Rocío Toro

Medicine Department, School of Medicine of Cadíz · Medicine

Excess lipid accumulation in the heart is associated with lipotoxicity and cardiac dysfunction due to excessive fatty acid oxidation. Peroxisome proliferator-activated receptor gamma (PPARγ) modulates the expression of key molecules involved in the FA metabolic pathway. Cardiomyocyte-specific overexpression of PPARγ causes dilated cardiomyopathy as...

Background/Objectives: Inherited arrhythmogenic syndromes comprise a heterogenic group of genetic entities that lead to malignant arrhythmias and sudden cardiac death. Genetic testing has become crucial to understand the disease etiology and allow for the early identification of relatives at risk; however, it requires an accurate interpretation of...

Genetic testing is recommended in the diagnosis of short QT syndrome. This rare inherited lethal entity is characterized by structural normal hearts with short QT intervals in the electrocardiogram. Few families diagnosed with this arrhythmogenic disease have been reported worldwide so far, impeding a comprehensive understanding of this syndrome. U...

Arrhythmogenic cardiomyopathy is an inherited entity characterized by irregular cell–cell adhesion, cardiomyocyte death and fibro-fatty replacement of ventricular myocytes, leading to malignant ventricular arrythmias, contractile dysfunction and sudden cardiac death. Pathogenic variants in genes that encode desmosome are the predominant cause of ar...

Sudden cardiac death is a rare but socially devastating event, especially if occurs in young people. Usually, this unexpected lethal event occurs during or just after exercise. One of the leading causes of sudden cardiac death is inherited arrhythmogenic syndromes, a group of genetic entities characterised by incomplete penetrance and variable expr...

Dilated cardiomyopathy (DCM) encompasses various acquired or genetic diseases sharing a common phenotype. The understanding of pathogenetic mechanisms and the determination of the functional effects of each etiology may allow for tailoring different therapeutic strategies. MicroRNAs (miRNAs) have emerged as key regulators in cardiovascular diseases...

Dilated cardiomyopathy is a heterogeneous entity that leads to heart failure and malignant arrhythmias. Nearly 50% of cases are inherited; therefore, genetic analysis is crucial to unravel the cause and for the early identification of carriers at risk. A large number of variants remain classified as ambiguous, impeding an actionable clinical transl...

A wide range of approaches can be used to detect micro RNA (miRNA)–target gene pairs (mTPs) from expression data, differing in the ways the gene and miRNA expression profiles are calculated, combined and correlated. However, there is no clear consensus on which is the best approach across all datasets. Here, we have implemented multiple strategies...

This chapter is developed with the intention of discussing the use of implantable defibrillator cardioverters (ICDs) in patients with left ventricular assist devices (LVADs). LVADs have become the standard treatment for patients with advanced heart failure who require prolonged mechanical circulatory support as a bridge to transplantation or as des...

Recognizing symptoms in elderly patients with severe aortic stenosis (AS) can be a challenge. Serum biomarkers such as Galectin-3 or N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are involved in remodeling and heart failure (HF) development and could support the diagnosis of AS. We set out to test the usefulness of NT-proBNP and Gale...

Arrhythmogenic cardiomyopathy is a rare inherited entity, characterized by a progressive fibro-fatty replacement of the myocardium. It leads to malignant arrhythmias and a high risk of sudden cardiac death. Incomplete penetrance and variable expressivity are hallmarks of this arrhythmogenic cardiac disease, where the first manifestation may be sync...

In the forensic medicine field, molecular autopsy is the post-mortem genetic analysis performed to attempt to unravel the cause of decease in cases remaining unexplained after a comprehensive forensic autopsy. This negative autopsy, classified as negative or non-conclusive, usually occurs in young population. In these cases, in which the cause of d...

Sudden death cases in the young population remain without a conclusive cause of decease in almost 40% of cases. In these situations, cardiac arrhythmia of genetic origin is suspected as the most plausible cause of death. Molecular autopsy may reveal a genetic defect in up to 20% of families. Most than 80% of rare variants remain classified with an...

Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by left ventricular or biventricular dilation and systolic dysfunction. In most cases, DCM is progressive, leading to heart failure (HF) and death. This cardiomyopathy has been considered a common and final phenotype of several entities. DCM occurs when cellular pathways fail to mai...

Objective There is increased interest in studying ATTR-CA, a pathology that primarily affects patients of geriatric age and is frequently underdiagnosed. We aim to establish the prevalence of ATTR-CA in a cohort of patients with a history of HFpEF and to describe its characteristics. Methods We conducted a prospective observational study. Patients...

The aim of this study was to assess whether the infection by SARS-CoV-2 has significantly influenced physical activity, diet, alcohol, and drug consumption habits, as well as the quality of life of students of the bachelor’s degree in Physical Activity and Sports Sciences. For this purpose, an online survey was conducted, which included socio-demog...

Atherosclerotic cardiovascular diseases (ASCVD) are the leading cause of morbidity and mortality in Western societies. Statins are the first-choice therapy for dislipidemias and are considered the cornerstone of ASCVD. Statin-associated muscle symptoms are the main reason for dropout of this treatment. There is an urgent need to identify new biomar...

Background: Previous studies showed conflicting results regarding the contribution of coronary collateral circulation (CCC) to myocardial perfusion and function in the setting of myocardial infarction (MI). In the primary angioplasty era, the role of CCC in these studies may have been influenced by the effect of early reperfusion. The true impact...

The titin gene (TTN) is associated with several diseases, including inherited arrhythmias. Most of these diagnoses are attributed to rare TTN variants encoding truncated forms, but missense variants represent a diagnostic challenge for clinical genetics. The proper interpretation of genetic data is critical for translation into the clinical setting...

Oxidative stress, defined as the excess production of reactive oxygen species (ROS) relative to antioxidant defense, plays a significant role in the development of cardiovascular diseases. Endoplasmic reticulum (ER) stress has emerged as an important source of ROS and its modulation could be cardioprotective. Previously, we demonstrated that miR-16...

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure. The multidisciplinary nature of testing — involving genetics, imaging, or cardiovascular techniques — makes its diagnosis challenging. Novel and reliable biomarkers are needed for early identification and tailored personalized management. Peripheral circular RNAs (circRNA...

Background: Elderly COVID-19 patients have a high risk of pulmonary embolism (PE), but factors that predict PE are unknown in this population. This study assessed the Wells and revised Geneva scoring systems as predictors of PE and their relationships with D-dimer (DD) in this population. Methods: This was a longitudinal, observational study tha...

A proper interpretation of the pathogenicity of rare variants is crucial before clinical translation. Ongoing addition of new data may modify previous variant classifications; however, how often a reanalysis is necessary remains undefined. We aimed to extensively reanalyze rare variants associated with inherited channelopathies originally classifie...

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure. The multidisciplinary nature of testing - involving genetics, imaging, or cardiovascular techniques - makes its diagnosis challenging. Novel and reliable biomarkers are needed for early identification and tailored personalized management. Peripheral circular RNAs (circRNA...

Background: The risk of pulmonary embolism (PE) has not been studied in older patients affected by COVID-19. We aimed to assess PE incidence and risk factors in a population of older patients infected with SARS-CoV-2. Methods: An ambispective, observational cohort study. A total of 305 patients ≥ 75 years old had the SARS-CoV-2 infection from Ma...

Introduction Acute total occlusion of the left main coronary artery (ATOLMA) usually leads to a catastrophic presentation. Prediction of ATOLMA by electrocardiogram (ECG) may contribute to early detection and reperfusion. Limited data have been reported previously. This study aims to identify the admission 12‑leads ECG features that can predict the...

Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, and the second most frequent congenital malfor...

The left ventricular (LV) ejection fraction (EF) is key to prognosis in dilated cardiomyopathy (DCM). Circulating microRNAs have emerged as reliable biomarkers for heart diseases, included DCM. Clinicians need improved tools for greater clarification of DCM EF categorization, to identify high-risk patients. Thus, we investigated whether microRNA pr...

A proper interpretation of the pathogenicity of rare variants is crucial before clinical translation. Ongoing addition of new data may modify previous variant classifications; however, how often a reanalysis is necessary remains undefined. We aimed to extensively reanalyze rare variants associated with inherited channelopathies originally classifie...

Genetic interpretation of rare variants associated with arrhythmogenic cardiomyopathy (ACM) is essential due to their diagnostic implications. New data may relabel previous variant classifications, but how often reanalysis is necessary remains undefined. Five years ago, 39 rare ACM-related variants were identified in patients with features of cardi...

The RBM20 gene encodes the muscle-specific splicing factor RNA-binding motif 20, a regulator of heart-specific alternative splicing. Nearly 40 potentially deleterious variants in RBM20 have been reported in the last ten years, being found to be associated with highly arrhythmogenic events in familial dilated cardiomyopathy. Frequently, malignant ar...

Resumen Introducción y objetivos Los niveles del microRNA-16-5p (miR-16) aumentan en la cardiopatía isquémica y modelos animales de miocardiopatía dilatada isquémica (MCDi) vinculándolo con la apoptosis. Proponemos determinar el papel del miR-16 en la respuesta adaptativa celular asociada al estrés del retículo endoplasmático (RE) y la autofagia e...

Introduction and objectives The expression levels of microRNA-16-5p (miR-16) are upregulated in ischemic cardiomyopathy and in animal models of ischemic dilated cardiomyopathy (iDCM), inducing myocardial apoptosis. We investigated the role of miR-16 in the adaptive cellular response associated with endoplasmic reticulum (ER) stress and autophagy in...

Inherited arrhythmogenic syndromes are the primary cause of unexpected lethal cardiac episodes in young people. It is possible that the first sign of the condition may be sudden death. Inherited arrhythmogenic syndromes are caused by genetic defects that may be analyzed using different technical approaches. A genetic alteration may be used as a mar...

Background Accurate interpretation of rare genetic variants is a challenge for clinical translation. Updates in recommendations for rare variant classification require the reanalysis and reclassification. We aim to perform an exhaustive re-analysis of rare variants associated with inherited arrhythmogenic syndromes, which were classified ten years...

Resumen Introducción y objetivos El pronóstico de la estenosis aórtica (EAo) grave asintomática en la población anciana, que a menudo asocia fragilidad y comorbilidades no ha sido estudiado. Se propuso analizar qué factores podrían influir en la mortalidad precoz esta población. Métodos Estudio ambispectivo de cohortes en 104 pacientes con edad ≥...

Etiology-based diagnosis of dilated cardiomyopathy (DCM) is challenging. We evaluated whether peripheral microRNAs (miRNAs) could be used to characterize the DCM etiology. We investigated the miRNA plasma profiles of 254 subjects that comprised 5 groups: Healthy subjects (n = 70), idiopathic DCM patients (n = 55), ischemic DCM patients (n = 60) and...

Funding Acknowledgements Alfonso X El Sabio University Introduction Familial dilated cardiomyopathy (fDCM) represents 20% to 30% of idiopathic DCM (iDCM) ethiology. The assessment of cardiac function of these patients is awfully complex. Usually, myocardial fiber damages can not be detected in the early DCM stages. In this sense echocardiogram cou...

Background The carcinoid syndrome is characterized by extensive and several clinical manifestations. The diarrhea, the cutaneous flushing are the most frequents symptoms while cardiac manifestations (carcinoid heart disease) (CHD) occurs in a mean of 40%. Nowadays, the number of cases of CHD is lower than 20%, as a consequence of the widespread use...

Funding Acknowledgements VII Convocatoria del Banco de Santander and Alfonso X el Sabio University. Background Detection of symptoms in geriatric population with aortic stenosis (AS) is challenging, especially when they associate other comorbidities or frailty. Left ventricular global longitudinal strain (GLS) occurs before left ventricular ejecti...

Introduction and objectives: The prognosis of asymptomatic severe aortic stenosis (AS) has not been widely documented in elderly patients who are frequently frail and have comorbidities. We sought to analyze the factors that influence early mortality in geriatric patients with asymptomatic severe AS. Methods: This ambispective cohort study inclu...

Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by ventricular dilation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease. This cardiac disorder is a major health problem due to its high prevalence, morbidity, and mortality. DCM is a complex disease with a common phenotype but het...

A new familial dilated cardiomyopathy (FDCM) was found related to mutations in BAG3 gene. MicroRNAs (miRNAs) represent new targets of FDCM, although no studies have assessed clinical association between Bcl2-associated athanogene 3 (BAG3)-related DCM and miRNAs. Here, we studied whether a clinical association between BAG3-related FDCM and circulati...

PurposeDegenerative aortic stenosis has become a new valvular epidemic in the last few decades due to its high prevalence in the geriatric population. We sought to analyse factors that could influence earlier hospitalization for congestive heart failure in geriatric patients with moderate–severe degenerative aortic stenosis. Methods This investigat...

The Spanish Arteriosclerosis Society has accredited more than 70 lipid units across the country. The main criteria for patients to be referred to these units are presented. These are not only grouped by the type of dyslipidaemia or the lipid levels, but also on certain clinical characteristics suggesting primary hyperlipidaemia, a complex diagnosis...

Background: The BAG3 (BLC2-associated athanogene 3) gene codes for an antiapoptotic protein located on the sarcomere Z-disc. Mutations in BAG3 are associated with dilated cardiomyopathy (DCM), but only a small number of cases have been reported to date, and the natural history of BAG3 cardiomyopathy is poorly understood. Objectives: This study s...

Lack of endothelial nitric oxide causes endothelial dysfunction and circulating monocyte infiltration, contributing to systemic atheroma plaque formation in arterial territories. Among the different inflammatory products, macrophage-derived foam cells and smooth muscle cells synthesize matrix metalloproteinases (MMPs), playing a pivotal role in ear...

Lamin A/C gene (LMNA)-related familial dilated cardiomyopathy (fDCM) is an aggressive heart disease that often leads to transplantation and sudden death. The aim of our study was to evaluate the circulating microRNA (miRNA) profiles of patients with LMNA pathogenic mutations. The study population (N = 75) included (i) patients with pathogenic LMNA...

There is overwhelming evidence that regular exercise training is protective against cardiovascular disease (CVD), the main cause of death worldwide. Despite the benefits of exercise, the intricacies of their underlying molecular mechanisms remain largely unknown. Non-coding RNAs (ncRNAs) have been recognized as a major regulatory network governing...

Objective: ILK (integrin-linked kinase) plays a key role in controlling vasomotor tone and is decreased in atherosclerosis. The objective of this study is to test whether nitric oxide (NO) regulates ILK in vascular remodeling. Approach and results: We found a striking correlation between increased levels of inducible nitric oxide and decreased I...

Background: A new familial dilated cardiomyopathy (DCM) was recently found related to mutations in the antiapoptotic BAG3 gene. MicroRNAs (miRNAs) are short non-coding RNAs playing significant roles in cardiac disease, including DCM, thus representing new potential targets of treatment. However, no previous study has evaluated the clinical associat...

Comprobar los resultados de un entrenamiento en habilidad para realizar ecocardioscopias para oncólogos por parte de cardiólogos y estudiar la variabilidad en las mediciones y la significación clínica de esa variabilidad.

Pioglitazone is a thiazolidinedione insulin sensitizer that improves left ventricle (LV) diastolic function in patients with type 2 diabetes mellitus (T2DM) [(1)][1]. Unfortunately, the clinical use of pioglitazone is limited by the risk of adverse effects [(2)][2]. Predictive tools are essential to

Contractile dysfunction is underdiagnosed in early stages of diabetic cardiomyopathy. We evaluated the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers of subclinical cardiac abnormalities in type 2 diabetes. Forty-eight men with well-controlled type 2 diabetes and 12 healthy age-matched volunteers were enrolled in the study. L...

Idiopathic dilated cardiomyopathy has become one of the most prevalent inherited cardiomyopathies over the past decades. Genetic screening of first-degree relatives has revealed that 30–50% of the cases have a familial origin. Similar to other heart diseases, familial dilated cardiomyopathy is characterized by a high genetic heterogeneity that comp...

Dilated cardiomyopathy is a rare cardiac disease characterized by left ventricular dilatation and systolic dysfunction leading to heart failure and sudden cardiac death. Currently, despite several conditions have been reported as aetiologies of the disease, a large number of cases remain classified as idiopathic. Recent studies determine that nearl...