Maria J. Forteza

Prognostic value of a comprehensive cardiac magnetic resonance assessment soon after a first ST-segment elevation myocardial infarction.

OBJECTIVES To evaluate the prognostic value of a comprehensive cardiac magnetic resonance (CMR) assessment soon after a first ST-segment elevation myocardial infarction (STEMI). BACKGROUND CMR allows for a simultaneous assessment of wall motion abnormalities (WMA), WMA with low-dose dobutamine (WMA-dobutamine), microvascular obstruction, and transmural necrosis. This approach has been proven to be useful to predict late systolic recovery soon after STEMI. Its prognostic value and the relative prognostic weight of these indexes are not well-defined. METHODS We studied 214 consecutive patients with a first STEMI treated with thrombolytic therapy or primary angioplasty discharged from hospital. In the first week (7 +/- 1 day after infarction), with CMR we determined the extent (number of segments) of WMA, WMA-dobutamine, microvascular obstruction, and transmural necrosis. RESULTS During a median follow-up of 553 days, 21 major adverse cardiac events (MACE) including 4 cardiac deaths, 6 nonfatal myocardial infarctions, and 11 readmissions for heart failure were documented. The MACE was associated with a larger extent of WMA (8 +/- 4 segments vs. 5 +/- 3 segments, p < 0.001), WMA-dobutamine (6 +/- 4 segments vs. 4 +/- 3 segments, p = 0.004), microvascular obstruction (3 +/- 3 segments vs. 1 +/- 2 segments p <0.001), and transmural necrosis (7 +/- 3 segments vs. 3 +/- 3 segments, p < 0.001). In a complete multivariate analysis that included baseline characteristics, electrocardiogram, biomarkers, angiography, ejection fraction, left ventricular volumes, and all CMR indexes, WMA/segment (hazard ratio: 1.29 [95% confidence interval: 1.11 to 1.49], p = 0.001) and the extent of transmural necrosis/segment (hazard ratio: 1.30 [95% confidence interval: 1.12 to 1.51], p < 0.001) were the only independent prognostic variables. CONCLUSIONS A comprehensive CMR assessment is useful for stratifying risk soon after STEMI, but only the extent of systolic dysfunction and of transmural necrosis provide independent prognostic information.

Right ventricular involvement in anterior myocardial infarction: a translational approach

AIMS The aim of the present study was to evaluate the involvement of the right ventricle (RV) in reperfused anterior ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS Left anterior descending (LAD)-perfused area (using thioflavin-S staining after selective infusion in proximal LAD artery, %), infarct size (using triphenyltetrazolium chloride staining, %), and salvaged myocardium (% of LAD-perfused area) in the right and left ventricle (LV) were quantified in a 90-min LAD occlusion 3-day reperfusion model in swine (n = 8). Additionally, we studied, using cardiovascular magnetic resonance, 20 patients with a first STEMI due to proximal LAD occlusion treated with primary angioplasty. Area at risk (T2-weighted sequence, %), infarct size (late enhancement imaging, %), and salvaged myocardium (% of area at risk) in the right and LV were quantified. In swine, a large LAD-perfused area was detected both in the right and LV (30 +/- 5 vs. 62 +/- 15%, P< 0.001) but more salvaged myocardium (94 +/- 6 vs. 73 +/- 11%, P< 0.001) resulted in a smaller right ventricular infarct size (2 +/- 1 vs. 16 +/- 5%, P< 0.001). Similarly, in patients a large area at risk was detected both in the right and LV (34 +/- 13 vs. 43 +/- 12%, P = 0.02). More salvaged myocardium (94 +/- 10 vs. 33 +/- 26%, P < 0.001) resulted in a smaller infarct size (2 +/- 3 vs. 30 +/- 16%, P< 0.001) in the RV. CONCLUSION In reperfused extensive anterior STEMI, a large area of the RV is at risk but the resultant infarct size is small.

Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine.

BACKGROUND Ischemic postconditioning (PCON) appears as a potentially beneficial tool in ST-segment elevation myocardial infarction (STEMI). We evaluated the effect of PCON on microvascular obstruction (MVO) in STEMI patients and in an experimental swine model. METHODS A prospective randomized study in patients and an experimental study in swine were carried out in two university hospitals in Spain. 101 consecutive STEMI patients were randomized to undergo primary angioplasty followed by PCON or primary angioplasty alone (non-PCON). Using late gadolinium enhancement cardiovascular magnetic resonance, infarct size and MVO were quantified (% of left ventricular mass). In swine, using an angioplasty balloon-induced anterior STEMI model, MVO was defined as the % of area at risk without thioflavin-S staining. RESULTS In patients, PCON (n=49) in comparison with non-PCON (n=52) did not significantly reduce MVO (0 [0-1.02]% vs. 0 [0-2.1]% p=0.2) or IS (18 ± 13% vs. 21 ± 14%, p=0.2). MVO (>1 segment in the 17-segment model) occurred in 12/49 (25%) PCON and in 18/52 (35%) non-PCON patients, p=0.3. No significant differences were observed between PCON and non-PCON patients in left ventricular volumes, ejection fraction or the extent of hemorrhage. In the swine model, MVO occurred in 4/6 (67%) PCON and in 4/6 (67%) non-PCON pigs, p=0.9. The extent of MVO (10 ± 7% vs. 10 ± 8%, p=0.9) and infarct size (23 ± 14% vs. 24 ± 10%, p=0.8) was not reduced in PCON compared with non-PCON pigs. CONCLUSIONS Ischemic postconditioning does not significantly reduce microvascular obstruction in ST-segment elevation myocardial infarction. Clinical Trial Registration http://www.clinicaltrials.gov. Unique identifier: NCT01898546.

La suma de la elevación del segmento ST predice mejor la obstrucción microvascular en pacientes tratados con éxito con una intervención coronaria percutánea primaria. Un estudio de resonancia magnética cardiovascular

Introduccion y objetivos La utilidad de la resolucion del segmento ST (RST) para la prediccion de la reperfusion epicardica esta bien establecida. La asociacion de los cambios del segmento ST con la obstruccion microvascular (OMV) observada en la resonancia magnetica cardiovascular (RMC) tras una intervencion coronaria percutanea primaria (ICPp) en el infarto de miocardio con elevacion del ST (IMEST) no se ha aclarado todavia. Metodos Estudiamos a 85 pacientes consecutivos ingresados por un primer IMEST y tratados con una ICPp que tenian una arteria relacionada con el infarto permeable. Se registro un ECG al ingreso, tras 90 min y tras 6, 24, 48 y 96 h de la ICPp. Se calculo la RST y la suma de la elevacion del ST (sumEST) en todas las derivaciones. Resultados La RMC revelo una OMV en 37 pacientes. En los infartos con OMV, el valor de la sumEST antes y despues de la revascularizacion fue mayor que en los infartos sin OMV (p ≤ 0,001 en todos los casos). En cambio, no hubo diferencias significativas en la cantidad de RST entre los infartos con y sin OMV a los 90 min de la revascularizacion (p = 0,1), sino solo a partir de las 6 h (p 3 mm a los 90 min de la ICPp, pero no una RST ≥ 70%, predijo de manera independiente la OMV observada en la RMC ( odds ratio = 3,1; intervalo de confianza del 95%, 1,2-8,4; p = 0,02). Conclusiones La OMV se asocio a un valor significativamente superior de la sumEST en todos los momentos de valoracion tras la revascularizacion. La diferencia en la cantidad de RST entre los infartos con OMV y sin OMV solo fue significativa a partir de las 6 h tras la revascularizacion. La OMV se predijo mejor con una sumEST > 3 mm a los 90 min de la ICPp.

Prediction of Reverse Remodeling at Cardiac MR Imaging Soon after First ST-Segment–Elevation Myocardial Infarction: Results of a Large Prospective Registry

PURPOSE To assess predictors of reverse remodeling by using cardiac magnetic resonance (MR) imaging soon after ST-segment-elevation myocardial infarction (STEMI). MATERIALS AND METHODS Written informed consent was obtained from all patients, and the study protocol was approved by the institutional committee on human research, ensuring that it conformed to the ethical guidelines of the 1975 Declaration of Helsinki. Five hundred seven patients (mean age, 58 years; age range, 24-89 years) with a first STEMI were prospectively studied. Infarct size and microvascular obstruction (MVO) were quantified at late gadolinium-enhanced imaging. Reverse remodeling was defined as a decrease in left ventricular (LV) end-systolic volume index (LVESVI) of more than 10% from 1 week to 6 months after STEMI. For statistical analysis, a simple (from a clinical perspective) multiple regression model preanalyzing infarct size and MVO were applied via univariate receiver operating characteristic techniques. RESULTS Patients with reverse remodeling (n = 211, 42%) had a lesser extent (percentage of LV mass) of 1-week infarct size (mean ± standard deviation: 18% ± 13 vs 23% ± 14) and MVO (median, 0% vs 0%; interquartile range, 0%-1% vs 0%-4%) than those without reverse remodeling (n = 296, 58%) (P < .001 in pairwise comparisons). The independent predictors of reverse remodeling were infarct size (odds ratio, 0.98; 95% confidence interval [CI]: 0.97, 0.99; P = .04) and MVO (odds ratio, 0.92; 95% CI: 0.86, 0.99; P = .03). Once infarct size and MVO were dichotomized by using univariate receiver operating characteristic techniques, the only independent predictor of reverse remodeling was the presence of simultaneous nonextensive infarct-size MVO (infarct size < 30% of LV mass and MVO < 2.5% of LV mass) (odds ratio, 3.2; 95% CI: 1.8, 5.7; P < .001). CONCLUSION Assessment of infarct size and MVO with cardiac MR imaging soon after STEMI enables one to make a decision in the prediction of reverse remodeling.

Linfopenia post-reperfusión y obstrucción microvascular en el infarto agudo de miocardio con elevación del segmento ST

Introduccion y objetivos La obstruccion microvascular tras un infarto agudo de miocardio con elevacion del segmento ST se asocia a mal pronostico. La fisiopatologia de este fenomeno no esta totalmente definida. Analizamos las implicaciones de la linfopenia post-reperfusion en la existencia de obstruccion microvascular. Metodos Estudiamos prospectivamente a 212 pacientes que habian sufrido un primer infarto agudo de miocardio con elevacion del segmento ST reperfundido con agentes tromboliticos o con angioplastia primaria y con la arteria responsable abierta. Cuantificamos de manera seriada las cifras de linfocitos, neutrofilos y monocitos. Usamos la resonancia magnetica cardiaca para determinar la existencia de obstruccion microvascular en la primera semana post-infarto. Se repitio el estudio a los 6 meses del infarto. Resultados Detectamos obstruccion microvascular en 67 (32%) pacientes. Observamos que una cifra de linfocitos post-reperfusion Conclusiones En el infarto de miocardio con elevacion del segmento ST, la linfopenia post-reperfusion es un predictor precoz y potente de la existencia de obstruccion microvascular. Las posibles implicaciones fisiopatologicas y terapeuticas de esta asociacion requieren mas estudios.

The sum of ST-segment elevation is the best predictor of microvascular obstruction in patients treated successfully by primary percutaneous coronary intervention. Cardiovascular magnetic resonance study.

INTRODUCTION AND OBJECTIVES The usefulness of ST-segment elevation resolution (STR) for predicting epicardial reperfusion is well established. However, it is still not clear how ST-segment changes are related to microvascular obstruction (MVO) observed by cardiovascular magnetic resonance (CMR) after primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI). METHODS The study involved 85 consecutive patients admitted for a first STEMI and treated by pPCI who had a patent infarct-related artery. An ECG was recorded on admission and 90 min and 6, 24, 48 and 96 h after pPCI. Thereafter, STR and the sum of ST-segment elevation (sumSTE) in all leads were determined. RESULTS Overall, CMR revealed MVO in 37 patients. In infarcts with MVO, sumSTE was greater both before and after revascularization than in infarcts without MVO (P≤.001 at all times). In contrast, there was no significant difference in the magnitude of STR between infarcts with and without MVO 90 min after revascularization (P=.1), though there was after 6 h (P< .05 at all times). The area under the receiver operating characteristic curve for detecting MVO was greater for sumSTE than STR (P< .05 for all measurements). On multivariate analysis, after adjusting for clinical, angiographic and ECG characteristics, a sumSTE >3 mm 90 min after pPCI was an independent predictor of MVO on CMR, while an STR ≥70% was not (odds ratio=3.1; 95% confidence interval, 1.2-8.4; P=.02). CONCLUSIONS MVO was associated with a significantly increased sumSTE at all times after revascularization. The difference in the magnitude of STR between infarcts with and without MVO was significant only >6 h after revascularization. The best predictor of MVO was a sumSTE >3 mm 90 min after pPCI.

Predictors of cardiovascular magnetic resonance-derived microvascular obstruction on patient admission in STEMI

BACKGROUND Early stratification of patients according to the risk for developing microvascular obstruction (MVO) after ST-segment elevation myocardial infarction (STEMI) is desirable. We aimed to identify predictors of cardiovascular magnetic resonance (CMR)-derived MVO from clinical+ECG, laboratory and angiographic parameters available on admission. METHODS Characteristics available on admission were documented in 97 STEMI patients referred for primary angioplasty. MVO was determined using contrast-enhanced CMR. RESULTS MVO was present in 44 patients (45%). The C-statistic for predicting MVO was: clinical+ECG (.832), laboratory (.743), and angiographic parameters (.669). Adding laboratory to clinical+ECG information did not improve the C-statistic (.873 vs. .832, p=.2). Further addition of angiographic data (.904) improved the C-statistic of clinical+ECG (p=.04) but not of clinical+ECG and laboratory (p=.2). Independent predictors of MVO using clinical and ECG parameters were: Killip class >1 (OR 15.97 95%CI [1.37-186.76], p=.03), diabetes (OR 6.15 95%CI [1.49-25.39], p=.01), age <55years (OR 4.70 95%CI [1.56-14.17], p=.006), sum of ST-segment elevation >10mm (OR 4.5 95%CI [1.58-12.69], p=.005) and delayed presentation >3h (OR 3.80 95%CI [1.19-12.1], p=.02). A score was constructed assigning Killip class >1 2 points and the remaining indexes 1 point. The incidence of MVO increased with the score: 0 point: 8.7%; 1 point: 28.1%; 2 points: 71.4%; and 3+ points: 93% (p<.0001). CONCLUSIONS MVO can be predicted using parameters already available on patient admission. We developed a clinical-ECG score allowing for early and reliable classification of STEMI patients according to the risk of MVO.

Post-Reperfusion Lymphopenia and Microvascular Obstruction in ST-Segment Elevation Acute Myocardial Infarction

INTRODUCTION AND OBJECTIVES The presence of microvascular obstruction after ST-segment elevation acute myocardial infarction is associated with a poor outcome. The pathophysiology of this process has not been fully defined. The aim of this study was to investigate the relationship between post-reperfusion lymphopenia and microvascular obstruction. METHODS This prospective study involved 212 patients with a first ST-segment elevation acute myocardial infarction who underwent reperfusion with thrombolytic agents or primary angioplasty and who had an open infarct-related artery. Serial measurements of lymphocyte, neutrophil and monocyte counts were taken. Cardiac magnetic resonance was used to detect microvascular obstruction during the first week after the infarction. Imaging was repeated 6 months after infarction. RESULTS Microvascular obstruction was observed in 67 patients (32%). A post-reperfusion lymphocyte count <1800 cells/ml was associated with a higher risk of microvascular obstruction (44% versus 20%; P< .001) as well as with a low left ventricular ejection fraction and large left ventricular volumes (P< .05). After adjustment for baseline characteristics, ECG findings, necrosis marker levels and angiographic variables, multivariate analysis showed that a post-reperfusion lymphocyte count <1800 cells/ml was independently associated with an increased risk of microvascular obstruction (odds ratio=3.2; 95% confidence interval 1.6-6.3; P< .001). CONCLUSIONS In ST-segment elevation myocardial infarction, post-reperfusion lymphopenia is an early and powerful predictor of the presence of microvascular obstruction. The pathophysiological and therapeutic implications of this association require further study.

Inhomogeneity of collagen organization within the fibrotic scar after myocardial infarction: results in a swine model and in human samples

We aimed to characterize the organization of collagen within a fibrotic scar in swine and human samples from patients with chronic infarctions. Swine were subjected to occlusion of the left anterior descending artery followed by reperfusion 1 week (acute myocardial infarction group) or 1 month (chronic myocardial infarction group) after infarction. The organization of the collagen fibers (Fast Fourier Transform of samples after picrosirius staining; higher values indicate more disorganization) was studied in 100 swine and 95 human samples. No differences in collagen organization were found between the acute and chronic groups in the core area of the scar in the experimental model. In the chronic group, the endocardium [0.90 (0.84–0.94); median (interquartile range)], epicardium [0.84 (0.79–0.91)] and peripheral area [0.73 (0.63–0.83)] displayed a much more disorganized pattern than the core area of the fibrotic scar [0.56 (0.45–0.64)]. Similarly, in human samples, the collagen fibers were more disorganized in all of the outer areas than in the core of the fibrotic scar (P < 0.0001). Both in a highly controlled experimental model and in patient samples, collagen fibers exhibited an organized pattern in the core of the infarction, whereas the outer areas displayed a high level of inhomogeneity. This finding contributes pathophysiological information regarding the healing process and may lead to a clearer understanding of the genesis and invasive treatment of arrhythmias after acute myocardial infarction.