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La obesidad es un factor de riesgo establecido para el desarrollo de enfermedad arterial coronaria, y se ha relacionado con diversos procesos inflamatorios y hormonales que podrían tener repercusión a nivel cardiaco. La hipótesis de este trabajo considera que los pacientes obesos con un primer infarto agudo de miocardio (IAM) tendrían mayores alteraciones en la morfología y función del corazón, respecto a los no obesos, y la caracterización tisular mediante mapeoT1 con resonancia magnética cardiaca (RMC) en este contexto sería de utilidad para identificar la presencia de fibrosis asociada a la obesidad.OBJETIVOS:1. Describir las características epidemiológicas y clínicas de pacientes con un primer episodio de IAM con base en su índice de masa corporal(IMC).2. Describir las características morfológicas y funcionales en el corazón delos pacientes con un primer episodio de IAM, estudiados mediante ecocardiograma transtorácica y RMC.3. Describir la relación de biomarcadores serológicos tales como interleucinas (IL), mieloperoxidasa (MPO), colágeno, galectina 3,lipocalina asociada a la gelatinasa de neutrófilos (NGAL) y moléculas no codificantes denominadas microRNA.4. Estimar el efecto del IAM en la morfología y función cardiaca (durante la hospitalización y en cualquier momento de la enfermedad) de los pacientes de acuerdo a su IMC, y su relación con los diversos parámetros de cuantificación mediante técnicas de imagen, así como su asociación con los biomarcadores circulantes..., Obesity is a well-known cardiovascular risk factor, and it has been related with different inflammatory and hormonal processes which might have a cardiovascular impact. We hypothesize that obese patients with a first episode of myocardial infarction (MI) will have higher abnormalities in morphological and functional cardiac parameters, compared to non-obese patients, and that tissue characterization by T1 mapping with cardiac magnetic resonance (CMR) will be able to identify obesity-related diffuse myocardial fibrosis. OBJECTIVES: 1. To describe epidemiological and clinical characteristics of patients with a first episode of MI, based on their body mass index (BMI). 2. To describe the morphological and functional cardiac parameters of these patients with transthoracic echocardiography and CMR.3. To describe the relationship of serological biomarkers such as interleukins (IL), myeloperoxidase (MPO), collagen, galectine-3,neutrophil gelatinase-associated lipocalin (NGAL), and non-codingmicro RNA.4. To estimate the potential impact of MI in cardiac morphology and function (during hospitalization and long-term) according to patients' BMI, and its relationship with different imaging parameters and serological biomarkers...

El delirium es un trastorno cognitivo que se produce con frecuencia durante la hospitalización en unidades de cuidados agudos cardiológicos (UCAC), pero su efecto tras la sustitución percutánea de la válvula aórtica (TAVI) no ha sido bien evaluado. El objetivo de este estudio es determinar la incidencia, los factores predictivos y el impacto pronóstico del delirium tras el implante de una TAVI. Métodos: Se incluyeron 501 pacientes consecutivos ingresados en una UCAC tras el implante de TAVI. Se utilizó el método de evaluación de la confusión para evaluar el delirium durante la estancia en la UCAC. Se evaluaron los factores de riesgo, el tratamiento farmacológico preventivo, las características periprocedimiento y las complicaciones. Se registraron los acontecimientos clínicos con una mediana de seguimiento de 24 meses. Resultados: La incidencia de delirium tras TAVI fue del 22,0% (n = 110). El deterioro cognitivo previo (OR 4,17; IC 95%: 1,11-15,71; p = 0,035), la enfermedad arterial periférica (OR 4,54; IC 95%: 1,79-11,54; p = 0,001), el uso de anestesia general (OR 2,55; IC 95%: 1,32-4,90; p = 0,005) y la ventilación mecánica prolongada (OR 18,86; IC 95%: 1,85-192,58; p = 0,013) se asociaron significativamente con el desarrollo de delirium. Los pacientes con delirium tuvieron una mayor estancia hospitalaria (7,5 [5,5-13,5] frente a 5,6 [4,6-8,2] días, y mayor mortalidad intrahospitalaria (OR 2,68; IC 95% 1,02-6,99; p = 0,045), a 1 año (HR 2,09; IC 95% 1,13-3,87; p = 0,018) y a 2 años (HR 1,94; IC 95% 1,12-3,34; p = 0,017). Conclusiones: El delirium es una complicación frecuente en los pacientes ingresados en la UCAC tras el implante de una TAVI, y se asocia con una estancia hospitalaria prolongada y una mayor mortalidad intrahospitalaria y a medio plazo., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Estudio retrospectivo unicéntrico que evaluó a 811 pacientes con un infarto agudo de miocardio. El estudio comparó el momento en el que presentaron el evento con el tamaño del infarto. Se pudo comprobar que los infartos fueron mas grandes en pacientes que lo padecieron durante la transición noche-día (entre las 6.00 y 12.00 am), resultados que ayudaron a interpretar el efecto cardioprotector de otras estrategias terapéuticas en pacientes con infarto de miocardio en ensayos clínicos posteriores., Background: The circadian clock influences a number of cardiovascular (patho)physiological processes including the incidence of acute myocardial infarction. A circadian variation in infarct size has recently been shown in rodents, but there is no clinical evidence of this finding. Objective: To determine the impact of time-of-day onset of ST segment elevation myocardial infarction (STEMI) on infarct size. Methods: A retrospective single-centre analysis of 811 patients with STEMI admitted between 2003 and 2009 was performed. Infarct size was estimated by peak enzyme release. The relationship between peak enzyme concentrations and time-of-day were characterised using multivariate regression splines. Time of STEMI onset was divided into four 6-hour periods in phase with circadian rhythms. Results: Model comparisons based on likelihood ratio tests showed a circadian variation in infarct size across time-of-day as evaluated by peak creatine kinase (CK) and troponin-I (TnI) concentrations (p=0.015 and p=0.012, respectively). CK and TnI curves described similar patterns across time, with a global maximum in the 6:00-noon period and a local minimum in the noon-18:00 period. Infarct size was largest in patients with STEMI onset in the dark-to-light transition period (6:00-noon), with an increase in peak CK and TnI concentrations of 18.3% (p=0.031) and 24.6% (p=0.033), respectively, compared with onset of STEMI in the 18:00-midnight period. Patients with anterior wall STEMI also had significantly larger infarcts than those with STEMI in other locations. Conclusions: Significant circadian oscillations in infarct size were found in patients according to time-of-day of STEMI onset. The infarct size was found to be significantly larger with STEMI onset in the dark-to-light transition period (6:00-noon). If confirmed, these results may have a significant impact on the interpretation of clinical trials of cardioprotective strategies in STEMI, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Estudio observacional unicéntrico que evaluó a 913 pacientes con infarto agudo de miocardio con elevación del segmento ST tratados con angioplastia primaria. Se analizaron los trazados electrocardiográficos para valorar aquellos pacientes que se presentaron con un bloqueo de rama (derecha / izquierda) y si tras la reperfusión, éste desaparece o permanece. El estudio concluye que los pacientes con bloqueo de rama persistente fueron aquellos con peor pronóstico., The presence of bundle branch block (BBB) in patients with ST-segment elevation myocardial infarction has been associated with a poor outcome. However, the implications of BBB in patients undergoing primary angioplasty in the stent era are poorly established. Furthermore, the prognostic implications of BBB type (right vs left and previous vs transient or persistent) remain unknown. We analyzed the data from 913 consecutive patients with ST-segment elevation myocardial infarction treated with primary angioplasty. All clinical, electrocardiographic, and angiographic data were prospectively collected. The median follow-up period was 19 months. The primary end point was the combined outcome of death and reinfarction. BBB was documented in 140 patients (15%). Right BBB (RBBB) was present in 119 patients (13%) and was previous in 27 (23%), persistent in 45 (38%), and transient in 47 (39%). Left BBB (LBBB) was present in 21 patients (2%) and was previous in 8 (38%), persistent in 9 (43%), and transient in 4 (19%). Patients with BBB were older, and more frequently had diabetes, anterior infarctions, a greater Killip class, a lower left ventricular ejection fraction, and greater mortality (all p <0.005) than patients without BBB. The short- and long-term primary outcome occurred more frequently in patients with persistent RBBB/LBBB than in those with previous or transient RBBB/LBBB. On multivariate analysis, persistent RBBB/LBBB emerged as an independent predictor of death and reinfarction. In conclusion, in patients undergoing primary angioplasty in the stent era, BBB is associated with poor short- and long-term prognosis. This risk appears to be particularly high among patients with persistent BBB, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Epicardial Connections Between PVs and the LA. Introduction: Some observations support the existence of epicardial connections (ECs) between ipsilateral pulmonary veins (vein to vein ECs [VVECs]), and we have observed venoatrial ECs inserted at distance from the pulmonary vein ostium (vein to atrium ECs [VAECs]). Our aim was to determine the prevalence of ECs and their relevance for pulmonary vein isolation. Methods and Results: We studied 100 consecutive patients with drug-refractory atrial fibrillation who underwent ostial pulmonary vein isolation by cooled radiofrequency catheter ablation. A VVEC was identified if pulmonary vein pacing activated the ipsilateral vein before the atrium, requiring ablation of both venous ostia to isolate either pulmonary vein. A VAEC was identified if pacing produced atrial breakthrough located at distance from the venous ostium, requiring extraostial ablation to isolate the pulmonary vein. Patients with ECs (20%) were younger (P = 0.02) and had a higher prevalence of structural heart disease (P = 0.01) than patients without ECs. VVECs and VAECs were identified in 32 pulmonary veins (10%) and VAECs in 10 veins (3%). Veins with ECs had a higher rate of early recurrence of conduction following isolation (29% vs 11%; P = 0.01). Conclusion: Twenty percent of patients with atrial fibrillation had ECs resistant to ostial ablation in one or more pulmonary veins. Isolating veins with ECs may require a different ablation approach. These connections are associated with an increased rate of early recurrence of conduction., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Background: A key point in atrial fibrillation (AF) ablation is the ability to identify the pulmonary vein (PVs) and locate their ostia. Objectives: The purpose of this study was to assess the error margin of PV identification and ostia location in the absence of previous PV imaging. Methods: This study was performed in patients referred for catheter ablation of AF. PVs were reconstructed before ablation using the CARTO system. The operator tagged the superior and inferior edges of the PV ostia before and after examining the corresponding PV angiograms. The distances between the tagged PV ostia were measured using CARTO software. Results: A total of 105 location estimations of 54 PVs were analyzed. The location of PV ostia without angiography deviated from the angiographic PV ostia by a median of 13 mm (95% confidence interval = 11-14 mm; P < .0001). In 84 of the 105 estimations (80%), wrong tagging was performed inside the PV. A multiple logistic regression revealed that, at sites displaying PV potentials, the left atrial potential amplitude was an independent predictor of location at the angiographic PV ostium (odds ratio 24 [95% confidence interval = 3.7-227] per 1-mV increase). Receiver operator characteristic analysis set the optimal cutoff level at 0.7 mV. Use of this criterion improved the accuracy of PV ostium location by 4 mm (95% confidence interval = 1-6 mm; P = .005). Conclusion: Attempts at PV identification and ostia location in the absence of previous PV imaging are subject to a broad error margin, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Objectives: Apical ballooning shares features with acute coronary syndromes. Recently, atypical forms have been reported without apical involvement. Usually, the prognostic reports have compared them with ST-segment elevation infarction. Left ventricular transient dyskinesias (LVTD), however, frequently occur without ST-segment elevation and when present, these patients always have open arteries. Our aim was to assess the baseline features, clinical presentation, natural history and compare long-term prognosis in an LVTD-cohort with a first non-ST-segment elevation acute coronary syndrome (NSTEMI) group. Methods: We performed a prospective observational study including consecutive patients in two groups: (i) LVTD group: 62 patients with this syndrome between 2003 and 2007. Inclusion criteria were LV segmental transient motion abnormalities; ECG new alterations and elevated troponin; absence of recent significant head trauma or obstructive coronary artery lesions. (ii) Control group: 169 patients admitted for a first NSTEMI in 2004. Results: Median follow-up was 35 months. Mean age was 65 years. LVTD group included 83.9% females. NSTEMI group was predominantly males. Eleven in-hospital deaths happened in NSTEMI cohort and none in LVTD. Four patients in the LVTD group required readmission and two patients died. In the NSTEMI group, heart failure, unstable angina, myocardial infarction (P<0.001) and death (P=0.11) were more frequent. Cox regression showed that diabetes mellitus, significant onset mitral regurgitation and NSTEMI versus LVTD were found as event-independent predictors. Conclusion: LVTD diagnosis represents a decreased risk of events when compared with classic non-ST-segment acute coronary syndrome, pointing out a different pathophysiologic mechanism., Depto. de Fisiología, Fac. de Medicina, TRUE, pub

Objective To assess the relationship between functional mitral regurgitation (MR) after a non-ST segment elevation acute coronary syndrome (NSTSEACS) and long-term prognosis, ventricular remodelling and further development of atrial fibrillation (AF), since functional MR is common after myocardial infarction. Design and setting Prospective cohort study conducted in a tertiary referral centre. Patients We prospectively studied 237 patients consecutively discharged in New York Heart Association class I–II (74% men; mean age 66.1 years) after a first NSTSEACS. All underwent an ECG the first week after admission and were echocardiographically and clinically followed-up (median 6.95 years). Results MR was detected in 95 cases (40.1%) and became an independent risk factor for the development of heart failure (HF) and major adverse cardiovascular events (MACE) (per MR degree, HRHF 1.71, 95% CI 1.138 to 2.588, p=0.01; HRMACE 1.49, 95% CI 1.158 to 1.921, p=0.002). Left ventricular diastolic (grade I 12.7±40.7; grade II 26.8±12.4; grade III 46.3±50.9 mL, p=0.01) and systolic (grade I 10.4±37.3; grade II 10.12±12.7; grade III 36.8±46.0 mL, p=0.02) mean volumes were higher after follow-up in patients with MR, in proportion to the initial degree of MR. In the rhythm analysis (126 patients; previously excluding those with any history of AF) during follow-up, 11.4% of patients with degree I MR, 14.3% with degree II MR and 75% with degree III MR developed AF, while only 5.1% of those with degree 0 developed AF, p<0.001. Conclusions MR is common after an NSTSEACS. The presence and greater degree of MR confers a worse long-term prognosis after a first NSTSEACS. This can in part be explained by increased negative ventricular remodelling and increased occurrence of AF., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Estudio observacional prospectivo donde se evaluaron 187 pacientes con enfermedad coronaria estable y diabetes mellitus y su respuesta a la inhibición plaquetaria con clopidogrel en función de las variaciones genéticas del receptor de substrato insulínico-1 de la plaqueta. El estudió concluyó que los portadores del alelo C en el marcador rs956115 del gen que codifica el receptor IRS-1 presenta mayor reactividad plaquetaria y un mayor riesgo de presentar eventos cardiovasculares., Objectives: The aim of this study was to assess the association between genetic variants of the insulin receptor substrate (IRS)-1 gene, platelet function, and long-term outcomes in patients with type 2 diabetes mellitus (DM) and stable coronary artery disease while on aspirin and clopidogrel therapy. Background: The effects of pharmacogenetic determinants on platelet function and cardiovascular outcomes in type DM patients are unknown. Methods: The association between IRS-1 genetic variants, platelet function, and the risk of major adverse cardiac events (MACE) at 2 years was assessed in 187 patients with type 2 DM and stable coronary artery disease on maintenance aspirin and clopidogrel therapy. Results: Seven tag single nucleotide polymorphisms were selected. Individuals with high platelet reactivity were more frequent among carriers of the C allele (GC and CC genotypes; approximately 20% of population) of the rs956115 marker (44.4% vs. 20.5%; odds ratio: 3.1, 95% confidence interval [CI]: 1.44 to 6.67; p = 0.006). These patients were at higher risk of MACE (28.0% vs. 10.9%; hazard ratio: 2.90, 95% CI: 1.38 to 6.11; p = 0.005). The C allele carriers of the rs956115 marker were more commonly associated with a hyperreactive platelet phenotype. This was confirmed in an external validation cohort of patients with type 2 DM but not in an external validation cohort of patients without DM. Carriers of the C allele of the rs956115 marker also had a significantly higher risk of MACE compared with noncarriers (30.6% vs. 11.4%; hazard ratio: 2.88, 95% CI: 1.35 to 6.14; p = 0.006). Conclusions: Type 2 DM patients who are carriers of the C allele of the rs956115 marker of the IRS-1 gene have a hyperreactive platelet phenotype and increased risk of MACE., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Apical transient left ventricular diskynesia is a recently described entity able to imitate acute coronary syndrome. The presence of previous coronary artery disease (CAD) is an exclusion criterion for this diagnosis in several studies. We report the case of a sixty-three year-old-caucasian man with previously known CAD, left anterior descending artery (LAD) stented-disease, presenting in the emergency room with angina and ST-segment elevation. A coronariography was urgently performed. No new coronary lesions could be demonstrated. LAD-placed stents were patent and showed no change in their angiographic appearance. Left ventriculogram demonstrated apical diskynesia (Takotsubo-like). Complete and rapid resolution of left ventricular dysfunction was echocardiographycally displayed seven days later. Months after, coronary lesions increased associated with new acute coronary syndromes and new revascularization procedures were required. The present case supports the idea that CAD and apical transient diskynesia could coexist in the same patient, arising further questions about the pathophysiology, prognosis and management of the latter., Depto. de Fisiología, Fac. de Medicina, TRUE, pub

Introduction: Radiofrequency (RF) ablation of accessory pathways (APs) is often a time-consuming procedure, mainly because conventional criteria have modest accuracy. Thus, additional mapping criteria are desirable. Our hypothesis was that comparison of paced atrial activation sequences with that obtained during orthodromic AV reentrant tachycardia might be useful for locating the atrial insertion of single APs. Methods and results: The study included 15 patients with a single AP referred for ablation. Analysis of the atrial activation sequence was simplified by measuring the activation time (AT) that elapsed between two atrial reference points placed next to the AV annulus on either side of the area containing the AP. Ablation was guided by conventional criteria. Before each RF delivery, a short pacing train was delivered from the ablation catheter and, after verification of atrial capture, the AT was compared with the AT obtained during orthodromic tachycardia. Fifty sites of RF delivery were appropriate for analysis. The multivariate model with the highest predictive power included a deviation of AT between pacing and tachycardia < or = 5 msec (P < 0.001), a local AV ratio > or = 1 (P = 0.04), and stability of the local electrogram (P = 0.05). The combination of all these criteria predicted a successful application with high sensitivity, specificity, and positive predictive value (92%, 86%, and 71% respectively). To validate the method prospectively, 10 additional consecutive patients underwent an AP ablation procedure guided by these criteria. Conclusion: This technique seems to be highly accurate in selecting the atrial site for RF ablation of single APs., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Introduction and objectives: Tako-tsubo syndrome produces a variable degree of transient left ventricular dysfunction. Our objective was to determine the short- and long-term prognosis of this syndrome, the incidence of and risk factors for the development of heart failure, and the influence on heart failure on the long-term outcome in our patient population. Methods: We prospectively recorded the clinical features and events during the hospital stay and follow-up of 100 patients with tako-tsubo syndrome. The risk factors for heart failure during hospital stay, considered as Killip class≥II, were assessed. Results: Most of the patients were women (89%), with a mean age of 68 years. The distribution according to Killip class was: Killip I, 70 patients; Killip II, 15; Killip III, 5; and Killip IV, 10. Cardiovascular risk factors, including diabetes, were common in the overall group, but were more so in the heart failure cohort. The left ventricular ejection fraction was lower in the heart failure group (51% vs 42%; P<.01). There were no differences in preadmission medications or biomarkers of necrosis. Over a median follow-up of 1380 days, the incidence of events reported during the hospital stay and long-term follow-up, both for death and the combined endpoints, was higher in the heart failure cohort. Conclusions: Although the prognosis in tako-tsubo syndrome is usually good, heart failure occurs quite frequently, mainly in patients with a greater number of comorbidities and poorer previous functional class. Moreover, heart failure is associated with a higher number of early and late adverse events. The overall long-term prognosis is good., Fundación Mutua Madrileña, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Background: Findings from animal studies and small series of patients support the greater safety of cryoenergy over radiofrequency in the ablation of arrhythmic substrates near the AV node. Objectives: The purpose of this study was to systematically evaluate the electrophysiologic effects of successive cryoenergy applications to the human AV node in order to better define the safety margin of cryothermal ablation. Methods: In 15 patients referred for AV nodal ablation, 94 cryomapping and 105 cryoablation applications were delivered through a 6-mm-tip cryothermal ablation catheter (Freezor Xtra, CryoCath) at predefined sites of the triangle of Koch. Results: Temporary effects on AV conduction were observed in 18 (19%) cryomapping and 38 (36%) cryoablation applications. Persistent effects were observed in 9 (9%) cryoablation applications. Persistent effects were associated with cryoablation at the superior third of the triangle of Koch (P = .05), nadir tip temperature < or = -79 degrees C (P = .007), and effect onset time < or =15 seconds (P = .03). Temperature and effect onset time remained statistically significant after multivariate adjustment (P = .01 and .02, respectively). Overall, persistent complete AV block was achieved with cryoenergy in only one patient. In two additional patients, AV conduction remained modified. In the remaining patients, persistent complete AV block was achieved with radiofrequency (median one application per patient). Conclusion: The low rate of persistent AV conduction impairment observed with attempts to cryoablate the AV node supports a great safety margin of perinodal cryothermal ablation., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Background: Results from randomized trials designed to compare cryoenergy with radiofrequency for pulmonary vein (PV) isolation are lacking. Objective: To compare the efficacy of a simplified strategy for PV cryoablation (group C) vs PV isolation with open-irrigated radiofrequency catheters (group R). Methods: Fifty patients with paroxysmal atrial fibrillation (AF) and 4 independent PVs received a Reveal XT implantable cardiac monitor and were randomized to group C or group R. In group C, PV ablation was done with a single Arctic Front balloon (23 or 28 mm) per patient and two 300-second applications per PV. No further applications were delivered to close residual conduction gaps. In group R, bidirectional PV conduction block was pursued with Lasso and Navistar ThermoCool catheters and the CARTO system. The primary end point was the proportion of patients remaining free from AF recurrences ≥2 minutes without taking antiarrhythmic drugs 12 months after ablation. Results: The primary end point was met by 12 (48%) patients in group C and 25 (68%) patients in group R (odds ratio 0.43; P = .05). This difference disappeared after adjustment for acute procedural outcome. In patients for whom all 4 PVs were blocked at the end of the procedure, there was no difference between group C and group R in the primary end point (67% vs 68%; P = .94). Conclusions: The efficacy of the simplified strategy for PV cryoablation tested in this study is inferior to PV isolation using open-irrigated radiofrequency catheters with electrophysiological and electroanatomical guidance. Complete PV conduction block is critical to the success of AF ablation., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Estudio observacional donde se evaluó a 306 pacientes con diabetes mellitus y enfermedad arterial coronaria en tratamiento antiagregante con aspirina y clopidogrel, en función de si presentaban enfermedad renal. El estudio concluyó que aquellos pacientes con enfermedad renal presentaron una peor respuesta a la inhibición plaquetaria que aquellos que no presentaban enfermedad renal relevante., Objectives: We sought to assess the impact of renal function on platelet reactivity in patients with diabetes mellitus (DM) and coronary artery disease on aspirin and clopidogrel therapy. Background: Diabetes mellitus is a key risk factor for chronic kidney disease (CKD). In aspirin-treated DM patients the presence of moderate/severe CKD is associated with reduced clinical efficacy of adjunctive clopidogrel therapy. Whether these findings may be attributed to differences in clopidogrel-induced effects is unknown. Methods: This was a cross-sectional observational study in which DM patients taking maintenance aspirin and clopidogrel therapy were studied. Patients were categorized into 2 groups according to the presence or absence of moderate/severe CKD. Platelet aggregation after adenosine diphosphate (ADP) and collagen stimuli were assessed with light transmittance aggregometry and defined patients with high post-treatment platelet reactivity (HPPR). Markers of platelet activation, including glycoprotein IIb/IIIa activation and P-selectin expression, were also determined using flow cytometry. Results: A total of 306 DM patients were analyzed. Patients with moderate/severe CKD (n = 84) had significantly higher ADP-induced (60 +/- 13% vs. 52 +/- 15%, p = 0.001) and collagen-induced (49 +/- 20% vs. 41 +/- 20%, p = 0.004) platelet aggregation compared with those without (n = 222). After adjustment for potential confounders, patients with moderate/severe CKD were more likely to have HPPR after ADP (adjusted odds ratio: 3.8, 95% confidence interval: 1.7 to 8.5, p = 0.001) and collagen (adjusted odds ratio: 2.4; 95% confidence interval: 1.1 to 5.4; p = 0.029) stimuli. Markers of platelet activation were significantly increased in patients with HPPR. Conclusions: In DM patients with coronary artery disease taking maintenance aspirin and clopidogrel therapy, impaired renal function is associated with reduced clopidogrel-induced antiplatelet effects and a greater prevalence of, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Estudio observacional donde se evaluó en 141 pacientes con enfermedad coronaria estable en tratamiento crónico con aspirina 100mg al día si una dosis adicional reduce el porcentaje de pacientes no respondedores al tratamiento antiagregante. Tras una dosis “extra” de aspirina 100mg, el número de pacientes no respondedores a la inhibición plaquetaria con aspirina se redujo un 15% (del 50,7 al 35%)., Aspirin resistance or aspirin non-responsiveness is a recently described phenomenon which has been consistently associated with an increased risk of cardiovascular events. This study was designed to determine the effects of an additional dose of 100 mg of aspirin on platelet function and proportion of aspirin non-responders using the platelet function analyzer-100 (PFA-100), in a well characterized population of stable coronary heart disease patients already on long-term aspirin treatment. Platelet function was assessed using PFA-100 in 141 patients (64.8 ± 10.1 years, 87.9% men) on long-term aspirin treatment (100 mg/day) before and 1 h after “in site” oral aspirin administration (100 mg). Prevalence of aspirin non-responders using PFA-100 was 50.7% (95% confidence interval 42.4–59). One hour after 100 mg of oral aspirin, reassessment of aspirin effects showed a prevalence of non-responders using PFA of 35.0% (95% CI 27.3–43.2) (P < 0.001 vs. pre-dose proportion). Using the PFA-100 system, reassessment of platelet function following oral administration of daily aspirin dosage significantly reduces the number of stable coronary disease patients considered to be non-responders to such treatment., Depto. de Medicina, Fac. de Medicina, TRUE, pub

El artículo habla del estudio realizado que investiga los mecanismos que causan la fibrilación ventricular (FV), un ritmo cardíaco peligroso. Se centra en el papel de los canales KATP y su relación con la formación de rotores estables durante la FV. Se realizó un experimento en ocho corazones de cerdo, donde se observó que la apertura de los canales KATP aumentaba la frecuencia cardíaca y la organización de los rotores durante la FV. Estos rotores estables no eran visibles externamente en la fase inicial de la FV. Además, se observó un fenómeno de batido, que sugiere la presencia de rotores en movimiento. Los resultados indican que la FV puede ser impulsada por rotores estables en corazones grandes, con implicaciones importantes para comprender y tratar este trastorno cardíaco., Aims The mechanisms underlying ventricular fibrillation (VF) are still disputed. Recent studies have highlighted the role of KATP-channels. We hypothesized that, under certain conditions, VF can be driven by stable and epicardially detectable rotors in large hearts. To test our hypothesis, we used a swine model of accelerated VF by opening KATP-channels with cromakalim. Methods and results Optical mapping, spectral analysis, and phase singularity tracking were performed in eight perfused swine hearts during VF. Pseudo-bipolar electrograms were computed. KATP-channel opening almost doubled the maximum dominant frequency (14.3 ± 2.2 vs. 26.5 ± 2.8 Hz, P < 0.001) and increased the maximum regularity index (0.82 ± 0.05 vs. 0.94 ± 0.04, P < 0.001), the density of rotors (2.0 ± 1.4 vs. 16.0 ± 7.0 rotors/cm2×s, P < 0.001), and their maximum lifespans (medians: 368 vs. ≥3410 ms, P < 0.001). Persistent rotors (≥1 movie = 3410 ms) were found in all hearts after cromakalim (mostly coinciding with the fastest and highest organized areas), but they were not epicardially visible at baseline VF. A ‘beat phenomenon’ ruled by inter-domain frequency gradients was observed in all hearts after cromakalim. Acceleration of VF did not reveal any significant regional preponderance. Complex fractionated electrograms were not found in areas near persistent rotors. Conclusion Upon KATP-channel opening, VF consisted of rapid and highly organized domains mainly due to stationary rotors, surrounded by poorly organized areas. A ‘beat phenomenon’ due to the quasi-periodic onset of drifting rotors was observed. These findings demonstrate the feasibility of a VF driven by stable rotors in hearts whose size is similar to the human heart. Our model also showed that complex fractionation does not seem to localize stationary rotors., Fundación Mutua Madrileña, Instituto de Salud Carlos III, Unión Europea, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Objective: This study was undertaken to analyze whether nitric oxide (NO) modulates the human potassium channel hKv1.5, which generates the ultrarapid delayed rectifier current (IKur) that determines the height and duration of atrial action potentials. Methods: Currents were recorded using the whole-cell patch-clamp in Ltk- cells expressing hKv1.5 channels. Results: The NO donors (+/-)-S-Nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside, a NO solution, and l-Arginine inhibited hKv1.5 currents in a concentration-dependent manner. The NO concentration in the cell chamber was monitored using a sensor, and the IC50 for NO-induced hKv1.5 block was 340+/-70 nM. SNAP also inhibited the IKur recorded in mouse ventricular myocytes. The NO effects were partially mediated by the activation of the soluble guanylate cyclase (sGC)/cGMP/cGMP-dependent protein kinase (PKG) pathway. The biotin-switch assay demonstrated the presence of S-nitrosylated cysteines (Cys) on the hKv1.5 protein in SNAP-treated cells. Molecular modeling of hKv1.5 channel structure suggests that S-nitrosylation of Cys331 (segment 2, S2) and Cys346 (S2) would be stabilized by hydrogen bridge bonds with Ile262 (S1) and Arg342 (S2), respectively. Conclusions: NO inhibits the hKv1.5 current by a cGMP-dependent mechanism and by the S-nitrosylation of the hKv1.5 protein, an effect that contributes to shaping the human atrial action potentials., Mutua Madrileña Foundation, Red HERACLES, Depto. de Farmacología y Toxicología, Fac. de Medicina, TRUE, pub

Introduction and objectives: Little is known about the timing of onset and outcome of conduction abnormalities (CA) following balloon-expandable transcatheter aortic valve implantation. The aim of this study was to examine the timing of CA and determine the impact of balloon aortic valvuloplasty (BAV) on the persistence of these abnormalities. Methods: A total of 347 patients were included. Of these, 75 had a continuous electrocardiogram recording and a 6-lead electrocardiogram at each step of the procedure. Results: In the transcatheter aortic valve implantation population undergoing continuous electrocardiogram monitoring, new-onset left bundle branch block (LBBB) or third-degree atrioventricular block occurred in 48 (64%) and 16 (21.3%) patients, with 51.5% of CA occurring before valve implantation. Left bundle branch block persisted more frequently at hospital discharge (53.8 vs 22.7%; P=.028) and at 1-month follow-up (38.5 vs 13.6%; P=.054) when occurring before valve implantation. Balloon aortic valvuloplasty prior to valve implantation was used in 264 (76.1%) patients, and 78 (22.5%) had persistent LBBB or complete atrioventricular block requiring pacemaker implantation. Persistent LBBB or unresolved atrioventricular block at 1 month occurred more frequently in the BAV group (76.1 vs 47.6%; P=.021), and the use of BAV was associated with a lack of CA resolution (OR, 3.5; 95%CI, 1.17-10.43; P=.021). Conclusions: In patients undergoing a balloon-expandable transcatheter aortic valve implantation, more than half of CA occurred before valve implantation. Early occurrence of CA was associated with a higher rate of persistence at 1-month follow-up. The use of BAV was associated with an increased risk of CA persistence., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Aims: Chronic atrial fibrillation (CAF) is characterized by a shortening of the plateau phase of the action potentials (AP) and a decrease in the bioavailability of nitric oxide (NO). In this study, we analysed the effects of NO on Kv4.3 (I(Kv4.3)) and on human transient outward K(+) (I(to1)) currents as well as the signalling pathways responsible for them. We also analysed the expression of NO synthase 3 (NOS3) in patients with CAF. Methods and results: I(Kv4.3) and I(to1) currents were recorded in Chinese hamster ovary cells and in human atrial and mouse ventricular dissociated myocytes using the whole-cell patch clamp. The expression of NOS3 was analysed by western blotting. AP were recorded using conventional microelectrode techniques in mouse atrial preparations. NO and NO donors inhibited I(Kv4.3) and human I(to1) in a concentration- and voltage-dependent manner (IC(50) for NO: 375.0 +/- 48 nM) as a consequence of the activation of adenylate cyclase and the subsequent activation of the cAMP-dependent protein kinase and the serine-threonine phosphatase 2A. The density of the I(to1) recorded in ventricular myocytes from wild-type (WT) and NOS3-deficient mice (NOS3(-/-)) was not significantly different. Furthermore, the duration of atrial AP repolarization in WT and NOS3(-/-) mice was not different. The increase in NO levels to 200 nM prolonged the plateau phase of the mouse atrial AP and lengthened the AP duration measured at 20 and 50% of repolarization of the human atrial CAF-remodelled AP as determined using a mathematical model. However, the expression of NOS3 was not modified in left atrial appendages from CAF patients. Conclusion: Our results suggested that the increase in the atrial NO bioavailability could partially restore the duration of the plateau phase of CAF-remodelled AP by inhibiting the I(to1) as a result of the activation of non-canonical enzymatic pathways., Ministerio de Educación y Ciencia, Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Sociedad Española de Cardiología, Fundación LILLY, Depto. de Farmacología y Toxicología, Fac. de Medicina, TRUE, pub

Objective: To analyse if platelet responsiveness to aspirin (ASA) may be associated with a different ability of platelets to generate nitric oxide (NO). Patients/methods: Platelets were obtained from 50 patients with stable coronary ischemia and were divided into ASA-sensitive (n = 26) and ASA-resistant (n = 24) using a platelet functionality test (PFA-100). Results: ASA-sensitive platelets tended to release more NO (determined as nitrite + nitrate) than ASA-resistant platelets but it did not reach statistical significance. Protein expression of nitric oxide synthase 3 (NOS3) was higher in ASA-sensitive than in ASA-resistant platelets but there were no differences in the platelet expression of nitric oxide synthase 2 (NOS2) isoform. The highest NOS3 expression in ASA-sensitive platelets was independent of the presence of T-to-C mutation at nucleotide position -786 (T(-786) → C) in the NOS3-coding gene. However, platelet content of phosphorylated NOS3 at Serine (Ser)(1177), an active form of NOS3, was higher in ASA-sensitive than in ASA-resistant platelets. The level of platelet NOS3 Ser(1177) phosphorylation was positively associated with the closure time in the PFA-100 test. In vitro, collagen failed to stimulate the aggregation of ASA-sensitive platelets, determined by lumiaggregometry, and it was associated with a significant increase (p = 0.018) of NOS3 phosphorylation at Ser(1177). On the contrary, collagen stimulated the aggregation of ASA-resistant platelets but did not significantly modify the platelet content of phosphorylated NOS3 Ser(1177). During collagen stimulation the release of NO from ASA-sensitive platelets was significantly enhanced but it was not modified in ASA-resistant platelets. Conclusions: Functional platelet responsiveness to ASA was associated with the platelet content of phosphorylated NOS3 at Ser(1177)., Instituto de Salud Carlos III, Unión Europea, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

Background: The Killip classification categorizes heart failure (HF) in acute myocardial infarction, and has a prognostic value. Although non-ST-elevation myocardial infarction (NSTEMI) is increasing steadily, little information is available about the prognostic value of low Killip class in this scenario. Our aim was to assess the prognostic value of mild HF in NSTEMI. Methods: 835 patients with NSTEMI between 2005 and 2007 were prospectively recruited. Patients in Killip-1 (K1=684) or Killip-2 class (K2=113) were selected (38, with K>2, excluded). Clinical, angiographic, treatment strategies, and 30-day all-cause mortality, together with other cardiovascular outcomes were recorded. Results: K2 patients were mostly women (K1 27.9% vs K2 48.0%, p<0.001) and older (K1 66.6years vs K2 73.8years, p<0.001) with a higher frequency of diabetes mellitus (p<0.001) and hypertension (p<0.001). Smoking was less frequent in the K2-group (p=0.003). A previous infarction/revascularization history was similar in both groups. The infarction size, assessed by Troponin I/Creatin kinase, did not differ between groups (p=0.378 and p=0.855). Multivessel coronary disease and revascularization procedures were less common in group K2 (p=0.015 and p=0.005 vs group K1, respectively). Patients in K2 had a worse prognosis in terms of maximum Killip class, death and major adverse cardiovascular events (p<0.001). After multivariate analysis, mild HF at presentation was an independent risk factor for mortality (OR=6.50; IC 95%: 2.48-16.95; p<0.001). Conclusion: Mild HF at presentation in NSTEMI is linked to a poor prognosis, with increased short-term mortality. Thus, a more aggressive approach including early cardiac catheterization and revascularization should be considered., Depto. de Fisiología, Fac. de Medicina, TRUE, pub

The purpose of this study was to compare the effect of dual antiplatelet therapy [clopidogrel + aspirin (ASA)] with respect to ASA on the protein expression of platelets from controlled type-2 diabetic patients with stable coronary ischemia. Patients had been taking ASA (100 mg day) and they were randomized to receive (n = 29) or not (n = 28) 75 mg day clopidogrel for 12 ± 2 weeks in a blind form. Protein expression was analyzed by two-dimensional electrophoresis and mass spectrometry. The protein expression of a limited number of proteins such as actin-binding protein isotypes 2 and 5, lactate dehydrogenase, serotransferrin isotype 4, protein disulfide isomerase-A3 isotype 1, fibrinogen beta chain isotype 5, Ras-related protein Rab-7b isotypes 1 and 6, and immunoglobulin heavy chain was changed after dual antiplatelet therapy. Plasma level of platelet factor 4 (PF4), an in vivo marker of platelet activity, was not different between both groups. These changes suggest lower platelet reactivity after dual antiplatelet therapy in the studied patients. However, the variation in platelet proteome was lower than it would be initially expected, taking into account the apparent clinical beneficial effects of dual antiplatelet therapy. PF4 plasma level was not further decreased in the platelets treated for a longer time than 9-12 months with ASA + clopidogrel, as compared with ASA alone., Fondo de Investigacion de la Seguridad Social, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

Cardiac tamponade is a life-threatening condition, whose current specific cause and outcome are unknown. Our purpose was to analyze it. We performed a retrospective observational study with prospective follow-up data including 136 consecutive patients admitted with diagnosis of cardiac tamponade, from 2003 to 2013. We thoroughly recorded variables as clinical features, drainage/pericardiocentesis, fluid characteristics, and long-term events (new cardiac tamponade ± death). The median age was 65 ± 17 years (55% men). In the baseline characteristics, 70% were no smokers, 12% were on anticoagulation, and 13 had suffered a previous myocardial infarction. In the preceding month, 15 patients had undergone a cardiac catheterization, 5 cardiac surgery, and 5 pacemaker insertion. Fever was observed in 16% of patients and 21% displayed other inflammatory symptoms. In 81% of patients, pericardiocentesis was needed. The fluid was hemorrhagic or a transudate in the majority, with positive cytology in 15% and bacteria in 3.7%. Main causes were malignancy (32%), infection (24%), idiopathic (16%), iatrogenic (15%), postmyocardial infarction (7%), uremic (4%), and other causes (2%). After a maximum follow-up of 10.4 years, cardiac tamponade recurred in 10% of the cases (62% in the neoplastic group) and the 48% of patients died (89% in the neoplastic cohort). In conclusion, most cardiac tamponades are due to malignancy, having this specific cause a poorer outcome, probably as a manifestation of an advanced disease. The rest of causes, after an aggressive intensive management, have a good prognosis, especially the iatrogenic, El taponamiento cardíaco es una afección potencialmente mortal, cuya causa específica y desenlace actuales se desconocen. Nuestro propósito fue analizarla. Se realizó un estudio retrospectivo con seguimiento prospectivo de 136 pacientes consecutivos ingresados con diagnóstico de taponamiento cardíaco entre 2003 y 2013. Se registraron exhaustivamente variables como características clínicas, pericardiocentesis, características del líquido y eventos a largo plazo (nuevo taponamiento cardiaco - muerte). La edad media fue de 65 años (55% hombres). En las características basales, el 70% no eran fumadores, el 12% estaban anticoagulados y 13 habían sufrido un infarto de miocardio previo. En el mes anterior, 15 pacientes habían sido sometidos a un cateterismo cardíaco, 5 a cirugía cardíaca y 5 a inserción de marcapasos. Se observó fiebre en el 16% de los pacientes y el 21% presentaba otros síntomas inflamatorios. En el 81% de los pacientes fue necesaria una pericardiocentesis. El líquido era hemorrágico o un trasudado en la mayoría, con citología positiva en el 15% y bacterias en el 3,7%. Las principales causas fueron malignidad (32%), infección (24%), idiopática (16%), iatrogénica (15%), postinfarto de miocardio (7%), urémica (4%) y otras causas (2%).Tras un seguimiento máximo de 10,4 años, el taponamiento cardiaco recidivó en el 10% de los casos (62% en el grupo neoplásico) y el 48% de los pacientes fallecieron (89% en la cohorte neoplásica). Conclusiones: nuestro estudio pone de manifiesto que la mayoría de los taponamientos cardiacos, al menos en nuestro entorno, se deben a neoplasia, teniendo esta causa específica un peor pronóstico, probablemente como manifestación de una enfermedad avanzada. El resto de causas, tras un manejo intensivo agresivo, mediante pericardiocentesis evacuadora, tienen un buen pronóstico, especialmente las iatrogénicas., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Depto. de Medicina, Fac. de Medicina, TRUE, pub

Background Several mechanisms have been proposed to explain why some platelets have a reduced response to aspirin (ASA). Among them, it was reported an increased circulating level of vitamin-D-binding protein (DBP). In addition, nitric oxide (NO) released from mononuclear cells was involved in the antiplatelet effects of ASA. The aim was to analyse the relationship between platelet response to ASA and both NO generation and vitamin-D-binding protein content in mononuclear cells. Materials and methods Mononuclear cells were obtained from patients with stable coronary artery disease that were divided by a platelet functionality test (PFA-100) as ASA-sensitive (n = 23) and ASA resistant (n = 27). Results Both the release of NO (determined by nitrite + nitrate concentration) and the expression of endothelial-type NO synthase (eNOS) were higher in mononuclear cells from ASA sensitive as compared with those from ASA-resistant patients. There was a positive correlation between either the release of NO and the expression of eNOS protein in mononuclear cells with the ability of ASA to inhibit platelet activity. DBP content in mononuclear cells was higher in ASA resistant than in ASA sensitive. The level of DBP content in mononuclear cells was negatively associated with the ability of ASA to inhibit platelets. However, in vitro experiments suggested that there was no association between DBP and NO production by mononuclear cells. Conclusions Mononuclear cells from patients with platelets with lower responsiveness to ASA showed a reduced ability to produce NO., Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, FALSE, pub

ntroducción y objetivos Analizar si el ingreso en fin de semana o festivo (IFSF), frente al ingreso en días laborables, influye en el tratamiento (angioplastia, intervención coronaria percutánea [ICP]) y los resultados (mortalidad hospitalaria) de los pacientes hospitalizados por síndrome coronario agudo en el Sistema Nacional de Salud. Métodos Estudio observacional retrospectivo de pacientes ingresados por infarto agudo de miocardio con elevación del segmento ST (IAMCEST) o con síndrome coronario agudo sin elevación del segmento ST (SCASEST) en los hospitales del Sistema Nacional de Salud durante el periodo 2003-2018. Resultados Se seleccionaron 438.987 episodios de IAMCEST y 486.565 de SCASEST, de los cuales fueron IFSF el 28,8 y el 26,1% respectivamente. El IFSF se mostraba como un factor de riesgo de mortalidad hospitalaria en los modelos ajustados por riesgo del IAMCEST (OR=1,05; IC95%, 1,03-1,08; p<0,001) y del SCASEST (OR=1,08; IC95%, 1,05-1,12; p <0,001). La tasa de ICP en el IAMCEST fue más de 2 puntos porcentuales mayor en los pacientes ingresados en días laborables durante el periodo 2003-2011 y similar o incluso más baja en 2012-2018, sin cambios significativos para el SCASEST. El IFSF se mostró como factor de riesgo estadísticamente significativo tanto para el IAMCEST como para el SCASEST. Conclusiones El IFSF puede aumentar el riesgo de muerte hospitalaria en un 5% (IAMCEST) y un 8% (SCASEST). La persistencia del riesgo de mayor mortalidad hospitalaria tras ajustar por la realización de ICP y las demás variables explicativas probablemente indique dficiencias en el tratamiento durante el fin de semana respecto de los días laborables., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Stroke patients have a high risk of vascular recurrence. Biomarkers related to vascular recurrence, however, remain to be identified. The aim of the study was to identify, through proteomic analysis, plasma biomarkers associated with vascular recurrence within one year after the first ischemic stroke. This is a substudy (n = 134) of a large prospective multicenter study of post-stroke patients with an ischemic stroke. Plasma samples were obtained at inclusion. Among the identified proteins, only plasma levels of desmoplakin I were associated with protection against a new vascular event (Odds ratio: 0.64; 95% CI: 0.46-0.89; p = 0.009) after adjustment for hypercholesterolemia, statins and previous atherothrombotic stroke subtype. A greater number of patients without vascular recurrence had been treated with statins within three months of the recent ischemic stroke. Only patients who had been taking statins for 3 months after the ischemic stroke and did not suffer vascular recurrence over a follow-up year, have higher levels of desmoplakin I at the time of inclusion (Odds ratio 0.49; 95% CI: 0.28-0.86; p = 0.013). Increased desmoplakin I levels, determined within 1-3 months of the first ischemic stroke, could be a biomarker for statin responsiveness against a new vascular event in post-ischemic stroke patients taking statins early (1-3 months) after the ischemic stroke., Brystol-Myers Squibb, Fondo de Investigaciones de la Seguridad Social, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

Introduction and objectives: The safety of physiology-based revascularization in patients with diabetes mellitus has been scarcely investigated. Our objective was to determine the safety of deferring revascularization based on the fractional flow reserve (FFR) or the instantaneous wave-free ratio (iFR) in diabetic patients. Methods: Single-center, retrospective analysis of patients with intermediate coronary stenoses in whom revascularization was deferred based on FFR > 0.80 or iFR > 0.89 values. The long-term rate of major adverse cardiovascular events, a composite of all-cause mortality, myocardial infarction, and target vessel revascularization (TVR), was assessed in diabetic and non-diabetic patients at the follow-up. The rate of TVR based on the type of physiological index used to defer the lesion was also evaluated. Results: We evaluated 164 diabetic (214 vessels) and 280 non-diabetic patients (379 vessels). No significant differences in the rate of major adverse cardiovascular events was seen between diabetic and non-diabetic patients (20.1% vs 13.2%; P = .245) at a median follow-up of 43 months. All-cause mortality and cardiac death were not statistically different between both groups in the adjusted analysis (P > .05). A trend towards a higher rate of myocardial infarction was seen in diabetic patients (6.7% vs 2.9%; P = .063). However, the rate of target vessel myocardial infarction was similar in both groups (P = .874). Overall, TVR was similar in diabetics and non-diabetics (4.7% vs 4.2%; P = .814); however, when analyzed based on the physiological index, numerically, diabetics had a higher rate of TVR when the FFR was used in the decision-making process compared to when the iFR was used (6.4% vs 0.0%; P = .064). Conclusions: Deferring the revascularization of intermediate stenoses in patients with DM based on the FFR or the iFR is safe regarding the risk of TVR or target vessel myocardial infarction, with a rate of events at the long-term follow-up simi, Introducción y objetivos: La seguridad de la revascularización fisiológica en pacientes diabéticos ha sido poco investigada. El objetivo fue determinar la seguridad de diferir la revascularización basándose en la reserva fraccional de flujo (FFR) o en el índice instantáneo libre de ondas (iFR) en pacientes con diabetes mellitus. Métodos: Análisis retrospectivo, unicéntrico, de pacientes con estenosis coronarias intermedias en quienes se había diferido la revascularización en función de unos valores de FFR > 0,80 o de iFR > 0,89. Se analizó la incidencia a largo plazo de eventos cardiovasculares adversos mayores, una combinación de muerte por cualquier causa, infarto miocárdico y revascularización del vaso diana (RVD) en pacientes con y sin diabetes. También se evaluó la incidencia de RVD según el tipo de índice fisiológico utilizado para diferir la revascularización. Resultados: Se evaluaron 164 pacientes diabéticos (214 vasos) y 280 pacientes no diabéticos (379 vasos), con una mediana de seguimiento de 43 meses. No se observaron diferencias significativas en los eventos cardiovasculares adversos mayores entre pacientes con y sin diabetes mellitus (20,1 frente a 13,2%; p = 0,245). La mortalidad por cualquier causa y de causa cardiaca no fue estadísticamente diferente entre ambos grupos en el análisis ajustado (p > 0,05). Se observó una tendencia a una mayor incidencia de infarto de miocardio en los pacientes con diabetes mellitus (6,7 frente a 2,9%; p = 0,063), pero el infarto relacionado con el vaso diana fue similar en ambos grupos (p = 0,906). En general, la RVD fue similar en diabéticos y no diabéticos (4,7 frente a 4,2%; p = 0,787); sin embargo, cuando se analizó según el índice fisiológico, los diabéticos tuvieron una mayor tasa numérica de RVD cuando se utilizó la FFR en la toma de decisiones en comparación con el iFR (6,4 frente a 0,0%; p = 0,064). Conclusiones: Diferir la revascularización de estenosis intermedias en pacientes con diabetes mellitus según la