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INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiomyopathy characterized by ventricular arrhythmias and heart failure. The variable phenotype suggesting that determined environmental factors may have an influence. The aim of our study was to discover the impact of the dynamic physical activity on patients with high-risk definite ARVC/D. METHODS AND RESULTS: Collection of data on physical activity at the time of diagnosis was conducted at an in-person clinical interview. The intensity of the activity was classified in accordance with the mean frequency of weekly physical exercise sessions in the 10 years before diagnosis and into the following three groups of dynamic activity: high/competitive (>3 h/wk), moderate (1 to 3 h) and minimal/inactive (<1 h). Seventeen patients practiced high dynamic physical activities. The intensity of dynamic activity was classified into three groups: 8 of high intensity, 9 moderate, and 19 inactive. The first major arrhythmic event and occurrence of severe right ventricular dysfunction were earlier in the high-intensity exercise group, followed by the moderate intensity group and at a later age in the low-intensity/inactive group. CONCLUSIONS: Dynamic exercise could be directly associated with the severity of the phenotype in relation to the precocity of major ventricular arrhythmic events and right ventricular systolic dysfunction in patients with high-risk definite ARVC/D.
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Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Exercício Físico/fisiologia , Esforço Físico/fisiologia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
INTRODUCTION AND OBJECTIVES: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of predominantly right ventricular myocardium. This cardiomyopathy is a frequent cause of sudden cardiac death in young people and athletes. The aim of our study was to determine the incidence of pathological or likely pathological desmosomal mutations in patients with high-risk definite ARVC. METHODS: This was an observational, retrospective cohort study, which included 36 patients diagnosed with high-risk ARVC in our hospital between January 1998 and January 2015. Genetic analysis was performed using next-generation sequencing. RESULTS: Most patients were male (28 patients, 78%) with a mean age at diagnosis of 45 ± 18 years. A pathogenic or probably pathogenic desmosomal mutation was detected in 26 of the 35 index cases (74%): 5 nonsense, 14 frameshift, 1 splice, and 6 missense. Novel mutations were found in 15 patients (71%). The presence or absence of desmosomal mutations causing the disease and the type of mutation were not associated with specific electrocardiographic, clinical, arrhythmic, anatomic, or prognostic characteristics. CONCLUSIONS: The incidence of pathological or likely pathological desmosomal mutations in ARVC is very high, with most mutations causing truncation. The presence of desmosomal mutations was not associated with prognosis.
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Displasia Arritmogênica Ventricular Direita/genética , Análise Mutacional de DNA/métodos , DNA/genética , Mutação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/mortalidade , Morte Súbita Cardíaca/epidemiologia , Eletrocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologia , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: Marfan syndrome (MFS) is a disorder of autosomal dominant inheritance, in which aortic root dilation is the main cause of morbidity and mortality. Fibrillin-1 (FBN-1) gene mutations are found in more than 90% of MFS cases. The aim of our study was to summarise variants in FBN-1 and establish the genotype-phenotype correlation, with particular interest in the onset of aortic events, in a broad population of patients with an initial clinical suspicion of MFS. MATERIAL AND METHODS: This single centre prospective cohort study included all patients presenting variants in the FBN-1 gene who visited a Hereditary Aortopathy clinic between September 2010 and October 2016. RESULTS: The study included 90 patients with FBN-1 variants corresponding to 58 non-interrelated families. Of the 57 FBN-1 variants found, 25 (43.9%) had previously been described, 23 of which had been identified as associated with MFS, while the the remainder are described for the first time. For 84 patients (93.3%), it was possible to give a definite diagnosis of Marfan syndrome in accordance with Ghent criteria. 44 of them had missense mutations, 6 of whom had suffered an aortic event (with either prophylactic surgery for aneurysm or dissection), whereas 20 of the 35 patients with truncating mutations had suffered an event (13.6% vs. 57.1%, p < 0.001). These events tended to occur at earlier ages in patients with truncating compared to those with missense mutations, although not significantly (41.33 ± 3.77 vs. 37.5 ± 9.62 years, p = 0.162). CONCLUSIONS: Patients with MFS and truncating variants in FBN-1 presented a higher proportion of aortic events, compared to a more benign course in patients with missense mutations. Genetic findings could, therefore, have importance not only in the diagnosis, but also in risk stratification and clinical management of patients with suspected MFS.
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Síndrome de Marfan/genética , Síndrome de Marfan/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Ecocardiografia , Feminino , Fibrilina-1/genética , Estudos de Associação Genética , Testes Genéticos , Genótipo , Humanos , Masculino , Mutação/genética , Fenótipo , Estudos Prospectivos , Adulto JovemRESUMO
Objectives: Sterol regulatory element-binding proteins (SREBP) genes are crucial in lipid biosynthesis and cardiovascular homeostasis. Their expression in epicardial adipose tissue (EAT) and their influence in the development of coronary artery disease (CAD) and type-2 diabetes mellitus remain to be determined. The aim of our study was to evaluate the expression of SREBP genes in EAT in patients with CAD according to diabetes status and its association with clinical and biochemical data. Methods: SREBP-1 and SREBP-2 mRNA expression levels were measured in EAT from 49 patients with CAD (26 with diabetes) and 23 controls without CAD or diabetes. Results: Both SREBPs mRNA expression were significantly higher in patients with CAD and diabetes (p<0.001) and were identified as independent cardiovascular risk factor for coronary artery disease in patients with type-2 diabetes (SREBP-1: OR 1.7, 95%CI 1.1-2.5, p=0.02; SREBP-2: OR 1.6, 95%CI 1.2-3, p=0.02) and were independently associated with the presence of multivessel CAD, left main and anterior descending artery stenosis, and higher total and LDL cholesterol levels, and lower HDL cholesterol levels, in patients with CAD and diabetes. Conclusions: SREBP genes are expressed in EAT and were higher in CAD patients with diabetes than those patients without CAD or diabetes. SREBP expression was associated as cardiovascular risk factor for the severity of CAD and the poor lipid control. In this preliminary study we suggest the importance of EAT in the lipid metabolism and cardiovascular homeostasis for coronary atherosclerosis of patients with diabetes and highlight a future novel therapeutic target.
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Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/sangue , Proteína de Ligação a Elemento Regulador de Esterol 1/sangue , Proteína de Ligação a Elemento Regulador de Esterol 2/sangue , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Idoso , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Metabolismo dos Lipídeos/genética , Masculino , Pessoa de Meia-Idade , Pericárdio/metabolismo , Pericárdio/patologia , Fatores de Risco , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Esteróis/metabolismoRESUMO
AIMS: Our aim was to describe the electrocardiographic findings of a large sample of Spanish workers from several different employment sectors. METHODS AND RESULTS: Between May 2008 and November 2010, 13 495 consecutive 12-lead resting electrocardiograms (ECGs) were obtained during health examinations of working adults aged 16-74 years in 5 cities in different regions of Spain. Of those, 13 179 ECGs suitable for interpretation were included in this study. All tracings were classified by the same cardiologist, according to the Minnesota Code criteria. The mean age of the sample was 40 years, and 73.4% were male. Frequencies of complete right bundle branch block, complete left bundle branch block, and left ventricular hypertrophy were 1.1, 0.2, and 3.6%, respectively. Major Q wave abnormalities were observed in 1.7% of the subjects, T wave abnormalities in 0.7%, early repolarization in 2.4%, and other ST segment abnormalities in 0.2%. Atrial fibrillation was present in 0.08% of the workers and atrial flutter in 0.02%. Frequencies of the Wolff-Parkinson-White pattern, Brugada pattern, long QT pattern, and short QT pattern were 0.2, 0.068, 0.038, and 0.015%, respectively. CONCLUSION: This study shows the electrocardiographic findings of a large sample of Spanish workers from several different employment sectors. The frequencies of many ECG patterns related to an adverse prognosis (left ventricular hypertrophy, complete left bundle branch block, T wave abnormalities, ST segment abnormalities, and atrial fibrillation) were low.
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Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Eletrocardiografia , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Descrição de Cargo , Saúde Ocupacional , Potenciais de Ação , Adolescente , Adulto , Idoso , Arritmias Cardíacas/fisiopatologia , Estudos Transversais , Feminino , Cardiopatias/fisiopatologia , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Espanha/epidemiologia , Adulto JovemRESUMO
AIMS: Hypertrophic cardiomyopathy is one of the main causes of sudden death in young people. Recent clinical practice guidelines include a risk prediction model for sudden death (HCM Risk-SCD), which facilitates the decision of whether to implant a defibrillator. The aim of our study was to ascertain the percentage of events in our series of primary prevention implantable cardioverter-defibrillator recipients with hypertrophic cardiomyopathy and whether HCM Risk-SCD predicts the onset of arrhythmic events. METHODS AND RESULTS: This was an observational, retrospective cohort study, which included 48 primary prevention defibrillator recipient patients with HCM. We compiled their demographic and clinical characteristics, estimated 5-year risk using HCM Risk-SCD, and collected the documentation on arrhythmias during follow-up. The majority was male (66.7%) and mean age at implantation was 44.44 ± 14.46 years. Non-sustained ventricular tachycardia was the most prevalent risk factor (66.67%), followed by a family history of sudden death (47.92%). Mean HCM Risk-SCD was 6.15 ± 5.01%. HCM Risk-SCD was the only factor independently associated with the onset of ventricular tachyarrhythmia, above any other classic risk factor or association [odds ratio = 1.46 (95% confidence interval 1.051-2.013); P = 0.02]. None of the 11 patients estimated as low risk using HCM Risk-SCD suffered any appropriate events (P < 0.05). CONCLUSIONS: During an average follow-up of 4 years, 16.67% presented appropriate events (4.16%/year). HCM Risk-SCD predicted the onset of events more suitably than classic risk factors.
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Arritmias Cardíacas/epidemiologia , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/terapia , Morte Súbita Cardíaca/epidemiologia , Prevenção Primária/métodos , Adulto , Arritmias Cardíacas/prevenção & controle , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , EspanhaRESUMO
AIMS: Interleukin-2 has a significant antitumor activity in some types of cancer, and has been associated with the development of atrial fibrillation (AF). In addition, IL-2 serum levels in recent onset AF have been related with pharmaceutical cardioversion outcomes. We evaluated the hypothesis that a relationship exists between inflammation and the outcome of catheter ablation of AF. METHODS: We studied 44 patients with paroxysmal AF who underwent catheter ablation. Patients with structural heart disease, coronary artery or valve disease, active inflammatory disease, known or suspected neoplasm, endocrinopathies, or exposure to anti-inflammatory drugs were excluded. All study participants underwent evaluation with a standardized protocol, including echocardiography, and cytokine levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumour necrosis factor-alpha, and gamma-interferon determination before procedure. Clinical and electrocardiographic follow-up were performed with Holter-ECG at 3, 6 and 12months in order to know if sinus rhythm was maintained. RESULTS: After catheter ablation of the 44 patients included (53±10years, 27.3% female), all patients returned to sinus rhythm. During the first year of follow-up seven patients (15.9%) experienced recurrence of AF. The demographics, clinical and echocardiographic features, and pharmacological treatments of these patients were similar to those who maintained sinus rhythm. The only independent factor predictive of recurrence of AF was an elevated level of IL-2 (OR 1.18, 95% CI 1.12-1.38). CONCLUSIONS: High serum levels of interleukin-2, a pro-inflammatory non-vascular cytokine, are associated with the recurrence of AF in patients undergoing catheter ablation.
Assuntos
Fibrilação Atrial/sangue , Fibrilação Atrial/etiologia , Ablação por Cateter/efeitos adversos , Interleucina-2/sangue , Veias Pulmonares/cirurgia , Fibrilação Atrial/diagnóstico por imagem , Estudos de Casos e Controles , Demografia , Feminino , Seguimentos , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Recidiva , UltrassonografiaRESUMO
Marfan syndrome (MFS) is a multisystem autosomal dominant heritable disorder and, although there are over 1700 mutations that have been identified in the fibrillin-1 (FBN1) gene associated with it, there are many variants that remain unknown. Here we report two family cases of MFS with two new undescribed variations (C914S and H2426C) in FBN1 gene. Both variations produce alterations in the structural conformation of the protein resulting in pathogenic events in these patients. Finally, this case report includes both pathogenic mutations that have also been clinically and genetically confirmed to result in MFS. This clinical, genetic, and in silico analysis of potentially harmful variations in unrelated MFS patients provides additional evidence for the suggested causative role of the mutations c.2740T > A (C914S), c.7276_7278delCAT (p.H2426C) in FBN1 gene in MFS.
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BACKGROUND: The Quartet quadripolar lead (St. Jude Medical Inc., St. Paul, MN, USA) offers 10 different left ventricle pacing configurations that may further influence hemodynamic parameters compared to traditional bipolar pacing configurations. The purpose of this study was to evaluate whether pacing from additional quadripolar lead vectors could enhance cardiac output (CO). METHODS: For each patient, CO was measured in "no-pacing" and in all the 10 configurations available, within 7 days of implantation of the device. Tip-ring, tip-right ventricular coil (RVC), and ring-RVC vectors were considered as traditional vectors. The seven additional configurations available in the quadripolar lead were considered as nontraditional vectors. CO was measured by ECHO. The best configuration was defined as the one presenting the highest CO measurement within configurations, which have a capture threshold <3 V and a safety margin between the capture and the phrenic nerve stimulation thresholds. RESULTS: Fifty-one standard cardiac resynchronization therapy patients were enrolled. The mean of each patient's best CO obtained with traditional vectors was higher than the baseline nonpaced CO (4.16 L/min vs 3.64 L/min). The mean of each patient's best CO, including all 10 available configurations, was also higher than the baseline nonpaced CO (4.33 L/min vs 3.64 L/min). In addition, the mean of each patient's best CO obtained with the best configuration available through a quadripolar lead was better than the mean of each patient's best CO obtained with a traditional configuration. In 53% of patients, the best CO was obtained with a nontraditional vector unique to the quadripolar lead. CONCLUSIONS: A quadripolar lead offers multiple additional pacing options to increase CO acutely compared to conventional bipolar leads.
Assuntos
Débito Cardíaco , Dispositivos de Terapia de Ressincronização Cardíaca , Eletrodos Implantados , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/prevenção & controle , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/prevenção & controle , Adulto , Idoso , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
INTRODUCTION AND OBJECTIVES: There is little data available for Spain on the outcomes of surgical treatment for severe tricuspid regurgitation. The aim of this study was to analyze clinical and echocardiographic outcomes in a series of patients who received surgical treatment for severe tricuspid regurgitation and to compare outcomes according to the operative approach to valve repair or replacement. METHODS: Retrospective study in 119 consecutive patients with severe tricuspid regurgitation undergoing valve surgery between April 1996 and February 2010. RESULTS: A total of 61 ringless and 23 ring annuloplasties were performed and 11 bioprostheses and 24 mechanical prostheses were implanted. Perioperative mortality was 18.5% and was associated with age and cardiopulmonary bypass time. During clinical follow-up (median, 41 [interquartile range, 24-89] months), 2 reoperations were required in the ring annuloplasty and mechanical prosthesis groups; prosthetic thrombosis was diagnosed in 4 patients in the latter group. Total mortality after follow-up was 29.9% and was associated with age>70 years and extracorporeal circulation time. The emergence of new severe tricuspid regurgitation was associated with age and ringless annuloplasty (P=.04). CONCLUSIONS: Ringless repair was significantly associated with recurrence of severe tricuspid regurgitation. The use of mechanical prostheses was associated with a high rate of thrombosis. No significant differences in perioperative or total mortality were found between the different methods used for repair or valve replacement.
Assuntos
Implante de Prótese de Valva Cardíaca/métodos , Insuficiência da Valva Tricúspide/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Following an acute myocardial infarction (AMI), bone-marrow derived endothelial progenitor cells (EPC) are mobilised into the peripheral blood. Our aim was to examine the factors influencing this spontaneous cell mobilisation. PATIENTS AND METHODS: In this study we analysed 47 patients with extensive AMI (left ventricular ejection fraction [LVEF] <50% by echocardiography during the first week post-AMI); we studied the peripheral blood EPC populations expressing CD133(+), CD34(+), KDR(+), CXCR4(+), as well as the cytokines VEGF (vascular endothelial growth factor), SDF-1 (stromal cell-derived factor 1) and TSP-1 (thrombospondin 1), measured on day 5±2.5 after AMI. RESULTS: The extension of AMI (CPK peak) correlated with the number of CD133(+) mobilised cells: (r=0.40; P=.011). Patients who did not receive perfusion during the acute phase (34%) had more CD34(+)CXCR4(+) cells with a median (interquartile ranges) of 2,401 (498-7,004) vs. 999 (100-1,600), P=.048, and strong correlations between VEGF and CD133(+)CD34(+)KDR(+) (r=.84; P<.01) and SDF-1 and CD34(+)CXCR4(+) (r=.67; P<.01), and between these 2 cytokines (r=.57; P=.01). In the reperfused patients, the correlation between VEGF and CD133(+)CD34(+)KDR(+) was lower (r=.38; P=.03) and the correlation between SDF-1 and CD34(+)CXCR4(+) and VEGF disappeared. Multivariate analysis showed that a VEGF >7pg/mL (P<.01) predicted the mobilisation of CD133(+)CD34(+)KDR(+), whereas hypertension showed a trend (P=.055). Diabetes (P=.045) predicted the number of CD34(+)CXCR4(+), with reperfusion treatment showing a trend in this subpopulation (P=.054). CONCLUSIONS: Mobilisation of progenitor cells after AMI is influenced by factors such as diabetes and the cytokine VEGF. Hypertension and reperfusion therapy during the acute phase also tend to influence the cell response.
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Citocinas/metabolismo , Endotélio Vascular/patologia , Hemangioblastos/fisiologia , Infarto do Miocárdio/fisiopatologia , Idoso , Angioplastia Coronária com Balão , Antígenos CD/análise , Quimiocina CXCL12/metabolismo , Complicações do Diabetes/fisiopatologia , Feminino , Fibrinolíticos/uso terapêutico , Hemangioblastos/química , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/terapia , Neovascularização Fisiológica , Receptores CXCR4/análise , Fatores de Risco , Trombospondina 1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/análiseAssuntos
Cardiomiopatia Dilatada/terapia , Remodelação Ventricular/fisiologia , Terapia de Ressincronização Cardíaca , Cardiomiopatia Dilatada/fisiopatologia , Ecocardiografia , Eletrocardiografia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
BACKGROUND: Preinfarction angina, a possible form of ischaemic preconditioning, improves the prognosis in patients who experience a major ischaemic event; though the associated pathophysiology is not yet fully understood. The aim of this study was to determine the possible involvement of endothelial progenitor cells (EPC), the vascular endothelial growth factor (VEGF) and the hepatocyte growth factor (HGF) in the development of preinfarction angina. METHODS AND RESULTS: We studied 41 patients (60·5 ± 12 years; 34% women) and 14 healthy controls; 43·9% of the patients had preinfarction angina. No differences were found in the baseline characteristics of the two groups. Although the EPC, VEGF and HGF were raised as compared with the control group, no significant differences were found according to the presence or absence of preinfarction angina in the levels of EPC (baseline, P = 0·25; day 3, P = 0·11; day 7, P = 0·32), VEGF (baseline, P = 0·96; day 3, P = 0·06; day 7, P = 0·57) or HGF (baseline, P = 0·18; day 3, P = 1; day 7, P = 0·86). An association was seen in the patients who had preinfarction angina between the EPC levels at baseline and on days 3 and 7 and the HGF on admission with the time from the angina to the STEMI (ß = -0·070; ß = -0·066; ß = -0·081; ß = -80·16; P < 0·05), showing a reduction in the level of EPC cells for each hour passed since the event. CONCLUSIONS: No differences were found in the release kinetics of EPC, VEGF or HGF after a first infarction according to whether the patients had angina during the week before the infarction.