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BACKGROUND: Genetic disease has recently emerged as a cause of cardiac conduction disorders (CCDs), but the diagnostic yield of genetic testing and the contribution of the different genes to CCD is still unsettled. OBJECTIVES: This study sought to determine the diagnostic yield of genetic testing in young adults with CCD of unknown etiology requiring pacemaker implantation. We also studied the prevalence of rare protein-altering variants across individual genes and functional gene groups. METHODS: We performed whole exome sequencing in 150 patients with CCD of unknown etiology who had permanent pacemaker implanted at age ≤60 years at 14 Spanish hospitals. Prevalence of rare protein-altering variants in patients with CCD was compared with a reference population of 115,522 individuals from gnomAD database (control subjects). RESULTS: Among 39 prioritized genes, patients with CCD had more rare protein-altering variants than control subjects (OR: 2.39; 95% CI: 1.75-3.33). Significant enrichment of rare variants in patients with CCD was observed in all functional gene groups except in the desmosomal genes group. Rare variants in the nuclear envelope genes group exhibited the strongest association with CCD (OR: 6.77; 95% CI: 3.71-13.87). Of note, rare variants in sarcomeric genes were also enriched (OR: 1.73; 95% CI: 1.05-3.10). An actionable genetic variant was detected in 21 patients (14%), with LMNA being the most frequently involved gene (4.6%). CONCLUSIONS: Unrecognized rare genetic variants increase the risk of CCD in young adults with CCD of unknown etiology. Genetic testing should be performed in patients age ≤60 years with CCD of unknown etiology. The role of genetic variants in sarcomeric genes as a cause of CCD should be further investigated.
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The p.Arg301Gln variant in the α -galactosidase A gene (GLA) has been poorly described in the literature. The few reports show controversial information, with both classical and nonclassical Anderson-Fabry Disease (AFD) presentation patterns. The aim of this study was to analyze the penetrance, clinical phenotype, and biochemical profile of an international cohort of patients carrying the p.Arg301Gln genetic variant in the GLA gene. This was an observational, international, and retrospective cohort case series study of patients carrying the p.Arg301Gln variant in the GLA gene associated with AFD disease. Forty-nine p.Arg301Gln GLA carriers, 41% male, were analyzed. The penetrance was 63% in the entire cohort and 1.5 times higher in men. The mean age of symptoms onset was 41 years; compared to women, men presented symptoms earlier and with a shorter delay to diagnosis. The typical clinical triad-cornea verticillate, neuropathic pain, and angiokeratomas-affected only 20% of the cohort, with no differences between genders. During follow-up, almost 20% of the patients presented some type of nonfatal cardiovascular and renal event (stroke, need for dialysis, heart failure, and arrhythmias requiring intracardiac devices), predominantly affecting men. Residual levels were the most common finding of α-GAL A enzyme activity, only a few women had a normal level; a small proportion of men had undetectable levels. The incidence of combined outcomes including all causes of death was 33%, and the cumulative incidence of all-cause mortality was 9% at the follow-up. Patients carrying the p.Arg301Gln GLA variant have a high penetrance, with predominantly cardiorenal involvement and clinical onset of the disease in middle age. Only a small proportion showed the classic clinical presentation of AFD. As in other X-linked diseases, males were more affected by severe cardiovascular and renal events. This genotype-phenotype correlation could be useful from a practical clinical point of view and for future decision making.
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Doença de Fabry , Fenótipo , alfa-Galactosidase , Humanos , Doença de Fabry/genética , Masculino , alfa-Galactosidase/genética , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , PenetrânciaRESUMO
BACKGROUND: Disease penetrance in genotype-positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES: This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. METHODS: The authors evaluated 779 G+ patients (age 35.8 ± 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN) without DCM followed at 25 Spanish centers. RESULTS: After a median follow-up of 37.1 months (Q1-Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person-years; 95% CI: 2.3-3.5 per 100 person-years). DCM penetrance and age at DCM onset was different according to underlying gene group (log-rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1-year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end-diastolic diameter (HR per 1-mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identified late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). CONCLUSIONS: Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end-diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM.
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Cardiomiopatia Dilatada , Genótipo , Penetrância , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/fisiopatologia , Conectina/genética , Eletrocardiografia , Seguimentos , Espanha/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Risk stratification in Brugada syndrome (BrS) remains controversial. In this respect, the role of the electrophysiology study (EPS) has been a subject of debate. In some centers, it is common practice to use an implantable loop recorder (ILR) after a negative EPS to help in risk stratification. However, the diagnostic value of this approach has never been specifically addressed. OBJECTIVE: The aim of this study was to describe the baseline characteristics and the main findings of a diagnostic workup strategy with an ILR after a negative EPS in BrS. METHODS: We conducted a retrospective international registry including patients with BrS and negative EPS (ie, noninducible ventricular tachycardia or ventricular fibrillation) before ILR monitoring. RESULTS: The study included 65 patients from 8 referral hospitals in The Netherlands, Spain, and the United Kingdom (mean age, 39 ± 16 years; 72% male). The main indication for ILR monitoring was unexplained syncope/presyncope (66.2%). During a median follow-up of 39.0 months (Q1 25.0-Q3 47.6 months), 18 patients (27.7%) experienced 21 arrhythmic events (AEs). None of the patients died during follow-up. Bradyarrhythmias were the most common finding (47.6%), followed by atrial tachyarrhythmias (38.1%). Only 3 patients presented with ventricular arrhythmias. AEs were considered incidental in 12 patients (66.7%). In 11 patients (61.1%), AEs led to specific changes in treatment. CONCLUSION: The use of ILR after a negative EPS in BrS is a safe strategy that reflected the high negative predictive value of EPS for ventricular arrhythmia in this syndrome. In addition, it allowed the detection of AEs in a significant proportion of patients, with therapeutic implications in most of them.
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Síndrome de Brugada , Sistema de Registros , Humanos , Masculino , Feminino , Síndrome de Brugada/fisiopatologia , Síndrome de Brugada/diagnóstico , Adulto , Estudos Retrospectivos , Eletrocardiografia Ambulatorial/métodos , Eletrocardiografia Ambulatorial/instrumentação , Técnicas Eletrofisiológicas Cardíacas/métodos , Pessoa de Meia-Idade , Seguimentos , Medição de Risco/métodosRESUMO
BACKGROUND: Variant transthyretin amyloidosis (ATTRv) can cause sensorimotor and autonomic neuropathy. Objective quantification of sudomotor function may be essential for early diagnosis and early initiation of treatment. The aim of this study is to evaluate the diagnostic value of the Sudoscan® in ATTRv. METHODS: Electrochemical skin conductance (ESC) was measured in V30M ATTRv patients, asymtomatic V30M carriers and healthy controls. Comparisons between the three groups were made using the Kruskal-Wallis test, and ROC curves were used to estimate the discriminatory power of ESC values between groups. RESULTS: ESC was measured in 52 ATTRv patients, 107 asymptomatic carriers and 40 healthy controls. ESC was significantly lower in ATTRv patients compared to asymptomatic carriers and healthy controls in both feet and hands; median values are as follows: 40 µS, 78 µS and 81 µS, respectively (p < 0.001), and 53 µS, 69 µS and 74 µS, respectively (p < 0.001). ESC in feet < 70.5 µS had a sensitivity of 89.7% and specificity of 84.6% to discriminate asymptomatic carriers from patients with ATTRv. CONCLUSION: The determination of ESC by Sudoscan® is a rapid, noninvasive and easily reproducible technique capable of discriminating patients with ATTRv from asymptomatic carriers and healthy controls with adequate sensitivity and specificity.
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Neuropatias Amiloides Familiares , Resposta Galvânica da Pele , Humanos , Masculino , Feminino , Neuropatias Amiloides Familiares/diagnóstico , Pessoa de Meia-Idade , Idoso , Resposta Galvânica da Pele/fisiologia , Sensibilidade e Especificidade , Adulto , Pré-Albumina , Mãos/fisiopatologia , Pé/fisiopatologiaRESUMO
BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is a rare genetic disease that negatively affects patients' quality of life through the involvement of various organs and tissues. Despite a large amount of research on medical and psychosocial interventions, the impact of occupational therapy (OT) on patients with ATTRv is not well understood. OBJECTIVE: The aim of this study was to develop an OT programme to improve the daily functioning and quality of life of patients with ATTRv. METHODS: Fourteen patients with ATTRv were interviewed. Together they developed short- and medium-term occupational goals. Patients received the OT intervention for six months. Outcomes were measured using scores for activities of daily living and psychological well-being. RESULTS: The study found that OT can have a positive impact as a complementary intervention to medical and other psychosocial treatments. Of the 14 patients, 12 maintained the same scores in activities of daily living. Two deteriorated and eight improved their psychological scores. CONCLUSION: This study highlights the need for further research in this area and the importance of OT in the management of patients with ATTRv. Early intervention is of paramount importance and further research is needed to evaluate the long-term effects of OT interventions in patients with ATTRv.
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Atividades Cotidianas , Neuropatias Amiloides Familiares , Humanos , Qualidade de Vida , Neuropatias Amiloides Familiares/terapia , Pesquisa Qualitativa , Doenças RarasRESUMO
AIMS: Late gadolinium enhancement (LGE) is frequently found in patients with dilated cardiomyopathy (DCM); there is little information about its frequency and distribution pattern according to the underlying genetic substrate. We sought to describe LGE patterns according to genotypes and to analyse the risk of major ventricular arrhythmias (MVA) according to patterns. METHODS AND RESULTS: Cardiac magnetic resonance findings and LGE distribution according to genetics were performed in a cohort of 600 DCM patients followed at 20 Spanish centres. After exclusion of individuals with multiple causative gene variants or with variants in infrequent DCM-causing genes, 577 patients (34% females, mean age 53.5 years, left ventricular ejection fraction 36.9 ± 13.9%) conformed to the final cohort. A causative genetic variant was identified in 219 (38%) patients, and 147 (25.5%) had LGE. Significant differences were found comparing LGE patterns between genes (P < 0.001). LGE was absent or rare in patients with variants in TNNT2, RBM20, and MYH7 (0, 5, and 20%, respectively). Patients with variants in DMD, DSP, and FLNC showed a predominance of LGE subepicardial patterns (50, 41, and 18%, respectively), whereas patients with variants in TTN, BAG3, LMNA, and MYBPC3 showed unspecific LGE patterns. The genetic yield differed according to LGE patterns. Patients with subepicardial, lineal midwall, transmural, and right ventricular insertion points or with combinations of LGE patterns showed an increased risk of MVA compared with patients without LGE. CONCLUSION: LGE patterns in DCM have a specific distribution according to the affected gene. Certain LGE patterns are associated with an increased risk of MVA and with an increased yield of genetic testing.
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Cardiomiopatia Dilatada , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/complicações , Meios de Contraste , Gadolínio , Volume Sistólico , Função Ventricular Esquerda , Arritmias Cardíacas , Estudos de Associação Genética , Valor Preditivo dos Testes , Imagem Cinética por Ressonância Magnética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genéticaRESUMO
BACKGROUND: Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. RESULTS: Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). CONCLUSIONS: Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation.
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Distrofias Hereditárias da Córnea , Doença de Fabry , Feminino , Humanos , Estudos Retrospectivos , Cognição , Doença de Fabry/epidemiologia , Doença de Fabry/genética , FenótipoRESUMO
AIMS: To describe the natural history of SARS-CoV-2 infection in patients with hypertrophic cardiomyopathy (HCM) compared with a control group and to identify predictors of adverse events. METHODS AND RESULTS: Three hundred and five patients [age 56.6 ± 16.9 years old, 191 (62.6%) male patients] with HCM and SARS-Cov-2 infection were enrolled. The control group consisted of 91 131 infected individuals. Endpoints were (i) SARS-CoV-2 related mortality and (ii) severe clinical course [death or intensive care unit (ICU) admission]. New onset of atrial fibrillation, ventricular arrhythmias, shock, stroke, and cardiac arrest were also recorded. Sixty-nine (22.9%) HCM patients were hospitalized for non-ICU level care, and 21 (7.0%) required ICU care. Seventeen (5.6%) died: eight (2.6%) of respiratory failure, four (1.3%) of heart failure, two (0.7%) suddenly, and three (1.0%) due to other SARS-CoV-2-related complications. Covariates associated with mortality in the multivariable were age {odds ratio (OR) per 10 year increase 2.25 [95% confidence interval (CI): 1.12-4.51], P = 0.0229}, baseline New York Heart Association class [OR per one-unit increase 4.01 (95%CI: 1.75-9.20), P = 0.0011], presence of left ventricular outflow tract obstruction [OR 5.59 (95%CI: 1.16-26.92), P = 0.0317], and left ventricular systolic impairment [OR 7.72 (95%CI: 1.20-49.79), P = 0.0316]. Controlling for age and sex and comparing HCM patients with a community-based SARS-CoV-2 cohort, the presence of HCM was associated with a borderline significant increased risk of mortality OR 1.70 (95%CI: 0.98-2.91, P = 0.0600). CONCLUSIONS: Over one-fourth of HCM patients infected with SARS-Cov-2 required hospitalization, including 6% in an ICU setting. Age and cardiac features related to HCM, including baseline functional class, left ventricular outflow tract obstruction, and systolic impairment, conveyed increased risk of mortality.
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Fibrilação Atrial , COVID-19 , Cardiomiopatia Hipertrófica , Disfunção Ventricular Esquerda , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , COVID-19/complicações , COVID-19/epidemiologia , SARS-CoV-2 , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/epidemiologia , Sistema de Registros , Disfunção Ventricular Esquerda/complicações , Fibrilação Atrial/complicaçõesRESUMO
The purpose of this study was to explore the occupational performance and needs of patients with hereditary transthyretin amyloidosis (ATTRv). A semi-structured interview was conducted by an occupational therapist with 44 patients with Val50Met-ATTRv recruited through patient associations. The interview addressed three related dimensions. The first one, the physical dimension, was evaluated using the Spanish versions of the Barthel Index, the Lawton and Brody scale, and the Norfolk questionnaire; the second one, the psychological dimension, was assessed with the Warwick-Edinburgh Mental Well-Being Scale and the SF-36 questionnaire; and the third dimension, the occupational performance, was assessed through unstructured questions on daily occupations, work, roles, and hobbies given the lack of standardized scales. Twenty participants (45.4%) responded that the disease had affected their basic activities of daily living, twenty- four (54.5%) perceived an impact on their instrumental activities of daily living, and all the participants reported that the disease symptoms had affected their ability to perform advanced activities as well as their employment status. Only three patients (6.8%) reported a lack of psychological impairment following disease diagnosis. These findings suggest that a semi-structured interview conducted by an occupational therapist can provide essential information that should be considered for the implementation of occupational therapy programs targeting patients living with a diagnosis of ATTRv.
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Neuropatias Amiloides Familiares , Terapia Ocupacional , Atividades Cotidianas , Neuropatias Amiloides Familiares/complicações , HumanosRESUMO
BACKGROUND: Although genotyping allows family screening and influences risk-stratification in patients with nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD), its result is negative in a significant number of patients, limiting its widespread adoption. OBJECTIVES: This study sought to develop and externally validate a score that predicts the probability for a positive genetic test result (G+) in DCM/LVSD. METHODS: Clinical, electrocardiogram, and echocardiographic variables were collected in 1,015 genotyped patients from Spain with DCM/LVSD. Multivariable logistic regression analysis was used to identify variables independently predicting G+, which were summed to create the Madrid Genotype Score. The external validation sample comprised 1,097 genotyped patients from the Maastricht and Trieste registries. RESULTS: A G+ result was found in 377 (37%) and 289 (26%) patients from the derivation and validation cohorts, respectively. Independent predictors of a G+ result in the derivation cohort were: family history of DCM (OR: 2.29; 95% CI: 1.73-3.04; P < 0.001), low electrocardiogram voltage in peripheral leads (OR: 3.61; 95% CI: 2.38-5.49; P < 0.001), skeletal myopathy (OR: 3.42; 95% CI: 1.60-7.31; P = 0.001), absence of hypertension (OR: 2.28; 95% CI: 1.67-3.13; P < 0.001), and absence of left bundle branch block (OR: 3.58; 95% CI: 2.57-5.01; P < 0.001). A score containing these factors predicted a G+ result, ranging from 3% when all predictors were absent to 79% when ≥4 predictors were present. Internal validation provided a C-statistic of 0.74 (95% CI: 0.71-0.77) and a calibration slope of 0.94 (95% CI: 0.80-1.10). The C-statistic in the external validation cohort was 0.74 (95% CI: 0.71-0.78). CONCLUSIONS: The Madrid Genotype Score is an accurate tool to predict a G+ result in DCM/LVSD.
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Cardiomiopatia Dilatada , Disfunção Ventricular Esquerda , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/genética , Estudos de Coortes , Genótipo , Humanos , Fatores de RiscoRESUMO
BACKGROUND: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. RESULTS: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare.
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Cardiomiopatia Dilatada , Insuficiência Cardíaca , Cadeias Pesadas de Miosina , Adolescente , Adulto , Arritmias Cardíacas/complicações , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/genética , Miosinas Cardíacas/genética , Cardiomiopatia Dilatada/genética , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/genética , Humanos , Masculino , Pessoa de Meia-Idade , Cadeias Pesadas de Miosina/genética , Fenótipo , Remodelação Ventricular/genética , Adulto JovemRESUMO
AIMS: To study the impact of genotype on the performance of the 2019 risk model for arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS AND RESULTS: The study cohort comprised 554 patients with a definite diagnosis of ARVC and no history of sustained ventricular arrhythmia (VA). During a median follow-up of 6.0 (3.1,12.5) years, 100 patients (18%) experienced the primary VA outcome (sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator intervention, aborted sudden cardiac arrest, or sudden cardiac death) corresponding to an annual event rate of 2.6% [95% confidence interval (CI) 1.9-3.3]. Risk estimates for VA using the 2019 ARVC risk model showed reasonable discriminative ability but with overestimation of risk. The ARVC risk model was compared in four gene groups: PKP2 (n = 118, 21%); desmoplakin (DSP) (n = 79, 14%); other desmosomal (n = 59, 11%); and gene elusive (n = 160, 29%). Discrimination and calibration were highest for PKP2 and lowest for the gene-elusive group. Univariable analyses revealed the variable performance of individual clinical risk markers in the different gene groups, e.g. right ventricular dimensions and systolic function are significant risk markers in PKP2 but not in DSP patients and the opposite is true for left ventricular systolic function. CONCLUSION: The 2019 ARVC risk model performs reasonably well in gene-positive ARVC (particularly for PKP2) but is more limited in gene-elusive patients. Genotype should be included in future risk models for ARVC.
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Displasia Arritmogênica Ventricular Direita , Arritmias Cardíacas , Displasia Arritmogênica Ventricular Direita/genética , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Genótipo , Humanos , Medição de Risco , Fatores de RiscoRESUMO
Metabolic syndrome (MetS) is characterized by increased pro-oxidative stress and a pro-inflammatory state. Several studies emphasized the protective effect of the Mediterranean dietary pattern (MDP). To assess the oxidative and inflammatory state according to the adherence to MDP using biomarkers in patients with MetS. Antioxidant and pro-inflammatory biomarkers were determined in plasma, peripheral blood mononuclear cells (PBMCs), and neutrophils of adults (aged 55-75 years old; 60% women) with MetS living in Mallorca (Spain). Anthropometrics, dietary intake by a validated semi-quantitative 143-item food frequency questionnaire, and a Dietary Inflammatory Index were measured. Patients with low adherence to MDP showed higher levels of glycated haemoglobin A1c and triglycerides, and lower levels of HDL cholesterol. Plasma levels of interleukin-1ß, IL-6, IL-15, tumour necrosis factor α, xanthine oxidase, and ghrelin, and activities of superoxide dismutase, and myeloperoxidase were higher in subjects with low adherence to the MDP. Reactive oxygen species production in PBMCs and neutrophils stimulated with lipopolysaccharide was higher in participants with low adherence to the MDP. Patients with MetS and higher adherence to the MDP showed less altered anthropometric parameters, blood biochemical profile, and better oxidative and inflammatory status.
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INTRODUCTION: Arrhythmogenic cardiomyopathy (ACM) is an inherited disease characterized by progressive fibroadipose replacement of cardiomyocytes. Its diagnosis is based on imaging, electrocardiographic, histological and genetic/familial criteria. The development of the disease is based mainly on desmosomal genes. Knowledge of the phenotypic expression of each of these genes will help in both diagnosis and prognosis. The objective of this study is to describe the genotype-phenotype association of an unknown PKP2 gene variant in a family diagnosed with ACM. METHODS: Clinical and genetic study of a big family carrying the p.Tyr168* variant in the PKP2 gene, in order to demonstrate pathogenicity of this variant, causing ACM. RESULTS: Twenty-two patients (proband and relatives) were evaluated. This variant presented with high arrhythmic load at an early age, but without evidence of structural heart disease after 20 years of follow-up, with low risk in predictive scores. We demonstrate evidence of its pathogenicity. CONCLUSIONS: The p.Tyr168* variant in the PKP2 gene causes ACM with a high arrhythmic load and with an absence of structural heart disease. This fact emphasizes the value of knowing the phenotypic expression of each variant.
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Cardiomiopatias , Cardiopatias , Arritmias Cardíacas/genética , Eletrocardiografia , Estudos de Associação Genética , HumanosRESUMO
This study was designed to investigate the global utilization of occupational therapy (OT) services by patients with hereditary transthyretin amyloidosis (ATTRv) in Spain. The main objective was to find out whether these patients have access to OT services and the types of interventions being offered to them, together with their satisfaction and real benefits as users. We developed an online questionnaire which was distributed to patients with ATTRv in Spain through patient associations. Seventy-four patients with a diagnosis of ATTRv residing in Spain participated in the study. Thirteen had already used OT services at least once, felt that OT interventions improved their quality of life, would recommend OT services to others, and would return to see an occupational therapist. However, 61 had never used this type of service before. Of these, 35 knew what OT is and 13 declared that they considered that OT interventions in ATTRv could be positive for them. The results suggest that the use of OT services by ATTRv patients is low, mainly because of the lack of information about the occupational profile of individuals with this disease. The low response rate obtained for the survey limits generalization, and thus further research to confirm these preliminary findings is needed.