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Pre-existing coronary artery disease (CAD), and thrombotic, inflammatory, or virus infectivity response phenomena have been associated with COVID-19 disease severity. However, the association of candidate single nucleotide variants (SNVs) related to mechanisms of COVID-19 complications has been seldom analysed. Our aim was to test and validate the effect of candidate SNVs on COVID-19 severity. CARGENCORS (CARdiovascular GENetic risk score for Risk Stratification of patients positive for SARS-CoV-2 [COVID-19] virus) is an age- and sex-matched case-control study with 818 COVID-19 cases hospitalized with hypoxemia, and 1636 controls with COVID-19 treated at home. The association between severity and SNVs related to CAD (n = 32), inflammation (n = 19), thrombosis (n = 14), virus infectivity (n = 11), and two published to be related to COVID-19 severity was tested with adjusted logistic regression models. Two external independent cohorts were used for meta-analysis (SCOURGE and UK Biobank). After adjustment for potential confounders, 14 new SNVs were associated with COVID-19 severity in the CARGENCORS Study. These SNVs were related to CAD (n = 10), thrombosis (n = 2), and inflammation (n = 2). We also confirmed eight SNVs previously related to severe COVID-19 and virus infectivity. The meta-analysis showed five SNVs associated with severe COVID-19 in adjusted analyses (rs11385942, rs1561198, rs6632704, rs6629110, and rs12329760). We identified 14 novel SNVs and confirmed eight previously related to COVID-19 severity in the CARGENCORS data. In the meta-analysis, five SNVs were significantly associated to COVID-19 severity, one of them previously related to CAD.
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COVID-19 , Doença da Artéria Coronariana , Trombose , Humanos , Estudos de Casos e Controles , SARS-CoV-2/genética , InflamaçãoRESUMO
Valvulopathies are among the most common cardiovascular diseases, significantly increasing morbidity and mortality. While many valvular heart diseases are acquired later in life, an important genetic component has been described, particularly in mitral valve prolapse and bicuspid aortic valve. These conditions can arise secondary to genetic syndromes such as Marfan disease (associated with mitral valve prolapse) or Turner syndrome (linked to the bicuspid aortic valve) or may manifest in a non-syndromic form. When cardiac valve disease is the primary cause, it can appear in a familial clustering or sporadically, with a clear genetic component. The identification of new genes, regulatory elements, post-transcriptional modifications, and molecular pathways is crucial to identify at-risk familial carriers and for developing novel therapeutic strategies. In the present review we will discuss the numerous genetic contributors of heart valve diseases.
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Treatment decisions in the context of severe aortic stenosis (AS) associated with other valvular heart diseases (VHDs) have become a major challenge in recent years. Transcatheter aortic valve replacement (TAVR) in AS has increased significantly in younger patients with lower surgical risk, which has complicated the choice of the best treatment in cases of other associated valvulopathies. The most frequently associated lesions in this clinical scenario are mitral regurgitation (MR), mitral stenosis, and tricuspid regurgitation (TR). Furthermore, it should be noted that different percutaneous techniques are now available to accommodate any associated valvulopathies, which has considerably broadened the range of therapeutic options. The management of AS treated in isolation, especially by TAVR, has also shown that many cases of significant MR or TR are substantially reduced without any intervention. However, although some parameters have been described as potential risk factors in predicting the poor outcome of untreated VHDs, which cases will progress in a clinically more aggressive way remains uncertain. This review aimed to evaluate the most recent publications to provide the pathophysiology and prognosis of severe AS associated with other significant VHDs and to evaluate the best invasive therapeutic approach depending on the associated valvular disease.
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Sudden infant death syndrome (SIDS) is still the leading cause of death for newborns in developed countries. The pathophysiological mechanisms have not been fully clarified, but in some of SIDS cases variants of genes associated with inherited cardiac conditions are found. In this study, an analysis of SCD-related genes was performed to determine the prevalence of rare pathogenic (P) or likely pathogenic (LP) variants that could provide an unambiguous explanation for the fatal event. A cohort of 76 SIDS cases underwent Next-Generation Sequencing (NGS) analysis with a custom panel of SCD-related genes. Rare variants were classified according to the guidelines provided by the American College of Medical Genetics and Genomics (ACMG) and the specifications of the ClinGen association. Post-mortem genetic testing identified 50 (65.8%) carriers of at least one variant in SCD genes. 104 rare genetic variants were found, 65.4% in genes encoding structural proteins. Only 4 out of 76 cases (5.3%) hosted at least a P or LP variant found in genes with structural or structural/arrhythmogenic functions (SLC22A5, SCN5A, MYL3and TTN). 99 variants were classified as of uncertain significance (VUS). The difference in the distribution of variants between gene groups by function was not statistically significant (chi square, p = 0,219). Despite this, most of the variants concerned structural genes that were supposed to have a close interaction with ion channels, thus providing an explanation for the arrhythmic event. Segregation analysis, reclassification of VUS variants and identification of new associated genes could clarify the implications of the current findings.
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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 translation. Our goal was to perform a comprehensive update of variants previously classified with an ambiguous role, applying a new algorithm of already available tools. In a cohort of 65 cases diagnosed with dilated cardiomyopathy, a total of 125 genetic variants were classified as ambiguous. Our reanalysis resulted in the reclassification of 12% of variants from an unknown to likely benign or likely pathogenic role, due to improved population frequencies. For all the remaining ambiguous variants, we used our algorithm; 60.9% showed a potential but not confirmed deleterious role, and 24.5% showed a potential benign role. Periodically updating the population frequencies is a cheap and fast action, making it possible to clarify the role of ambiguous variants. Here, we perform a comprehensive reanalysis to help to clarify the role of most of ambiguous variants. Our specific algorithms facilitate genetic interpretation in dilated cardiomyopathy.
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Cardiomiopatia Dilatada , Insuficiência Cardíaca , Humanos , Cardiomiopatia Dilatada/genética , Algoritmos , Frequência do GeneRESUMO
INTRODUCTION: Cardiogenic shock is associated with high in-hospital morbidity and mortality. Improvements in this care process could lead to better outcomes. METHODS: This retrospective study of patients with cardiogenic shock compared two periods: no specific program to address cardiogenic shock and implementation of a cardiogenic shock program. This program included the establishment of a multidisciplinary team (shock team), early alert to the transplant hospital, initiation of a ventricular assist extracorporeal membrane oxygenation (ECMO) program, and extension of continuous care by acute cardiovascular care specialists. The primary objective was to analyse whether there were differences between in-hospital mortality and mortality during follow-up. Predictors of in-hospital mortality were examined as a secondary objective. RESULTS: A total of 139 patients were enrolled: 69 of them in the previous period and 70 in the cardiogenic shock program period. There was a significant reduction in in-hospital mortality (55.1% vs 37.1%; p=0.03) and mortality during follow-up (62.7% vs 44.6%; p=0.03) in the second period. Diabetes mellitus, ejection fraction, out-of-hospital cardiac arrest, and implementation of the cardiogenic shock program were independent predictors of in-hospital mortality. CONCLUSIONS: The implementation of a comprehensive cardiogenic shock program in a non-transplanting hospital improved in-hospital and follow-up mortality of patients in cardiogenic shock.
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Oxigenação por Membrana Extracorpórea , Parada Cardíaca Extra-Hospitalar , Humanos , Choque Cardiogênico , Estudos Retrospectivos , Mortalidade Hospitalar , Oxigenação por Membrana Extracorpórea/efeitos adversosRESUMO
BACKGROUND: Elevated glycated hemoglobin (HbA1c) is associated with a higher burden of subclinical atherosclerosis (SA). However, the association with SA of earlier insulin resistance markers is poorly understood. The study assessed the association between the homeostatic model assessment of insulin resistance index (HOMA-IR) and SA in addition to the effect of cardiovascular risk factors (CVRFs) in individuals with normal HbA1c. METHODS: A cohort of 3,741 middle-aged individuals from the Progression of Early Subclinical Atherosclerosis (PESA) study with basal HbA1c < 6.0% (< 42 mmol/mol) and no known CV disease underwent extensive imaging (multiterritorial vascular ultrasound and coronary artery calcium score, CACS) to assess the presence, burden, and extent of SA. RESULTS: Individuals with higher HOMA-IR values had higher rates of CVRFs. HOMA-IR showed a direct association with the multiterritorial extent of SA and CACS (p < 0.001) and with global plaque volume measured by 3-dimensional vascular ultrasound (p < 0.001). After adjusting for key CVRFs and HbA1c, HOMA-IR values ≥ 3 were associated with both the multiterritorial extent of SA (odds ratio 1.41; 95%CI: 1.01 to 1.95, p = 0.041) and CACS > 0 (odds ratio 1.74; 95%CI: 1.20 to 2.54, p = 0.004), as compared with the HOMA-IR < 2 (the reference HOMA-IR category). In a stratified analysis, this association remained significant in individuals with a low-to-moderate SCORE2 risk estimate (75.6% of the cohort) but not in high-risk individuals. CONCLUSIONS: The use of HOMA-IR identified low-risk individuals with a higher burden of SA, after adjusting for the effects of key traditional CVRFs and HbA1c. HOMA-IR is a simple measure that could facilitate earlier implementation of primary CV prevention strategies in clinical practice.
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Aterosclerose , Resistência à Insulina , Placa Aterosclerótica , Pessoa de Meia-Idade , Humanos , Hemoglobinas Glicadas , Fatores de Risco , Aterosclerose/diagnóstico por imagem , Aterosclerose/epidemiologiaRESUMO
Cancer and its treatments affect cardiovascular (CV) health, including an increased risk of CV death, decreased cardiorespiratory fitness (CRF), and cardiac dysfunction. Moreover, cancer-related fatigue and worse quality of life (QoL) are highly prevalent adverse effects experienced by patients during treatment and can persist years after therapy ends. Physical exercise has been proposed as a strategy to improve different aspects of life of cancer patients, and is recommended as a therapy in cardio-oncology guidelines. Exercise interventions reduce fatigue and improve QoL in patients with both solid tumors and hematological malignancies, although there is a lack of awareness of exercise recommendations, timing, and referral to such programs. New evidence indicates that physical activities improve CRF, which can lead to a reduction in CV mortality. Furthermore, cardiac dysfunction is a side effect of many oncological treatments, which may be mitigated by exercise interventions according to preclinical studies and recent publications. Nevertheless, specific physical exercise programs are not widely used in cancer patients. Thus, the goal of this review was to describe the current evidence on the benefits of exercise in cancer patients, the gaps that remain, and an approach to exercise prescription.
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Autopsia , Humanos , Tamanho do Órgão , Miocárdio/patologia , Patologia Legal , Coração/diagnóstico por imagemRESUMO
Inherited cardiovascular diseases are rare diseases that are difficult to diagnose by non-expert professionals. Genetic analyses play a key role in the diagnosis of these diseases, in which the identification of a pathogenic genetic variant is often a diagnostic criterion. Therefore, genetic variant classification and routine reinterpretation as data become available represent one of the main challenges associated with genetic analyses. Using the genetic variants identified in an inherited cardiovascular diseases unit during a 10-year period, the objectives of this study were: 1) to evaluate the impact of genetic variant reinterpretation, 2) to compare the reclassification rates between different cohorts of cardiac channelopathies and cardiomyopathies, and 3) to establish the most appropriate periodicity for genetic variant reinterpretation. All the evaluated cohorts (full cohort of inherited cardiovascular diseases, cardiomyopathies, cardiac channelopathies, hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic cardiomyopathy, Brugada syndrome, long QT syndrome and catecholaminergic polymorphic ventricular tachycardia) showed reclassification rates above 25%, showing even higher reclassification rates when there is definitive evidence of the association between the gene and the disease in the cardiac channelopathies. Evaluation of genetic variant reclassification rates based on the year of the initial classification showed that the most appropriate frequency for the reinterpretation would be 2 years, with the possibility of a more frequent reinterpretation if deemed convenient. To keep genetic variant classifications up to date, genetic counsellors play a critical role in the reinterpretation process, providing clinical evidence that genetic diagnostic laboratories often do not have at their disposal and communicating changes in classification and the potential implications of these reclassifications to patients and relatives.
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Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/diagnóstico , Canalopatias/genética , Canalopatias/diagnóstico , Testes Genéticos/métodos , Variação Genética , Cardiomiopatias/genética , Cardiomiopatias/diagnóstico , Síndrome do QT Longo/genética , Síndrome do QT Longo/diagnóstico , Síndrome de Brugada/genética , Síndrome de Brugada/diagnósticoRESUMO
OBJECTIVE: This study aimed to provide a long-term follow-up of PRKAG2 syndrome and describe the new phenotypic aspects of the condition. PRKAG2 syndrome is a rare autosomal-dominant glycogen storage disease characterized by cardiac hypertrophy, ventricular pre-excitation, and conduction system disease. Fatal arrhythmias occur frequently. METHODS: A family cohort of 66 participants was recruited. Clinical and genetic analyses were performed. RESULTS: Median age of 36.97±17.28 years, with 69.9% being men. Nineteen subjects carried the deleterious variant p.K290I of the PRKAG2 gene. This group experienced many malignant events, including eight pacemaker implants, three sudden cardiac deaths, five aborted cardiac arrests, four strokes, four premature neonatal deaths, two spontaneous abortions, five forceps deliveries, and 12 cesarean procedures. Extracardiac involvement, such as in neurocognitive and psychiatric disorders, has been observed only in carriers of mutations. Palpitations, Syncope, atrial fibrillation, atrial flutter, sinus pauses, and bradycardia were strongly and significantly associated with major or severe adverse events (sudden cardiac death, aborted cardiac arrest, pacemaker use, stroke, and congestive heart failure). Early diagnosis and intervention through antiarrhythmic drugs, anticoagulation, pacemaker implantation, radiofrequency catheter ablation, and cesarean section surgery improved the symptoms and survival rates. Mutations carriers were advised to avoid pregnancy. CONCLUSION: This study identified that the p.K291I_PRKAG2 mutation is associated with poor prognosis, highlighting the need for early intervention. Further research may uncover the potential connections between intellectual disability, miscarriage, and neonatal death in individuals with this syndrome.
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Cardiomiopatia Hipertrófica , Humanos , Feminino , Masculino , Adulto , Seguimentos , Adulto Jovem , Pessoa de Meia-Idade , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/complicações , Brasil/epidemiologia , Adolescente , Mutação , Proteínas Quinases Ativadas por AMP/genética , Fenótipo , Criança , Arritmias Cardíacas/genética , Arritmias Cardíacas/etiologia , Síndrome , IdosoRESUMO
BACKGROUND: The use of technological innovations in ST elevation myocardial infarction (STEMI) care networks has been shown to be effective in improving information flow and coordination, and thus reducing the time to reperfusion. We developed a smartphone application called ODISEA to improve our STEMI care network and evaluated the results of its use. METHOD: Quasi-experimental study that compared the outcomes of STEMI suspected patients with an alert and indication for transfer to a cath lab during a previous period and a period in which the ODISEA APP was used. The main objective was to examine differences in reperfusion time and the proportion of patients with a final diagnosis other than acute coronary syndrome. RESULTS: A total of 699 patients were included (415 before and 284 during the ODISEA-APP period). No differences were observed in patient characteristics, infarct type, or acute complications. We observed a reduction in the time from diagnostic ECG to wire crossing with the use of the ODISEA APP (117 vs 102 min, p < 0.001) and a reduction in the percentage of patients with a final diagnosis other than acute coronary syndrome (17.1% vs 9.5%, p = 0.004). CONCLUSIONS: The use of the ODISEA APP in the management of patients with suspected STEMI may be useful for reducing the time from diagnostic ECG to wire crossing and the percentage of patients with a final diagnosis other than acute coronary syndrome.
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Aplicativos Móveis , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Eletrocardiografia , Smartphone , Tempo para o TratamentoRESUMO
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) may cause sudden cardiac death (SCD) despite medical therapy. Therefore, implantable cardioverter-defibrillators (ICDs) are commonly advised. However, there is limited data on the outcomes of ICD use in children. OBJECTIVE: The purpose of this study was to compare the risk of arrhythmic events in pediatric patients with CPVT with and without an ICD. METHODS: We compared the risk of SCD in patients with RYR2 (ryanodine receptor 2) variants and phenotype-positive symptomatic CPVT patients with and without an ICD who were younger than 19 years and had no history of sudden cardiac arrest at phenotype diagnosis. The primary outcome was SCD; secondary outcomes were composite end points of SCD, sudden cardiac arrest, or appropriate ICD shocks with or without arrhythmic syncope. RESULTS: The study included 235 patients, 73 with an ICD (31.1%) and 162 without an ICD (68.9%). Over a median follow-up of 8.0 years (interquartile range 4.3-13.4 years), SCD occurred in 7 patients (3.0%), of whom 4 (57.1%) were noncompliant with medications and none had an ICD. Patients with ICD had a higher risk of both secondary composite outcomes (without syncope: hazard ratio 5.85; 95% confidence interval 3.40-10.09; P < .0001; with syncope: hazard ratio 2.55; 95% confidence interval 1.50-4.34; P = .0005). Thirty-one patients with ICD (42.5%) experienced appropriate shocks, 18 (24.7%) inappropriate shocks, and 21 (28.8%) device-related complications. CONCLUSION: SCD events occurred only in patients without an ICD and mostly in those not on optimal medical therapy. Patients with an ICD had a high risk of appropriate and inappropriate shocks, which may be reduced with appropriate device programming. Severe ICD complications were common, and risks vs benefits of ICDs need to be considered.
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Intramyocardial dissecting hematoma (IDH), in the setting of an acute coronary syndrome, is a rare type of cardiac rupture. However, the best treatment for IDH in each clinical scenario is not clearly defined. We present a case in which the best approach for IDH and its final outcome are discussed.
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Morte Súbita , Humanos , Adolescente , Feminino , Masculino , Adulto Jovem , Adulto , Morte Súbita/etiologia , Morte Súbita Cardíaca/etiologia , Família/psicologiaRESUMO
ABSTRACT Objective This study aimed to provide a long-term follow-up of PRKAG2 syndrome and describe the new phenotypic aspects of the condition. PRKAG2 syndrome is a rare autosomal-dominant glycogen storage disease characterized by cardiac hypertrophy, ventricular pre-excitation, and conduction system disease. Fatal arrhythmias occur frequently. Methods A family cohort of 66 participants was recruited. Clinical and genetic analyses were performed. Results Median age of 36.97±17.28 years, with 69.9% being men. Nineteen subjects carried the deleterious variant p.K290I of the PRKAG2 gene. This group experienced many malignant events, including eight pacemaker implants, three sudden cardiac deaths, five aborted cardiac arrests, four strokes, four premature neonatal deaths, two spontaneous abortions, five forceps deliveries, and 12 cesarean procedures. Extracardiac involvement, such as in neurocognitive and psychiatric disorders, has been observed only in carriers of mutations. Palpitations, Syncope, atrial fibrillation, atrial flutter, sinus pauses, and bradycardia were strongly and significantly associated with major or severe adverse events (sudden cardiac death, aborted cardiac arrest, pacemaker use, stroke, and congestive heart failure). Early diagnosis and intervention through antiarrhythmic drugs, anticoagulation, pacemaker implantation, radiofrequency catheter ablation, and cesarean section surgery improved the symptoms and survival rates. Mutations carriers were advised to avoid pregnancy. Conclusion This study identified that the p.K291I_PRKAG2 mutation is associated with poor prognosis, highlighting the need for early intervention. Further research may uncover the potential connections between intellectual disability, miscarriage, and neonatal death in individuals with this syndrome.
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No disponible
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Traumatismos Torácicos/embriologia , Reanimação Cardiopulmonar/efeitos adversos , Massagem Cardíaca/efeitos adversos , Traumatismos Torácicos/etiologia , Fatores de RiscoRESUMO
Introducción y objetivos: La enfermedad de Danon (ED) es una enfermedad producida por mutaciones en el gen LAMP2. Se la considera una enfermedad multisistémica caracterizada por miocardiopatía hipertrófica con preexcitación e hipertrofia extrema, discapacidad intelectual, miopatía, presentación infantil y peor pronóstico en varones. Hay pocas series que permitan conocer las características clínicas y el pronóstico de la ED. Métodos: Se analizaron los registros clínicos de los pacientes con ED de 10 hospitales españoles. Resultados: Se incluyó a 27 pacientes (edad, 31 +/- 19 años; el 78% mujeres). Los varones mostraron una elevada prevalencia de manifestaciones extracardiacas -miopatía (80%), trastornos del aprendizaje (83%) y alteraciones visuales (60%)- que eran infrecuentes en las mujeres (el 5, el 0 y el 27% respectivamente). Aunque la miocardiopatía hipertrófica era la cardiopatía más habitual (61%), el grosor ventricular máximo fue 15 +/- 7 mm y 12 pacientes (10 mujeres) presentaron miocardiopatía dilatada. Solo 11 pacientes (49%) mostraron preexcitación y en 16 (65%) la enfermedad se inició después de los 20 años. Tras una mediana de seguimiento de 4 años [intervalo intercuartílico, 2-9], 4 varones (67%) y 9 mujeres (43%) fallecieron o se sometieron a trasplante. El daño cardiaco y los eventos adversos ocurrieron más tardíamente en las mujeres (37 +/- 9 frente a 23 +/- 16 años y 36 +/- 20 frente a 20 +/- 11 años). Conclusiones: Las características clínicas de la ED difieren sustancialmente de lo considerado tradicionalmente. La edad de presentación de la ED es más tardía, no se expresa como una enfermedad multisistémica en las mujeres y la preexcitación es poco frecuente
Introduction and objectives: Danon disease (DD) is caused by mutations in the LAMP2 gene. It is considered a multisystemic disease characterized by hypertrophic cardiomyopathy with pre-excitation and extreme hypertrophy, intellectual disability, myopathy, childhood presentation, and worse prognosis in men. There are scarce data on the clinical characteristics and prognosis of DD. Methods: We analyzed the clinical records of patients with DD from 10 Spanish hospitals. Results: Twenty-seven patients were included (mean age, 31 +/- 19 years; 78% women). Male patients showed a high prevalence of extracardiac manifestations: myopathy (80%), learning disorders (83%), and visual alterations (60%), which were uncommon findings in women (5%, 0%, and 27%, respectively). Although hypertrophic cardiomyopathy was the most common form of heart disease (61%), the mean maximum wall thickness was 15 +/- 7 mm and dilated cardiomyopathy was present in 12 patients (10 women). Pre-excitation was found in only 11 patients (49%). Age at presentation was older than 20 years in 16 patients (65%). After a median follow-up of 4 years (interquartile range, 2-9), 4 men (67%) and 9 women (43%) died or required a transplant. Cardiac disease and adverse events occurred later in women (37 +/- 9 vs 23 +/- 16 and 36 +/- 20 vs 20 +/- 11 years, respectively). Conclusions: The clinical characteristics of DD differ substantially from traditional descriptions: age at presentation of DD is older, the disease is not multisystemic in women, and pre-excitation is infrequent