Luis Mainar

Usefulness of the Neutrophil to Lymphocyte Ratio in Predicting Long-Term Mortality in ST Segment Elevation Myocardial Infarction

Neutrophil to lymphocyte ratio (N/L) has been associated with poor outcomes in patients who underwent cardiac angiography. Nevertheless, its role for risk stratification in acute coronary syndromes, specifically in patients with ST-segment elevation myocardial infarction (STEMI), has not been elucidated. We sought to determine the association of N/L maximum value (N/L max) with mortality in the setting of STEMI and to compare its predictive ability with total white blood cell maximum count (WBC max). We analyzed 515 consecutive patients admitted with STEMI to a single university center. White blood cells (WBC) and differential count were measured at admission and daily for the first 96 hours afterward. Patients with cancer, inflammatory diseases, or premature death were excluded, and 470 patients were included in the final analysis. The association between N/L max and WBC max with mortality was assessed by Cox regression analysis. During follow-up, we registered 106 deaths (22.6%). A positive trend between mortality and N/L max quintiles was observed; 6.4%, 12.4%, 11.7%, 34%, and 47.9% of deaths occurred from quintiles 1 to 5 (p <0.001), respectively. In a multivariable setting, after adjusting for standard risk factors, patients in the fourth (Q4 vs Q1) and fifth quintile (Q5 vs Q1) showed the highest mortality risk (hazard ratio 2.58, 95% confidence interal 1.06 to 6.32, p = 0.038 and hazard ratio 4.20, 95% confidence interal 1.73 to 10.21, p = 0.001, respectively). When WBC max and cells subtypes were entered together, N/L max remained as the only WBC parameter; furthermore, the model with N/L max showed the most discriminative ability. In conclusion, N/L max is a useful marker to predict subsequent mortality in patients admitted for STEMI, with a superior discriminative ability than total WBC max.

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.

Alteration of Ventricular Fibrillation by Flecainide, Verapamil, and Sotalol An Experimental Study

BACKGROUND The purpose of this study was to determine whether the myocardial electrophysiological properties are useful for predicting changes in the ventricular fibrillatory pattern. METHODS AND RESULTS Thirty-two Langendorff-perfused rabbit hearts were used to record ventricular fibrillatory activity with an epicardial multiple electrode. Under control conditions and after flecainide, verapamil, or d,l-sotalol, the dominant frequency (FrD), type of activation maps, conduction velocity, functional refractory period, and wavelength (WL) of excitation were determined during ventricular fibrillation (VF). Flecainide (1.9+/-0.3 versus 2.4+/-0.6 cm, P<0. 05) and sotalol (2.1+/-0.3 versus 2.5+/-0.5 cm, P<0.05) prolonged WL and diminished FrD during VF, whereas verapamil (2.0+/-0.2 versus 1. 7+/-0.2 cm, P<0.001) shortened WL and increased FrD. Simple linear regression revealed an inverse relation between FrD and the functional refractory period (r=0.66, P<0.0001), a direct relation with respect to conduction velocity (r=0.33, P<0.01), and an inverse relation with respect to WL estimated during VF (r=0.49, P<0.0001). By stepwise multiple regression, the functional refractory periods were the only predictors of FrD. Flecainide and sotalol increased the circuit size of the reentrant activations, whereas verapamil decreased it. The 3 drugs significantly reduced the percentages of more complex activation maps during VF. CONCLUSIONS The activation frequency is inversely related to WL during VF, although a closer relation is observed with the functional refractory period. Despite the diverging effects of verapamil versus flecainide and sotalol on the activation frequency, WL, and size of the reentrant circuits, all 3 drugs reduce activation pattern complexity during VF.

Frailty and other geriatric conditions for risk stratification of older patients with acute coronary syndrome.

BACKGROUND Geriatric conditions may predict outcomes beyond age and standard risk factors. Our aim was to investigate a wide spectrum of geriatric conditions in survivors after an acute coronary syndrome. METHODS A total of 342 patients older than 65 years were included. At hospital discharge, 5 geriatric conditions were evaluated: frailty (Fried and Green scores), physical disability (Barthel index), instrumental disability (Lawton-Brody scale), cognitive impairment (Pfeiffer questionnaire), and comorbidity (Charlson and simple comorbidity indexes). The outcomes were postdischarge mortality and the composite of death/myocardial infarction during a 30-month median follow-up. RESULTS Seventy-four (22%) patients died and 105 (31%) suffered from the composite end point. Through univariable analysis, all individual geriatric indexes were associated with outcomes, mainly mortality. Of all of them, frailty using the Green score had the strongest discriminative accuracy (area under the receiver operating characteristic curve 0.76 for mortality). After full adjustment including clinical and geriatric data, the Green score was the only independent predictive geriatric condition (per point; mortality: hazard ratio 1.25, 95% CI 1.15-1.36, P = .0001; composite end point: hazard ratio 1.16, 95% CI 1.09-1.24, P = .0001). A Green score ≥ 5 points was the strongest mortality predictor. The addition of the Green score to the clinical model improved discrimination (area under the receiver operating characteristic curve 0.823 vs 0.846) and significantly reclassified mortality risk (net reclassification improvement 26.3, 95% CI 1.4-43.5; integrated discrimination improvement 4.0, 95% CI 0.8-9.0). The incremental predictive information was even greater over the GRACE score. CONCLUSIONS Frailty captures most of the prognostic information provided by geriatric conditions after acute coronary syndromes. The Green score performed better than the other geriatric indexes.

Uncontrolled immune response in acute myocardial infarction: Unraveling the thread

Recently, the theory that hyperinflammation is the bodys primary response to potent stimulus has been challenged. Indeed, a deregulation of the immune system could be the cause of multiple organ failure. So far, clinicians have focused on the last steps of the inflammatory cascade. However, little attention has been paid to lymphocytes, which play an important role as strategists of the inflammatory response. Experimental evidence suggests a crucial role of T lymphocytes in the pathophysiology of atherosclerosis and acute myocardial infarction (AMI). In summary, from the bottom of an imaginary inverted pyramid, a few regulatory T-cells control the upper parts represented by the wide spectrum of the inflammatory cascade. In AMI, a loss of regulation of the inflammatory system occurs in patients with a decreased activity of regulatory T-cells. As a consequence, aggressive T-cells boost and anti-inflammatory T-cells drop. A pleiotropic proinflammatory imbalance with damaging effects in terms of left ventricular performance and patient outcome is the result of this uncontrolled immune response. It is needed to unravel the thread of the inflammatory cells to better understand the pathophysiology as well as to open innovative therapeutic options in AMI.

Prognostic and therapeutic implications of dipyridamole stress cardiovascular magnetic resonance on the basis of the ischaemic cascade

Objective: To determine the prognostic and therapeutic implications of stress perfusion cardiovascular magnetic resonance (CMR) on the basis of the ischaemic cascade. Setting: Single centre study in a teaching hospital in Spain. Patients: Dipyridamole stress CMR was performed on 601 patients with ischaemic chest pain and known or suspected coronary artery disease. On the basis of the ischaemic cascade, patients were categorised in C1 (no evidence of ischaemia, n = 354), C2 (isolated perfusion deficit at stress first-pass perfusion imaging, n = 181) and C3 (simultaneous perfusion deficit and inducible wall motion abnormalities, n = 66). CMR-related revascularisation (n = 102, 17%) was defined as the procedure prompted by the CMR results and carried out within the next three months. Results: During a median follow-up of 553 days, 69 major adverse cardiac events (MACE), including 21 cardiac deaths, 14 non-fatal myocardial infarctions and 34 admissions for unstable angina with documented abnormal angiography were detected. In non-revascularised patients (n = 499), the MACE rate was 4% (14/340) in C1, 20% (26/128) in C2 and 39% (12/31) in C3 (adjusted p value = 0.004 vs C2 and <0.001 vs C1). CMR-related revascularisation had neutral effects in C2 (20% vs 19%, 1.1 (0.5 to 2.4), p = 0.7) but independently reduced the risk of MACE in C3 (39% vs 11%, 0.2 (0.1 to 0.7), p = 0.01). Conclusions: Dypiridamole stress CMR is able to stratify risk on the basis of the ischaemic cascade. A small group of patients with severe ischaemia—simultaneous perfusion deficit and inducible wall motion abnormalities—are at the highest risk and benefit most from MACE reduction due to revascularisation.

Modificaciones agudas de la longitud de onda del proceso de activación auricular inducidas por la dilatación. Estudio experimental

Objetivos Estudiar en un modelo experimental las modificaciones agudas de la longitud de onda del proceso de activacion auricular inducidas por la dilatacion auricular. Material y metodos En 10 preparaciones de corazon aislado y perfundido de conejo segun la tecnica de Langendorff, mediante mapeo epicardico con un electrodo multiple se determina en la auricula derecha la longitud de onda del proceso de activacion auricular (periodo refractario funcional × velocidad de conduccion) y se analiza la inducibilidad de respuestas repetitivas auriculares rapidas, cuantificando su numero tras 20 episodios de sobreestimulacion auricular rapida. Las determinaciones se efectuan en situacion basal, tras provocar dos grados de estiramiento de la pared auricular con un balon intraauricular derecho (D1 y D2), y tras suprimir la dilatacion auricular. Resultados En el estudio basal la longitud de onda es 72,6 ± 7,7 mm (ciclos de 250 ms) y 54,0 ± 5,1 mm (ciclos de 100 ms). En el estadio D1 (incremento longitudinal de la pared auricular = 24 ± 3%) la longitud de onda disminuye a 59,8 ± 6,6 mm (ciclos de 250 ms; p Conclusiones En el modelo experimental utilizado la dilatacion auricular aguda provoca un acortamiento de la refractariedad y una disminucion de la velocidad de conduccion. Ambos efectos dan lugar a una disminucion de la longitud de onda del proceso de activacion auricular que facilita la induccion de arritmias auriculares. Los efectos observados revierten tras suprimir la dilatacion auricular.

Contractile Reserve and Extent of Transmural Necrosis in the Setting of Myocardial Stunning: Comparison at Cardiac MR Imaging

PURPOSE To perform a comparison of cardiac magnetic resonance (MR) imaging-derived ejection fraction (EF) during low-dose dobutamine infusion (EF(D)) with the extent of segments with transmural necrosis in more than 50% of their wall thickness (ETN) for the prediction of major adverse cardiac events (MACEs) and late systolic recovery soon after a first ST-segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS Institutional ethics committee approval and written informed consent were obtained. One hundred nineteen consecutive patients with a first STEMI, a depressed left ventricular EF, and an open infarct-related artery underwent MR imaging at 1 week after infarction. EF(D) and ETN (by using a 17-segment model) were determined, and the prediction of MACEs and systolic recovery at follow-up was assessed by using area under the receiver operating characteristic curve (AUC) and multivariable regression analysis. RESULTS During follow-up (median, 613 days; range, 312-1243 days), 18 MACEs (five cardiac deaths, six myocardial infarctions, seven readmissions for heart failure) occurred. MACEs were associated with a lower EF(D) (43% +/- 12 [standard deviation] vs 49% +/- 10, P = .02) and a larger ETN (seven segments +/- three vs four segments +/- three, P < .001). Patients with systolic recovery (increase in EF of >5% at follow-up compared with baseline EF, n = 44) displayed a higher EF(D) (51% +/- 10 vs 47% +/- 9, P = .04) and a smaller ETN (three segments +/- two vs five segments +/- three, P = .002) at 1 week. ETN and EF(D) both related to MACEs (AUC: 0.78 vs 0.67, respectively, P = .1) and systolic recovery (AUC: 0.68 vs 0.62, respectively, P = .3). According to multivariable analysis, ETN was the only MR variable associated with time to MACEs (hazard ratio, 1.38; 95% confidence interval: 1.19, 1.60; P < .001) and systolic recovery (odds ratio, 0.76; 95% confidence interval: 0.64, 0.92; P = .004) independent of baseline characteristics. CONCLUSION ETN is as useful as EF(D) for the prediction of MACEs and systolic recovery soon after STEMI.

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.

Quantification of the Modifications in the Dominant Frequency of Ventricular Fibrillation under Conditions of Ischemia and Reperfusion: An Experimental Study

The characteristics of ventricular fibrillatory signals vary as a function of the time elapsed from the onset of arrhythmia and the maneuvers used to maintain coronary perfusion. The dominant frequency (FrD) of the power spectrum of ventricular fibrillation (VF) is known to decrease after interrupting coronary perfusion, though the corresponding recovery process upon reestablishing coronary flow has not been quantified to date. With the aim of investigating the recovery of the FrD during reperfusion after a brief ischemic, period, 11 isolated and perfused rabbit heart preparations were used to analyze the signals obtained with three unipolar epicardial electrodes (E1‐E3) and a bipolar electrode immersed in the thermostatizfid organ bath (E4), following the electrical induction of VF. Recordings were made under conditions of maintained coronary perfusion (5 min), upon interrupting perfusion (15 mini, and after reperfusion (5 min), FrD was determined using Welchs method. The variations in FrD were quantified during both ischemia and reperfusion, based on an exponential model AFrD = A exp (‐t/C). During ischemia ΔFrD is the difference between FrD and the minimum value, while t is the time elapsed from the interruption of coronary perfusion. During reperfusion ΔFrD is the difference between the maximum value and FrD, while t is the time elapsed from the restoration of perfusion, A is one of the constants of the model, and C is the time constant. FrD exhibited respective initial values of 16.20 ± 1.67, 16.03 ± 1.38, and 16.03 ± 1.80 Hz in the epicardial leads, and 15.09 ±1.07 Hz in the bipolar lead within the bath. No significant variations were observed during maintained coronary perfusion. The fit of the FrD variations to the model during ischemia and reperfusion proved significant in nine experiments. The mean time constants C obtained on fitting to the model during ischemia were as follows: El =294.4 ± 75.6, E2 = 225.7 ± 48.5, E3 = 327.4 ± 79.7, and E4 = 298.7 ± 43.9 seconds. The mean values of C obtained during reperfusion, and the significance of the differences with respect to the ischemic period were: El = 57.5 ± 8.4 (P ± 0.01), E2 = 64.5 ± 11.2 (P0.01), E3 = 80.7 ± 13.3 (P < 0.01), and E4 = 74.9 ± 13.6 (P < 0.0001). The time course variations of the FrD of the VF power spectrum fit an exponential model during ischemia and reperfusion. The time constants of the model during reperfusion after a brief ischemic period are significantly shorter than those obtained during ischemia.