Linking In Vitro Models of Endothelial Dysfunction with Cell Senescence.

Endothelial cell dysfunction is the principal cause of several cardiovascular diseases that are increasing in prevalence, healthcare costs, and mortality. Developing a standardized, representative in vitro model of endothelial cell dysfunction is fundamental to a greater understanding of the pathophysiology, and to aiding the development of novel pharmacological therapies. We subjected human umbilical vein endothelial cells (HUVECs) to different periods of nutrient deprivation or increasing doses of H2O2 to represent starvation or elevated oxidative stress, respectively, to investigate changes in cellular function. Both in vitro cellular models of endothelial cell dysfunction-associated senescence developed in this study, starvation and oxidative stress, were validated by markers of cellular senescence (increase in ß-galactosidase activity, and changes in senescence gene markers SIRT1 and P21) and endothelial dysfunction as denoted by reductions in angiogenic and migratory capabilities. HUVECs showed a significant H2O2 concentration-dependent reduction in cell viability (p < 0.0001), and a significant increase in oxidative stress (p < 0.0001). Furthermore, HUVECs subjected to 96 h of starvation, or exposed to concentrations of H2O2 of 400 to 1000 µM resulted in impaired angiogenic and migratory potentials. These models will enable improved physiological studies of endothelial cell dysfunction, and the rapid testing of cellular efficacy and toxicity of future novel therapeutic compounds.

Long-term impact of diabetes in patients with ST-segment elevation myocardial infarction: Insights from the EXAMINATION randomized trial.

BACKGROUND: Long-term outcomes of diabetic patients suffering from ST-segment elevation myocardial infarction (STEMI) and treated with second-generation drug-eluting stent have been scarcely evaluated. The aim of this posthoc subanalysis of the EXAMINATION trial was to compare 5-year outcomes according to the presence of diabetes mellitus. METHODS: From a total of 1,497 patients included in the trial, 258 were diabetics (n = 137, received everolimus-eluting stent (EES) and n = 121 bare-metal stent (BMS); whereas 1,239 were nondiabetics (n = 613 treated with EES and n = 626 with BMS). Patient-oriented combined endpoint (POCE) defined as all-cause death, any MI or any revascularization, and other clinical parameters were collected up to 5-years. All results were adjusted for various potential confounders. RESULTS: At 5-years, patients with diabetes showed similar rates of POCE between diabetics treated with EES and those treated with BMS (32.8% vs. 32.2%; p = 0.88). However, rates of TLR were significantly lower in the EES group (4.4% vs. 9.9%; HR 0.52 (0.29-0.94); P = 0.03). In non-diabetics, the use of EES was associated with a significant improvement in all-clinical parameters except for MI rate: POCE: [10.0% vs. 12.6%; HR 0.78(0.62-0.98); P = 0.038], all cause death: [7.0% vs. 12.1%; HR 0.62(0.42-0.90); P = 0.014], and [TLR: 4.2 vs. 6.7; HR 0.60 (0.37-0.98); P = 0.04]. Overall, diabetics showed higher rate of POCE at 5-years (32.6% vs. 21.5% in nondiabetics HR1.45[1.03-2.04];p = 0.03) driven by increased rates of MI and the need for revascularization that occurred in coronary segments remote from target lesions [2.7% vs. 1.1%; HR: 2.27 (1.12-5.23); P = 0.02 and 14% vs. 6.2%; HR: 2.11 (1.38-3.22); P = 0.001, respectively]. CONCLUSIONS: Diabetics had worse clinical outcomes than nondiabetics after STEMI mainly due to atherosclerosis progression. At 5-years, the treatment with EES did not reduce the rate of POCE in diabetics but reduced the need for revascularization compared with BMS.

Erythrocyte-heme proteins and STEMI: implications in prognosis.

The role of erythrocytes in thrombus formation has been often neglected, but some studies have highlighted their active role in thrombotic events. Free-haemoglobin (Hb) has shown to induce oxidative-stress damage. Herein we have investigated the coordinated changes in heme-related proteins in patients with acute-coronary-syndromes (ACS), their association to ongoing thrombosis and their impact on patients' prognosis. The serum proteome of STEMI-patients (N=27) within the first 6h after event-onset and 3d after were compared to controls (N=60). Changes in heme-metabolism were characterized in a second STEMI-group by a dual proteomic approach analyzing in-vivo aspirated coronary thrombi at PCI (N=24) and the associated peripheral-blood changes (N=10). A third STEMI-group (N=132) was studied to analyze the impact of the observed changes in prognosis at 6-months-follow-up. The haptoglobin/hemopexin(Hpg/Hpx)-scavenging-system revealed a time-dependent response after STEMI with an early increase in Hpg circulating levels in the acute phase (P=0.01) and a late increase in Hpx levels 3d after (P=0.045). Beta-Hb content in coronary thrombi was directly correlated with systemic beta-Hb and Hpg (R=0.804,P=0.0029; R=0.859,P=0.0007) levels. The presence of a fully-occlusive thrombus was associated to higher circulating levels of beta-Hb (P=0.03) and unbound-Hpg (P=0.03). ELISA validation demonstrated a decreased survival rate at 6-months follow-up in STEMI-patients with lower Hpg plasma levels at admission (P=0.027). Our results show active Hb-release form erythrocytes in ACS. This release is followed by a systemic early increase in Hpg levels and a late increase in Hpx levels that can co-ordinately help to prevent systemic pro-oxidative effects. The Hb-scavenging ability of haptoglobin is related to patients' prognosis.

2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases.

Full text available at: http://eurheartj.oxfordjournals.org/content/early/2015/08/28/eurheartj.ehv318.

Guía ESC 2015 sobre el diagnóstico y tratamiento de las enfermedades del pericardio / 2015 ESC guidelines for the diagnosis and management of pericardial diseases

No disponible

Eficacia y seguridad a más de 10 años de la ablación septal percutánea en la miocardiopatía hipertrófica obstructiva / Effectiveness and Safety Beyond 10 Years of Percutaneous Transluminal Septal Ablation in Hypertrophic Obstructive Cardiomyopathy

Introducción y objetivos La ablación septal percutánea es una alternativa terapéutica en la miocardiopatía hipertrófica obstructiva. Debido a su introducción relativamente reciente, no hay información sobre eficacia y seguridad a muy largo plazo. Este estudio multicéntrico evalúa sus resultados en seguimiento superior a 10 años. Métodos Se incluyó consecutivamente a pacientes tratados con ablación septal en cinco centros entre 1998 y 2003. Se han analizado datos clínicos, hemodinámicos y ecocardiográficos basales y de seguimiento. Resultados Se ha incluido a 45 pacientes (media de edad, 62,4 ± 14 años), de los que 31 eran mujeres y 39 (86,6%) estaban en clase funcional III - IV . El grosor del septo era 21,8 ± 3,5 mm; el gradiente máximo basal por ecocardiografía, 77 ± 39 mmHg, y la insuficiencia mitral era de grado al menos moderado en 22 pacientes (48,8%). Durante la hospitalización, 3 casos precisaron implante de marcapasos definitivo y 1 paciente sufrió perforación ventricular por electrodo de marcapasos, que requirió cirugía. Tras seguimiento de 12,3 (11,0-13,5) años, 2 pacientes (4,4%) sufrieron muerte cardiaca (insuficiencia cardiaca y postrasplante); 3, implante de desfibrilador automático implantable (1 caso por prevención primaria y 2 por taquicardia ventricular sostenida tras cirugía cardiaca), y 2, cirugía cardiaca (endocarditis e insuficiencia mitral). En la última evaluación clínica, la clase funcional era I - II en 39 (86,6%) (p < 0,0001); el gradiente máximo basal, 16 ± 23 mmHg (p < 0,0001), y la insuficiencia mitral, nula o ligera en 34 pacientes (75,5%) (p < 0,03).Conclusiones Estos resultados a más de 10 años indican seguridad y eficacia a muy largo plazo para la ablación septal. No hubo incidencia significativa de arritmias ventriculares sintomáticas o muerte súbita (AU)

Introduction and objectives: Percutaneous transluminal septal ablation is an alternative treatment in patients with hypertrophic obstructive cardiomyopathy. However, due to the relatively new introduction of this technique, there is no information on its very long term results (>10 years).Methods: The present study included consecutive patients treated in 5 centers between 1998 and 2003.We analyzed clinical, hemodynamic, and echocardiographic data at baseline and follow-up. Results: A total of 45 patients were included; there were 31 (69%) women, the mean age was62.4 (14) years, and 39 patients (86.6%) showed functional class III or IV. Septal thickness was 21.8 (3.5) mm, the peak resting gradient on echocardiography was 77 (39) mmHg, and mitral regurgitation was at least moderate in 22 patients (48.8%). During hospitalization, permanent pacemaker implantation was required in 3 patients and ventricular perforation (by pacing lead) occurred in 1 patient, requiring surgery. After a follow-up of 12.3 years (11.0-13.5 years), 2 patients (4.4%) died from cardiac causes (heart failure and posttransplantation), 3 patients required an implantable cardioverter-defibrillator (1 for primary prevention and 2 due to sustained ventricular tachycardia after cardiac surgery), and 2 underwent cardiac surgery (due to endocarditis and mitral regurgitation). In the last clinical review, functional class was I-II in 39 patients (86.6%) (P<.0001), the peak resting gradient was 16 (23) mmHg (P<.0001), and mitral regurgitation was absent or mild in 34 patients (75.5%) (P<.03).Conclusions: The results of this study suggest that septal ablation is safe and effective in the very longterm. The procedure was not associated with a significant incidence of sudden death or symptomatic ventricular arrhythmias (AU)

Effectiveness and safety beyond 10 years of percutaneous transluminal septal ablation in hypertrophic obstructive cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Percutaneous transluminal septal ablation is an alternative treatment in patients with hypertrophic obstructive cardiomyopathy. However, due to the relatively new introduction of this technique, there is no information on its very long term results (>10 years). METHODS: The present study included consecutive patients treated in 5 centers between 1998 and 2003. We analyzed clinical, hemodynamic, and echocardiographic data at baseline and follow-up. RESULTS: A total of 45 patients were included; there were 31 (69%) women, the mean age was 62.4 (14) years, and 39 patients (86.6%) showed functional class III or IV. Septal thickness was 21.8 (3.5) mm, the peak resting gradient on echocardiography was 77 (39) mmHg, and mitral regurgitation was at least moderate in 22 patients (48.8%). During hospitalization, permanent pacemaker implantation was required in 3 patients and ventricular perforation (by pacing lead) occurred in 1 patient, requiring surgery. After a follow-up of 12.3 years (11.0-13.5 years), 2 patients (4.4%) died from cardiac causes (heart failure and posttransplantation), 3 patients required an implantable cardioverter-defibrillator (1 for primary prevention and 2 due to sustained ventricular tachycardia after cardiac surgery), and 2 underwent cardiac surgery (due to endocarditis and mitral regurgitation). In the last clinical review, functional class was I-II in 39 patients (86.6%) (P<.0001), the peak resting gradient was 16 (23) mmHg (P<.0001), and mitral regurgitation was absent or mild in 34 patients (75.5%) (P<.03). CONCLUSIONS: The results of this study suggest that septal ablation is safe and effective in the very long term. The procedure was not associated with a significant incidence of sudden death or symptomatic ventricular arrhythmias.

High-molecular-weight kininogen and the intrinsic coagulation pathway in patients with de novo acute myocardial infarction.

After an acute ischaemic event serum proteins may change reflecting the ischaemic damage. Proteomic studies could provide new insights into potential biomarkers in the evolution of ischaemic syndromes. In this study we have investigated the coordinated changes in coagulation-related proteins in the evolution after an acute myocardial infarction (AMI). Serum proteome (2D-electrophoresis and MALDI-TOF/TOF) of AMI-patients within the first 6 hours after event onset (admission-time) and 3 days after were compared to controls. Systems biology and bioinformatic analysis were performed to identify the differentially expressed canonical pathways. In silico analysis of differential proteins revealed changes in the intrinsic coagulation pathway in the early phase post-AMI. The two identified high-molecular weight kininogen (HMWK) clusters were inversely correlated in AMI patients at admission, being the intensity of the low-molecular-weight form inversely related to myocardial necrosis (p<0.05). Factor XI (FXI) levels were decreased in AMI patients at admission and normalised 3 days after (p<0.05). There was an early increase in fibrinogen gamma and D-dimer at admission, followed by a decrease in fibrinogen turnover 3 days after (p<0.05). The influence of elapsed time of ischaemia on fibrinogen distribution changes was validated in coronary thrombi retrieved by thromboaspiration. In conclusion, our results demonstrate an active exchange between HMWK forms and a decrease in FXI indicative of intrinsic pathway activation, together with an increase in fibrinogen gamma turnover and D-dimer formation in the early phase post-AMI. Moreover, coronary thrombi showed a dynamic evolution in fibrinogen composition depending on the duration of ischaemia influencing serum fibrinogen-related products content.

Actualización en cardiología intervencionista / Update on interventional cardiology

En el presente artículo se hace una revisión de las publicaciones y los estudios presentados más relevantes en el ámbito de la cardiología intervencionista en el año 2012. El intervencionismo coronario en el contexto del infarto con elevación del ST ocupa un lugar destacado con estudios que confirman la importancia de reducir los tiempos de reperfusión y otros que evalúan diferentes dispositivos y estrategias farmacológicas en la angioplastia primaria. Los estudios comparativos entre stents farmacoactivos de diferentes generaciones son múltiples e indican una progresión positiva en eficacia y especialmente en seguridad. Con las nuevas generaciones de stents farmacoactivos, la trombosis tardía resulta casi equivalente a la de los stents metálicos. Los resultados con stents en la lesión del tronco común o en la enfermedad multivaso también se han abordado en importantes ensayos. Entre las técnicas de diagnóstico intracoronario, destacan los estudios de correlación entre técnicas de imagen y de presión intracoronaria. El intervencionismo cardiaco estructural y concretamente el implante de válvula aórtica y la reparación mitral continúan generando muchas publicaciones, especialmente la primera. Finalmente, la denervación renal ocupa ya un lugar destacado en la literatura médica (AU)

This article provides a detailed review of the most important studies on interventional cardiology reported in publications or presentations during the year 2012. With regard to coronary interventions, ST-elevation myocardial infarction is extensively addressed in studies focusing on the relevance of reducing the reperfusion time and the utility of various devices and pharmacological strategies in primary angioplasty. Multiple comparative studies involving different generations of drug-eluting stents are available and indicate a favorable progression in terms of safety and efficacy. The risk of late thrombosis with the new generations of drug-eluting stents seems to be equivalent to that observed with bare-metal stents. The clinical outcomes with these stents in the elderly, in left main coronary artery, or in multivessel disease have also been the subject of important trials. Among the studies on intracoronary diagnostic techniques, those correlating imaging and pressure-based techniques are of special interest. The percutaneous treatment of structural heart disease, particularly transcatheter aortic valve implantation, followed by mitral repair, continues to be the subject of a great number of publications. Finally, renal denervation is currently being widely discussed in the literature (AU)

Reperfusion-triggered stress protein response in the myocardium is blocked by post-conditioning. Systems biology pathway analysis highlights the key role of the canonical aryl-hydrocarbon receptor pathway.

AIMS: Ischaemic post-conditioning (IPost-Co) exerts cardioprotection by diminishing ischaemia/reperfusion injury. Yet, the mechanisms involved in such protection remain largely unknown. We have investigated the effects of IPost-Co in cardiac cells and in heart performance using molecular, proteomic and functional approaches. METHODS AND RESULTS: Pigs underwent 1.5 h mid-left anterior descending balloon occlusion and then were sacrificed without reperfusion (ischaemia; n= 7), subjected to 2.5 h of cardiac reperfusion and sacrificed (n= 5); or subjected to IPost-Co before reperfusion and sacrificed 0.5 h (n= 4) and 2.5 h (n= 5) afterwards. A sham-operated group was included (n= 4). Ischaemic and non-ischaemic myocardium was obtained for molecular/histological analysis. Proteomic analysis was performed by two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization-time-of-flight identification. Potential protein networks involved were identified by bioinformatics and Ingenuity Pathway Analysis (IPA). Cardiac function was assessed by echocardiography. IPost-Co diminished (up to 2.5 h) reperfusion-induced apoptosis of both the intrinsic and extrinsic pathways whereas it did not affect reperfusion-induced Akt/mammalian target of rapamycin (mTOR)/P70S6K activation. Proteomic studies showed that IPost-Co reverted 43% of cardiac cytoplasmic protein changes observed during ischaemia and ischaemia + reperfusion. Systems biology assessment revealed significant changes in the aryl-hydrocarbon receptor (AhR) pathway (cell damage related). Bioinformatic data were confirmed since the expression of HSP90, AhR, ANRT, and ß-tubulin (involved in AhR-signalling transduction) were accordingly modified after IPost-Co. IPost-Co rescued 52% of the left ventricle-at-risk compared with reperfusion alone and resulted in a ≈30% relative improvement in left ventricular ejection fraction (P <0.05). CONCLUSION: IPost-Co improves cardiac function post-myocardial infarction and reduces reperfusion-induced cell damage by down-regulation of the AhR-signalling transduction pathway ultimately leading to infarct size reduction.

Update on interventional cardiology.

This article provides a detailed review of the most important studies on interventional cardiology reported in publications or presentations during the year 2012. With regard to coronary interventions, ST-elevation myocardial infarction is extensively addressed in studies focusing on the relevance of reducing the reperfusion time and the utility of various devices and pharmacological strategies in primary angioplasty. Multiple comparative studies involving different generations of drug-eluting stents are available and indicate a favorable progression in terms of safety and efficacy. The risk of late thrombosis with the new generations of drug-eluting stents seems to be equivalent to that observed with bare-metal stents. The clinical outcomes with these stents in the elderly, in left main coronary artery, or in multivessel disease have also been the subject of important trials. Among the studies on intracoronary diagnostic techniques, those correlating imaging and pressure-based techniques are of special interest. The percutaneous treatment of structural heart disease, particularly transcatheter aortic valve implantation, followed by mitral repair, continues to be the subject of a great number of publications. Finally, renal denervation is currently being widely discussed in the literature.

Actualizacion en cardiologia intervencionista / Update on interventional cardiology

En el presente artículo se hace una revisión de las publicaciones y los estudios presentados más relevantes en el ámbito de la cardiología intervencionista. En cuanto al intervencionismo coronario, el contexto del infarto con ST alto ocupa un lugar destacado, con estudios que establecen la importancia de los tiempos adecuados y otros que confirman la seguridad de los stents farmacoactivos. Los estudios comparativos entre stents farmacoactivos de diferentes generaciones son múltiples e indican una progresión positiva en eficacia y seguridad. Los resultados con estos en la lesión del tronco común o en la enfermedad multivaso se abordan también en importantes ensayos. Entre las técnicas de diagnostico intracoronario destaca latomografia de coherencia óptica aplicada al estudio de los stents farmacoactivos. El intervencionismo cardiaco estructural, concretamente el implante percutaneo de válvula aortica, suscita un interés cada vez mayor, y más tras la publicación del primer estudio aleatorizado que ha arrojado resultados positivos (AU)

This article contains a review of the most important studies on interventional cardiology reported in either publications or presentations. In the area of coronary interventions, ST-elevation myocardial infarction continues to take center place: recent studies have confirmed the importance of timely intervention and the safety of drug-eluting stents. The numerous studies that have compared different generations of drugeluting stents indicate that there has been a steady improvement in safety and efficacy. In addition, the use of stents in the left main coronary artery and in multivessel disease have also been investigated in major studies. Of the different intracoronary diagnostic techniques, optical coherence tomography is highlighted by this review, particularly for its use in the study of drug-eluting stents. There is increasing interest in the percutaneous treatment of structural heart disease, specifically percutaneous aortic valve implantation,especially following the publication of the first randomized trial, which produced encouraging results (AU)

Actualizacion en cardiologia intervencionista / Update in interventional cardiology

En el presente artículo se hace una revisión detallada de las publicaciones y los estudios presentados más relevantes en el ámbito de la cardiología intervencionista. En cuanto al intervencionismo coronario, el contexto del infarto con ST alto ocupa un lugar destacado, dada la progresivamente mayor expansión de los programas de angioplastia primaria. Los stents farmacoactivos continúan siendo objeto de multiples estudios, especialmente los de nueva generación. Los resultados en el paciente diabético, en casos con lesión del tronco común o con enfermedad multivaso, también se tratan en numerosos trabajos. Las técnicas de diagnostico intracoronario, y especialmente la tomografía de coherencia óptica, también se abordan. Finalmente, el intervencionismo cardiaco estructural y concretamente el implante percutaneo de válvula aortica suscitan un interés cada vez mayor (AU)

This article contains a detailed review of the most important studies on interventional cardiology reported in either publications or presentations. With regard to coronary interventions, ST-elevation myocardial infarction is highlighted because of the ongoing substantial expansion in primary angioplasty programs. Drug-eluting stents, especially new-generation stents, continue to be the focus of numerous studies. Clinical outcomes in diabetic patients with left main coronary artery or (..) (AU)

Situación actual de la intervención coronaria percutánea primaria en España / The current status of primary percutaneous coronary intervention in Spain

A partir de los datos del Registro Nacional de Hemodinámica y Cardiología Intervencionista de 2009, se presenta la situación de la intervención coronaria percutánea primaria en España. Se analiza la actividad por comunidades autónomas, con énfasis en los principales condicionantes que inciden en la implantación de la intervención coronaria percutánea primaria. En 2009 se realizaron 216 (65-427) intervenciones coronarias percutáneas primarias/millón de habitantes. La utilización de la intervención coronaria percutánea primaria no parece condicionada por el número de laboratorios con alerta las 24 h ni el presupuesto por persona de cada comunidad. Sin embargo, se advierte cierta influencia del grado de desarrollo del intervencionismo en cada comunidad (intervención es coronarias percutáneas totales/millón habitantes) y, fundamentalmente, de la implantación de programas centralizados de ámbito comunitario que implican a la administración sanitaria (AU)

This article describes the current status of primary percutaneous coronary intervention in Spain by using data from the national cardiac catheterization and interventional cardiology registry. Activity in individual Spanish autonomous regions was analyzed, and special attention was paid to the main factors that influenced the implementation of primary percutaneous coronary intervention in each region. In 2009, 216 (range, 65-427) primary percutaneous coronary interventions per million inhabitants were performed. The use of primary percutaneous coronary intervention did not appear to be influenced by the number of emergency facilities that operated on a 24-hour basis or by per capita expenditure in a region. However, the level of development of coronary intervention provision (i.e. the number of percutaneous coronary interventions per million inhabitants) in a particular region and, especially, the introduction of centralized community programs that involved health-care authorities were observed to have some influence (AU)

Función endotelial en segmentos arteriales previamente sometidos a angioplastia coronaria / Endothelial function in coronary segments previously treated with balloon angioplasty

Introducción y objetivo. La angioplastia coronaria comporta una denudación endotelial y una posterior reendotelización. El objetivo de nuestro estudio ha sido determinar el estado de la función endotelial en segmentos coronarios sometidos a angioplastia y sin reestenosis. Métodos. Se analizó la respuesta vasodilatadora dependiente del endotelio en 12 pacientes con enfermedad de un vaso a los 6 meses de practicada la angioplastia mediante la infusión intracoronaria selectiva a dosis crecientes de acetilcolina (10-6, 10-5, 10-4 M) en la arteria previamente tratada. Siete pacientes con arterias coronarias normales o con mínimas irregularidades y sin factores de riesgo constituyeron el grupo control. La respuesta vasomotora a las diferentes dosis de acetilcolina se analizó mediante angiografía coronaria cuantitativa. Resultados. El estudio de la función endotelial demostró una respuesta global vasodilatadora en el segmento dilatado a la máxima dosis de acetilcolina (incremento del diámetro del 3,6 ñ 3,5 por ciento), similar a la respuesta observada en el grupo control (incremento del diámetro del 3 ñ 6 por ciento; p = NS).En particular, se observó una función endotelial normal en 8 pacientes (67 por ciento) y una respuesta vasoconstrictora en 4 enfermos (33 por ciento). Se ha detectado una correlación positiva entre la respuesta a la máxima dosis de acetilcolina y la lesión residual a los 6 meses de evolución (r = 0,67; p = 0,02). Conclusiones. En pacientes que han sido tratados mediante angioplastia y que no presentan reestenosis, los segmentos dilatados muestran frecuentemente una función endotelial normal. Un mayor grado de estenosis residual en las zonas dilatadas se asocia a una menor alteración de la función endotelial (AU)