Showing papers by "José Luis Zamorano published in 2021"

The management of secondary mitral regurgitation in patients with heart failure: a joint position statement from the Heart Failure Association (HFA), European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA), and European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Abstract: Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology-the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)-presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach.

Safety of low-dose oral minoxidil for hair loss: A multicenter study of 1404 patients

Abstract: Background The major concern regarding the use of low-dose oral minoxidil (LDOM) for the treatment of hair loss is the potential risk of systemic adverse effects. Objective To describe the safety of LDOM for the treatment of hair loss in a large cohort of patients. Methods Retrospective multicenter study of patients treated with LDOM for at least 3 months for any type of alopecia. Results A total of 1404 patients (943 women [67.2%] and 461 men [32.8%]) with a mean age of 43 years (range 8-86) were included. The dose of LDOM was titrated in 1065 patients, allowing the analysis of 2469 different cases. The most frequent adverse effect was hypertrichosis (15.1%), which led to treatment withdrawal in 14 patients (0.5%). Systemic adverse effects included lightheadedness (1.7%), fluid retention (1.3%), tachycardia (0.9%), headache (0.4%), periorbital edema (0.3%), and insomnia (0.2%), leading to drug discontinuation in 29 patients (1.2%). No life-threatening adverse effects were observed. Limitations Retrospective design and lack of a control group. Conclusion LDOM has a good safety profile as a treatment for hair loss. Systemic adverse effects were infrequent and only 1.7% of patients discontinued treatment owing to adverse effects.

New insights of tricuspid regurgitation: a large-scale prospective cohort study.

Abstract: Aims To evaluate the burden of tricuspid regurgitation (TR) in a large cohort, determine the right ventricle involvement of patients with TR and determine the characteristics of isolated TR. Methods and results Prospective study where consecutive patients undergoing an echocardiographic study in 10 centres were included. All studies with significant TR (at least moderate) were selected. We considered that patients with one of pulmonary systolic hypertension >50 mmHg, left ventricular ejection fraction Conclusion Significant TR is a prevalent condition and a high proportion of these patients have an indication for valve intervention. More than a half of patients with severe, massive, or torrential TR had a high surgical risk. Massive/torrential TR may have implications regarding selection and monitoring patients for percutaneous treatment.

Anticoagulation in patients with atrial fibrillation and active cancer: an international survey on patient management.

Abstract: Background In patients with active cancer and atrial fibrillation (AF) anticoagulation, thrombotic and bleeding risk still entail uncertainty. Aim We explored the results of an international survey examining the knowledge and behaviours of a large group of physicians. Methods and results A web-based survey was completed by 960 physicians (82.4% cardiologists, 75.5% from Europe). Among the currently available anticoagulants for stroke prevention in patients with active cancer, direct oral anticoagulants (DOACs) were preferred by 62.6%, with lower values for low molecular weight heparin (LMWH) (24.1%) and for warfarin (only 7.3%). About 46% of respondents considered that DOACs should be used in all types of cancers except in non-operable gastrointestinal cancers. The lack of controlled studies on bleeding risk (33.5% of respondents) and the risk of drug interactions (31.5%) were perceived as problematic issues associated with use of anticoagulants in cancer. The decision on anticoagulation involved a cardiologist in 27.8% of cases, a cardiologist and an oncologist in 41.1%, and a team approach in 21.6%. The patient also was involved in decision-making, according to ∼60% of the respondents. For risk stratification, use of CHA2DS2-VASc and HAS-BLED scores was considered appropriate, although not specifically validated in cancer patients, by 66.7% and 56.4%, respectively. Conclusion This survey highlights that management of anticoagulation in patients with AF and active cancer is challenging, with substantial heterogeneity in therapeutic choices. Direct oral anticoagulants seems having an emerging role but still the use of LMWH remains substantial, despite the absence of long-term data on thromboprophylaxis in AF.

The structural heart disease interventional imager rationale, skills and training: a position paper of the European Association of Cardiovascular Imaging.

Abstract: Percutaneous therapeutic options for an increasing variety of structural heart diseases (SHD) have grown dramatically. Within this context of continuous expansion of devices and procedures, there has been increased demand for physicians with specific knowledge, skills, and advanced training in multimodality cardiac imaging. As a consequence, a new subspecialty of 'Interventional Imaging' for SHD interventions and a new dedicated professional figure, the 'Interventional Imager' with specific competencies has emerged. The interventional imager is an integral part of the heart team and plays a central role in decision-making throughout the patient pathway, including the appropriateness and feasibility of a procedure, pre-procedural planning, intra-procedural guidance, and post-procedural follow-up. However, inherent challenges exist to develop a training programme for SHD imaging that differs from traditional cardiovascular imaging pathways. The purpose of this document is to provide the standard requirements for the training in SHD imaging, as well as a starting point for an official certification process for SHD interventional imager.

European position paper on the management of patients with patent foramen ovale. Part II - Decompression sickness, migraine, arterial deoxygenation syndromes and select high-risk clinical conditions.

Abstract: Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.

Advanced cancer is also a heart failure syndrome: a hypothesis.

Abstract: We present the hypothesis that advanced stage cancer is also a heart failure syndrome. It can develop independently of or in addition to cardiotoxic effects of anti-cancer therapies. This includes an increased risk of ventricular arrhythmias. We suggest the pathophysiologic link for these developments includes generalized muscle wasting (i.e. sarcopenia) due to tissue homeostasis changes leading to cardiac wasting associated cardiomyopathy. Cardiac wasting with thinning of the ventricular wall increases ventricular wall stress, even in the absence of ventricular dilation. In addition, arrhythmias may be facilitated by cellular wasting processes affecting structure and function of electrical cells and conduction pathways. We submit that in some patients with advanced cancer (but not terminal cancer), heart failure therapy or defibrillators may be relevant treatment options. The key points in selecting patients for such therapies may be the predicted life expectancy, quality of life at intervention time, symptomatic burden, and consequences for further anti-cancer therapies. The cause of death in advanced cancer is difficult to ascertain and consensus on event definitions in cancer is not established yet. Clinical investigations on this are called for. Broader ethical considerations must be taken into account when aiming to target cardiovascular problems in cancer patients. We suggest that focused attention to evaluating cardiac wasting and arrhythmias in cancer will herald a further evolution in the rapidly expanding field of cardio-oncology. This article is protected by copyright. All rights reserved.

European position paper on the management of patients with patent foramen ovale. Part II - Decompression sickness, migraine, arterial deoxygenation syndromes and select high-risk clinical conditions.

Abstract: Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.

Advanced cancer is also a heart failure syndrome: a hypothesis.

Abstract: We present the hypothesis that advanced stage cancer is also a heart failure syndrome. It can develop independently of or in addition to cardiotoxic effects of anti-cancer therapies. This includes an increased risk of ventricular arrhythmias. We suggest the pathophysiologic link for these developments includes generalized muscle wasting (i.e. sarcopenia) due to tissue homeostasis changes leading to cardiac wasting associated cardiomyopathy. Cardiac wasting with thinning of the ventricular wall increases ventricular wall stress, even in the absence of ventricular dilatation. In addition, arrhythmias may be facilitated by cellular wasting processes affecting structure and function of electrical cells and conduction pathways. We submit that in some patients with advanced cancer (but not terminal cancer), heart failure therapy or defibrillators may be relevant treatment options. The key points in selecting patients for such therapies may be the predicted life expectancy, quality of life at intervention time, symptomatic burden, and consequences for further anti-cancer therapies. The cause of death in advanced cancer is difficult to ascertain and consensus on event definitions in cancer is not established yet. Clinical investigations on this are called for. Broader ethical considerations must be taken into account when aiming to target cardiovascular problems in cancer patients. We suggest that focused attention to evaluating cardiac wasting and arrhythmias in cancer will herald a further evolution in the rapidly expanding field of cardio-oncology.

The year in cardiovascular medicine 2020 : imaging

Abstract: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

Abstract: In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR.

Prognostic implications of cardiac magnetic resonance feature tracking derived multidirectional strain in patients with chronic aortic regurgitation

Abstract: Speckle-tracking echocardiography (STE) deformation parameters detect latent LV dysfunction in chronic aortic regurgitation (AR) and are associated with outcomes. The aim of the study was to evaluate cardiac magnetic resonance (CMR) feature tracking (FT) deformation parameters in asymptomatic patients with AR and implications in outcomes. Fifty-five patients with AR and 54 controls were included. Conventional functional CMR parameters, aortic regurgitant volume, and fraction were assessed. CMR-FT analysis was performed with a dedicated software. Clinical data was obtained from hospital records. A combined endpoint included all-cause mortality, cardiovascular mortality, aortic valve surgery, or cardiovascular hospital admission due to heart failure. Left ventricular (LV) mechanics is impaired in patients with significant AR. Significant differences were noted in global longitudinal strain (GLS) between controls and AR patients (− 19.1 ± 2.9% vs − 16.5 ± 3.2%, p < 0.001) and among AR severity groups (− 18.3 ± 3.1% vs − 16.2 ± 1.6% vs − 15 ± 3.5%; p = 0.02 for AR grades I–II, III, and IV). In univariate and multivariate analyses, circumferential strain (GCS) and global radial strain (GRS) but not GLS were associated with and increased risk of the end point with a HR of 1.26 (p = 0.016, 1.04–1.52) per 1% worsening for GCS and 0.90 (p = 0.012, 0.83–0.98) per 1% worsening for GRS. CMR-FT myocardial deformation parameters are impaired in patients with AR not meeting surgical criteria. GLS decreases early in the course of the disease and is a marker of AR severity while GCS and GRS worsen later but predict a bad prognosis, mainly the need of aortic valve surgery. • CMR feature tracking LV mechanic parameters may be reduced in significant chronic AR with normal EF. • LV mechanics, mainly global longitudinal strain, worsens as AR severity increases. • LV mechanics, specially global radial and circumferential strain, is associated with a worse prognosis in AR patients.

High-density mapping with fragmentation analysis in patients with reentrant atrial tachycardias (MAP-FLURHY study)

Abstract: Reentrant atrial tachycardias (ATs) use areas of slow conduction that can be visualized as fragmented electrograms. We aimed to test an ablation strategy based on the identification and ablation of spots with fragmented electrograms in reentrant ATs, using Rhythmia navigation system. All consecutive patients from June 2016 to June 2019 were included. The IntellaMap ORION Catheter was used to detect sites with fragmentation, arbitrarily defined as fragmented electrograms > 70 ms. Entrainment was used to check if these areas belonged to the AT circuit. Ablation targeted the longest fragmented electrogram within the circuit: focal ablation for microreentries and lines for macroreentries. Ablation success was defined from each AT as conversion to sinus rhythm or another AT. Twenty-seven consecutive patients with 44 mappable ATs were included. All ATs showed sites with fragmented electrograms (104 sites; 2.4 sites per AT); 43/44 ATs had fragmented electrograms within the circuit, which were the target of ablation. Ablation success: 34/36 ATs (94%); success could not be assessed in 8 circuits, in 6 due to mechanical conversion to sinus rhythm at the target fragmented site. Fragmented electrograms within the AT circuits were longer than electrograms outside the circuits (110 ± 30 vs 90 ± 15 ms, p 100 ms/ > 40% of the AT cycle length predicted to be a successful site for ablation with 72.3%/73.8% specificity, respectively. Sixty-two percent of the patients were free from atrial arrhythmias at 1 year. Most ATs had detectable fragmented electrograms within the circuit, which could be the target of ablation with high efficacy.

A 3-Biomarker 2-Point-Based Risk Stratification Strategy in Acute Heart Failure.

Abstract: Introduction and Objectives: Most multi-biomarker strategies in acute heart failure (HF) have only measured biomarkers in a single-point time. This study aimed to evaluate the prognostic yielding of NT-proBNP, hsTnT, Cys-C, hs-CRP, GDF15, and GAL-3 in HF patients both at admission and discharge. Methods: We included 830 patients enrolled consecutively in a prospective multicenter registry. Primary outcome was 12-month mortality. The gain in the C-index, calibration, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) was calculated after adding each individual biomarker value or their combination on top of the best clinical model developed in this study (C-index 0.752, 0.715-0.789) and also on top of 4 currently used scores (MAGGIC, GWTG-HF, Redin-SCORE, BCN-bioHF). Results: After 12-month, death occurred in 154 (18.5%) cases. On top of the best clinical model, the addition of NT-proBNP, hs-CRP, and GDF-15 above the respective cutoff point at admission and discharge and their delta during compensation improved the C-index to 0.782 (0.747-0.817), IDI by 5% (p < 0.001), and NRI by 57% (p < 0.001) for 12-month mortality. A 4-risk grading categories for 12-month mortality (11.7, 19.2, 26.7, and 39.4%, respectively; p < 0.001) were obtained using combination of these biomarkers. Conclusion: A model including NT-proBNP, hs-CRP, and GDF-15 measured at admission and discharge afforded a mortality risk prediction greater than our clinical model and also better than the most currently used scores. In addition, this 3-biomarker panel defined 4-risk categories for 12-month mortality.

Teofilina para o Alívio da Dispneia Relacionada ao Ticagrelor

Abstract: Dyspnea is one of the most frequent adverse reaction of ticagrelor, leading to premature discontinuation in 15-20% of the patients.1The mechanism is unclear, but it is thought to be related to increased tissue adenosine concentrations or to the direct reversible inhibition of P2Y12receptors on sensory neurons.2 Theophylline has been used as a bronchodilator since 1922, and its effects seem to be partly mediated through nonselective adenosine receptors blockade.3 The authors hypothesized that theophylline could attenuate the dyspnea caused by ticagrelor administration and reported their initial clinical experience with 10 patients.

Ivabradine induces cardiac protection by preventing cardiogenic shock-induced extracellular matrix degradation.

Abstract: Introduction and objectives Ivabradine reduces heart rate by blocking the I(f) current and preserves blood pressure and stroke volume through unknown mechanisms. Caveolin-3 protects the heart by forming protein complexes with several proteins, including extracellular matrix (ECM)-metalloproteinase-inducer (EMMPRIN) and hyperpolarization-activated cyclic nucleotide-gated channel 4 (HN4), a target of ivabradine. We hypothesized that ivabradine might also exert cardioprotective effects through inhibition of ECM degradation. Methods In a porcine model of cardiogenic shock , we studied the effects of ivabradine on heart integrity, the levels of MMP-9 and EMMPRIN , and the stability of caveolin-3/HCN4 protein complexes with EMMPRIN. Results Administration of 0.3 mg/kg ivabradine significantly reduced cardiogenic shock-induced ventricular necrosis and expression of MMP-9 without affecting EMMPRIN mRNA , protein, or protein glycosylation (required for MMP activation). However, ivabradine increased the levels of the caveolin-3/LG-EMMPRIN (low-glycosylated EMMPRIN) and caveolin-3/HCN4 protein complexes and decreased that of a new complex between HCN4 and high-glycosylated EMMPRIN formed in response to cardiogenic shock. We next tested whether caveolin-3 can bind to HCN4 and EMMPRIN and found that the HCN4/EMMPRIN complex was preserved when we silenced caveolin-3 expression, indicating a direct interaction between these 2 proteins. Similarly, EMMPRIN-silenced cells showed a significant reduction in the binding of caveolin-3/HCN4, which regulates the I(f) current, suggesting that, rather than a direct interaction, both proteins bind to EMMPRIN. Conclusions In addition to inhibition of the I(f) current, ivabradine may induce cardiac protection by inhibiting ECM degradation through preservation of the caveolin-3/LG-EMMPRIN complex and control heart rate by stabilizing the caveolin-3/HCN4 complex.

Prognostic implications of left atrial dilation in aortic regurgitation due to bicuspid aortic valve

Abstract: Objective: To investigate the prognostic value of left atrial volume index (LAVI) in patients with moderate to severe aortic regurgitation (AR) and bicuspid aortic valve (BAV). Methods: 554 individuals (45 (IQR 33-57) years, 80% male) with BAV and moderate or severe AR were selected from an international, multicentre registry. The association between LAVI and the combined endpoint of all-cause mortality or aortic valve surgery was investigated with Cox proportional hazard regression analyses. Results: Dilated LAVI was observed in 181 (32.7%) patients. The mean indexed aortic annulus, sinus of Valsalva, sinotubular junction and ascending aorta diameters were 13.0±2.0 mm/m2, 19.4±3.7 mm/m2, 16.5±3.8 mm/m2 and 20.4±4.5 mm/m2, respectively. After a median follow-up of 23 (4-82) months, 272 patients underwent aortic valve surgery (89%) or died (11%). When compared with patients with normal LAVI (<35 mL/m2), those with a dilated LAVI (≥35 mL/m2) had significantly higher rates of aortic valve surgery or mortality (43% and 60% vs 23% and 36%, at 1 and 5 years of follow-up, respectively, p<0.001). Dilated LAVI was independently associated with reduced event-free survival (HR=1.450, 95% CI 1.085 to 1.938, p=0.012) after adjustment for LV ejection fraction, aortic root diameter, LV end-diastolic diameter and LV end-systolic diameter. Conclusions: In this large, multicentre registry of patients with BAV and moderate to severe AR, left atrial dilation was independently associated with reduced event-free survival. The role of this parameter for the risk stratification of individuals with significant AR merits further investigation.

Antithrombotic management and outcomes of patients with atrial fibrillation treated with NOACs early at the time of market introduction: Main results from the PREFER in AF Prolongation Registry

Abstract: The management of patients with atrial fibrillation (AF) has rapidly changed with increasing use of non-vitamin K antagonist oral anticoagulants (NOACs) and changes in the use of rhythm control therapy. The prevention of thromboembolic events European Registry in Atrial Fibrillation Prolongation Registry (PREFER Prolongation) enrolled consecutive patients with AF on NOACs between 2014 and 2016 in a multicentre, prospective, observational study with one-year follow-up, focusing on the time of introduction of NOACs. Overall, 3783 patients were enrolled, with follow-up information available in 3223 (85%). Mean age was 72.2 ± 9.4 years, 40% were women, mean CHA2DS2VASc score was 3.4 ± 1.6, and 2587 (88.6%) had a CHA2DS2VASc score ≥ 2. Rivaroxaban was used in half of patients, and dabigatran and apixaban were used in about a quarter of patients each; edoxaban was not available for use in Europe at the time. Major cardiovascular event rate was low: serious events occurred in 74 patients (84 events, 2%), including 24 strokes (1%), 62 major bleeds (2%), of which 30 were life-threatening (1%) and 3 intracranial (0.1%), and 28 acute coronary syndromes (1%). Mortality was 2%. Antiarrhythmic drugs were used in about 50% of patients, catheter ablation in 5%. Adverse events were low in this contemporary European cohort of unselected AF patients treated with NOACs already at the time of their first introduction, despite high thromboembolic risk.

La ivabradina induce cardioprotección previniendo la degradación de la matriz extracelular inducida por shock cardiogénico

Abstract: Resumen Introduccion y objetivos La ivabradina reduce el ritmo cardiaco bloqueando la corriente I(f) y conserva la presion sanguinea y el volumen sistolico por mecanismos aun desconocidos. La caveolina-3 induce cardioproteccion formando complejos con varias proteinas, como el inductor de metaloproteinasas EMMPRIN y HCN4, la diana de la ivabradina. Consideramos que la cardioproteccion de la ivabradina se basa en la inhibicion la degradacion de la matriz extracelular. Metodos En un modelo porcino de shock cardiogenico, se estudio la integridad del corazon, las concentraciones de MMP-9 y EMMPRIN y la estabilidad de los complejos proteicos caveolina-3/HCN4 con EMMPRIN en respuesta a la ivabradina. Resultados La administracion de ivabradina 0,3 mg/kg redujo significativamente la necrosis y la expresion de MMP-9 tras el shock cardiogenico, mientras que el ARNm de EMMPRIN, su proteina y la glucosilacion (requerida para la activacion de las MMP) no se vieron afectados. Sin embargo, los complejos caveolina-3/LG-EMMPRIN (EMMPRIN poco glucosilado) y caveolina-3/HCN4 aumentaron, mientras que la ivabradina inhibio tambien el nuevo complejo encontrado entre HCN4 y el EMMPRIN muy glucosilado. Para comprobar si la caveolina-3 puede ser puente entre HCN4 y EMMPRIN, el complejo HCN4/EMMPRIN se mantuvo incluso tras el silenciamiento genico de la caveolina-3, lo que indica una interaccion directa de ambas proteinas. De manera similar, el silenciamiento de EMMPRIN redujo significativamente el complejo caveolina-3/HCN4, que regula la I(f). Conclusiones Ademas de la inhibicion de la I(f), la ivabradina puede inducir cardioproteccion al inhibir la degradacion de la matriz extracelular por conservar el complejo caveolina-3/LG-EMMPRIN y controlar el ritmo cardiaco estabilizando el complejo caveolina-3/HCN4.

Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR.

Abstract: Background The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied. Methods We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding. Results A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11). Conclusions In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).

Hydroxyzine inhibits SARS-CoV-2 Spike protein binding to ACE2 in a qualitative in vitro assay

Abstract: COVID-19 currently represents a major public health problem. Multiple efforts are being performed to control this disease. Vaccinations are already in progress. However, no effective treatments have been found so far. The disease is caused by the SARS-CoV-2 coronavirus that through the Spike protein interacts with its cell surface receptor ACE2 to enter into the host cells. Therefore, compounds able to block this interaction may help to stop disease progression. In this study, we have analyzed the effect of compounds reported to interact and modify the activity of ACE2 on the binding of the Spike protein. Among the compounds tested, we found that hydroxyzine could inhibit the binding of the receptor-binding domain of Spike protein to ACE2 in a qualitative in vitro assay. This finding supports the reported clinical data showing the benefits of hydroxyzine on COVID-19 patients, raising the need for further investigation into its effectiveness in the treatment of COVID-19 given its well-characterized medical properties and affordable cost.

Metformin in the era of new antidiabetics.

Abstract: Type II diabetes mellitus is a known cardiovascular risk factor and its prevalence continues to increase. A revolution in the Type II diabetes mellitus treatment has occurred with the arrival of new antidiabetic drugs, which are thought to compromise metformin place. We aim to review the pharmacology, available evidence and clinical aspects of metformin use in the era of new antidiabetics.