Publications by authors named "Marcelo Sanmartin"

52 Publications

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

[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

Telemedicine consultation for the clinical cardiologists in the era of COVID-19: present and future. Consensus document of the Spanish Society of Cardiology.

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

Servicio de Cardiología, Hospital Universitario de Bellvitge, IDIBELL, Universidad de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.

The coronavirus disease 2019 (COVID-19) pandemic has changed how we view our consultations. To reduce the risk of spread in the most vulnerable patients (those with heart disease) and health personnel, most face-to-face consultations have been replaced by telemedicine consultations. Although this change has been rapidly introduced, it will most likely become a permanent feature of clinical practice. Nevertheless, there remain serious doubts about organizational and legal issues, as well as the possibilities for improvement etc. In this consensus document of the Spanish Society of Cardiology, we attempt to provide some keys to improve the quality of care in this new way of working, reviewing the most frequent heart diseases attended in the cardiology outpatient clinic and proposing some minimal conditions for this health care process. These heart diseases are ischemic heart disease, heart failure, and arrhythmias. In these 3 scenarios, we attempt to clarify the basic issues that must be checked during the telephone interview, describe the patients who should attend in person, and identify the criteria to refer patients for follow-up in primary care. This document also describes some improvements that can be introduced in telemedicine consultations to improve patient care.
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http://dx.doi.org/10.1016/j.rec.2020.06.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456304PMC
August 2020

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

[Telemedicine consultation for the clinical cardiologists in the era of COVID-19: present and future. Consensus document of the Spanish Society of Cardiology].

Rev Esp Cardiol 2020 Nov 8;73(11):910-918. Epub 2020 Jul 8.

Servicio de Cardiología, Hospital Universitario de Bellvitge, IDIBELL, Universidad de Barcelona, L'Hospitalet de Llobregat, Barcelona, España.

The coronavirus disease 2019 (COVID-19) pandemic has changed how we view our consultations. To reduce the risk of spread in the most vulnerable patients (those with heart disease) and health personnel, most face-to-face consultations have been replaced by telemedicine consultations. Although this change has been rapidly introduced, it will most likely become a permanent feature of clinical practice. Nevertheless, there remain serious doubts about organizational and legal issues, as well as the possibilities for improvement etc. In this consensus document of the Spanish Society of Cardiology, we attempt to provide some keys to improve the quality of care in this new way of working, reviewing the most frequent heart diseases attended in the cardiology outpatient clinic and proposing some minimal conditions for this health care process. These heart diseases are ischemic heart disease, heart failure, and arrhythmias. In these 3 scenarios, we attempt to clarify the basic issues that must be checked during the telephone interview, describe the patients who should attend in person, and identify the criteria to refer patients for follow-up in primary care. This document also describes some improvements that can be introduced in telemedicine consultations to improve patient care.
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http://dx.doi.org/10.1016/j.recesp.2020.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345370PMC
November 2020

A genetic risk score predicts recurrent events after myocardial infarction in young adults.

Rev Esp Cardiol (Engl Ed) 2020 Aug 17;73(8):623-631. Epub 2019 Oct 17.

Servicio de Cardiología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain; Hospital La Zarzuela, Madrid, Spain.

Introduction And Objectives: To evaluate whether a genetic risk score (GRS) improves prediction of recurrent events in young nondiabetic patients presenting with an acute myocardial infarction (AMI) and identifies a more aggressive form of atherosclerosis.

Methods: We conducted a prospective study with consecutive nondiabetic patients aged <55 years presenting with AMI. We performed a genetic test, cardiac computed tomography, and analyzed several biomarkers. We studied the association of a GRS composed of 11 genetic variants and a primary composite endpoint (cardiovascular mortality, a recurrent event, and cardiac hospitalization).

Results: A total of 81 patients were studied and followed up for a median of 4.1 years. There were 24 recurrent cardiovascular events. Compared with the general population, study participants had a higher prevalence of 9 out of 11 risk alleles. The GRS was significantly associated with recurrent cardiovascular events, especially when baseline low-density lipoprotein cholesterol (LDL-C) levels were elevated. Compared with the low-risk GRS tertile, the multivariate-adjusted HR for recurrences was 10.2 (95%CI, 1.1-100.3; P=.04) for the intermediate-risk group and was 20.7 (2.4-181.0; P=.006) for the high-risk group when LDL-C was≥2.8mmol/L (≥ 110mg/dL). Inclusion of the GRS improved the C-statistic (ΔC-statistic=0.086), cNRI (continuous net reclassification improvement) (30%), and the IDI (integrated discrimination improvement) index (0.05). Cardiac computed tomography frequently detected coronary calcified atherosclerosis but had limited value for prediction of recurrences. No association was observed between metalloproteinases, GRS and recurrences.

Conclusions: A multilocus GRS may identify individuals at increased risk of long-term recurrences among young nondiabetic patients with AMI and improve clinical risk stratification models, particularly among patients with high baseline LDL-C levels.
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http://dx.doi.org/10.1016/j.rec.2019.08.006DOI Listing
August 2020

Role of rivaroxaban in the prevention of atherosclerotic events.

Expert Rev Clin Pharmacol 2019 Aug 9;12(8):771-780. Epub 2019 Jul 9.

j Internal Medicine Department, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid , Madrid , Spain.

: The current approach of using only antiplatelet therapy for secondary prevention leaves a substantial risk of recurrent cardiovascular complications and mortality. : In this manuscript, the role of coagulation in atherothrombosis is reviewed, as well as the impact of vascular doses of rivaroxaban on major cardiovascular outcomes and major adverse limb events. : In COMPASS, among patients with coronary heart disease and/or peripheral artery disease, compared to aspirin, the addition of rivaroxaban 2.5 mg twice daily to aspirin, significantly reduced the risk of major atherosclerotic outcomes, cardiovascular death and death for any cause, with a significant increase in the risk of major bleeding, but not fatal or intracranial bleedings. Preclinical data strongly suggest that rivaroxaban exerts vascular protection through different mechanisms, including improvement of endothelial functionality and fibrinolytic activity at endothelium, anti-inflammatory properties, and platelet-dependent thrombin generation. All these data indicate that among patients with atherosclerotic vascular disease, the addition of rivaroxaban 2.5 mg may provide further vascular protection.
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http://dx.doi.org/10.1080/17512433.2019.1637732DOI Listing
August 2019

Dyspnoea in the GLOBAL LEADERS trial.

Lancet 2019 06;393(10189):2393

Cardiology Department, Ramón y Cajal Hospital, Alcalá University, 28049 Madrid, Spain.

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http://dx.doi.org/10.1016/S0140-6736(19)30697-XDOI Listing
June 2019

Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial.

Cardiol J 2020 29;27(1):62-71. Epub 2018 Aug 29.

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

Background: Acute heart failure patients could benefit from heart rate reduction, as myocardial consumption and oxidative stress are related to tachycardia. Ivabradine could have a clinical role attenuating catecholamine-induced tachycardia. The aim of this study was to evaluate hemodynamic effects of ivabradine in a swine model of acute heart failure.

Methods: Myocardial infarction was induced by 45 min left anterior descending artery balloon occlusion in 18 anesthetized pigs. An infusion of dobutamine and noradrenaline was maintained aiming to preserve adequate hemodynamic support, accompanied by fluid administration to obtain a pulmonary wedged pressure ≥ 18 mmHg. After reperfusion, rhythm and hemodynamic stabilization, the animals were randomized to 0.3 mg/kg ivabradine intravenously (n = 9) or placebo (n = 9). Hemodynamic parameters were observed over a 60 min period.

Results: Ivabradine was associated with a significant reduction in heart rate (88.4 ± 12.0 bpm vs. 122.7 ± 17.3 bpm after 15 min of ivabradine/placebo infusion, p < 0.01) and an increase in stroke volume (68.8 ± 13.7 mL vs. 52.4 ± 11.5 mL after 15 min, p = 0.01). There were no significant differences in systemic or pulmonary arterial pressure, or significant changes in pulmonary capillary pressure. However, after 15 min, cardiac output was significantly reduced with ivabradine (-5.2% vs. +15.0% variation in ivabradine/placebo group, p = 0.03), and central venous pressure increased (+4.2% vs. -19.7% variation, p < 0.01).

Conclusions: Ivabradine reduces heart rate and increases stroke volume without modifying systemic or left filling pressures in a swine model of acute heart failure. However, an excessive heart rate reduction could lead to a decrease in cardiac output and an increase in right filling pressures. Future studies with specific heart rate targets are needed.
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http://dx.doi.org/10.5603/CJ.a2018.0078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086495PMC
June 2021

The Role of Frailty in Acute Coronary Syndromes in the Elderly.

Gerontology 2018 1;64(5):422-429. Epub 2018 Jun 1.

CIBERCV, Hospital Ramón y Cajal, Madrid, Spain.

Background: Myocardial infarction (MI) patients are increasingly older, and common risk scores include chronological age, but do not consider chronic comorbidity or biological age. Frailty status reflects these variables and may be independently correlated with prognosis in this setting.

Objective: This study investigated the impact of frailty on the prognosis of elderly patients admitted due to MI.

Methods: This prospective and observational study included patients ≥75 years admitted to three tertiary hospitals in Spain due to MI. Frailty assessment was performed at admission using the Survey of Health, Ageing and Retirement in Europe Frailty Index (SHARE-FI) tool. The primary endpoint was the composite of death or non-fatal reinfarction during a follow-up of 1 year. Overall mortality, reinfarction, the composite of death, reinfarction and stroke, major bleeding, and readmission rates were also explored.

Results: A total of 285 patients were enrolled. Frail patients (109, 38.2%) were older, with a higher score in the Charlson Comorbidity Index and with a higher risk score addressed in the GRACE and CRUSADE indexes. On multivariate analysis including GRACE, CRUSADE, maximum creatinine level, culprit lesion revascularization, complete revascularization, and dual antiplatelet therapy at discharge, frailty was an independent predictor of the composite of death and reinfarction (2.81, 95% CI 1.16-6.78) and overall mortality (3.07, 95% CI 1.35-6.98).

Conclusion: Frailty is an independent prognostic marker of the composite of mortality and reinfarction and of overall mortality in patients aged ≥75 years admitted due to MI.
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http://dx.doi.org/10.1159/000488390DOI Listing
December 2018

Nanotechnology Applied to Preserve Extracelular Matrix as Teranostic Tool in Acute Myocardial Infarction.

Rev Esp Cardiol (Engl Ed) 2019 Feb 9;72(2):171-174. Epub 2018 Apr 9.

Servicio de Cardiología, Unidad de Investigación del Hospital Ramón y Cajal (IRYCIS)-Universidad Francisco de Vitoria, Madrid, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.rec.2017.12.023DOI Listing
February 2019

Invasive Versus Conservative Strategy in Frail Patients With NSTEMI: The MOSCA-FRAIL Clinical Trial Study Design.

Rev Esp Cardiol (Engl Ed) 2019 Feb 7;72(2):154-159. Epub 2018 Mar 7.

Servicio de Cardiología, Hospital Universitario del Sureste, Arganda del Rey, Madrid, Spain.

Introduction And Objectives: Although clinical guidelines recommend invasive management in non-ST-segment elevation myocardial infarction (NSTEMI), this strategy is underused in frail elderly patients in the real world. Furthermore, these patients are underrepresented in clinical trials and therefore the evidence is scarce. Our hypothesis is that an invasive strategy will improve prognosis in elderly frail patients with NSTEMI.

Methods: This will be a prospective, multicenter, randomized trial, in which the conservative and invasive strategies will be compared in patients meeting all of the following inclusion criteria: NSTEMI diagnosis, age ≥ 70 years, and frailty defined by a category ≥ 4 in the Clinical Frailty Scale. Participants will be randomized to an invasive (coronary angiogram and revascularization if anatomically amenable) or conservative (medical treatment and coronary angiogram only if persistent clinical instability) strategy. The primary endpoint will be the number of days alive out of hospital during the first year. The coprimary endpoint will be the time until the first cardiac event (cardiac death, reinfarction or postdischarge revascularization). We estimate a sample size of 178 patients (89 per arm), considering an increase of 20% in the proportion of days alive out of hospital with the invasive management.

Results: The results of this study will add important knowledge to inform the management of frail elderly patients hospitalized with NSTEMI.

Conclusions: We hypothesize that the invasive strategy will improve outcomes in frail elderly patients with NSTEMI. If this is confirmed, frailty status should not dissuade physicians from implementing an invasive management strategy.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov.Identifier: NCT03208153.
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http://dx.doi.org/10.1016/j.rec.2018.02.007DOI Listing
February 2019

Frailty is an independent prognostic marker in elderly patients with myocardial infarction.

Clin Cardiol 2017 Oct 16;40(10):925-931. Epub 2017 Jul 16.

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

Background: Acute coronary syndrome (ACS) patients are increasingly older. Conventional prognostic scales include chronological age but do not consider vulnerability. In elderly patients, a frail phenotype represents a better reflection of biological age.

Hypothesis: This study aims to determine the prevalence of frailty and its influence on patients age ≥75 years with ACS.

Methods: Patients age ≥75 years admitted due to type 1 myocardial infarction were included in 2 tertiary hospitals, and clinical data were collected prospectively. Frailty was defined at admission using the previously validated Survey of Health Ageing and Retirement in Europe Frailty Index (SHARE-FI) tool. The primary endpoint was the combination of death or nonfatal myocardial reinfarction during a follow-up of 6 months. Major bleeding (hemoglobin decrease ≥3 g/dL or transfusion needed) and readmission rates were also explored.

Results: A total of 234 consecutive patients were included. Frail patients (40.2%) had a higher-risk profile, based on higher age and comorbidities. On multivariate analysis, frailty was an independent predictor of the combination of death or nonfatal myocardial reinfarction (adjusted hazard ratio [aHR]: 2.54, 95% confidence interval [CI]: 1.12-5.79), an independent predictor of the combination of death, nonfatal myocardial reinfarction, or major bleeding (aHR: 2.14, 95% CI: 1.13-4.04), and an independent predictor of readmission (aHR: 1.80, 95% CI: 1.00-3.22).

Conclusions: Frailty phenotype at admission is common among elderly patients with ACS and is an independent predictor for severe adverse events. It should be considered in future risk-stratification models.
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http://dx.doi.org/10.1002/clc.22749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490378PMC
October 2017

Effects of Ivabradine on Heart Rate and Hemodynamic Parameters in a Swine Model of Cardiogenic Shock.

Rev Esp Cardiol (Engl Ed) 2017 Dec 28;70(12):1139-1141. Epub 2017 Mar 28.

Servicio de Cardiología, Unidad de Investigación del Hospital Ramón y Cajal (IRYCIS)-Universidad Francisco de Vitoria, Madrid, Spain.

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http://dx.doi.org/10.1016/j.rec.2017.03.009DOI Listing
December 2017

Direct oral anticoagulants and cardiovascular prevention in patients with nonvalvular atrial fibrillation.

Expert Opin Pharmacother 2017 Jan 15;18(1):67-77. Epub 2016 Dec 15.

c Jefe de Sección SCA. H.U. Ramón y Cajal , Madrid , Spain.

Introduction: Patients with atrial fibrillation have an increased risk for stroke, systemic embolism and cardiovascular events, including myocardial infarction and cardiovascular death. However, the majority of studies that have analyzed the efficacy of anticoagulants have been focused only on their effects on the risk of stroke. Areas covered: The available evidence about the association between atrial fibrillation and cardiovascular disease as well as the effects of oral anticoagulation on cardiovascular death and myocardial infarction, with a particular focus on direct oral anticoagulants, was updated in this review. Expert opinion: The management of patients with atrial fibrillation should not be limited to the prevention of stroke, but should also include the prevention of cardiovascular events. Despite treatment with vitamin K antagonists, many patients with atrial fibrillation still develop cardiovascular complications, particularly individuals whose anticoagulation is difficult to control. Direct oral anticoagulants overcome the majority of limitations of vitamin K antagonists and compared with warfarin, they lead to a greater reduction in the risk of stroke or systemic embolism, all-cause mortality, and intracranial hemorrhage. Although these drugs can only be compared indirectly, it seems that not all direct oral anticoagulants are equal with regard to the prevention of myocardial infarction.
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http://dx.doi.org/10.1080/14656566.2016.1267140DOI Listing
January 2017

The frailty syndrome and mortality among very old patients with symptomatic severe aortic stenosis under different treatments.

Int J Cardiol 2016 Dec 14;224:125-131. Epub 2016 Sep 14.

Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid/IdiPaz, CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Background: The role of frailty as a prognostic factor in non-selected patients with symptomatic severe aortic stenosis (SAS) is still uncertain. This study aims to examine the association between the frailty syndrome and mortality among very old patients with symptomatic SAS, and to assess whether the association varies with the type of SAS treatment.

Methods And Results: Prospective study of 606 patients aged ≥75years with symptomatic SAS, recruited from February 2010 to January 2015, who were followed up through June 2015. At baseline, frailty was defined as having at least three of the following five criteria: muscle weakness, slow gait speed, low physical activity, exhaustion, and unintentional weight loss. Statistical analyses were performed with multivariate Cox regression. At baseline, 49.3% patients were frail. During a mean follow-up of 98weeks, 35.3% of patients died. The hazard ratio (95% confidence interval) of mortality among frail versus non-frail patients was 1.83 (1.33-2.51). The corresponding results were 1.58 (1.09-2.28) among patients under medical treatment, 3.06 (1.25-7.50) in those with transcatheter aortic valve replacement, and 1.97 (0.83-4.67) in those with surgical aortic valve replacement, p for interaction=0.21. When the frailty criteria were considered separately, mortality was also higher among patients with slow gait speed [1.52 (1.05-2.19)] or low physical activity [1.35 (1.00-1.85)].

Conclusions: Frailty is associated with increased mortality among patients with symptomatic SAS, and this association does not vary with the type of SAS treatment. Future studies evaluating the benefits of different treatments in SAS patients should account for baseline frailty.
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http://dx.doi.org/10.1016/j.ijcard.2016.09.020DOI Listing
December 2016

Impact of thrombus burden on procedural and mid-term outcomes after primary percutaneous coronary intervention.

Coron Artery Dis 2016 May;27(3):169-75

Interventional Cardiology Unit, Department of Cardiology, Ramón y Cajal Hospital, University of Alcalá, Madrid, Spain.

Objective: Angiographic thrombus burden (TB) can be assessed early and enable a decision on intervention. The aim of this study was to analyze its effect on the incidence of cardiac events after a primary percutaneous coronary intervention.

Patients And Methods: We carried out a prospective study of 480 consecutive ST-segment elevation myocardial infarction patients treated by systematic primary percutaneous coronary intervention. Large TB was defined as thrombus length at least 2 vessel diameters or as solid thrombus obtained through catheter aspiration. The primary outcome measure was a composite of death, reinfarction, or target vessel revascularization.

Results: A total of 205 (47%) patients fulfilled the criteria for large TB. These patients were more frequently treated with abciximab (62.0 vs. 35.8%, P<0.001), showed more angiographic complications (26.6 vs. 13.7%, P=0.001), and had larger infarcts (peak troponin I, 74 vs. 50 ng/ml, P=0.015). During a follow-up of 19 ± 5 months, the rates of primary outcome were similar between groups of small and large TB (16.2 vs. 12.8%, hazard ratio: 0.88, 95% confidence interval: 0.46-1.67, P=0.691). There were no differences in the rates of definite stent thrombosis (0.5 vs. 2.2%, P=0.190).

Conclusion: Large TB is associated with larger infarct size, but not with worse mid-term outcomes. Selective use of adjuvant therapies according to TB may be an effective approach to reduce thrombotic complications.
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http://dx.doi.org/10.1097/MCA.0000000000000317DOI Listing
May 2016

Incidence, angiographic features and outcomes of patients presenting with subtle ST-elevation myocardial infarction.

Am Heart J 2014 Dec 16;168(6):884-90. Epub 2014 Sep 16.

Interventional Cardiology Unit, Department of Cardiology, Ramón y Cajal Hospital, University of Alcalá, Madrid, Spain.

Background: Borderline electrocardiograms represent a challenge in ST-segment elevation myocardial infarction (STEMI) management and are associated with inappropriate discharges and delays to intervention.

Objectives: To assess angiographic characteristics and outcomes of patients presenting with subtle ST-elevation (STE) myocardial infarction.

Methods: A total of 504 consecutive patients with suspected STEMI treated by systematic primary percutaneous coronary intervention were prospectively included. Subtle STE was defined as a maximal preinterventional STE of 0.1 to 1 mm. Angiograms were interpreted by investigators unaware of the electrocardiographic data.

Results: The proportion of patients with subtle STE was 18.3%, 86% of them presented with Thrombolysis In Myocardial Infarction flow grade 0/1 and 91% underwent percutaneous coronary intervention. Despite having smaller infarcts, subtle STE patients associated more frequent multivessel disease (57% vs 44%, P = .02) and larger delays to reperfusion. During a follow-up of 19.0 ± 4.9 months, the rates of death or reinfarction were similar among groups (10.0% vs 12.6%, P = .467). Subtle STE was not associated with better outcomes neither in univariate nor after adjustment in a multivariate analysis (adjusted hazard ratio 0.79, 95% CI 0.37-1.69, P = .546).

Conclusions: Subtle STEMI is frequent in clinical practice and is usually associated with acute total coronary occlusion. Therefore, it should be diagnosed and treated in the same expeditiously manner as marked STEMI.
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http://dx.doi.org/10.1016/j.ahj.2014.08.009DOI Listing
December 2014

Myocardial ischemia evaluation with dual-source computed tomography: comparison with magnetic resonance imaging.

Rev Esp Cardiol (Engl Ed) 2013 Nov 12;66(11):864-70. Epub 2013 Sep 12.

Servicio de Cardiología, Hospital POVISA, Vigo, Pontevedra, Spain.

Introduction And Objectives: Computed tomography does not accurately determine which coronary lesions lead to myocardial ischemia and consequently further tests are required to evaluate ischemia induction. The aim of this study was to compare diagnostic accuracy between dual-energy computed tomography and magnetic resonance imaging in the assessment of myocardial perfusion and viability in patients suspected of coronary artery disease.

Methods: A prospective study was performed in 56 consecutive patients (39 men [69.6%]; mean age [standard deviation], 63 [10]; range, 23-81). Computed tomography was performed with the following protocol: 1, adenosine stress perfusion; 2, coronary angiography; and 3, delayed enhancement. Magnetic resonance imaging for the evaluation of stress perfusion and delayed enhancement was performed within 30 days. Two observers in consensus analyzed the perfusion and delayed enhancement images.

Results: We studied 952 myocardial segments and 168 vascular territories. In a per-segment analysis, the sensitivity, specificity, and positive and negative predictive values of computed tomography compared with magnetic resonance were 76%, 99%, 89%, and 98% for perfusion defects, and 64%, 99%, 82%, and 99% for delayed enhancement, respectively. In a per-vascular territory analysis, the same measures were 78%, 97%, 86%, and 95% for perfusion defects, and 72%, 99%, 93%, and 97% for delayed enhancement, respectively. The mean radiation dose was 8.2 (2) mSv.

Conclusions: Dual-source computed tomography may allow accurate and concomitant evaluation of perfusion defects and myocardial viability and analysis of coronary anatomy.
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http://dx.doi.org/10.1016/j.rec.2013.05.026DOI Listing
November 2013

Update in cardiology: Vascular risk and cardiac rehabilitation.

Rev Esp Cardiol (Engl Ed) 2013 Feb 23;66(2):124-30. Epub 2012 Dec 23.

Servicio de Cardiología, Hospital Puerta de Hierro, Majadahonda, Madrid, Spain.

Atherosclerotic cardiovascular disease remains the major cause of premature death in developed and developing countries. Nevertheless, surveys show that most patients still do not achieve the lifestyles, risk factor levels, and therapeutic targets recommended in primary and secondary prevention. The present update reflects the most recent novelties in risk classification and estimation of risk and documents the latest changes in fields such as smoking, diet and nutrition, physical activity, lipids, hypertension, diabetes, and cardiovascular rehabilitation, based on experimental trials and population-based observational studies.
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http://dx.doi.org/10.1016/j.rec.2012.10.007DOI Listing
February 2013

A campaign for information and diagnosis of atrial fibrillation: "pulse week".

Rev Esp Cardiol (Engl Ed) 2013 Jan 8;66(1):34-8. Epub 2012 Sep 8.

Servicio de Cardiología, Hospital Povisa, Vigo, Pontevedra, España.

Introduction And Objectives: Atrial fibrillation occurs in 5%-15% of elderly patients and causes one-fourth to one-fifth of all cerebrovascular events. These patients are frequently asymptomatic. We conducted a public campaign aiming to evaluate the effectiveness of a program for information on and diagnosis of atrial fibrillation in individuals aged 65 years old or more from the primary care perspective.

Methods: We sent letters containing informative materials and an invitation to attend a special nurse appointment to all individuals≥65 years old, without a previous diagnosis of atrial fibrillation or flutter. Patients were from 3 specific areas in Pontevedra province. The procedures were performed according to a specially designed program called "Pulse Week" within 5 working days. A group of trained nurses obtained a brief medical history and performed pulse palpation for 15 s and blood pressure measurement. A complete 12-lead electrocardiogram was performed if arrhythmic pulsations were detected.

Results: A total of 8869 letters were sent. During the specified week, 1532 individuals were evaluated (877 women); the mean age was 72.5 (6.5) years old, 833 had hypertension (54%), 232 had diabetes (15%), 61 had previous stroke (4%) and 88 had had a myocardial infarction (6%). Electrocardiograms were performed in 187 patients. There were 17 patients with newly diagnosed atrial fibrillation.

Conclusions: A public, 5-day campaign based on pulse palpation and targeting elderly individuals had little impact on the detection of new cases of atrial fibrillation in our environment.
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http://dx.doi.org/10.1016/j.recesp.2012.05.012DOI Listing
January 2013

Assessment of silent microembolism by magnetic resonance imaging after cardioversion in atrial fibrillation.

Rev Esp Cardiol (Engl Ed) 2012 Feb 5;65(2):139-42. Epub 2011 Dec 5.

Servicio de Cardiología, Hospital Povisa, Vigo, Pontevedra, Spain.

Introduction And Objectives: To study electrical cardioversion in patients with atrial fibrillation as a potential cause of acute ischemic brain lesions.

Methods: We performed prospective analysis of 62 consecutive patients (62 [10] years, 16 female). All of them were anticoagulated for at least 3 weeks with an international normalized ratio of 2.69 (0.66). In all cases a magnetic resonance imaging of the brain was performed before and 24h after the cardioversion, including diffusion-weighted sequences. A neurological exploration was also performed before and after the procedure, using the modified Ictus on the National Institute of Health Stroke Scale and the modified Rankin scale. Written informed consent was obtained in all cases.

Results: Of the 62 patients, 51 (85%) reverted to sinus rhythm. The neurological examination showed no changes after cardioversion. The pre-procedure magnetic resonance imaging showed microvascular disease in 35 (56%), including 2 patients with known cerebrovascular disease, and did not depict new clinically silent ischemic areas after cardioversion.

Conclusions: After electrical cardioversion no acute ischemic lesions in the brain nor alteration in the neurological scales were found. Nevertheless, in 35 patients (56%) with persistent atrial fibrillation, the magnetic resonance imaging showed clinically silent ischemic lesions.
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http://dx.doi.org/10.1016/j.recesp.2011.08.017DOI Listing
February 2012

Drug-eluting stent thrombosis: results from the multicenter Spanish registry ESTROFA (Estudio ESpañol sobre TROmbosis de stents FArmacoactivos).

J Am Coll Cardiol 2008 Mar;51(10):986-90

Hospital Marques de Valdecilla, Santander, Spain.

Objectives: This study sought to assess the incidence, predictors, and outcome of drug-eluting stent(DES) thrombosis in real-world clinical practice.

Background: The DES thromboses in randomized trials could not be comparable to those observed in clinical practice, frequently including off-label indications.

Methods: We designed a large-scale, nonindustry-linked multicentered registry, with 20 centers in Spain. The participant centers provided follow-up data for their patients treated with DES, reporting a detailed standardized form in the event of any angiography-documented DES-associated thrombosis occurring.

Results: Of 23,500 patients treated with DES, definite stent thrombosis(ST) developed in 301: 24 acute, 125 subacute, and 152 late. Of the late, 62 occurred >1 year(very late ST). The cumulative incidence was 2% at 3 years. Antiplatelet treatment had been discontinued in 95 cases(31.6%). No differences in incidences were found among stent types. Independent predictors for subacute ST analyzed in a subgroup of 14,120 cases were diabetes, renal failure, acute coronary syndrome, ST-segment elevation myocardial infarction, stent length, and left anterior descending artery stenting, and for late ST were ST-segment elevation myocardial infarction, stenting in left anterior descending artery, and stent length. Mortality at 1-year follow-up was 16% and ST recurrence 4.6%. Older age, left ventricular ejection fraction <45%, nonrestoration of Thrombolysis In Myocardial Infarction flow grade 3, and additional stenting were independent predictors for mortality.

Conclusions: The cumulative incidence of ST after DES implantation was 2% at 3 years. No differences were found among stent types. Patient profiles differed between early and late ST. Short-term prognosis is poor, especially when restoration of normal flow fails.
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http://dx.doi.org/10.1016/j.jacc.2007.10.057DOI Listing
March 2008

The learning curve for transradial procedures.

Indian Heart J 2008 Jan-Feb;60(1 Suppl A):A14-7

Servicio de Cardiologia, Hospital Povisa, C, Salamanca 5, Vigo, Pontevedra, CP 36211, Spain.

The learning curve for transradial procedure represents a major limitation for the widespread use of the technique. The rate of procedural failure can be as high as 10-16% during the first 30 or 40 cases. With appropriate training, persistence, and attention to the selection of patients and devices, most interventionalists manage to gain confidence after the first 100-200 cases.
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May 2009
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