Publications by authors named "Jose Luis Zamorano"

270 Publications

The use of Bayes factor in clinical cardiology research. Response.

Rev Esp Cardiol (Engl Ed) 2021 Apr 22. Epub 2021 Apr 22.

Servicio de Cardiología, Hospital Universitario Ramón y Cajal, Madrid, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.rec.2021.03.011DOI Listing
April 2021

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

Int J Mol Sci 2021 Mar 12;22(6). Epub 2021 Mar 12.

Hospital Ramón y Cajal Research Unit (IRYCIS), Cardiology Department, Universidad Francisco de Vitoria, 28223 Madrid, Spain.

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.
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http://dx.doi.org/10.3390/ijms22062902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001911PMC
March 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.

Eur Heart J 2021 Mar 18. Epub 2021 Mar 18.

Department of Cardiology, Inselspital, University of Bern, Bern, Switzerland.

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.
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http://dx.doi.org/10.1093/eurheartj/ehab086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014526PMC
March 2021

Imaging techniques: Paving the way for paravalvular leak closure.

Rev Port Cardiol (Engl Ed) 2021 Apr 12;40(4):271-272. Epub 2021 Mar 12.

Cardiology Department. University Hospital Ramon y Cajal, Madrid, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.repc.2021.02.003DOI Listing
April 2021

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

J Am Acad Dermatol 2021 Jun 24;84(6):1644-1651. Epub 2021 Feb 24.

Sinclair Dermatology, Melbourne, Australia.

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.
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http://dx.doi.org/10.1016/j.jaad.2021.02.054DOI Listing
June 2021

Cardio-oncology: the questions to be solved.

Kardiol Pol 2021 02 25;79(2):112-113. Epub 2021 Feb 25.

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http://dx.doi.org/10.33963/KP.15826DOI Listing
February 2021

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

Eur J Prev Cardiol 2021 May;28(6):611-621

School of Medicine, University of Insubria, Via Ravasi, 2, 21100 Varese, Italy.

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.
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http://dx.doi.org/10.1093/eurjpc/zwaa054DOI Listing
May 2021

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

Eur Heart J Cardiovasc Imaging 2021 Apr;22(5):471-479

Dept of Cardiology, Oslo University Hospital, Pb 4950 Nydalen, 0424, Oslo, Norway.

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.
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http://dx.doi.org/10.1093/ehjci/jeab005DOI Listing
April 2021

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

Eur Radiol 2021 Jan 15. Epub 2021 Jan 15.

Cardiology Department, University Hospital Ramón y Cajal, Carretera de Colmenar km 9, 100 28034, Madrid, Spain.

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Key Points: • 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.
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http://dx.doi.org/10.1007/s00330-020-07651-6DOI Listing
January 2021

The year in cardiovascular medicine 2020: imaging.

Eur Heart J 2021 02;42(7):740-749

Department of Cardiology, Bristol Heart Institute, University Hospitals Bristol and Weston NHS Trust and University of Bristol, UK.

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http://dx.doi.org/10.1093/eurheartj/ehaa1035DOI Listing
February 2021

Hospital Ramón y Cajal, Madrid, Spain.

Eur Heart J 2021 04;42(16):1540-1541

Cardiology Department University Hospital Ramón y Cajal. Madrid, Spain. CIBERCV Instituto de Salud Carlos III (ISCIII) Spain.

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http://dx.doi.org/10.1093/eurheartj/ehaa999DOI Listing
April 2021

Feasibility and Reproducibility of Left Atrium Measurements Using Different Three-Dimensional Echocardiographic Modalities.

Diagnostics (Basel) 2020 Dec 3;10(12). Epub 2020 Dec 3.

Centrum Voor Hart-en Vaatziekten (CHVZ), Department of Cardiology, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.

Left atrium (LA) volume is a biomarker of cardiovascular outcomes. Three-dimensional echocardiography (3DE) provides an accurate LA evaluation, but data regarding the optimal 3DE method is scarce. We assessed the feasibility and reproducibility of LA measurements using different 3DE methods. One hundred and ninety-four patients were prospectively analyzed. Conventional 3DE and two semi-automatic 3DE algorithms (Tomtec™ and Dynamic Heart Model (DHM)) were used in 110 patients. Intra- and interobserver reproducibility and intervendor comparison were performed in additional patients' subsets. Forty patients underwent cardiac magnetic resonance (CMR). Feasibility was 100% for Tomtec, 98.2% for DHM, and 72.8% for conventional 3DE. Tomtec volumes were higher than 3DE and DHM ( < 0.001). Reproducibility was better for DHM (intraobserver LA maximum volume (LAmax) ICC 0.99 (95% CI 1.0-0.99), LA minimum volume (LAmin) 0.98 (95% CI 0.95-0.99), LApreA 0.96 (95% CI 0.91-0.98); interobserver LAmax ICC 0.98 (95% CI 0.96-0.99), LAmin 0.99 (95% CI 0.99-1.00), and LApreA 0.97 (95% CI 0.94-0.99)). Intervendor comparison showed differences between left ventricle (LV) software adapted for LA ( < 0.001). Tomtec underestimated the least LA volumes compared to CMR. These findings emphasize that dedicated software should be used for LA assessment, for consistent clinical longitudinal follow-up and research.
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http://dx.doi.org/10.3390/diagnostics10121043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761745PMC
December 2020

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

Rev Esp Cardiol (Engl Ed) 2020 Oct 29. Epub 2020 Oct 29.

Unidad de Investigación Cardiovascular, Departamento de Cardiología, Universidad Francisco de Vitoria, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain; Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Spain. Electronic address:

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.
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http://dx.doi.org/10.1016/j.rec.2020.09.012DOI Listing
October 2020

The right ventricle in "left-sided" cardiomyopathies. Where are we and where are we heading.

Trends Cardiovasc Med 2020 Oct 28. Epub 2020 Oct 28.

Cardiology Department, Ramon y Cajal University Hospital (IRYCIS), Alcalá de Henares University, Madrid, Spain.

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http://dx.doi.org/10.1016/j.tcm.2020.10.009DOI Listing
October 2020

Simultaneous percutaneous repair in mitral and tricuspid regurgitation: step by step.

Rev Esp Cardiol (Engl Ed) 2020 12 17;73(12):1085-1086. Epub 2020 Oct 17.

Servicio de Cardiología, Hospital Universitario Ramón y Cajal, Madrid, Spain.

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http://dx.doi.org/10.1016/j.rec.2020.08.017DOI Listing
December 2020

[Risk factors for in-hospital mortality in patients with acute myocardial infarction during the COVID-19 outbreak].

Rev Esp Cardiol 2020 Dec 17;73(12):985-993. Epub 2020 Sep 17.

Departamento de Cardiología, Hospital Universitario Ramón y Cajal, Madrid, España.

Introduction And Objectives: Despite advances in treatment, patients with acute myocardial infarction (AMI) still exhibit unfavorable short- and long-term prognoses. In addition, there is scant evidence about the clinical outcomes of patients with AMI and coronavirus disease 2019 (COVID-19). The objective of this study was to describe the clinical presentation, complications, and risk factors for mortality in patients admitted for AMI during the COVID-19 pandemic.

Methods: This prospective, multicenter, cohort study included all consecutive patients with AMI who underwent coronary angiography in a 30-day period corresponding chronologically with the COVID-19 outbreak (March 15 to April 15, 2020). Clinical presentations and outcomes were compared between COVID-19 and non-COVID-19 patients. The effect of COVID-19 on mortality was assessed by propensity score matching and with a multivariate logistic regression model.

Results: In total, 187 patients were admitted for AMI, 111 with ST-segment elevation AMI and 76 with non-ST-segment elevation AMI. Of these, 32 (17%) were diagnosed with COVID-19. GRACE score, Killip-Kimball classification, and several inflammatory markers were significantly higher in COVID-19-positive patients. Total and cardiovascular mortality were also significantly higher in COVID-19-positive patients (25% vs 3.8% [ < .001] and 15.2% vs 1.8% [ = .001], respectively). GRACE score > 140 (OR, 23.45; 95%CI, 2.52-62.51;  = .005) and COVID-19 (OR, 6.61; 95%CI, 1.82-24.43;  = .02) were independent predictors of in-hospital death.

Conclusions: During this pandemic, a high GRACE score and COVID-19 were independent risk factors associated with higher in-hospital mortality.:www.revespcardiol.org/en.
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http://dx.doi.org/10.1016/j.recesp.2020.07.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498230PMC
December 2020

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.

Intern Emerg Med 2021 Apr 21;16(3):591-599. Epub 2020 Sep 21.

Chair of Cardiology, University Cardiology Division, University of Pisa, Pisa University Hospital, Pisa, and Fondazione VillaSerena Per La Ricerca, Città Sant'Angelo, Pescara, Italy.

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 CHADSVASc score was 3.4 ± 1.6, and 2587 (88.6%) had a CHADSVASc 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.
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http://dx.doi.org/10.1007/s11739-020-02442-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049932PMC
April 2021

Ivabradine-Stimulated Microvesicle Release Induces Cardiac Protection against Acute Myocardial Infarction.

Int J Mol Sci 2020 Sep 8;21(18). Epub 2020 Sep 8.

Cardiology Department, Universidad Francisco de Vitoria/Hospital Ramón y Cajal Research Unit (IRYCIS), 28223 Madrid, Spain.

Ivabradine can reduce heart rate through inhibition of the current I() by still unexplored mechanisms. In a porcine model of ischemia reperfusion (IR), we found that treatment with 0.3 mg/kg Ivabradine increased plasma release of microvesicles (MVs) over Placebo, as detected by flow cytometry of plasma isolated from pigs 7 days after IR, in which a tenfold increase of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) containing (both high and low-glycosylated) MVs, was detected in response to Ivabradine. The source of MVs was investigated, finding a 37% decrease of CD31+ endothelial cell derived MVs, while CD41+ platelet MVs remained unchanged. By contrast, Ivabradine induced the release of HCN4+ (mostly cardiac) MVs. While no differences respect to EMMPRIN as a cargo component were found in endothelial and platelet derived MVs, Ivabradine induced a significant release of EMMPRIN+/HCN4+ MVs by day 7 after IR. To test the role of EMMPRIN+ cardiac MVs (EMCMV), H9c2 cell monolayers were incubated for 24 h with 10 EMCMVs, reducing apoptosis, and increasing 2 times cell proliferation and 1.5 times cell migration. The in vivo contribution of Ivabradine-induced plasma MVs was also tested, in which 10 MVs isolated from the plasma of pigs treated with Ivabradine or Placebo 7 days after IR, were injected in pigs under IR, finding a significant cardiac protection by increasing left ventricle ejection fraction and a significant reduction of the necrotic area. In conclusion ivabradine induces cardiac protection by increasing at least the release of EMMPRIN containing cardiac microvesicles.
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http://dx.doi.org/10.3390/ijms21186566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555962PMC
September 2020

Risk factors for in-hospital mortality in patients with acute myocardial infarction during the COVID-19 outbreak.

Rev Esp Cardiol (Engl Ed) 2020 Dec 31;73(12):985-993. Epub 2020 Jul 31.

Departamento de Cardiología, Hospital Universitario Ramón y Cajal, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. Electronic address:

Introduction And Objectives: Despite advances in treatment, patients with acute myocardial infarction (AMI) still exhibit unfavorable short- and long-term prognoses. In addition, there is scant evidence about the clinical outcomes of patients with AMI and coronavirus disease 2019 (COVID-19). The objective of this study was to describe the clinical presentation, complications, and risk factors for mortality in patients admitted for AMI during the COVID-19 pandemic.

Methods: This prospective, multicenter, cohort study included all consecutive patients with AMI who underwent coronary angiography in a 30-day period corresponding chronologically with the COVID-19 outbreak (March 15 to April 15, 2020). Clinical presentations and outcomes were compared between COVID-19 and non-COVID-19 patients. The effect of COVID-19 on mortality was assessed by propensity score matching and with a multivariate logistic regression model.

Results: In total, 187 patients were admitted for AMI, 111 with ST-segment elevation AMI and 76 with non-ST-segment elevation AMI. Of these, 32 (17%) were diagnosed with COVID-19. GRACE score, Killip-Kimball classification, and several inflammatory markers were significantly higher in COVID-19-positive patients. Total and cardiovascular mortality were also significantly higher in COVID-19-positive patients (25% vs 3.8% [P <.001] and 15.2% vs 1.8% [P=.001], respectively). GRACE score> 140 (OR, 23.45; 95%CI, 2.52-62.51; P=.005) and COVID-19 (OR, 6.61; 95%CI, 1.82-24.43; P=.02) were independent predictors of in-hospital death.

Conclusions: During this pandemic, a high GRACE score and COVID-19 were independent risk factors associated with higher in-hospital mortality.
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http://dx.doi.org/10.1016/j.rec.2020.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832619PMC
December 2020

The cancer patient and cardiology.

Eur J Heart Fail 2020 12 2;22(12):2290-2309. Epub 2020 Oct 2.

Campus Bio-Medico University School of Medicine, Rome, Italy.

Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short- and long-term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long-term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio-oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and management, and long-term follow-up strategies for patients at risk of cancer therapy-related cardiotoxicities. Research to better define strategies for early identification, follow-up and management is highly necessary. Although the academic cardio-oncology community may be the best vehicle to foster awareness and research in this field, additional stakeholders (industry, government agencies and patient organizations) must be involved to facilitate cross-discipline interactions and help in the design and funding of cardio-oncology trials. The overarching goals of cardio-oncology are to assist clinicians in providing optimal care for patients with cancer and cancer survivors, to provide insight into future areas of research and to search for collaborations with industry, funding bodies and patient advocates. However, many unmet needs remain. This document is the product of brainstorming presentations and active discussions held at the Cardiovascular Round Table workshop organized in January 2020 by the European Society of Cardiology.
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http://dx.doi.org/10.1002/ejhf.1985DOI Listing
December 2020

Targeting TLR4 with ApTOLL Improves Heart Function in Response to Coronary Ischemia Reperfusion in Pigs Undergoing Acute Myocardial Infarction.

Biomolecules 2020 08 9;10(8). Epub 2020 Aug 9.

Cardiology Department, Universidad Francisco de Vitoria/Hospital Ramón y Cajal Research Unit (IRYCIS), CIBERCV, 28223 Madrid, Spain.

Toll-like receptor 4 (TLR4) contributes to the pathogenesis of coronary ischemia/reperfusion (IR). To test whether the new TLR4 antagonist, ApTOLL, may prevent coronary IR damage, we administered 0.078 mg/kg ApTOLL or Placebo in pigs subjected to IR, analyzing the levels of cardiac troponins, matrix metalloproteinases, pro-, and anti-inflammatory cytokines, heart function, and tissue integrity over a period of 7 days after IR. Our results show that ApTOLL reduced cardiac troponin-1 24 h after administration, improving heart function, as detected by a significant recovery of the left ventricle ejection fraction (LVEF) and the shortening fraction (FS) cardiac parameters. The extension of necrotic and fibrotic areas was also reduced, as detected by Evans blue/2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxylin/Eosine, and Masson Trichrome staining of heart sections, together with a significant reduction in the expression of the extracellular matrix-degrading, matrix metalloproteinase 9. Finally, the expression of the following cytokines, CCL1, CCL2, MIP1-A-B, CCL5, CD40L, C5/C5A, CXCL1, CXCL10, CXCL11, CXCL12, G-CSF, GM-CSF, ICAM-1, INF-g, IL1-a, ILI-b, IL-1Ra, IL2, IL4, IL5, IL6, IL8, IL10, IL12, IL13, IL16, IL17-A, IL17- E, IL18, IL21, IL27, IL32, MIF, SERPIN-E1, TNF-a, and TREM-1, were also assayed, detecting a pronounced decrease of pro-inflammatory cytokines after 7 days of treatment with ApTOLL. Altogether, our results show that ApTOLL is a promising new tool for the treatment of acute myocardial infarction (AMI).
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http://dx.doi.org/10.3390/biom10081167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464507PMC
August 2020

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

Eur Heart J Cardiovasc Imaging 2021 Jan;22(2):196-202

Department of Cardiology, CIBERCV University Hospital Ramon y Cajal, Carretera de Colmenar Km 9.100, Madrid 28034, Spain.

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 <35%, New York Heart Association III-IV, or older than 85 years, had a high surgical risk. A total of 35 088 echocardiograms were performed. Significant TR was detected in 6% of studies. Moderate TR was found in 69.6%, severe in 25.5%, massive in 3.9%, and torrential in 1.0% of patients. Right ventricle was dilated in 81.7% of patients with massive/torrential TR, in 55.9% with severe TR, and in 29.3% with moderate TR (P < 0.001). Primary TR was present in 7.4% of patients whereas secondary TR was present in 92.6%. Mitral or aortic valve disease was the most common aetiology (54.6%), following by isolated TR (16%). Up to 51.9% of patients with severe, massive, or torrential primary TR and 57% of patients with severe, massive, or torrential secondary TR had a high surgical risk.

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.
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http://dx.doi.org/10.1093/ehjci/jeaa205DOI Listing
January 2021

Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC).

Eur J Heart Fail 2020 09 21;22(9):1504-1524. Epub 2020 Aug 21.

Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands.

Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio-Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio-oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three-dimensional ejection fraction, are proposed. The protocol for baseline pre-treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr-Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio-oncology are discussed.
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http://dx.doi.org/10.1002/ejhf.1957DOI Listing
September 2020

Myocardial injury determination improves risk stratification and predicts mortality in COVID-19 patients.

Cardiol J 2020 26;27(5):489-496. Epub 2020 Jun 26.

Department of Cardiology, University Hospital Ramon y Cajal, Madrid, Spain.

Background: Despite being associated with worse prognosis in patients with COVID-19, systematic determination of myocardial injury is not recommended. The aim of the study was to study the effect of myocardial injury assessment on risk stratification of COVID-19 patients.

Methods: Seven hundred seven consecutive adult patients admitted to a large tertiary hospital with confirmed COVID-19 were included. Demographic data, comorbidities, laboratory results and clinical outcomes were recorded. Charlson comorbidity index (CCI) was calculated in order to quantify the degree of comorbidities. Independent association of cardiac troponin I (cTnI) increase with outcomes was evaluated by multivariate regression analyses and area under curve. In addition, propensity-score matching was performed to assemble a cohort of patients with similar baseline characteristics.

Results: In the matched cohort (mean age 66.76 ± 15.7 years, 37.3% females), cTnI increase above the upper limit was present in 20.9% of the population and was associated with worse clinical outcomes, including all-cause mortality within 30 days (45.1% vs. 23.2%; p = 0.005). The addition of cTnI to a multivariate prediction model showed a significant improvement in the area under the time-dependent receiver operating characteristic curve (0.775 vs. 0.756, DC-statistic = 0.019; 95% confidence interval 0.001-0.037). Use of renin-angiotensin-aldosterone system inhibitors was not associated with mortality after adjusting by baseline risk factors.

Conclusions: Myocardial injury is independently associated with adverse outcomes irrespective of baseline comorbidities and its addition to multivariate regression models significantly improves their performance in predicting mortality. The determination of myocardial injury biomarkers on hospital admission and its combination with CCI can classify patients in three risk groups (high, intermediate and low) with a clearly distinct 30-day mortality.
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http://dx.doi.org/10.5603/CJ.a2020.0089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078990PMC
November 2020

Current perspectives on the use of statins in the treatment of dyslipidaemic patients: focus on pitavastatin.

Drugs Context 2020 12;9. Epub 2020 Jun 12.

University Hospital Ramon y Cajal, Madrid, Spain.

A meeting entitled 'Current Perspective on the Use of Statins in the Treatment of Dyslipidemic Patients' was held in Stresa, Italy, on 27-28th June 2019. The presentations covered the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines on dyslipidaemia, with discussion about the importance of controlling low-density lipoprotein cholesterol (LDL-C) and the pharmacological opportunities to reach the novel lipid goals. The roles of statins to manage dyslipidaemia in patients with different cardiovascular risks were also discussed. In particular, the efficacy and safety of pitavastatin for the treatment of dyslipidaemia were reviewed, highlighting its further advantages beyond LDL-C reduction. Therefore, the impact of statins on the glycaemic profile was discussed in view of the null/lower effect of pitavastatin as compared with other statins, as well as the interaction profile with other drugs commonly used. This meeting report summarizes the main messages of the discussion with a special focus on pitavastatin, whose main features in different settings are described.
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http://dx.doi.org/10.7573/dic.2020-4-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295107PMC
June 2020

Admission of patients with STEMI since the outbreak of the COVID-19 pandemic: a survey by the European Society of Cardiology.

Eur Heart J Qual Care Clin Outcomes 2020 07;6(3):210-216

NIHR Oxford Biomedical Research Centre, UK.

Aims: The COVID-19 pandemic required a significant redeployment of worldwide healthcare resources. Fear of infection, national lockdowns and altered healthcare priorities have the potential to impact utilisation of healthcare resources for non-communicable diseases. To survey health professionals' views of the impact of the COVID-19 pandemic on the rate and timing of admission of patients with ST-elevation myocardial infarction (STEMI), the European Society of Cardiology (ESC) administered an internet-based questionnaire to cardiologists and cardiovascular nurses across 6 continents.

Methods And Results: 3101 responses were received from 141 countries across 6 continents. 88.3% responded that their country was in "total lockdown" and 7.1% in partial lockdown. 78.8% responded that the number of patients presenting with STEMI was reduced since the coronavirus outbreak and 65.2% indicated that the reduction in STEMI presentations was >40%. Approximately 60% of all respondents reported that STEMI patients presented later than usual and 58.5% that >40% of STEMI patients admitted to hospital presented beyond the optimal window for primary percutaneous intervention (PCI) or thrombolysis. Independent predictors of the reported higher rate of delayed STEMI presentation were a country in total lockdown, >100 COVID-19 cases admitted locally, and the complete restructuring of the local cardiology service.

Conclusion: The survey indicates that the impact of COVID-19 on STEMI presentations is likely to be substantial, with both lower presentations and a higher rate of delayed presentations occurring. This has potentially important ramifications for future healthcare and policy planning in the event of further waves of this pandemic.
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http://dx.doi.org/10.1093/ehjqcco/qcaa046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543872PMC
July 2020

Echocardiographic reference ranges for normal left ventricular layer-specific strain: results from the EACVI NORRE study.

Eur Heart J Cardiovasc Imaging 2020 08;21(8):896-905

Department of Cardiology, University Alcala, Hospital Ramón y Cajal, Madrid, Spain.

Aims: To obtain the normal range for 2D echocardiographic (2DE) measurements of left ventricular (LV) layer-specific strain from a large group of healthy volunteers of both genders over a wide range of ages.

Methods And Results: A total of 287 (109 men, mean age: 46 ± 14 years) healthy subjects were enrolled at 22 collaborating institutions of the EACVI Normal Reference Ranges for Echocardiography (NORRE) study. Layer-specific strain was analysed from the apical two-, three-, and four-chamber views using 2DE software. The lowest values of layer-specific strain calculated as ±1.96 standard deviations from the mean were -15.0% in men and -15.6% in women for epicardial strain, -16.8% and -17.7% for mid-myocardial strain, and -18.7% and -19.9% for endocardial strain, respectively. Basal-epicardial and mid-myocardial strain decreased with age in women (epicardial; P = 0.008, mid-myocardial; P = 0.003) and correlated with age (epicardial; r = -0.20, P = 0.007, mid-myocardial; r = -0.21, P = 0.006, endocardial; r = -0.23, P = 0.002), whereas apical-epicardial, mid-myocardial strain increased with the age in women (epicardial; P = 0.006, mid-myocardial; P = 0.03) and correlated with age (epicardial; r = 0.16, P = 0.04). End/Epi ratio at the apex was higher than at the middle and basal levels of LV in men (apex; 1.6 ± 0.2, middle; 1.2 ± 0.1, base 1.1 ± 0.1) and women (apex; 1.6 ± 0.1, middle; 1.1 ± 0.1, base 1.2 ± 0.1).

Conclusion: The NORRE study provides useful 2DE reference ranges for novel indices of layer-specific strain.
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http://dx.doi.org/10.1093/ehjci/jeaa050DOI Listing
August 2020

Right ventricle assessment in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.

Echocardiography 2020 04 25;37(4):586-591. Epub 2020 Mar 25.

Hospital Universitario Ramón y Cajal, Madrid, Spain.

Introduction: Limited data are available regarding the evaluation of right ventricular (RV) performance in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI).

Objective: To evaluate the prevalence of RV dysfunction in patients with severe AS undergoing TAVI and long-term changes.

Methods: Consecutive patients with severe AS undergoing TAVI from January 2016 to July 2017 were included. RV anatomical and functional parameters were analyzed: RV diameters, fractional area change, tricuspid annular plane systolic excursion (TAPSE), S-wave tissue Doppler of the tricuspid annulus (RV-S'TDI), global longitudinal strain (RV-GLS), and free wall strain (RV-FWS). Preprocedure and 1-year echo were analyzed.

Results: Final population included 114 patients, mean age 83.63 ± 6.31 years, and 38.2% women. The prevalence of abnormal RV function was high, variable depending on the parameter that we analyzed, and it showed a significant reduction 1 year after TAVI implantation: 13.9% vs 6.8% (TAPSE < 17mm), P = .04; 26.3% vs 20% (fractional area change < 35%), P = .048; 41.2% vs 29.2% (RV-S'TDI < 9.5cm/s), P = .04; 48.7% vs 39.5% (RV-GLS > [20]), P = .049; and 48.7% vs 28.9% (RV-FWS > [20]), P = .03. Significant differences were noted between patients with low-flow (LF) vs normal-flow (NF) AS in RV dysfunction prevalence as well as in RV function recovery which is less evident in LF compared with NF patients.

Conclusions: RV dysfunction is high among symptomatic AS patients undergoing TAVI, with variable prevalence depending on the echocardiographic parameter used.
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http://dx.doi.org/10.1111/echo.14633DOI Listing
April 2020