Endothelial dysfunction and impaired angiogenesis are hallmarks of ischemic heart disease and critical determinants of adverse cardiovascular outcomes after myocardial infarction (MI). While conventional cardiovascular risk factors (CVRFs) are known contributors, the specific role of MI itself triggering endothelial dysfunction remains unclear. This study aims to assess the direct impact of MI on endothelial function, independent of cardiovascular risk factors, using human and porcine endothelial colony-forming cells (ECFCs) as a surrogate cellular model. Human ECFCs (hECFCs) were isolated from the peripheral blood of healthy volunteers (Control-hECFCs, n = 6), patients immediately after MI (AMI-hECFCs, n = 6), and patients 6 months after MI (CMI-hECFCs, n = 6). To evaluate the direct effect of MI independently of CVRFs, a porcine model was used: healthy pigs (n = 6) underwent 90 min of myocardial ischemia by coronary balloon occlusion followed by reperfusion. Porcine ECFCs (pECFCs) were isolated before MI (Control-pECFCs) and one month after MI (CMI-pECFCs, n = 6). In vitro, CMI-hECFCs and CMI-pECFCs had delayed colony formation, whereas AMI-hECFCs did not. Morphological alterations were observed in AMI-hECFCs and CMI-hECFCs (area and shape), while only shape changes were found in CMI-pECFCs. Senescence was increased in AMI-hECFCs and CMI-hECFCs, but not in CMI-pECFCs. Elevated oxidative stress was only detected in CMI-hECFCs. Functional angiogenic and proliferative capacities were reduced in AMI-hECFCs, CMI-hECFCs and CMI-pECFCs; however, only CMI-hECFCs and CMI-pECFCs displayed impaired migration. Molecular analysis showed overactivation of the MSK2/MKK3/p53 signalling axis in dysfunctional ECFCs, while synergistic inhibition of the axis partially restored ECFC function. MI induces sustained ECFC dysfunction independently of cardiovascular risk factors. Targeting the MSK2/MKK3/p53 pathway may be a promising therapeutic strategy to restore endothelial function and improve angiogenesis after MI.

Background Several aspects of the occurrence and management of mycotic aneurysm (MA) in patients with infective endocarditis (IE) have not been studied.Objectives To determine the incidence and factors associated with MA presence and rupture and to assess the evolution of those initially unruptured MA.Methods Prospective multicenter cohort including all patients with definite IE between January 2008 and December 2020.Results Of 4548 IE cases, 85 (1.9%) developed MA. Forty-six (54.1%) had intracranial MA and 39 (45.9%) extracranial MA. Rupture of MA occurred in 39 patients (45.9%). Patients with ruptured MA had higher 1-year mortality (hazard ratio, 2.33; 95% confidence interval, 1.49-3.67). Of the 55 patients with initially unruptured MA, 9 (16.4%) presented rupture after a median of 3 days (interquartile range, 1-7) after diagnosis, being more frequent in intracranial MA (32% vs 3.3%, P = .004). Of patients with initially unruptured MA, there was a trend toward better outcomes among those who received early specific intervention, including lower follow-up rupture (7.1% vs 25.0%, P = .170), higher rate of aneurysm resolution in control imaging (66.7% vs 31.3%, P = .087), lower MA-related mortality (7.1% vs 16.7%, P = .232), and lower MA-related sequalae (0% vs 27.8%, P = .045).Conclusions MA occurred in 2% of the patients with IE. Half of the Mas occurred in an intracranial location. Their rupture is frequent and associated with poor prognosis. A significant proportion of initially unruptured aneurysms result from rupture during the first several days, being more common in intracranial aneurysms. Early specific treatment could potentially lead to better outcomes. In this prospective multicenter cohort with 4,548 infective endocarditis cases, mycotic aneurysms (MA) developed in 2%, with half being intracranial. Rupture was common, correlating with poor prognosis. A notable portion of initially intact intracranial MA ruptured within the initial days.

BACKGROUND:Center-based cardiac rehabilitation programs (CRPs) reduce morbidity and mortality after an ischemic cardiac event; however, they are widely underused. Home-based CRP has emerged as an alternative to improve patient adherence; however, its safety and efficacy remain unclear, especially for older patients and female patients.OBJECTIVE:This study aimed to develop a holistic home-based CRP for patients with ischemic heart disease and evaluate its safety and impact on functional capacity, adherence to a healthy lifestyle, and quality of life.METHODS:The 8-week home-based CRP included patients of both sexes, with no age limit, who had overcome an acute myocardial infarction in the previous 3 months, had a left ventricular ejection fraction of ≥40%, and had access to a tablet or mobile device. The CRP was developed using a dedicated platform designed explicitly for this purpose and included 3 weekly exercise sessions combining tailored aerobic and strength training and 2 weekly educational session focused on lifestyle habits, therapeutic adherence, and patient empowerment.RESULTS:We initially included 62 patients, of whom 1 was excluded for presenting with ventricular arrhythmias during the initial stress test, 5 were excluded because of incompatibility, and 6 dropped out because of a technological barrier. Ultimately, 50 patients completed the program: 85% (42/50) were male, with a mean age of 58.9 (SD 10.3) years, a mean left ventricular ejection fraction of 52.1% (SD 6.72%), and 25 (50%) New York Heart Association functional class I and 25 (50%) New York Heart Association II-III. The CRP significantly improved functional capacity (+1.6 metabolic equivalent tasks), muscle strength (arm curl test +15.5% and sit-to-stand test +19.7%), weekly training volume (+803 metabolic equivalent tasks), adherence to the Mediterranean diet, emotional state (anxiety), and quality of life. No major complications occurred, and adherence was excellent (>80%) in both the exercise and educational sessions. In the subgroup analysis, CRP showed equivalent beneficial effects irrespective of sex and age. In addition, patient preferences for CRP approaches were equally distributed, with one-third (14/50, 29%) of the patients preferring a face-to-face CRP, one-third (17/50, 34%) preferring a telematic CRP, and one-third (18/50, 37%) preferring a hybrid approach. Regarding CRP duration, 63% (31/50) of the patients considered it adequate, whereas the remaining 37% (19/50) preferred a longer program.CONCLUSIONS:A holistic telematic CRP dedicated to patients after an ischemic cardiac event, irrespective of sex and age, is safe and, in our population, has achieved positive results in improving maximal aerobic capacity, weekly training volume, muscle strength, quality of life, compliance with diet, and anxiety symptoms. The preference for a center- or home-based CRP approach is diverse among the study population, emphasizing the need for a tailored CRP to improve adherence and completion rates.

Los datos sobre el perfil clínico y los resultados de los pacientes jóvenes con infarto agudo de miocardio con elevación del segmento ST (SCACEST) son escasos. Este estudio compara las características y los resultados clínicos entre pacientes de edades < 45 años y ≥ 45 con IAMCEST atendidos por el sistema catalán Codi IAM. También se analizaron las diferencias por sexo en el grupo de menores de 45 años. Entre 2015 y 2020, se incluyó a todos los pacientes ingresados por IAMCEST. Los objetivos primarios fueron la mortalidad por cualquier causa en los primeros 30 días, a 1 año y 2 años. Se incluyó a 18.933 pacientes (el 23% mujeres). De ellos, 1.403 (7,4%) eran menores de 45 años. Los pacientes más jóvenes eran más fumadores (p < 0,001) y presentaron tasas más altas de muerte súbita y flujo TIMI 0 antes de la ICPp (p < 0,05), pero el tiempo desde el primer contacto médico hasta el paso de la guía fue más corto en comparación con el grupo de más edad (p < 0,05). Se observaron tasas de mortalidad por cualquier causa más bajas en los pacientes menores de 45 (p < 0,001). Con respecto a las diferencias estratificadas por sexo en los pacientes más jóvenes, el shock cardiogénico fue más frecuente en las mujeres que en los varones (p = 0,002) y el tiempo desde el inicio de los síntomas hasta la reperfusión fue más largo (p < 0,05) en el grupo de las mujeres. En comparación con los varones de menos de 45, las mujeres más jóvenes tenían menos probabilidades de tratarse con ICPp (p = 0,004). Pese a presentar características de alto riesgo al ingreso, los pacientes jóvenes que sufren un IAMCEST tienen mejor pronóstico que sus contrapartes mayores. Se observaron diferencias en los tiempos de isquemia y tratamiento entre varones y mujeres. Data on the clinical profile and outcomes of younger patients with ST-elevation myocardial infarction (STEMI) is scarce. This study compared clinical characteristics and outcomes between patients aged < 45 years and those aged ≥ 45 years with STEMI managed by the acute myocardial infarction code (AMI Code) network. Sex-based differences in the younger cohort were also analyzed. This multicenter study collected individual data from the Catalonian AMI Code network. Between 2015 and 2020, we enrolled patients with an admission diagnosis of STEMI. Primary endpoints were all-cause mortality within 30 days, 1 year, and 2 years. Overall, 18 933 patients (23% female) were enrolled. Of them, 1403 participants (7.4%) were aged < 45 years. Younger patients with STEMI were more frequently smokers (P < .001) and presented with cardiac arrest and TIMI flow 0 before pPCI (P < .05), but the time from first medical contact to wire crossing was shorter than in the older group (P < .05). All-cause mortality rates were lower in patients aged < 45 years (P < .001). Among younger patients, cardiogenic shock was most prevalent in women than in their male counterparts (P = .002), with the time from symptom onset to reperfusion being longer (P < .05). Compared with men aged < 45 years, younger women were less likely to undergo pPCI (P = .004). Despite showing high-risk features on admission, young patients exhibit better outcomes than older patients. Differences in ischemia times and treatment were observed between men and women.

After myocardial infarction (MI), angiogenesis in the ischemic myocardium is essential for an optimal reparative process to limit the development of ventricular dysfunction. Cell-derived extracellular vehicles (EVs) are emerging as the next-generation strategy in tissue engineering. In this study, we aimed to determine the role of EVs derived from endothelial progenitor cells (EPC) in cardiac function post-MI. EVs were purified from the supernatant of EPC by density gradient centrifugation. MI was induced in C57BL/6 mice (n=23) by left coronary artery ligation and confirmed by EKG. Mice were randomized to receive purified EVs (n=10) or saline (n=10) in two zones of the myocardium, peri-ischemic and central ischemia zones, followed by weekly I.P. injection of EVs or saline for six weeks. Three mice underwent sham surgical procedures without coronary artery ligation. Cardiac magnetic resonance at the end of the follow-up showed significant impairment of left ventricle (LV) performance in the saline group, which was better preserved in mice treated with EVs (Fig 1) . Histological analysis in the LV showed increased collagen deposition in both MI groups (Fig 2A) . However, capillary density decreased more pronouncedly in the saline than in the EV group (Fig 2B) . Quantitative mRNA array revealed a differential relative mRNA expression in the EV group compared to saline (Fig 3) . The administration of EPC-derived EVs has a modest effect on preventing the development of LV adverse remodeling after ischemia, as it limits LV dilation at the long term in a mouse model of chronic MI.Funding: ISCIII (PI19/00264, SEC/FECINV- BAS 20/012)

Introduction and objectives: Dual antiplatelet therapy (DAPT) duration after ST-segment elevation myocardial infarction (STEMI) remains a matter of debate.Methods: We analyzed the effect of DAPT on 5-year all-cause mortality, cardiovascular mortality, and cardiovascular readmission or mortality in a cohort of 1-year survivor STEMI patients.Results: A total of 3107 patients with the diagnosis of STEMI were included: 93% of them were discharged on DAPT, a therapy that persisted in 275 high-risk patients at 5 years. Cardiovascular mortality in patients on single antiplatelet therapy vs DAPT at 5 years was 1.4% vs 3.6% (P <.01), respectively, whereas noncardiovascular mortality was 3.3% vs 5.8% (P = .049) at 5 years. Cardiovascular readmission or mortality in patients with single antiplatelet therapy vs DAPT was 11.4% vs 46.5% (P < .001). Extended DAPT was independently associated with worse 5-year all-cause mortality (HR, 2.16; 95%CI, 1.40-3.33), cardiovascular mortality (HR, 2.83; 95%CI, 1.37-5.84), and cardiovascular readmission or mortality (HR, 5.20; 95%CI, 3.96-6.82). These findings were confirmed in propensity score matching and inverse probability weighting analyses.Conclusions: Our results suggest the hypothesis that, in 1-year STEMI survivors, extending DAPT up to 5 years in high-risk patients does not improve their long-term prognosis.C 2022 Sociedad Espan & SIM;ola de Cardiologia. Published by Elsevier Espan & SIM;a, S.L.U. All rights reserved.

We evaluated modifications in the hemostatic balance of different concentrations of apixaban (APIX) in 25 healthy donors and 53 patients treated with aspirin (ASA, n = 21), ASA and clopidogrel (ASA + CLOPI, n = 11), or ASA and ticagrelor (ASA + TICA, n = 21). Blood samples from participants were spiked ex vivo with apixaban 0 (APIX0), 40 (APIX40), and 160 ng/mL (APIX160). We assessed the effects of APIX on (1) clot formation, by ROTEM thromboelastometry; (2) thrombin generation primed by platelets; and (3) platelet and fibrin interactions with a thrombogenic surface, in a microfluidic model with circulating blood. APIX caused dose-related prolongations of clotting time with minimal impact on other ROTEM parameters. Thrombin generation was significantly inhibited by APIX160, with ASA + TICA actions showing the strongest inhibition (p < 0.01 vs APIX0). Microfluidic studies showed that APIX160 was more potent at suppressing platelet and fibrin interactions (p < 0.001 vs. APIX0). APIX40 demonstrated a consistent antithrombotic action but with a favorable protective effect on the structural quality of fibrin. APIX potentiated the antithrombotic effects of current antiplatelet regimens. APIX at 40 ng/mL, enhanced the antithrombotic action of single or dual antiplatelet regimens but was more conservative for hemostasis than the 160 ng/mL concentration.

La duración adecuada de la doble terapia antiagregante (DAPT) después de un infarto de miocardio con elevación del segmento ST (IAMCEST) está todavía en discusión. Analizamos el efecto de la DAPT extendida a 5 años sobre la mortalidad global, mortalidad cardiovascular y reingreso o mortalidad cardiovascular, en una cohorte multicéntrica de pacientes con IAMCEST supervivientes al año. Se incluyeron 3.107 pacientes hospitalizados por IAMCEST de los que el 93% recibió DAPT al alta. A los 5 años se mantenía en 275 pacientes con un perfil alto de gravedad. La mortalidad cardiovascular de los pacientes con antiagregación simple (SAPT) frente a DAPT a 5 años fue de 1,4 y 3,6% (p < 0,01), respectivamente. La mortalidad no-cardiovascular fue del 3,3 frente a 5,8% (p = 0,049) a 5 años, respectivamente. La incidencia del evento combinado a un año fue del 14,6% en SAPT frente a 11,8% en DAPT (p = 0,496), y del 11,4 frente a 46,5% (p < 0,001) a 5 años, respectivamente. El mantenimiento de la DAPT hasta los 5 años se asoció de forma independiente a mayor mortalidad: por cualquier causa (HR = 2,16; IC95%, 1,40-3,33), cardiovascular (HR = 2,83; IC95%, 1,37-5,84) y rehospitalización cardiovascular y mortalidad (HR = 5,20; IC95%, 3,96-6,82). Un análisis emparejado por puntuación de propensión, y uno con ponderación de probabilidad inversa, confirman estos resultados. Nuestros resultados sugieren la hipótesis de que, en supervivientes a un año de IAMCEST, alargar la DAPT hasta 5 años en pacientes de alto riesgo no mejora su pronóstico a largo plazo. Dual antiplatelet therapy (DAPT) duration after ST-segment elevation myocardial infarction (STEMI) remains a matter of debate. We analyzed the effect of DAPT on 5-year all-cause mortality, cardiovascular mortality, and cardiovascular readmission or mortality in a cohort of 1-year survivor STEMI patients. A total of 3107 patients with the diagnosis of STEMI were included: 93% of them were discharged on DAPT, a therapy that persisted in 275 high-risk patients at 5 years. Cardiovascular mortality in patients on single antiplatelet therapy vs DAPT at 5 years was 1.4% vs 3.6% (P < .01), respectively, whereas noncardiovascular mortality was 3.3% vs 5.8% (P = .049) at 5 years. Cardiovascular readmission or mortality in patients with single antiplatelet therapy vs DAPT was 11.4% vs 46.5% (P < .001). Extended DAPT was independently associated with worse 5-year all-cause mortality (HR, 2.16; 95%CI, 1.40-3.33), cardiovascular mortality (HR, 2.83; 95%CI, 1.37-5.84), and cardiovascular readmission or mortality (HR, 5.20; 95%CI, 3.96-6.82). These findings were confirmed in propensity score matching and inverse probability weighting analyses. Our results suggest the hypothesis that, in 1-year STEMI survivors, extending DAPT up to 5 years in high-risk patients does not improve their long-term prognosis.

Introduction and objectives: Data on the clinical profile and outcomes of younger patients with ST-elevation myocardial infarction (STEMI) is scarce. This study compared clinical characteristics and outcomes between patients aged < 45 years and those aged >= 45 years with STEMI managed by the acute myocardial infarction code (AMI Code) network. Sex-based differences in the younger cohort were also analyzed.Methods: This multicenter study collected individual data from the Catalonian AMI Code network. Between 2015 and 2020, we enrolled patients with an admission diagnosis of STEMI. Primary endpoints were all-cause mortality within 30 days, 1 year, and 2 years.Results: Overall, 18 933 patients (23% female) were enrolled. Of them, 1403 participants (7.4%) were aged < 45 years. Younger patients with STEMI were more frequently smokers (P < .001) and presented with cardiac arrest and TIMI flow 0 before pPCI (P < .05), but the time from first medical contact to wire crossing was shorter than in the older group (P < .05). All-cause mortality rates were lower in patients aged < 45 years (P < .001). Among younger patients, cardiogenic shock was most prevalent in women than in their male counterparts (P = .002), with the time from symptom onset to reperfusion being longer (P < .05). Compared with men aged < 45 years, younger women were less likely to undergo pPCI (P = .004).Conclusions: Despite showing high-risk features on admission, young patients exhibit better outcomes than older patients. Differences in ischemia times and treatment were observed between men and women.@2023 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

Introduction: Endothelial Colony Forming Cells (ECFCs) present a dysfunctional and senescent phenotype in ischemic heart disease. However, the effect of myocardial infarction (MI), independently of common cardiovascular comorbidities (CCVC), on ECFCs functionality has not been evaluated up to date. Hypothesis: MI induces dysfunction of ECFCs with independence of CCVC Methods: To determine the potential effect of MI on ECFCs, human ECFCs (hECFCs) were isolated from peripheral blood from healthy volunteers (n=6), patients immediately after MI (n=6) (AMI-hECFCs) and patients 6 months after MI (n=6) (CMI-hECFCs). To determine the effect of MI on ECFCs impairment, isolated from the effect of common cardiovascular comorbidities that are found in patients, 6 healthy pigs were subjected to 90 minutes of myocardial ischemia by coronary balloon occlusion followed by reperfusion. Porcine ECFCs (pECFCs) (n=6) were isolated from blood samples before the MI and 1 month after the procedure (CMI-pECFCs) (n=6). For all groups, the following parameters were determined: days until colonies appearance, morphometry, percentage of senescent cells, and migratory, proliferatory and angiogenic capacities. Results: Both CMI-hECFCs and CMI-pECFCs showed a delayed time until colonies appearance (p-ANOVA=0,0117 and p-ANOVA=0,0159 respectively) but no differences were found in AMI-hECFCs. AMI- and CMI-hECFCs showed changes in their area and shape, but only shape changes were observed in CMI-pECFCs. In terms of senescence, both AMI- and CMI-hECFCs, but not CMI-pECFCs, presented an increment of senescence (p-ANOVA= 0,0011). In terms of functionality, AMI- and CMI-hECFCs and CMI-pECFCs showed a significant reduction of angiogenesis and proliferation, and only CMI-hECFCs showed an impaired migratory capacity. Conclusions: MI Induces dysfunction of ECFCs with independence of CCVC

Abstract BACKGROUND: Treatment with triple antithrombotic therapies increases bleeding risks. AIM: We evaluated the antithrombotic and prohemorrhagic actions of different concentrations of apixaban (APIX) in healthy donors and patients exposed to currently used antiplatelet regimens. METHODS: 25 healthy subjects and 53 patients treated with aspirin (ASA, n=21), ASA and clopidogrel (ASA+CLOPI, n=11), or ASA and ticagrelor (ASA+TICA, n=21) participated in the study. Blood samples from participants were spiked ex vivo with apixaban 0 (APIX0), 40 (APIX40), and 160 ng/mL (APIX160). We assessed the effects of APIX on 1) clot formation, by ROTEM thromboelastometry; 2) thrombin generation primed by platelets; and 3) platelet and fibrin interactions with a thrombogenic surface, in a microfluidic model with circulating blood. RESULTS: APIX caused dose-related prolongations of clotting time with minimal impact on other ROTEM parameters. Thrombin generation was significantly inhibited by APIX160 and moderately affected by the antiplatelets, with ASA+TICA actions being the strongest among them (p<0.01 vs APIX0). Confocal analysis of microfluidic studies showed the additional inhibitory effect of the APIX160 to the antiplatelet therapies. APIX160 was the more potent at suppressing platelet and fibrin interactions (p<0.001 vs. APIX0). APIX40 showed a consistent antithrombotic action but with a favorable protective effect on the structural quality of fibrin. CONCLUSIONS: APIX potentiated the antithrombotic effects of current antiplatelet regimens. APIX at 40 ng/mL, enhanced the antithrombotic action of single or dual antiplatelet regimens but appears more conservative for hemostasis than the concentrations of 160 ng/mL that corresponds to the Cmax reached after the standard dose for thromboprophylaxis.

HomeCirculation: Heart FailureVol. 15, No. 12Edge-to-Edge Transcatheter Mitral Valve Repair Versus Optimal Medical Treatment in Nonresponders to Cardiac Resynchronization Therapy: The MITRA-CRT Trial Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBEdge-to-Edge Transcatheter Mitral Valve Repair Versus Optimal Medical Treatment in Nonresponders to Cardiac Resynchronization Therapy: The MITRA-CRT Trial Xavier Freixa, Jose María Tolosana, Pedro L. Cepas-Guillen, Marco Hernández-Enríquez, Laura Sanchis, Eduardo Flores-Umanzor, Marta Farrero, Rut Andrea, Mercè Roqué, Maria José Carretero, Ander Regueiro, Salvatore Brugaletta, Josep Rodés-Cabau, Lluís Mont, Marta Sitges, Manel Sabaté and M. Ángeles Castel Xavier FreixaXavier Freixa Correspondence to: Xavier Freixa, PhD, or Jose María Tolosana, PhD, Hospital Clinic, Cardiology Department, C/Villarroel, 170, 08036 Barcelona, Spain. Email E-mail Address: [email protected] or E-mail Address: [email protected] https://orcid.org/0000-0002-3203-9060 Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Jose María TolosanaJose María Tolosana Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Pedro L. Cepas-GuillenPedro L. Cepas-Guillen https://orcid.org/0000-0001-8814-7039 Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Marco Hernández-EnríquezMarco Hernández-Enríquez Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Laura SanchisLaura Sanchis https://orcid.org/0000-0003-2516-8953 Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Eduardo Flores-UmanzorEduardo Flores-Umanzor https://orcid.org/0000-0002-6428-241X Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Marta FarreroMarta Farrero https://orcid.org/0000-0002-2404-8821 Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Rut AndreaRut Andrea https://orcid.org/0000-0002-8409-5013 Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Mercè RoquéMercè Roqué https://orcid.org/0000-0001-9036-4825 Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Maria José CarreteroMaria José Carretero https://orcid.org/0000-0002-5887-6326 Anesthesiology Department (M.J.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Ander RegueiroAnder Regueiro Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Salvatore BrugalettaSalvatore Brugaletta https://orcid.org/0000-0001-5845-1435 Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Josep Rodés-CabauJosep Rodés-Cabau https://orcid.org/0000-0001-8237-7095 Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. Quebec Heart and Lung Institute, Quebec City, Canada (J.R.-C.). , Lluís MontLluís Mont https://orcid.org/0000-0002-8115-5906 Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Marta SitgesMarta Sitges Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. , Manel SabatéManel Sabaté https://orcid.org/0000-0002-2316-3705 Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. and M. Ángeles CastelM. Ángeles Castel Cardiology Department, Cardiovascular Institute (ICCV) (X.F., J.M.T., P.L.C.-G., M.H.-E., L.S., E.F.-U., M.F., R.A., M.R., A.R., S.B., J.R.-C., L.M., M. Sitges, M. Sabaté, M.Á.C.), Hospital Clinic, IDIBAPS, University of Barcelona, Spain. Originally published20 Sep 2022https://doi.org/10.1161/CIRCHEARTFAILURE.121.009501Circulation: Heart Failure. 2022;15Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 20, 2022: Ahead of Print Transcatheter mitral valve repair (TMVr) with “edge-to-edge” systems have shown promising results in patients with dilated cardiomyopathy (DCM) and reduced left ventricular ejection fraction (LVEF).1 Recent randomized trials comparing optimal medical therapy (OMT) versus TMVr in patients with functional mitral regurgitation (FMR) >2 have shown divergent results. One of them, the COAPT trial (Cardiovascular Outcomes Assessment of the Mitraclip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation), reported reduced mortality and heart failure (HF) admissions after 2 years in patients undergoing TMVr on top of OMT.1,2 In addition, a subgroup analysis of this latter study focusing on patients with and without cardiac resynchronization therapy (CRT) also revealed improved 2-year prognosis in the TMVr group.3 Auricchio et al4 analyzed a cohort of DCM patients with CRT and FMR >2, showing significant clinical improvement, LVEF recovery, and left ventricle volume reduction after TMVr. Nonetheless, the post hoc or retrospective nature of the aforementioned studies and the absence of stratification according to the CRT response represent major limitations. The hypothesis of our trial was that TMVr in nonresponder patients to CRT and significant FMR (grade ≥2, 100%) would be associated with improved functional class, LVEF recovery, and reduced left ventricle volumes. Thus, the objective of the present pilot study was to compare OMT versus OMT+TMVr in DCM patients who received CRT and remained with FMR >2 and advanced HF.The MITRA CRT trial (Transcatheter Mitral Valve Repair in non-Responders to Cardiac Resynchronization Therapy) was a pilot, single-center, randomized, controlled and open-label trial comparing OMT versus OMT+“edge-to-edge” TMVr with the Mitraclip device in DCM patients with CRT who were clinically symptomatic (nonresponders) and had FMR >2. Clinical candidates had DCM with LVEF between 15% and 40%, CRT implantation >6 months with effective therapy defined as biventricular stimulation in >95% of heart beats5 and moderate-to-severe3 or severe4 MR. Inclusion required advanced heart failure symptoms defined by the presence of a New York Heart Association class III or IV or II with a hospital admission for HF within the previous year despite the use of stable maximal doses of guideline-directed medical therapy. If mitral anatomy was suitable for TMVr with Mitraclip, the patient signed consent and was randomized 1:1 to control or TMVr. The study was approved by the Ethics Committee of Hospital Clinic Barcelona and consistent to the principles outlined in the Declaration of Helsinki. The data that support the findings of this study are available from the corresponding author upon reasonable request. All participants gave written informed consent. Clinical and echocardiographic follow-up was performed at 1, 3, and 12 months. Categorical data are reported as percentages (percentages) were compared with Fisher exact test. Continuous data are reported as means±SD or as a median (interquartile range) and were tested between groups using the Kruskal-Wallis test. The primary efficacy end point was defined as the combined of CV death, heart transplantation, or HF hospitalizations at 12 months. A secondary safety end point included the number of procedure- or device-related serious adverse events.From 2015 to 2019, a total of 53 patients were initially screened. Among them, 31 patients were finally included in the study: 15 in the control and 16 in the TMVr group. All patients but one received the allocated treatment (a patient randomized to TMVr refused the intervention). Baseline characteristics showed no differences among groups but a higher prevalence of COPD patients in the control group and a trend toward older age in the TMVr group (Table). Clinical status was relatively advanced as depicted by the small percentage of patients in New York Heart Association class II (13%) and the high percentage of admissions for HF within the previous year (60%). As shown in the Table, LVEF was very low in most of patients (median of 21%) and left ventricles exhibited significant enlargements in both groups (mean LVED volume of 136.8±40.6 mL/m2). Technical and procedural success was achieved in all patients. Transesophageal echocardiography after clip implantation showed residual MR≤2 in all patients, and no procedural- or device-related serious adverse events were registered.Table. Baseline Characteristics and Procedural and Follow-Up Outcomes at 1 YearTotal (n=31)TMVr group (n=16)Control group (n=15)Baseline clinical characteristics Age, y69.7±772.1±767.2±6 Male sex25 (81)13 (81)12 (80) Body mass index26 (23–30)27.5 (23–30)25.4 (23–31) Diabetes7 (23)2 (13)5 (33) Ischemic cardiomyopathy14 (45)8 (50)6 (40) Previous stroke or TIA2 (7)1 (7)1 (7) Previous NVAF or flutter19 (61)11 (69)8 (53) Persistent atrial fibrillation14 (45)9 (56)5 (33) CRT implantation time before inclusion, d1510 (700–2555)1699 (829–2829)1012 (268–2555) Percentage of biventricular CRT stimulation, %98 (95–99)98 (94.5–99)99 (95–100) Anterior LV lead position000 Mean GFR, mL/min59±1856.4±1861.7±19 EUROSCORE II3.96 (3.1–7)4.23 (3.2–7.5)3.75 (2.7–6.1) NYHA class II4 (13)1 (6)3 (20) III25 (81)13 (81)12 (80) IV (ambulatory)2 (7)2 (13)0 Previous hospitalization for HF in the last year19 (61)12 (75)7 (47) Number of hospitalizations for HF in the last year (median)2 (1–3)1.5 (1–3)2 (1–3) BNP667 (373–1183)623 (373–1341)711 (433–1176) 6MWT, m384±96353±99407±90 HF medical treatment ACEI/ARB11 (35)5 (35)5 (33) ARNI10 (32)6 (38)4 (27) Beta-blockers29 (94)15 (94)14 (93) MRA25 (81)13 (81)12 (80) Hydralazine4 (13)1 (6)3 (20) Nitrates4 (13)1 (6)3 (20) Digoxin3 (10)1 (6)2 (13) Loop diuretics30 (97)16 (100)14 (93)Baseline echocardiographic characteristics MR severity Moderate (grade 2)1 (3)1 (6)0 Moderate-severe (grade 3)8 (26)3 (19)5 (33) Severe (grade 4)22 (71)12 (75)10 (67) ERO area*0.51±0.120.54±0.460.46±0.10 LVEF, %21 (17–25)20 (16.5–27)22 (19–25) LVESD, mm58.4±8.7258.8±8.0157.9±9.68 LVEDD, mm70.0±7.7871.2±8.0168.8±7.61 LVES volume (indexed)107.3±37.0107.1±40.9107.6±33.7 LVED volume (indexed)136.8±40.6136.3±43.1137.4±39.0 LA volume (indexed)74.4±5.476.5±27.972.4±30.8 Spap48.5±14.649.6±12.447.5±16.6Procedural outcomes (TMVr group) Implant success rate15 (100)† Patients with procedure- or device-related SAEs0 Vascular complication0 Atrial septum lesion0 Cardiogenic shock resulting in intravenous inotropic support0 Cardiac embolism0 Cardiac tamponade0 Urgent conversion to hear surgery0 Admission days related to procedure2.93±1.7 Procedural MR severity after clip implantation Mild (1)14 (93) Moderate (2)7 (1) Moderate to severe (3)0 Severe (4)0Total (n=31)TMVr group (n=16)Control group (n=15)P valueClinical follow-up at 12 mo Combined end point (CV death, HF rehospitalization, heart transplant)12 (39; 95% CI, 21.8–57.8)2 (13; 95% CI, 1.6–38.3)10 (67; 95% CI, 38.8–88.2)0.003 All-cause mortality5 (16; 95% CI, 5.5–33.8)2 (13; 95% CI, 1.6–38.4)3 (20; 95% CI, 4.3–48.1)0.65 Cardiovascular mortality3 (10; 95% CI, 5.5–33.8)1 (7; 95% CI, 0.15–30.2)2 (13; 95% CI, 1.7–40.5)0.60 HF rehospitalization11 (37; 95% CI, 19.9–56.1)1 (7; 95% CI, 0.1–32.9)10 (67; 95% CI, 38.4–88.2)0.002 Number of HF hospitalizations0.003 019 (63)14 (93)5 (33) 18 (27)1 (7)7 (7) 21 (3)01 (7) 31 (3)01 (7) 41 (3)01 (7) Heart transplant2 (7; 95% CI, 0.79–21.4)02 (13; 95% CI, 1.7–40.5)0.23 NYHA class<0.001 I2 (7)2 (14)0 II11 (41)10 (72)1 (8) III9 (33)2 (14)7 (54) IV5 (19)015 (38) 6MWT distance, m402.7±89.1410.4±97.8393.7±86.10.75 Change in distance on 6MWT from baseline19.33±77.282.5±57.5−31.2±47.50.014 BNP level457 (280–992)543 (280–1889)385.5 (254–550)0.35 Change in BNP level−130.2±1329.9−186±1719.6−46.5±455.10.85Total (n=31)TMVr group (n=16)Control group (n=15)P value Increase in diuretic treatment14 (50; 95% CI, 30.7–69.4)2 (14; 95% CI, 1.8–42.8)12 (86; 95% CI, 57.2–98.2)<0.001Echocardiographic follow-up at 12 mo MR severity Mild (1)6 (24)5 (39)1 (8)0.005 Moderate (2)8 (32)6 (46)2 (17) Moderate-to-severe (3)4 (16)2 (15)2 (17) Severe (4)7 (28)07 (58) LVEF, %20 (18–25)22 (19–25)20 (16–25)0.23 Change in LVEF, %−0.28±5.810±7.12−0.58±4.360.81 LVES volume (indexed)103.7±40.1111.5±43.295.9±37.10.38 Change in LVES volume2.48±19.48.8±16.7−3.8±20.50.13 LVED volume (indexed)134.7±45.4144±48.6126.2±42.80.39 Change in LVED volume3.97±21.579.29±16.65−0.87±25.040.29 sPAP, mm Hg45.9±10.946.6±10.445.1±12.20.81 Change in sPAP, mm Hg−2.94±14.4−7.44±14.32.86±13.30.16Values are expressed as n (%), mean±SD‚ or median (IQR). 6MWT indicates 6-minute walking test; BNP, B-type natriuretic peptide level; ACEI, angiotensin convertering enzyme inhibitor; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor-neprilysin inhibitor; CRT, cardiac resynchronization therapy; CV, cardiovascular; ERO, effective regurgitant orifice; GFR, glomerular filtration rate; HF, heart failure; LA, left atrium; LV, left ventricle; LVED, left ventricle end-diastolic; LVEDD, left ventricle end-diastolic diameter; LVEF, left ventricle ejection fraction; LVES, left ventricle end-systolic; LVESD, left ventricle end-systolic diameter; MR, mitral regurgitation; MRA, mineralocorticoid receptor antagonist; NVAF, nonvalvular atrial fibrillation; NYHA, New York Heart Association; SAE, serious adverse event; sPAP, systolic pulmonary artery pressure; TIA, transient ischemic attack; and TMVr, transcatheter mitral valve repair.*Five missing values.† One patient was randomized to device group, but he finally refused the intervention.At 12 months follow-up, TMVr patients showed reduction of the combined end-point of CV death, heart transplantation, and HF hospitalizations (13% [95% CI, 1.6–38.3] versus 67% [95% CI, 38.8–88.2]; P=0.003; Table). Additionally, patients in the TMVr group reduced the number of HF hospitalizations, the need of diuretic scalation and also showed improved functional class and 6MWT distance. Transthoracic echocardiography at 12 months showed residual MR≤2 in 85% of TMVr patients and 25% of controls (P=0.005). No differences in left ventricle dimensions, and LVEF were observed between groups, but systolic pulmonary artery pressure values exhibited a trend toward a reduction in the TMVr group (Table). This observation may reflect the advanced status of the left ventricle dilatation/dysfunction or the limited number of included patients.In conclusion, in patients with DCM and CRT who were clinically nonresponders and present FMR >2, “edge-to-edge” TMVr, as compared with OMT, was associated with a reduction of the combined end point of CV death, heart transplantation, and CHF hospitalizations and a reduction in the number of CHF hospitalizations and the need of diuretic treatment scalation at 1 year. Regarding the safety end point, no procedure-related serious adverse events were observed in the TVMr group. The advance status of the DCM in both clinical and echocardiographic parameters of referred patients with the aforementioned inclusion criteria highlight the need to anticipate more preventive strategies. The limitations of this pilot study preclude using it for clinical decision-making, and they should be considered as hypothesis-generating. Further studies with larger samples are warranted.Article InformationSources of FundingThis was an investigator-initiated study supported by Abbott Medical. Dr Hernández-Enríquez received a formation grant from the Spanish Society of Cardiology.Disclosures Drs Freixa, Sitges, and Sanchis are proctors for Abbott Medical. Dr Rodés-Cabau has an institutional research grant from Boston Scientific.Footnotes*X. Freixa and J.M. Tolosana contributed equally.For Sources of Funding and Disclosures, see page 1159.Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02592889.Correspondence to: Xavier Freixa, PhD, or Jose María Tolosana, PhD, Hospital Clinic, Cardiology Department, C/Villarroel, 170, 08036 Barcelona, Spain. Email [email protected]cat or [email protected]catReferences1. Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, Whisenant B, Grayburn PA, Rinaldi M, Kapadia SR, et al; COAPT Investigators.Transcatheter mitral-valve repair in patients with heart failure.N Engl J Med. 2018; 379:2307–2318. doi: 10.1056/NEJMoa1806640CrossrefMedlineGoogle Scholar2. Obadia JF, Messika-Zeitoun D, Leurent G, Iung B, Bonnet G, Piriou N, Lefèvre T, Piot C, Rouleau F, Carrié D, et al; MITRA-FR Investigators.Percutaneous repair or medical treatment for secondary mitral regurgitation.N Engl J Med. 2018; 379:2297–2306. doi: 10.1056/NEJMoa1805374CrossrefMedlineGoogle Scholar3. Kosmidou I, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, Whisenant BK, Kipperman RM, Boudoulas KD, Redfors B, et al. Transcatheter mitral valve repair in patients with and without cardiac resynchronization therapy: the COAPT trial.Circ Heart Fail. 2020; 13:e007293. doi: 10.1161/CIRCHEARTFAILURE.120.007293LinkGoogle Scholar4. Auricchio A, Schillinger W, Meyer S, Maisano F, Hoffmann R, Ussia GP, Pedrazzini GB, van der Heyden J, Fratini S, Klersy C, et al; PERMIT-CARE Investigators.Correction of mitral regurgitation in nonresponders to cardiac resynchronization therapy by MitraClip improves symptoms and promotes reverse remodeling.J Am Coll Cardiol. 2011; 58:2183–2189. doi: 10.1016/j.jacc.2011.06.061CrossrefMedlineGoogle Scholar5. Mullens W, Auricchio A, Martens P, Witte K, Cowie MR, Delgado V, Dickstein K, Linde C, Vernooy K, Leyva F, et al. Optimized implementation of cardiac resynchronization therapy: a call for action for referral and optimization of care: A joint position statement from the Heart Failure Association (HFA), European Heart Rhythm Association (EHRA), and European Association of Cardiovascular Imaging (EACVI) of the European Society of Cardiology.Eur J Heart Fail. 2020; 22:2349–2369. doi: 10.1002/ejhf.2046CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails December 2022Vol 15, Issue 12 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCHEARTFAILURE.121.009501PMID: 36124767 Originally publishedSeptember 20, 2022 Keywordsretrospectiveprognosisheart failuremitral valvecardiomyopathy, dilatedPDF download Advertisement SubjectsCatheter-Based Coronary and Valvular InterventionsHeart Failure

Large animal models of acute myocardial infarction (AMI) play a crucial role in translating novel therapeutic approaches to patients as denoted by their use in the right-before-human testing platform. At present, the porcine model of AMI is used most frequently as it mimics the human condition and its anatomopathological features accurately. We want to describe to, and share with, the translational research community our experience of how different anaesthetic protocols (sevoflurane, midazolam, ketamine+xylazine+midazolam, and propofol) and pig breeds [Large White and Landrace x Large White (LLW)] can dramatically modify the outcomes of a well-established porcine model of closed-chest AMI. Our group has extensive experience with the porcine model of reperfused AMI and, over time, we reduced the time of ischaemia used to induce the disease from 90 to 50 min to increase the salvageable myocardium for cardioprotection studies. For logistical reasons, we changed both the anaesthetic protocol and the pig breed used, but these resulted in a dramatic reduction in the size of the myocardial infarct, to almost zero in some cases (sevoflurane, 50-min ischaemia, LLW, 2.4 ± 3.9% infarct size), and the cardiac function was preserved. Therefore, we had to re-validate the model by returning to 90 min of ischaemia. Here, we report the differences in infarct size and cardiac function, measured by different modalities, for each combination of anaesthetic protocol and pig breed we have used. Furthermore, we discuss these combinations and the limited literature pertaining to how these two factors influence cardiac function and infarct size in the porcine model of AMI.

Introduction: Early revascularization of infarcted zone is crucial to improve patient′s outcomes. Despite their primary actions, major lipid-lowering drugs may also reduce cardiovascular events by pleiotropic mechanisms. Hypothesis: Conventional (statin) and novel lipid-lowering therapies [(PSCK9-inhibitor (PCSK9i) and eicosatetraenoic acid (EPA)] can improve endothelial progenitor cells (EPC) phenotype and favor neovascularization. Methods: EPC were isolated from peripheral blood of patients with acute coronary syndrome (n=62) who were statin-naïve (n=34) or chronic statin treatment (n=28) at time of inclusion. A set of statin-naïve EPC and mature endothelial cells (HUVEC) were treated in vitro with statin (20nM), PCSKi (1μM) and EPA (3μM). EPC phenotype was determined as EPC colony number and time of appearance, proliferative rate, and ability to form capillary-like structures. Serum PCSK9 and markers of angiogenesis and endothelial function were determined by multiplexed protein assay. Results: Frequency of EPC appearance was higher in samples of statin group (78%) compared to naïve group (66%) (Fig A). They also appeared much earlier (Fig B), in greater quantity (4.7 vs 2.1 colony, p = 0.0009) and had higher proliferative rate than EPCs of naïve group. Besides they had increased potential of tube formation and shaped more branched vessel-like structures (Fig C). No differences in serum levels of biomarkers were found. In vitro treatment of EPC with statin, PCSK9i and EPA did not modify colonies behavior (Fig D). PCSK9 levels showed negative correlation with EPC proliferation (r -0.4150, p=0.004), and PCSK9i treatment increased angiogenic potential of HUVEC (Fig E). Conclusions: Statin and PCSK9i have pleiotropic effects on EPC, boosting their potential to form endothelial cells colonies and to induce angiogenesis. These effects could contribute to the progression and outcomes of coronary artery disease. Funding: ISCIII - FEDER-ERDF (PI19/00264)

Background: Data on the impact of chronic kidney disease (CKD) on clinical outcomes in chronic total occlusion (CTO) patients is scarce, and the optimal treatment strategy for this population is not well established. This study aims to compare differences in CTO management and long-term clinical outcomes, including all-cause and cardiac mortalities, according to baseline glomerular filtration rate (GFR). Methods: All patients with at least one CTO diagnosed in our center between 2010 and 2014 were included. Demographic and clinical data were registered. All-cause and cardiac mortalities were assessed during a median follow-up of 4.03 years (IQR 2.6-4.8). Clinical outcomes were compared between patients with CKD (GFR < 60 mL/min/1.73 m(2)) and without CKD (GFR >= 60 mL/min/1.73 m(2)). Results: A total of 1248 patients (67.3 +/- 10.9 years; 32% CKD) were identified. CKD patients were older and had a higher prevalence of hypertension, type 2 diabetes, peripheral arterial disease, and severe left ventricular dysfunction compared to patients with normal renal function (p < 0.05). Subjects with renal dysfunction were more often treated with MT alone, compared to patients without CKD (63% vs 45%; p < 0.001), who were more likely to undergo PCI or surgery. During follow-up, 386 patients [31%] died. CKD patients had a higher rate of all-cause and cardiac mortalities compared to patients without CKD (p < 0.001). The independent predictors for all-cause mortality were age, GFR < 60 mL/min/1.73 m(2), Syntax Score I, and successful revascularization of the CTO (CABG or PCI-CTO). Among patients with CKD, advanced age, eGFR <30 mL/ min/1.73 m(2), and CTO successful revascularization were predictors of all-cause mortality. Conclusions: Patients with CKD were more often treated with MT alone. At long-term follow-up, revascularization of the CTO is associated with lower all-cause and cardiac mortalities in this population. (C) 2021 Elsevier Inc. All rights reserved.

Aims: The aim of this study was to evaluate the impact of pulmonary ridge (PR) coverage on both clinical and imaging follow-up outcomes in patients undergoing left atrial appendage occlusion (LAAO). Methods and results: The study included consecutive patients with non-valvular atrial fibrillation who underwent LAAO with disc and lobe devices. Patients were classified into two groups according to the PR coverage. A total of 147 patients were included. Among these, the PR was covered in 109 (74%) and uncovered in 38 (26%). Successful implantation was achieved in 98.6%. No differences in procedural outcomes were observed between the groups. The rate of procedural major adverse events was 3% (only major bleedings and/or vascular access complications). No device embolisation, cardiac tamponade or in-hospital mortality was observed. After a mean follow-up of 1.77±2.2 years, the annualised ischaemic stroke and major bleeding rate was 1.3%/year and 6.5%/year, respectively, without differences between groups. At follow-up, patients with a covered PR presented a lower incidence of device-related thrombosis (DRT) (1%) than those with an uncovered PR (27%); p<0.001. In multivariable analysis, the presence of PR coverage emerged as an independent predictor of DRT. Conclusions: Pulmonary ridge coverage was associated with a lower incidence of DRT after LAAO. Procedural and follow-up clinical outcomes did not differ between covered PR and uncovered PR patients.

The exact mechanisms leading to myocardial injury in the coronavirus disease 2019 (COVID-19) are still unknown. In this retrospective observational study, we include all consecutive COVID-19 patients admitted to our center. They were divided into two groups according to the presence of myocardial injury. Clinical variables, Charlson Comorbidity Index (CCI), C-reactive protein (CRP), CAC (COVID-19-associated coagulopathy), defined according to the ISTH score, treatment and in-hospital events were collected. Between March and April 2020, 331 COVID-19 patients were enrolled, 72 of them (21.8%) with myocardial injury. Patients with myocardial injury showed a higher CCI score (median (interquartile range), 5 (4–7) vs. 2 (1–4), p = 0.001), higher CRP values (18.3 (9.6–25.9) mg/dL vs. 12.0 (5.4–19.4) mg/dL, p ˂ 0.001) and CAC score (1 (0–2) vs. 0 (0–1), p = 0.001), and had lower use of any anticoagulant (57 patients (82.6%) vs. 229 patients (90.9%), p = 0.078), than those without. In the adjusted logistic regression, CRP, myocardial injury, CCI and CAC score were positive independent predictors of mortality, whereas anticoagulants resulted as a protective factor. Myocardial injury in COVID-19 patients is associated with inflammation and coagulopathy, resulting in a worse in-hospital prognosis. Treatment with anticoagulant agents may help to improve in-hospital outcomes.

BACKGROUND Large clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia. OBJECTIVES The purpose of this study was to assess the effect of empagliflozin on left ventricular (LV) function and volumes, functional capacity, and quality of life (QoL) in nondiabetic HFrEF patients. METHODS In this double-blind, placebo-controlled trial, nondiabetic HFrEF patients (n = 84) were randomized to empagliflozin 10 mg daily or placebo for 6 months. The primary endpoint was change in LV end-diastolic and-systolic volume assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life. RESULTS Empagliflozin was associated with a significant reduction of LV end-diastolic volume (-25.1 +/- 26.0 ml vs.-1.5 +/- 25.4 ml for empagliflozin vs. placebo, respectively; p < 0.001) and LV end-systolic volume (-26.6 +/- 20.5 ml vs.-0.5 +/- 21.9 ml for empagliflozin vs. placebo; p < 0.001). Empagliflozin was associated with reductions in LV mass (-17.8 +/- 31.9 g vs. 4.1 +/- 13.4 g, for empagliflozin vs. placebo, respectively; p < 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 +/- 4.2 vs.-0.1 +/- 3.9; p < 0.001). Patients who received empagliflozin had significant improvements in peak O2 consumption (1.1 +/- 2.6 ml/min/kg vs.-0.5 +/- 1.9 ml/min/kg for empagliflozin vs. placebo, respectively; p = 0.017), oxygen uptake efficiency slope (111 +/- 267 vs.-145 +/- 318; p < 0.001), as well as in 6-min walk test (81 +/- 64 m vs.-35 +/- 68 m; p < 0.001) and quality of life (Kansas City Cardiomyopathy Questionnaire-12: 21 +/- 18 vs. 2 +/- 15; p < 0.001). CONCLUSIONS Empagliflozin administration to nondiabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status. (C) 2021 by the American College of Cardiology Foundation.

Background: Sex differences in coronary artery disease presentation and outcomes have been described. The aim of this study was to compare sex disparities in chronic total occlusion (CTO) management and long-term outcomes. Methods: All consecutive patients with at least one CTO diagnosed in our center between 2010 and 2014 were included. Demographic and clinical data were registered. All-cause and cardiac mortality were assessed during a median follow-up of 4.03 years (IQR 2.6-4.8). Results: A total of 1248 patients (67.3 +/- 10.9 years; 16% female) were identified. Women were older, had a higher prevalence of type 2 DM and a lower ventricle ejection fraction compared to men (p < .05). Although women had major proportion of positive result for severe ischemia-viability test (86% vs. 74%; p=.01), they were more often treated with MT alone compared to male (57% vs 51%; p = .02). During follow-up, 386 patients (31%) died. Women presented a higher rate of all-cause and cardiac mortality, and hospitalizations for heart failure independently of treatment strategy, compared to men (p < .001). In multivariable analysis female sex was associated with higher cardiac mortality [HR 1.67, 95% CI 1.10-2.57; p < .001]. Among women, the independent predictors for all-cause and cardiac mortalities were age, MT of the CTO and ACEF (age, creatinin and ejection fraction) score. Conclusions: A significant sex gap regarding CTO treatment was observed. Female sex was an independent predictor for cardiac mortality at long-term follow-up. More data are needed to support these findings. (C) 2020 Elsevier B.V. All rights reserved.