Comparación de una estrategia de revascularización coronaria completa vs revascularización coronaria guiada por ecocardiograma de esfuerzo en pacientes con infarto agudo de miocardio y enfermedad coronaria multivaso

Programa Oficial de Doutoramento en Ciencias da Saúde. 5007V01[Resumo] Esta tese doutoral é un ensaio clínico que, en doentes con infarto agudo de miocardio con elevación do segmento ST e enfermidade multivaso nos que se trata con éxito a arteria responsable do infarto con intervencionismo coronario, compara dúas estratexias de revascularización das lesións non responsables do infarto. Os doentes foron randomizados a revascularización percutánea de todas as lesións non responsables do infarto nun segundo procedemento (154 doentes) ou á realización dun ecocardiograma de esforzo e revascularización das lesións que produciran una isquemia extensa (152 doentes). O evento primario definiuse como o combinado de morte cardiovascular, infarto de miocardio, revascularización coronaria ou novo ingreso por insuficiencia cardíaca aos 12 meses de seguemento e non amosou diferenzas significativas entre as dúas estratexias de tratamento, nin sequera cando o seguemento extendeuse a un máximo de tres anos. No grupo de revascularización guiada con ecocardiograma de esforzo detectouse isquemia miocárdica en 64 doentes e en 44 realizouse un procedemento de revascularización de algunha lesión non responsable do infarto. Os costes de tratamento ao alta e a un ano de seguemento foron significativamente menores nos doentes randomizados a unha estratexia de revascularización guiada con ecocardiograma de esforzo.[Resumen] Esta tesis doctoral es un ensayo clínico que, en pacientes con infarto agudo de miocardio con elevación del segmento ST y enfermedad multivaso en los que se trata con éxito la arteria responsable del infarto mediante intervencionismo coronario, compara dos estrategias de revascularización de las lesiones no responsables del infarto. Los pacientes fueron aleatorizados a revascularización percutánea de todas las lesiones no responsables del infarto en un segundo procedimiento (154 pacientes) o a realización de ecocardiograma de esfuerzo y revascularización sólo de las lesiones que mostraran isquemia miocárdica extensa (152 pacientes). El evento primario, el combinado de muerte cardiovascular, infarto agudo de miocardio, revascularización coronaria o reingreso por insuficiencia cardíaca tras 12 meses de seguimiento no mostró diferencias significativas entre las dos estrategias y tampoco cuando el seguimiento se extendió hasta un máximo de tres años. En el grupo de revascularización guiada con ecocardiograma de esfuerzo se detectó isquemia miocárdica en 64 pacientes y en 44 se realizó un procedimiento de revascularización de alguna lesión no responsable del infarto. Los costes del tratamiento al alta hospitalaria y tras un año de seguimiento fueron significativamente menores en los pacientes aleatorizados a una estrategia de revascularización guiada con ecocardiograma de esfuerzo.[Abstract] This doctoral thesis is a clinical trial that compares two non-culprit vessel revascularization strategies in patients with ST segment elevation acute myocardial infarction and multivesel disease who have a successful percutaneous revascularization procedure in the infarct related artery. Patients were randomized to percutaneous revascularization of all non-infarct related coronary lesions in a second elective procedure (154 patients) or to a stress echocardiography and percutaneous revascularization of those coronary stenoses showing extensive myocardial isquemia (152 patients). The primary endpoint (the composite of cardiovascular death, myocardial infarction, coronary revascularization or readmission due to heart failure at 12 months follow-up) did not show any significant difference between study groups even when follow-up was extended up to three years. Myocardial isquemia was detected in 64 patients randomized to stress echocardiography and in 44 patients of this study group a revascularization procedure in a non-infarct related coronary lesion was performed. Medical expenses at hospital discharge and after one year follow-up were significantly lower in the stress echocardiography-guided revascularization strategy

Redesign and performance of an automatic segmentation method

[Resumen] La información más relevante de las angiografías coronarias se extrae empleando técnicas de segmentación, que pueden ser automáticas, semiautomáticas o manuales. Existen numerosos algoritmos de segmentación vascular, obteniendo mejores resultados, por normal general, aquellos que emplean múltiples técnicas e imágenes a diferentes escalas para proporcionar los resultados requeridos. Se presenta un nuevo método de segmentación automatizado basado en el método manual de Hamarneh incluyendo un estudio estadístico que demuestra su idoneidad para el problema

Automatic multiscale vascular image segmentation algorithm for coronary angiography

[Abstract] Cardiovascular diseases, particularly severe stenosis, are the main cause of death in the western world. The primary method of diagnosis, considered to be the standard in the detection and quantification of stenotic lesions, is a coronary angiography. This article proposes a new automatic multiscale segmentation algorithm for the study of coronary trees that offers results comparable to the best existing semi-automatic method. According to the state-of-the-art, a representative number of coronary angiography images that ensures the generalisation capacity of the algorithm has been used. All these images were selected by clinics from an Haemodynamics Unit. An exhaustive statistical analysis was performed in terms of sensitivity, specificity and Jaccard. Algorithm improvements imply that the clinician can perform tests on the patient and, bypassing the images through the system, can verify, in that moment, the intervention of existing differences in a coronary tree from a previous test, in such a way that it could change its clinical intra-intervention criteria.Galicia. Consellería de Cultura, Educación e Ordenación Universitaria; GRC2014/049Ministerio de Economía y Competitividad; TIN2015-70648-

lncRNA CDKN2B-AS1 is downregulated in patients with ventricular fibrillation in acute myocardial infarction

[Abstract] Ventricular fibrillation (VF) in acute myocardial infarction (AMI) is the main cause of deaths occurring in the acute phase of an ischemic event. Although it is known that genetics may play an important role in this pathology, the possible role of long non-coding RNAs (lncRNA) has never been studied. Therefore, the aim of this work is to study the expression of 10 lncRNAs in patients with and without VF in AMI. For this purpose, the expression of CDKN2B-AS1, KCNQ1OT1, LIPCAR, MALAT1, MIAT, NEAT1, SLC16A1-AS1, lnc-TK2-4:2, TNFRSF14-AS1, and UCA1 were analyzed. After the analysis and Bonferroni correction, the lncRNA CDKN2B-AS showed a statistical significance lower expression (P values of 2.514 x 10-5). In silico analysis revealed that six proteins could be related to the possible effect of lncRNA CDKN2B-AS1: AGO3, PLD4, POU4F1, ZNF26, ZNF326 and ZNF431. These in silico proteins predicted to have a low cardiac expression, although there is no literature indicating a potential relationship with VF in AMI. Thus, the lncRNA CDKN2B-AS1 shows a significant lower expression in patients with VF in AMI vs patients without VF in AMI. Literature data suggest that the role of CDKN2B1-AS is related to the miR-181a/SIRT1 pathway

Impacto en la mortalidad tras la implantación de una red de atención al infarto agudo de miocardio con elevación del segmento ST: Estudio IPHENAMIC

[Abstract] Introduction and objectives: Little is known about the impact of networks for ST-segment elevation myocardial infarction (STEMI) care on the population. The objective of this study was to determine whether the PROGALIAM (Programa Gallego de Atención al Infarto Agudo de Miocardio) improved survival in northern Galicia. Methods: We collected all events coded as STEMI between 2001 and 2013. A total of 6783 patients were identified and divided into 2 groups: pre-PROGALIAM (2001-2005), with 2878 patients, and PROGALIAM (2006-2013), with 3905 patients. Results: In the pre-PROGALIAM period, 5-year adjusted mortality was higher both in the total population (HR, 1.22, 95%CI, 1.14-1.29; P <.001) and in each area (A Coruña: HR, 1.12; 95%CI, 1.02-1.23; P=.02; Lugo: HR, 1.34; 95%CI, 1.2-1.49; P <.001 and Ferrol: HR, 1.23; 95%CI, 1.1-1.4; P=.001). Before PROGALIAM, 5-year adjusted mortality was higher in the areas of Lugo (HR, 1.25; 95%CI, 1.05-1.49; P=.02) and Ferrol (HR, 1.32; 95%CI, 1.13-1.55; P=.001) than in A Coruña. These differences disappeared after the creation of the STEMI network (Lugo vs A Coruña: HR, 0.88; 95%CI, 0.72-1.06; P=.18, Ferrol vs A Coruña: HR, 1.04; 95%CI, 0.89-1.22; P=.58. Conclusions: For patients with STEMI, the creation of PROGALIAM in northern Galicia decreased mortality and increased equity in terms of survival both overall and in each of the areas where it was implemented. This study was registered at ClinicalTrials.gov (Identifier: NCT02501070).[Resumen] Introducción y objetivos. Se sabe muy poco del impacto que las redes de atención del infarto agudo de miocardio con elevación del segmento ST (IAMCEST) tienen en la población. El objetivo de este estudio es averiguar si el PROGALIAM (Programa Gallego de Atención al Infarto Agudo de Miocardio) mejoró la supervivencia en la zona norte de Galicia. Métodos. Se recogieron todos los eventos codificados como IAMCEST entre 2001 y 2013. Se identificó a 6.783 pacientes, divididos en 2 grupos: pre-PROGALIAM (2001-2005), 2.878 pacientes, y PROGALIAM (2006-2013), 3.905 pacientes. Resultados. En la etapa pre-PROGALIAM, la mortalidad ajustada a 5 años fue superior tanto en la población total (HR = 1,22; IC95%, 1,14-1,29; p < 0,001), como en cada una de las áreas (A Coruña, HR = 1,12; IC95%, 1,02-1,23; p = 0,02; Lugo, HR = 1,34; IC95%, 1,2-1,49; p < 0,001, y Ferrol, HR = 1,23; IC95%, 1,1-1,4; p = 0,001). Antes del PROGALIAM, la mortalidad a 5 años en las áreas de Lugo (HR = 0,8; IC95%, 0,67-0,95; p = 0,02) y Ferrol (HR = 0,75; IC95%, 0,64-0,88; p = 0,001) era superior que en A Coruña. Estas diferencias desaparecieron tras el desarrollo de la red (Lugo comparado con A Coruña, HR = 0,88; IC95%, 0,72-1,06; p = 0,18; Ferrol comparado con A Coruña, HR = 1,04; IC95%, 0,89-1,22; p = 0,58. Conclusiones. El desarrollo del PROGALIAM en el área norte de Galicia disminuyó la mortalidad e incrementó la equidad de los pacientes con IAMCEST tanto en general como en cada una de las áreas donde se implantó. Estudio registrado en ClinicalTrials.gov (Identificador: NCT02501070)

Long-term results of heart transplant in recipients older and younger than 65 years: a comparative study of mortality, rejections, and neoplasia in a cohort of 445 patients

[Resumen] Background. Whether being older than 65 years should be considered an absolute counterindication to heart transplant (HT), as it is in some centers, is controversial. In our centre, patients older than 65 years are accepted for HT if they satisfy stringent conditions. The aim of this study was to examine whether heart recipients older than 65 years have a greater risk of rejection, neoplasia, or mortality than younger ones. Methods. We studied 445 patients who underwent HT between April 1991 and December 2003, 42 of whom were older than 65 years and 403 who were 65 years or younger. The parameters evaluated were the cumulative incidences of neoplasias and rejections (ISHLT grade ≥ 3A), and the survival rates 1 month, 1 year, and 5 years post-HT. Results. The two groups had similar percentages of patients with at least one rejection episode (≤65 years 56.9%, >65 years 51.3%; P > .05), and although there were proportionally almost twice as many tumors in the older group (14.2%) as in the younger (7.9%), this difference was not statistically significant either. Nor were there any significant differences in survival, the 1-month, 1-year, and 5-year rates being 87.8%, 82.1%, and 68.8%, respectively, in the younger group and 85.7%, 78.6%, and 73.4%, respectively, in the older. Conclusions. Among carefully selected patients aged more than 65 years, HT can be performed without incurring greater risk of rejection, malignancy, or death than is found among recipients younger than 65 years

Prevalence, etiology, and outcome of catheterization laboratory false alarms in patients with suspected ST-elevation myocardial infarction

[Abstract] Introduction and objectives. To investigate the prevalence, causes and outcome of catheterization laboratory false alarms (CLFAs) in a regional primary angioplasty network. Methods. A prospective registry of 1,662 patients referred for primary angioplasty between January 2003 and August 2008 was reviewed to identify CLFAs (i.e. when no culprit coronary lesion could be found). Results. No culprit coronary lesion could be identified in 120 patients (7.2%; 95% confidence interval [CI], 5.9- 8.5%). Of these, 104 (6.3%, 95% CI, 5.1-7.4%) had a discharge diagnosis other than ST-elevation myocardial infarction, 91 (5.5%; 95% CI, 4.3-6.6%) had no significant coronary disease, and 64 (3.8%; 95% CI, 2.9-4.8%) tested negative for cardiac biomarkers. The most frequent alternative diagnoses were: previous Q-wave myocardial infarction (18 cases), nonspecific ST-segment abnormalities (11), pericarditis (10) and transient apical dyskinesia (10). The 30-day mortality rate was similar in patients with and without culprit lesions (5.8% vs. 5.8%; P=.99). The prevalence of CLFAs was slightly higher in patients not previously evaluated by a cardiologist and referred from emergency departments in hospitals without catheterization laboratories than in those referred by cardiologists from emergency departments at hospitals with such facilities (9.5% vs. 6.1%; P=.02; odds ratio=1.64; 95% CI, 1.08-2.5). The prevalence of CLFAs was not significantly higher in patients referred by physicians with out-of-hospital emergency medical services (7.2%; P=.51; odds ratio=1.37; 95% CI, 0.79-2.37). Conclusions. The prevalence of CLFAs was 7.2%, with the criterion of no culprit coronary lesion. Our findings suggest that different patterns of referral to catheterization laboratories could account for small variations in the prevalence of CLFAs.[Resumen] Introducción y objetivos. Determinar prevalencia, causas y pronóstico de las «falsas alarmas» al laboratorio de hemodinámica (FALH) en una red regional de angioplastia primaria. Métodos. Registro prospectivo de 1.662 pacientes remitidos para angioplastia primaria entre enero de 2003 y agosto de 2008. Se definió FALH como ausencia de lesión coronaria causal. Resultados. En 120 pacientes (7,2%; intervalo de confianza [IC] del 95%, 5,9-8,5) no se identificó ninguna lesión coronaria causal. De ellos, 104 (6,3%; IC del 95%, 5,1-7,4) recibieron un diagnóstico alternativo a IAMCEST, 91 (5,5%; IC del 95%, 4,3-6,6) no presentaron enfermedad coronaria significativa y 64 (3,8%; IC del 95%, 2,9-4,8) presentaron marcadores de daño miocárdico negativos. Los diagnósticos alternativos más frecuentes fueron: infarto con onda Q previo (18 casos), alteraciones inespecíficas del segmento ST (11), pericarditis (10) y discinesia apical transitoria (10). La mortalidad a 30 días fue similar en los pacientes con y sin lesión causal (el 5,8 frente al 5,8%; p = 0,99). La prevalencia de FALH fue discretamente superior entre los pacientes remitidos desde los servicios de urgencias de hospitales no intervencionistas sin evaluación previa por un cardiólogo que entre los remitidos por cardiólogos desde el servicio de urgencias del hospital intervencionista (el 9,5 frente al 6,1%; p = 0,02; odds ratio [OR] = 1,64; IC del 95%, 1,08-2,5). No observamos un exceso de FALH entre los pacientes remitidos por médicos de UVI Móviles-061 (7,2%; p = 0,51; OR = 1,37; IC del 95%, 0,79-2,37). Conclusiones. Hemos observado una prevalencia de FALH del 7,2% de acuerdo con el criterio de ausencia de lesión coronaria causal. Nuestros resultados indican que diferentes modelos de activación del laboratorio de hemodinámica podrían justificar discretas variaciones en la prevalencia de FALH

Clinical follow-up of long nontapered sirolimus-eluting coronary stent in real-world patients with de novo lesions. The Billar registry

Introduction and objectives: Coronary lesions with stent overlapping are associated with higher neointimal proliferation that leads to more restenosis. Furthermore, the tapering of coronary arteries is a major challenge when treating long coronary lesions. This study attempted to assess the safety and clinical level of performance of long nontapered sirolimus-eluting coronary stent systems (> 36 mm) to treat long and diffused de novo coronary lesions in real-world scenarios. Methods: This was a prospective, non-randomized, multicentre study that included 696 consecutive patients treated with the long nontapered BioMime sirolimus-eluting coronary stent system in long and diffused de novo coronary lesions. The safety endpoint was major adverse cardiovascular events defined as a composite of cardiac death, myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, and major bleeding at the 12-month follow-up. Results: Of a total of 696 patients, 38.79% were diabetic. The mean age of all the patients was 64.6 +/- 14 years, and 80% were males. The indication for revascularization was acute coronary syndrome in 63.1%. A total of 899 lesions were identified out of which 742 were successfully treated with long BioMime stents (37 mm, 40 mm, 44 mm, and 48 mm). The cumulative incidence of major adverse cardiovascular events was 8.1% at the 12-month follow-up including cardiac death (2.09%), myocardial infarction (1.34%), and total stent thrombosis (0.5%). Conclusions: This study confirms the safety and good performance of long nontapered BioMime coronary stents to treat de novo coronary stenosis. Therefore, it can be considered a safe and effective treatment for long and diffused de novo coronary lesions in the routine clinical practice

Presence of Bacterial DNA in Thrombotic Material of Patients with Myocardial Infarction

[Abstract] Infectious agents have been suggested to be involved in etiopathogenesis of Acute Coronary Syndrome (ACS). However, the relationship between bacterial infection and acute myocardial infarction (AMI) has not yet been completely clarified. The objective of this study is to detect bacterial DNA in thrombotic material of patients with ACS with ST-segment elevation (STEMI) treated with Primary Percutaneous Coronary Intervention (PPCI). We studied 109 consecutive patients with STEMI, who underwent thrombus aspiration and arterial peripheral blood sampling. Testing for bacterial DNA was performed by probe-based real-time Polymerase Chain Reaction (PCR). 12 probes and primers were used for the detection of Aggregatibacter actinomycetemcomitans, Chlamydia pneumoniae, viridans group streptococci, Porphyromonas gingivalis, Fusobacterium nucleatum, Tannarella forsythia, Treponema denticola, Helycobacter pylori, Mycoplasma pneumoniae, Staphylococus aureus, Prevotella intermedia and Streptococcus mutans. Thus, DNA of four species of bacteria was detected in 10 of the 109 patients studied. The most frequent species was viridans group streptococci (6 patients, 5.5%), followed by Staphylococus aureus (2 patients, 1.8%). Moreover, a patient had DNA of Porphyromonas gingivalis (0.9%); and another patient had DNA of Prevotella intermedia (0.9%). Bacterial DNA was not detected in peripheral blood of any of our patients. In conclusion, DNA of four species of endodontic and periodontal bacteria was detected in thrombotic material of 10 STEMI patients. Bacterial DNA was not detected in the peripheral blood of patients with bacterial DNA in their thrombotic material. Bacteria could be latently present in plaques and might play a role in plaque instability and thrombus formation leading to ACS

Pulmonary vascular remodeling and prognosis in patients evaluated for heart transplantation: insights from the OCTOPUS-CHF study

[Abstract] Objective: In patients with advanced heart failure, the intravascular optical coherence tomography (OCT) of subsegmental pulmonary artery measurements is correlated with right heart catheterization parameters. Our aim was to study the prognostic value of pulmonary OCT, right heart catheterization data, and the echocardiographic estimation of pulmonary pressure in patients studied for elective heart transplants. Methods: This research is an observational, prospective, multicenter study involving 90 adults with a one-year follow-up. Results: A total of 10 patients (11.1%) died due to worsening heart failure before heart transplantation, 50 underwent a heart transplant (55.6%), and 9 died in the first year after the transplant. The patients with and without events (mortality or heart failure-induced hospitalization) had similar data regarding echocardiography, right heart catheterization, and pulmonary OCT (with a median estimated pulmonary artery systolic pressure of 42.0 mmHg, interquartile range (IQR) of 30.3-50.0 vs. 47.0 mmHg, IQR 34.6-59.5 and p = 0.79, median pulmonary vascular resistance of 2.2 Wood units, IQR 1.3-3.7 vs. 2.0 Wood units, IQR 1.4-3.2 and p = 0.99, and a median pulmonary artery wall thickness of 0.2 ± 0.5 mm vs. 0.2 ± 0.6 mm and p = 0.87). Conclusion: Pulmonary vascular remodeling (evaluated with echocardiography, right heart catheterization, and pulmonary OCT) was not associated with prognosis in a selected sample of adults evaluated for elective heart transplants. Pulmonary OCT is safe and feasible for the evaluation of these patients.Instituto de Salud Carlos III; PI18/00254European Regional Development Fund; CB16/11/0050