this study, we aimed to evaluate the impact of in-hospital nonculprit-lesion revascularization vs. delayed (after discharge) revascularization on the length of index hospitalization.MethodsIn this single-center study, we randomly assigned patients with STEMI and MVD who underwent successful culprit-lesion PCI to a strategy of either CR during in-hospital admission or a delayed CR after discharge. The first primary endpoint was the length of hospital stay. The second endpoint was the composite of cardiovascular death, myocardial infarction or ischemia-driven revascularization at 12 months (MACE).ResultsFrom January 2018 to December 2022, we enrolled 258 patients (131 allocated to CR during in-hospital admission and 127 to an after-discharge CR). We found a significant reduction in the length of hospital stay in those assigned to after-discharge CR strategy [4 days (3-5) versus 7 days (5-9); p = 0.001]. At 12-month of follow-up, no differences were found in the occurrence of MACE, 7 (5.34%) patients in in-hospital CR and 4 (3.15%) in after-discharge CR strategy; (hazard ratio, 0.59; 95% confidence interval, 0.17 to 2.02; p = 0.397).ConclusionsIn STEMI patients with MVD, an after-discharge CR strategy reduces the length of index hospitalization without an increased risk of MACE after 12 months of follow-up.Trial registrationClinicalTrials.gov number: NCT04743154

Resultados de la estrategia farmacoinvasiva y de la angioplastia primaria en la reperfusión del infarto con elevación del segmento ST. Estudio con resonancia magnética cardiaca en la primera semana y en el sexto mes

[EN] Introduction and objectives: Pharmacoinvasive strategy represents an attractive alternative to primary angioplasty. Using cardiovascular magnetic resonance imaging we compared the left ventricular outcome of the pharmacoinvasive strategy and primary angioplasty for the reperfusion of ST-segment elevation myocardial infarction. Methods: Cardiovascular magnetic resonance was performed 1 week and 6 months after infarction in two consecutive cohorts of patients included in a prospective university hospital ST-segment elevation myocardial infarction registry. During the period 2004-2006, 151 patients were treated with pharmacoinvasive strategy (thrombolysis followed by routine non-immediate angioplasty). During the period 2007-2008, 93 patients were treated with primary angioplasty. A propensity score matched population was also evaluated. Results: At 1-week cardiovascular magnetic resonance, pharmacoinvasive strategy and primary angioplasty patients showed a similar extent of area at risk (29 ± 15 vs. 29 ± 17%, P = .9). Non-significant differences were detected by cardiovascular magnetic resonance at 1 week and at 6 months in infarct size, salvaged myocardium, microvascular obstruction, ejection fraction, end-diastolic volume index and end-systolic volume index (P > .2 in all cases). The same trend was observed in 1-to-1 propensity score matched patients. The rate of major adverse cardiac events (death and/or re-infarction) at 1 year was 6% in pharmacoinvasive strategy and 7% in primary angioplasty patients (P = .7). Conclusions: A pharmacoinvasive strategy including thrombolysis and routine non-immediate angioplasty represents a widely available and logistically attractive approach that yields identical short-term and long-term cardiovascular magnetic resonance-derived left ventricular outcome compared to primary angioplasty. © 2010 Sociedad Española de Cardiología.The present study was supported by the "Instituto de Salud Carlos III'' (PI080128 and Heracles grants).Bodí, V.; Rumiz, E.; Merlos, P.; Nunez, J.; Lopez-Lereu, MP.; Monmeneu, JV.; Chaustre Mendoza, LF.... (2011). One-Week and 6-month cardiovascular magnetic resonance outcome of the pharmacoinvasive strategy and primary angioplasty for the reperfusión of ST-segment elevation myocardial infarction. Revista Española de Cardiología. 64(2):111-120. https://doi.org/10.1016/j.rec.2010.10.010S11112064

Prognostic implications of dipyridamole cardiac MR imaging: a prospective multicenter registry

Purpose: To evaluate dipyridamole cardiac magnetic resonance (MR) imaging in the prediction of major events (MEs) in patients with ischemic chest pain in a large multicenter registry. Materials and Methods: Institutional ethics committee approval and written informed consent were obtained. A total of 1722 patients who were undergoing cardiac MR imaging for chest pain were included. Wall motion abnormalities (WMAs) at rest, hyperemia perfusion defect (PD), late gadolinium enhancement (LGE), and inducible WMA were analyzed (abnormal if more than one abnormal segment was seen) with the 17-segment model. A cardiac MR categorization was created: category 1, no PD, LGE, or inducible WMA; category 2, PD without LGE and inducible WMA; category 3, LGE without inducible WMA; and category 4, inducible WMA. The association with ME was analyzed by using Cox proportional hazard regression multivariate models. Results: During a median follow-up period of 308 days, 61 MEs (4%) occurred (36 cardiac deaths, 25 nonfatal myocardial infarctions). MEs were associated with a greater extent of WMA, PD, LGE, and inducible WMA (P ¿ .001 for all analyses). In multivariable analyses, PD (P = .002) and inducible WMA (P = .0001) were the only cardiac MR predictors. ME rate in categories 1, 2, 3, and 4 was 2% (14 of 901 patients), 3% (six of 219 patients), 4% (15 of 409 patients), and 14% (26 of 193 patients), respectively (category 4 vs category 1, adjusted P < .001). Cardiac MR¿directed revascularization was performed in 242 patients (14%) and reduced the risk of ME in only category 4 (7% [six of 92 patients] vs 26% [26 of 101 patients], P = .0004). Conclusion: Dipyridamole cardiac MR imaging can be used to predict MEs in patients with ischemic chest pain. Patients with inducible WMA are at the highest risk for MEs and benefit the most from revascularization.Bodi, V.; Husser, O.; Sanchis, J.; Núñez, J.; Monmeneu, JV.; López-Lereu, MP.; Bosch, MJ.... (2012). Prognostic implications of dipyridamole cardiac MR imaging: a prospective multicenter registry. Radiology. 262(1):91-100. doi:10.1148/radiol.11110134S91100262

Metabolomic Profile of Human Myocardial Ischemia by Nuclear Magnetic Resonance Spectroscopy of Peripheral Blood Serum A Translational Study Based on Transient Coronary Occlusion Models

Objectives The aim of this study was to investigate the metabolomic profile of acute myocardial ischemia (MIS) using nuclear magnetic resonance spectroscopy of peripheral blood serum of swine and patients undergoing angioplasty balloon-induced transient coronary occlusion. Background Biochemical detection of MIS is a major challenge. The validation of novel biosignatures is of utmost importance. Methods High-resolution nuclear magnetic resonance spectroscopy was used to profile 32 blood serum metabolites obtained (before and after controlled ischemia) from swine (n = 9) and patients (n = 20) undergoing transitory MIS in the setting of planned coronary angioplasty. Additionally, blood serum of control patients (n = 10) was sequentially profiled. Preliminary clinical validation of the developed metabolomic biosignature was undertaken in patients with spontaneous acute chest pain (n = 30). Results Striking differences were detected in the blood profiles of swine and patients immediately after MIS. MIS induced early increases (10 min) of circulating glucose, lactate, glutamine, glycine, glycerol, phenylalanine, tyrosine, and phosphoethanolamine; decreases in choline-containing compounds and triacylglycerols; and a change in the pattern of total, esterified, and nonesterified fatty acids. Creatine increased 2 h after ischemia. Using multivariate analyses, a biosignature was developed that accurately detected patients with MIS both in the setting of angioplasty-related MIS (area under the curve 0.94) and in patients with acute chest pain (negative predictive value 95%). Conclusions This study reports, to the authors' knowledge, the first metabolic biosignature of acute MIS developed under highly controlled coronary flow restriction. Metabolic profiling of blood plasma appears to be a promising approach for the early detection of MIS in patients. (J Am Coll Cardiol 2012;59:1629-41) (c) 2012 by the American College of Cardiology FoundationFrom the *Cardiology Department, Hospital Clinico Universitario-INCLIVA, Universidad de Valencia, Valencia, Spain; dagger Unidad Central de Investigacion en Medicina, Universidad de Valencia, Valencia, Spain; double dagger Centro de Biomateriales e Ingenier a Tisular, Universidad Politecnica de Valencia, Valencia, Spain; Department of Clinical Analyses, Hospital Clinico Universitario-INCLIVA, Valencia, Spain; parallel to Cardiology Department, Hospital Clinic, IDIBAPS, Universidad de Barcelona, Barcelona, Spain; Department of Biochemistry and Molecular Biology, Facultad de Medicina, Universidad de Valencia, Valencia, Spain; and the #Fundacion Investigacion, Hospital Clinico Universitario-INCLIVA, Valencia, Spain. The present study was supported by Instituto de Salud Carlos III (PI 11/02323 and Heracles grants to Dr. Bodi), Fundacion Gent per Gent (to Drs. Bodi and Monleon), the Ministry of Science and Innovation of Spain (grant SAF2008- 00270 to Dr. Monleon), and Generalitat Valenciana (grant GVASAN AP014/2009 to Dr. Monleon and grant PROMETEO2010-075 to Dr. Vina). Dr. Monleon gratefully acknowledges a 2006 Ramon y Cajal contract from the Ministry of Education of Spain. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.Bodi, V.; Sanchis, J.; Morales, JM.; Marrachelli, VG.; Nunez, J.; Forteza, MJ.; Chaustre Mendoza, LF.... (2012). Metabolomic Profile of Human Myocardial Ischemia by Nuclear Magnetic Resonance Spectroscopy of Peripheral Blood Serum A Translational Study Based on Transient Coronary Occlusion Models. Journal of the American College of Cardiology. 59(18):1629-1641. https://doi.org/10.1016/j.jacc.2011.09.083S16291641591