Progression of Early Subclinical Atherosclerosis (PESA) Study: JACC Focus Seminar 7/8.

Atherosclerosis starts early in life and progresses silently for decades. Considering atherosclerosis as a "systemic disease" invites the use of noninvasive methodologies to detect disease in various regions before symptoms appear. The PESA-(Progression of Early Subclinical Atherosclerosis) CNIC-SANTANDER study is an ongoing prospective cohort study examining imaging, biological, and behavioral parameters associated with the presence and progression of early subclinical atherosclerosis. Between 2010 and 2014, PESA enrolled 4,184 asymptomatic middle-aged participants who undergo serial 3-yearly follow-up examinations including clinical interviews, lifestyle questionnaires, sampling, and noninvasive imaging assessment of multiterritorial subclinical atherosclerosis (carotids, iliofemorals, aorta, and coronaries). PESA tracks the trajectories of atherosclerosis and associated disorders from early stages to the transition to symptomatic phases. A joint venture between the CNIC and the Santander Bank, PESA is expected to run until at least 2029, and its significant contributions to date are presented in this review paper.The PESA study is funded by the CNIC and Santander Bank. The study has also received funding from the Carlos III Institute of Health (ISCIII, PI15/02019, PI17/00590, and PI20/00819) and the European Regional Development Fund. The CNIC is supported by the ISCIII, the MICIN, and the Pro CNIC Foundation. Dr Ibanez is the recipient of a European Research Council grant MATRIX (ERC-COG-2018-ID: 819775). Dr Andrés is supported by grant PID2019-108489RB-I00 from the Spanish Ministerio de Ciencia e Innovación (MICIN), with cofunding from the European Regional Development Fund/Fondo Europeo de Desarrollo Regional (ERDF/FEDER, “A way to build Europe”). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.S

Magnetic resonance imaging reference values for cardiac morphology, function and tissue composition in adolescents.

BACKGROUND Cardiovascular magnetic resonance (CMR) is a precise tool for the assessment of cardiac anatomy, function, and tissue composition. However, studies providing CMR reference values in adolescence are scarce. We aim to provide sex-specific CMR reference values for biventricular and atrial dimensions and function and myocardial relaxation times in this population. METHODS Adolescents aged 15-18 years with no known cardiovascular disease underwent a non-contrast 3-T CMR scan between March 2021 and October 2021. The imaging protocol included a cine steady-state free-precession sequence for the analysis of chamber size and function, as well as T2-GraSE and native MOLLI T1-mapping for the characterization of myocardial tissue. FINDINGS CMR scans were performed in 123 adolescents (mean age 16 ± 0.5 years, 52% girls). Mean left and right ventricular end-diastolic indexed volumes were higher in boys than in girls (91.7 ± 11.6 vs 78.1 ± 8.3 ml/m2, p < 0.001; and 101.3 ± 14.1 vs 84.1 ± 10.5 ml/m2, p < 0.001), as was the indexed left ventricular mass (48.5 ± 9.6 vs 36.6 ± 6.0 g/m2, p < 0.001). Left ventricular ejection fraction showed no significant difference by sex (62.2 ± 4.1 vs 62.8 ± 4.2%, p = 0.412), whereas right ventricular ejection fraction trended slightly lower in boys (55.4 ± 4.7 vs. 56.8 ± 4.4%, p = 0.085). Indexed atrial size and function parameters did not differ significantly between sexes. Global myocardial native T1 relaxation time was lower in boys than in girls (1215 ± 23 vs 1252 ± 28 ms, p < 0.001), whereas global myocardial T2 relaxation time did not differ by sex (44.4 ± 2.0 vs 44.1 ± 2.4 ms, p = 0.384). Sex-stratified comprehensive percentile tables are provided for most relevant cardiac parameters. INTERPRETATION This cross-sectional study provides overall and sex-stratified CMR reference values for cardiac dimensions and function, and myocardial tissue properties, in adolescents. This information is useful for clinical practice and may help in the differential diagnosis of cardiac diseases, such as cardiomyopathies and myocarditis, in this population. FUNDING Instituto de Salud Carlos III (PI19/01704).Instituto de Salud Carlos III (PI19/01704). The authors are indebted to the adolescents who participated in this study. Rodrigo Fernández-Jiménez is recipient of grant PI19/01704 by the Instituto de Salud Carlos III (ISCIII) - Fondo de Investigación Sanitaria and the European Regional Development Fund/European Social Fund (A way to make Europe/Investing in your future), which funded the EnIGMA (Early ImaGing Markers of unhealthy lifestyles in Adolescents) study. Jesús Martínez-Gómez was a postgraduate fellow of the Ministerio de Ciencia e Innovación at the Residencia de Estudiantes (2020–2022) and is a recipient of grant FPU21/04891 (Ayudas para la formación de profesorado universitario, FPU-2021) from the Ministerio de Educación, Cultura y Deporte Gloria Santos-Beneit is recipient of grant LCF/PR/MS19/12220001 funded by ““la Caixa” Foundation (ID 100010434). The SHE Foundation is supported by “la Caixa” Foundation (LCF/PR/CE16/10700001). The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). Simon Bartlett (CNIC) provided English editing.S

Bone marrow activation in response to metabolic syndrome and early atherosclerosis.

Experimental studies suggest that increased bone marrow (BM) activity is involved in the association between cardiovascular risk factors and inflammation in atherosclerosis. However, human data to support this association are sparse. The purpose was to study the association between cardiovascular risk factors, BM activation, and subclinical atherosclerosis. Whole body vascular 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) was performed in 745 apparently healthy individuals [median age 50.5 (46.8-53.6) years, 83.8% men] from the Progression of Early Subclinical Atherosclerosis (PESA) study. Bone marrow activation (defined as BM 18F-FDG uptake above the median maximal standardized uptake value) was assessed in the lumbar vertebrae (L3-L4). Systemic inflammation was indexed from circulating biomarkers. Early atherosclerosis was evaluated by arterial metabolic activity by 18F-FDG uptake in five vascular territories. Late atherosclerosis was evaluated by fully formed plaques on MRI. Subjects with BM activation were more frequently men (87.6 vs. 80.0%, P = 0.005) and more frequently had metabolic syndrome (MetS) (22.2 vs. 6.7%, P < 0.001). Bone marrow activation was significantly associated with all MetS components. Bone marrow activation was also associated with increased haematopoiesis-characterized by significantly elevated leucocyte (mainly neutrophil and monocytes) and erythrocyte counts-and with markers of systemic inflammation including high-sensitivity C-reactive protein, ferritin, fibrinogen, P-selectin, and vascular cell adhesion molecule-1. The associations between BM activation and MetS (and its components) and increased erythropoiesis were maintained in the subgroup of participants with no systemic inflammation. Bone marrow activation was significantly associated with high arterial metabolic activity (18F-FDG uptake). The co-occurrence of BM activation and arterial 18F-FDG uptake was associated with more advanced atherosclerosis (i.e. plaque presence and burden). In apparently healthy individuals, BM 18F-FDG uptake is associated with MetS and its components, even in the absence of systemic inflammation, and with elevated counts of circulating leucocytes. Bone marrow activation is associated with early atherosclerosis, characterized by high arterial metabolic activity. Bone marrow activation appears to be an early phenomenon in atherosclerosis development.[Progression of Early Subclinical Atherosclerosis (PESA); NCT01410318].The PESA study is funded by the CNIC and Santander Bank. The present study was partially funded by an intramural grant CNIC-Severo Ochoa to D.S. and B.I. B.I. is supported by the European Commission (H2020-HEALTH 945118 and ERC-CoG 819775). The CNIC is supported by the ISCIII, the Ministry of Science and Innovation, and the Pro CNIC Foundation. CNIC is a Severo Ochoa Center of Excellence (CEX2020-001041-S).S

Clinical Validation of a 3-Dimensional Ultrafast Cardiac Magnetic Resonance Protocol Including Single Breath-Hold 3-Dimensional Sequences

Objectives: This study sought to clinically validate a novel 3-dimensional (3D) ultrafast cardiac magnetic resonance (CMR) protocol including cine (anatomy and function) and late gadolinium enhancement (LGE), each in a single breath-hold. Background: CMR is the reference tool for cardiac imaging but is time-consuming. Methods: A protocol comprising isotropic 3D cine (Enhanced sensitivity encoding [SENSE] by Static Outer volume Subtraction [ESSOS]) and isotropic 3D LGE sequences was compared with a standard cine&#43;LGE protocol in a prospective study of 107 patients (age 58 ± 11 years; 24% female). Left ventricular (LV) mass, volumes, and LV and right ventricular (RV) ejection fraction (LVEF, RVEF) were assessed by 3D ESSOS and 2D cine CMR. LGE (% LV) was assessed using 3D and 2D sequences. Results: Three-dimensional and LGE acquisitions lasted 24 and 22 s, respectively. Three-dimensional and LGE images were of good quality and allowed quantification in all cases. Mean LVEF by 3D and 2D CMR were 51 ± 12% and 52 ± 12%, respectively, with excellent intermethod agreement (intraclass correlation coefficient [ICC]: 0.96; 95% confidence interval [CI]: 0.94 to 0.97) and insignificant bias. Mean RVEF 3D and 2D CMR were 60.4 ± 5.4% and 59.7 ± 5.2%, respectively, with acceptable intermethod agreement (ICC: 0.73; 95% CI: 0.63 to 0.81) and insignificant bias. Both 2D and 3D LGE showed excellent agreement, and intraobserver and interobserver agreement were excellent for 3D LGE. Conclusions: ESSOS single breath-hold 3D CMR allows accurate assessment of heart anatomy and function. Combining ESSOS with 3D LGE allows complete cardiac examination in less than 1 min of acquisition time. This protocol expands the indication for CMR, reduces costs, and increases patient comfort. (J Am Coll Cardiol Img 2021;14:1742–1754)Funding included Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF) Grants DTS17/00136 to Dr. Ibáñez and PI19/01704 to Dr. Fernandez-Jimenez; Spanish Society of Cardiology Translational Research Grant 2016 to Dr. Ibáñez; European Research Council ERC-CoG 819775-MATRIX to Dr. Ibáñez; Comunidad de Madrid S2017/BMD-3867-RENIM-CM to Drs. Desco and Ibáñez; and Ministerio de Ciencia e Innovación (MICINN) RETOS2019-107332RB-I00 to Dr. Ibáñez. Dr. Fernandez-Jimenez received funding from the European Union Horizon 2020 research and innovation programme under Marie Sklodowska-Curie Hrant Agreement No. 707642. The CNIC is supported by the ISCIII, the MICINN, and the Pro CNIC Foundation. Drs. Fernandez-Jimenez, Nothnagel, Fuster, Ibáñez, and Javier Sánchez-González are inventors of a joint patent (Philips/CNIC) for the new cine imaging method here described and validated/protected under the IP #2014P00960EP. Drs. Nothnagel, Kouwenhoven, Clemence, and Javier Sánchez-González are Philips employees. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose

Priorities in Cardio-Oncology Basic and Translational Science

Despite improvements in cancer survival, cancer therapy–related cardiovascular toxicity has risen to become a prominent clinical challenge. This has led to the growth of the burgeoning field of cardio-oncology, which aims to advance the cardiovascular health of cancer patients and survivors, through actionable and translatable science. In these Global Cardio-Oncology Symposium 2023 scientific symposium proceedings, we present a focused review on the mechanisms that contribute to common cardiovascular toxicities discussed at this meeting, the ongoing international collaborative efforts to improve patient outcomes, and the bidirectional challenges of translating basic research to clinical care. We acknowledge that there are many additional therapies that are of significance but were not topics of discussion at this symposium. We hope that through this symposium-based review we can highlight the knowledge gaps and clinical priorities to inform the design of future studies that aim to prevent and mitigate cardiovascular disease in cancer patients and survivors.</p

Efecto de la denervación arterial pulmonar en un modelo experimental traslacional de hipertensión pulmonar postcapilar crónica

Tesis inédita presentada en la Universidad Europea de Madrid. Facultad de Ciencias Biomédicas y de la Salud. Programa de Doctorado en Biomedicina y Ciencias de la SaludAntecedentes y objetivos: La hipertensión pulmonar (HP) es una enfermedad de prevalencia elevada y con escasas alternativas terapéuticas, limitadas casi exclusivamente a los subgrupos 1 y 4. La HP crónica se asocia con un aumento del tono simpático, lo que conlleva efectos hemodinámicos y remodelado vascular adverso a nivel pulmonar. Evidencia experimental muy reciente sugiere que la denervación de la arteria pulmonar (DNV-AP) podría ser una terapia potencialmente eficaz en la HP, pero todavía existen muchas dudas acerca del mecanismo a través del cual podría ejercer su potencial efecto beneficioso y, sobre todo, de su acción en la HP crónica. Nuestro objetivo fue llevar a cabo un estudio del efecto de la DNV-AP utilizando dos abordajes quirúrgicos diferentes (mediante sección y reanastomosis de la arteria pulmonar y aplicación directa externa de pinzas de radiofrecuencia) en un modelo traslacional porcino de HP crónica postcapilar, estudiando sus efectos sobre la hemodinámica pulmonar y el remodelado ventricular a medio y largo plazo. En segundo lugar, nos propusimos analizar la factibilidad y eficacia en cuanto a interrupción de la inervación, de la DNV-AP percutánea con catéter de radiofrecuencia intravascular. Métodos y resultados: Se incluyó a un total de 49 cerdos. Dieciseis cerdos con HP crónica postcapilar (inducida mediante un banding quirúrgico del confluente venoso pulmonar inferior) se aleatorizaron a DNV-AP quirúrgica (mediante sección y reanastomosis de la rama arterial pulmonar izquierda) o procedimiento control (sham) y fueron evaluados en situación basal y a los 2 meses de la cirugía con cateterismo cardíaco derecho (CCD) y resonancia magnética cardíaca (RMC) [subestudio 1]. De forma similar, 19 cerdos con HP crónica postcapilar fueron aleatorizados a DNV-AP con pinzas de radiofrecuencia del tronco arterial pulmonar y ambas ramas o cirugía control. Estos animales fueron evaluados mediante CCD y RMC en situación basal y a los 2 y 3 meses postprocedimiento, análisis sanguíneo e histología al completar el protocolo [subestudio 2]. Para estudio del efecto hemodinámico y sobre el remodelado biventricular a largo plazo de la DNV-AP con pinzas de radiofrecuencia, empleamos un grupo adicional de 8 cerdos con HP crónica postcapilar aleatorizados a DNV-AP con pinzas de radiofrecuencia o procedimiento control y evaluados con CCD y RMC en situación basal y a los 4 y 6 meses postprocedimiento [subestudio 3]. Por último, se realizó DNV-AP percutánea a 6 animales sanos para comparar la lesión generada a nivel de la AP con el catéter intravascular vs. las pinzas de radiofrecuencia [subestudio 4]. Ocho animales completaron el seguimiento en el subestudio 1 (4 DNV-AP quirúrgica y 4 controles). Encontramos una elevación significativa de la presión arterial pulmonar (PAP) media en el brazo DNV-AP a los 2 meses de la intervención (valores medianos de 39,0 vs. 32,0 mmHg en DNV-AP vs. controles, p=0,029), sin cambios significativos en el resto de los parámetros hemodinámicos o de RMC. En el subestudio 2, doce animales (6 DNV-AP con pinzas y 6 controles) completaron el protocolo. La severidad hemodinámica de la HP no fue significativamente diferente entre ambos grupos en situación basal (valores medianos de PAP media 32,0 vs. 27,5 mmHg, P=0,394 y resistencia vascular pulmonar [RVP] indexada de 5,9 vs. 4,7 UW.m 2, p=0,394 para los grupos DNV-AP y control respectivamente) y tampoco en ninguno de los seguimientos (PAP media de 35,0 vs. 35,0 mmHg, p=0,236 y RVP indexada de 8,3 vs. 6,7 UW.m2, p=0,477 al final del seguimiento en los grupos DNV-AP/control). La DNV-AP con pinzas tampoco se asoció a ningún beneficio en términos de remodelado o función de ventrículo derecho (VD) mediante RMC e histología. En el subestudio 3, el efecto de la DNV- AP con pinzas fue neutro en términos hemodinámicos y de remodelado biventricular a largo plazo. En el subestudio 4, la lesión producida con las pinzas de radiofrecuencia fue completa y transmural mientras que con la DNV-AP percutánea solo se observó un daño focal de las fibras nerviosas adventiciales. Conclusión: En un modelo traslacional de HP crónica postcapilar, la DNV-AP quirúrgica o mediante pinzas de radiofrecuencia no se asoció con mejoría hemodinámica o sobre el remodelado biventricular a medio ni a largo plazo. Un abordaje percutáneo con catéter intravascular es factible, pero produce solo una DNV-AP incompleta. Más estudios que evalúen el efecto de esta terapia en la HP crónica, especialmente en la HP postcapilar, son necesarios antes de continuar aplicándola en pacientes. [Resumen Teseo]UE

Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: Results from the Metocard-CNIC trial (Effect of Metoprolol in Cardioprotection during an Acute Myocardial Infarction)

The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up. Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046). In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions.Sin financiación16.503 JCR (2014) Q1, 1/123 Cardiac and cardiovascular systemsUE

Magnetic Resonance Characterization of Cardiac Adaptation and Myocardial Fibrosis in Pulmonary Hypertension Secondary to Systemic-To-Pulmonary Shunt

BACKGROUND Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are strong predictors of morbidity and mortality among patients with congenital heart disease. Early detection of RV involvement may be useful in the management of these patients. We aimed to assess progressive cardiac adaptation and quantify myocardial extracellular volume in an experimental porcine model of PH because of aorto-pulmonary shunt using cardiac magnetic resonance (CMR). METHODS AND RESULTS To characterize serial cardiac adaptation, 12 pigs (aorto-pulmonary shunt [n=6] or sham operation [n=6]) were evaluated monthly with right heart catheterization, CMR, and computed tomography during 4 months, followed by pathology analysis. Extracellular volume by CMR in different myocardial regions was studied in 20 animals (aorto-pulmonary shunt [n=10] or sham operation [n=10]) 3 months after the intervention. All shunted animals developed PH. CMR evidenced progressive RV hypertrophy and dysfunction secondary to increased afterload and left ventricular dilatation secondary to volume overload. Shunt flow by CMR strongly correlated with PH severity, left ventricular end-diastolic pressure, and left ventricular dilatation. T1-mapping sequences demonstrated increased extracellular volume at the RV insertion points, the interventricular septum, and the left ventricular lateral wall, reproducing the pattern of fibrosis found on pathology. Extracellular volume at the RV insertion points strongly correlated with pulmonary hemodynamics and RV dysfunction. CONCLUSIONS Prolonged systemic-to-pulmonary shunting in growing piglets induces PH with biventricular remodeling and myocardial fibrosis that can be detected and monitored using CMR. These results may be useful for the diagnosis and management of congenital heart disease patients with pulmonary overcirculation.This work was supported by a competitive grant from the Spanish Ministry of Economy and Competitiveness (MINECO) through the Carlos III Institute of Health-Fondo de Investigación Sanitaria and European Regional Development Fund (ERDF/FEDER) funds (PI13/02339 to Dr García-Álvarez) and by the competitive grant CNIC-Translational 01-2009 (to Dr Ibáñez). Other sponsors were a grant TIN2012–37546-C03-02 from the Ministerio de Economía y Competitividad (to Dr Sánchez-Quintana), a FPU program (13/02662) from the Ministerio de Educación, Cultura y Deporte (to F. Sierra) and a Master Research Agreement (MRA) between Philips healthcare and CNIC. Drs García-Álvarez and Ibáñez are members of the Spanish “Red de Investigación Cardiovascular” (RIC, RD 12/0042/0054). The CNIC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505).S

El entrenamiento mediante simulación integrado en el programa del Grado de Medicina

El entrenamiento basado en la simulación consiste en sustituir la realidad por un escenario simulado en el que los alumnos pueden entrenarse para adquirir habilidades de liderazgo, comunicación, psicomotrices, de trabajo en equipo ó determinadas técnicas ó procedimientos de trabajo. Algunas de estas competencias son difíciles de adquirir mediante la enseñanza tradicional de la lección magistral. La práctica diaria habitual podría ser un escenario adecuado para mostrar y repetir algunas de estas competencias transversales, sin embargo, dada la importante carga de trabajo actual en ocasiones el alumno no tiene tiempo para practicar sobre lo visto y reflexionar sobre sus áreas de mejora. No hemos de olvidar que muchas de las técnicas y actuaciones médicas resultan invasivas y potencialmente lesivas en sí para el paciente por lo que es habitual que el alumno sólo llegue a observar y no se le permita practicar muchas de ellas. En el Hospital Universitario Quirón Madrid, hemos introducido la simulación como herramienta docente en todos los cursos donde hay formaciones clínicas del grado de Medicina. La nueva metodología ha sido valorada con excelente calificación por parte de los alumnos y una gran implicación y colaboración por parte de los docentes.SIN FINANCIACIÓNNo data 2014UE