Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus

Objective

To assess whether genetically determined Amerindian ancestry predicts increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus (SLE).

Methods

Single‐nucleotide polymorphisms (SNPs) within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation between ancestry and the presence of risk alleles was analyzed using linear regression.

Results

A meta‐analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, ITGAM, and IRF5 were associated with lupus in a Hispanic Mestizo cohort enriched for European and Amerindian ancestry. In addition, 2 SNPs within the major histocompatibility complex region, previously shown to be associated in a genome‐wide association study in Europeans, were also associated in Mestizos. Using linear regression, we predicted an average increase of 2.34 risk alleles when comparing an SLE patient with 100% Amerindian ancestry versus an SLE patient with 0% Amerindian ancestry (P < 0.0001). SLE patients with 43% more Amerindian ancestry were predicted to carry 1 additional risk allele.

Conclusion

Our results demonstrate that Amerindian ancestry is associated with an increased number of risk alleles for SLE.

     

The SHIFT model combines clinical,electrocardiographic and echocardiographic parameters to predict sudden cardiac death in hypertrophic cardiomyopathy

IntroductionLimitations have been pointed out in the clinical risk prediction model for sudden cardiac death (SCD) of the European Society of Cardiology (ESC), which is recommended for hypertrophic cardiomyopathy (HCM) patients. The aim of this study was to determine the SCD risk of the HCM patients enrolled in a Portuguese nationwide registry and to develop a new SCD risk prediction model applicable to our population.Methods and resultsThe cohort consisted of 1022 patients (mean age 53.2±16.4 years, 59% male) enrolled in a Portuguese national HCM registry. During the follow-up period (median five years), 19 patients (1.9%) died suddenly or had aborted SCD or appropriate implantable cardioverter-defibrillator (ICD) shock therapy. Through a Cox proportional hazards model, four variables were independently associated with SCD or equivalent: unexplained Syncope, Heart failure signs, Interventricular septum thickness ≥19 mm and FragmenTed QRS complex. These predictors were included in the SHIFT model and individual risk probabilities of SCD at five years were estimated. This model was internally validated using bootstrapping. The C-index of the SHIFT model was 0.81 (95% CI: 0.77-0.83) and the C-index of the ESC model (performed in a subgroup of 349 HCM patients) was 0.77 (95% CI: 0.73-0.81) (p=0.246).ConclusionThe SHIFT model may potentially provide prognostic value and contribute to the clinical decision-making process for ICD implantation for primary prevention of SCD.     

Anticuerpos anti-RNA polimerasa III en esclerosis sistémica: estudio multicéntrico de Argentina

ObjectiveTo describe the frequency of anti-RNA polymerase III antibody in patients with Systemic Sclerosis (SSc) of a group of healthcare centres from Argentina and to explore differences among patients with positive and negative anti-RNA polymerase III antibody.Patients and MethodsData from clinical records, anamnesis and physical examination were collected from 135 patients with SSc (ACR/EULAR 2013). A serum sample from each patient was obtained for the detection of anti-RNA polymerase III IgG antibodies by ELISA.ResultsIn all, 97.8% were women and the median age at diagnosis was 53 years (range: 12-87), 77.7% had limited cutaneous SSc (lcSSC), 19,3% patients had diffuse cutaneous SSc (dcSSC) and 2.9% had scleroderma sine scleroderma. The 67.5% of the patients were from a Mestizos or Amerindian ethnic group. Anti-RNA polymerase III was positive in 5.9% of the patients. In 36 patients, the anticentromere (ACA) and anti-Scl70 antibodies were negative; anti-RNA polymerase III was positive in 16.7% of these 36 patients. Pitting scars and pulmonary artery hypertension were more frequent in anti-RNA polymerase III positive patients who were also older at diagnosis. No association with gastric antral vascular ectasia was found. The only patient with scleroderma renal crisis was anti-RNA polymerase III positive.ConclusionsAnti-RNA polymerase III frequency found in this study was one of the lowest reported, which could be related to the predominance of the Amerindian and Mestizo ethnic group. It is possible that the detection of anti-RNA polymerase III allows better classification of SSc patients, to know their prognosis and to improve their follow-up, therefore more studies are needed.     

Systemic lupus erythematosus: association with KIR and SLC11A1 polymorphisms, ethnic predisposition and influence in clinical manifestations at onset revealed by ancestry genetic markers in an urban Brazilian population

Systemic lupus erythematosus (SLE) is an autoimmune disorder of the connective tissue with a wide and heterogeneous spectrum of manifestations, with renal and neurological involvement usually related to worse prognosis. SLE more frequently affects females of reproductive age, and a high prevalence and renal manifestation seem to be associated with non-European ethnicity. The present study aims to investigate candidate loci to SLE predisposition and evaluate the influence of ethnic ancestry in the disease risk and clinical phenotypic heterogeneity of lupus at onset. Samples represented by 111 patients and 345 controls, originated from the city of Belém, located in the Northern Region of Brazil, were investigated for polymorphisms in HLA-G, HLA-C, SLC11A1, MTHFR, CASP8 and 15 KIR genes, in addition to 89 Amerindian samples genotyped for SLC11A1. We also investigated 48 insertion/deletion ancestry markers to characterize individual African, European and Amerindian ancestry proportions in the samples. Predisposition to SLE was associated with GTGT deletion at the SLC11A1 3'UTR, presence of KIR2DS2 +/KIR2DS5 +/KIR3DS1?+?profile, increased number of stimulatory KIR genes, and European and Amerindian ancestries. The ancestry analysis ruled out ethnic differences between controls and patients as the source of the observed associations. Moreover, the African ancestry was associated with renal manifestations.     

Outcome in Dilated Cardiomyopathy Related to the Extent,Location, and Pattern of Late Gadolinium Enhancement

ObjectivesThis study sought to investigate the association between the extent, location, and pattern of late gadolinium enhancement (LGE) and outcome in a large dilated cardiomyopathy (DCM) cohort.BackgroundThe relationship between LGE and prognosis in DCM is incompletely understood.MethodsThe authors examined the association between LGE and all-cause mortality and a sudden cardiac death (SCD) composite based on the extent, location, and pattern of LGE in DCM.ResultsOf 874 patients (588 men, median age 52 years) followed for a median of 4.9 years, 300 (34.3%) had nonischemic LGE. Estimated adjusted hazard ratios for patients with an LGE extent of 0 to 2.55%, 2.55% to 5.10%, and >5.10%, respectively, were 1.59 (95% confidence interval [CI]: 0.99 to 2.55), 1.56 (95% CI: 0.96 to 2.54), and 2.31 (95% CI: 1.50 to 3.55) for all-cause mortality, and 2.79 (95% CI: 1.42 to 5.49), 3.86 (95% CI: 2.09 to 7.13), and 4.87 (95% CI: 2.78 to 8.53) for the SCD endpoint. There was a marked nonlinear relationship between LGE extent and outcome such that even small amounts of LGE predicted a substantial increase in risk. The presence of septal LGE was associated with increased mortality, but SCD was most associated with the combined presence of septal and free-wall LGE. Predictive models using LGE presence and location were superior to models based on LGE extent or pattern.ConclusionsIn DCM, the presence of septal LGE is associated with a large increase in the risk of death and SCD events, even when the extent is small. SCD risk is greatest with concomitant septal and free-wall LGE. The incremental value of LGE extent beyond small amounts and LGE pattern is limited.     

Estimating the post‐neonatal prevalence of sickle cell disease in a Brazilian Population

Objective To estimate the prevalence of individuals with sickle cell disease (SCD) in Aracaju, Brazil, using the capture–recapture (CRC) method. SCD is a significant public health problem with long‐term life‐threatening complications. There are no reliable estimates of the number of individuals with this condition in Aracaju, north‐east Brazil. The CRC method has been used to quantify other ubiquitous populations. Method Three independent lists of individuals with homozygous (HbSS) SCD were constructed from patients attending the main specialist ambulatory service, all patients with SCD admitted to three government hospitals and a clinic providing specialist immunisation services to patients with SCD. Individuals were matched to ascertain whether they appeared in one, two or three lists, and population size was estimated using the log‐linear model. Results The lists identified 374 individuals. Two hundred and one appeared in one, 99 in two and 74 in three lists with an estimated number 400 (95% CI 387–418) HbSS SCD individuals; 51.6% patients with SCD were men and age ranged from 1–62 years (median 14). Conclusion The CRC method resulted in a smaller population estimate than expected. The causes of this discrepancy may include list dependence, high mortality with a survival cohort effect and the method of identifying the more severe cases. The CRC method has potential to estimate the size of this population and could supplement neonatal screening to further characterise the SCD population in this region.     

Sickle cell disease in Madhya Pradesh,Central India: A comparison of clinical profile of sickle cell homozygote vs. sickle-beta thalassaemia individuals

Background and objectives: The clinical manifestation in sickle cell disease (SCD) patients varies from one individual to another due to factors like the presence of alpha-thalassaemia mutation, foetal haemoglobin, and β-globin gene haplotype. The present study enumerates the clinical profile of sickle cell anaemia patients from Central India.

Methods: Seven hundred seventy-six SCD patients from Jabalpur and surrounding districts (Madhya Pradesh) in central India were registered with the sickle cell clinic of NIRTH, Jabalpur. The present study reveals recorded signs and symptoms of genetically confirmed sickle cell anaemia (404) and sickle beta thalassaemia (92) patients.

Results: Majority of the patients were from scheduled caste communities (47.9%) and Gond tribal community (13.8%). Splenomegaly was the most common clinical manifestation observed (71.4%). Overall, 63.5% patients had a history of blood transfusion. The most frequent signs and symptoms observed were Pallor, Icterus, Joint pain, Fever, and Fatigue. Majority of the patients revealed onset of disease prior to attaining the age of 3 years (sickle cell anaemia 44.3% and sickle beta thalassaemia 35.9%). Mean haemoglobin levels among SCA individuals were marginally higher than SBT patients. On the other hand, mean foetal haemoglobin levels among SBT individuals showed the reverse trend. Notably, the present study reports the first incidence of priapism recorded in Central India.

Conclusions: The study revealed a high prevalence of SCD among scheduled caste, backward caste, and tribal communities. Dissemination of study findings, screening, pre-marriage counselling, and pre-natal diagnosis are fundamental to preventing or lowering of birth of sickle cell anaemia children in the affected populations.     

Sudden Cardiac Death in Heart Failure Patients With Preserved Ejection Fraction

BackgroundWhereas sudden cardiac death (SCD) risk has been recognized in heart failure (HF) patients with reduced ejection fraction (HFrEF), less is known about SCD risk in HF patients with preserved EF (HFpEF). We examined the incidence and predictors of SCD in HFpEF in a large population sample.Methods and ResultsMedical records of patients discharged with a primary diagnosis of HF from hospitals in Minneapolis–St Paul in 1995 and 2000 were abstracted. HFpEF was defined as EF ≥45%. SCD was defined as cardiac arrest or out-of-hospital death due to coronary heart disease (CHD) on death certificates. A total of 2,203 patients (age 70 ± 11 years, 53% male) were included. The 787 patients (36%) with HFpEF were older, more often female and more likely to have hypertension than the 1,416 (64%) with HFrEF. All-cause mortality (52% vs 58%; P = .01) and SCD (6% vs 14%; P < .0001) rates were lower in HFpEF than in HFrEF 5 years after hospital discharge. Age, sex, CHD, and length of index hospitalization were the only independent predictors of SCD in HFpEF.ConclusionsIncidence of SCD in HFpEF is lower than in HFrEF. Present markers of SCD in HFpEF are sparse and insufficient to identify the patient at risk.     

Early response does not predict outcome in children and adolescents with chronic myeloid leukaemia treated with high‐dose imatinib

Approximately 3500 children with sickle cell disease (SCD) are born in Brazil each year, but the burden of SCD morbidity is not fully characterised. A large, multi‐centre cohort was established to characterise clinical outcomes in the Brazilian SCD population and create the infrastructure to perform genotype‐phenotype association studies. Eligible patients were randomly selected from participating sites and recruited at routine visits. A biorepository of blood samples was created and comprehensive demographic and clinical outcome data were entered in a centralized electronic database. Peripheral blood genome‐wide single nucleotide polymorphism (SNP) genotyping was performed using a customized Transfusion Medicine (TM) Array. A total of 2795 participants at six Brazilian sites were enrolled between 2013 and 2015. The cohort included slight predominance of children <18 years (55·9%) and females (53·0%). Haemoglobin (Hb) SS was the most common SCD genotype (70·7%), followed by HbSC (23%), Sβ0 (3·0%) and Sβ+ (2·9%). SNP data from the TM Array were analysed to evaluate the genetic ancestry of the cohort and revealed significant admixture among the population. Demographics and clinical complications, stratified by age and SCD genotype, are summarized and future studies in this cohort are discussed.     

Epidemiology and clinical characteristics of herpes zoster in a tertiary care hospital in Brazil

BackgroundThere is little information on herpes zoster from hospital registries in South America. The aim of this study was to describe the epidemiological and clinical aspects of herpes zoster (HZ) in hospitalized patients.’MethodsWe searched for hospital-based records during the period from March 2000 to January 2017 in a 700-bed tertiary-care hospital located in southern Brazil. The medical records of all eligible patients were reviewed, and data regarding demographics, medical history, clinical and laboratory characteristics, treatment regimens, and clinical outcomes were collected. Patients were also evaluated for mortality.ResultsThere were 801 records of herpes zoster according to the proposed criteria. Most patients with HZ presented a cutaneous clinical form of the disease with involvement of a single dermatome (n = 589, 73.5%). Additional clinical characteristics included postherpetic neuralgia (22.1%), ophthalmic HZ (7.6%) and meningoencephalitis (2.7%). Most patients presented immunocompromised conditions (64.9%) including HIV, administration of immunosuppressive agents, and malignant neoplasms. During this period, there were 105 (13.1%) deaths, which were mostly unrelated to HZ. Five deaths were related to HZ meningoencephalitis.ConclusionThe results of this study demonstrate a high burden of HZ disease in a Brazilian tertiary care hospital in the HZ vaccination era. Awareness of the incidence and comorbidity factors associated with HZ in Latin American countries such as Brazil contribute for adoption and implementation of strategies for immunization in this area.     

Hepatitis C virus genotypes and associated risk factors in the state of Pará, Northern Brazil

BackgroundDespite the emergence of more effective therapies, hepatitis C virus (HCV) infection remains a serious public health problem at the global level. Currently, this virus is classified into seven genotypes and 67 subgenotypes, which in turn are distributed heterogeneously in Brazil and worldwide. Studies have shown that this genetic divergence results in differences in the progression of chronic disease associated with HCV infection and its treatment.ObjectiveThe aim of this study was to report the frequency of HCV genotypes in the state of Pará, Northern Brazil, and to assess the association between genotype and different clinical and laboratory characteristics, as well as risk factors for infection.MethodData from 85 medical records of untreated patients who had chronic hepatitis C infection were analyzed; the patients were evaluated at two hospitals in Belem, Pará, Brazil.ResultsCirculation of genotypes 1 and 3 was detected, with a higher prevalence of genotype 1 (75.3%) than genotype 3 (24.7%). In addition, there was a predominance of subgenotype 1b (60.34%) compared to 1a (20.69%) and 3a (18.97%). Reuse of needles and/or glass syringes was significantly associated with infection by HCV genotype 1 than genotype 3; however, the small number of patients infected with genotype 3 may have biased the results. No associations between genotype and the evaluated clinical and laboratory characteristics were observed.ConclusionThis study reinforces the differences in the distribution of HCV genotypes in Brazil and showed no association between HCV genotype and progression of chronic hepatitis C in the studied group.     

Demographic and clinical features of atrial myxomas: A case series analysis

Aim: Cardiac myxomas are uncommon tumors and have a wide clinical spectrum. Their diagnosis can therefore be elusive because symptoms are nonspecific and misleading. Our aim was to characterize and analyze the clinical findings in patients presenting with cardiac myxomas. Methods: We conducted a retrospective, hospital-based case study using the electronic records of a Spanish general hospital, caring for a population of 155,000. Patients’ data were collected for the period between 2000 and 2016. Demographic data and clinical features were analyzed. Results: Our series included 22 patients over a 15-year period (annual incidence of 0.94 patients per 100,000 inhabitants). Men were predominant (68%) and the median age was 69 years. Cardiac (40.9%), systemic (27.3%), and neurological manifestations (13.6%) were the main clinical features. Left atrium (81.8%) was the predominant location. Surgical treatment was performed in all patients and the overall outcome was good in all cases. Conclusions: Cardiac myxomas are uncommon, benign tumors, predominantly located in the left atrium and mainly affecting middle-aged and elderly male patients. Congestive heart failure, stroke, and systemic symptoms, although misleading and nonspecific, are the most frequent forms of clinical presentation.     

Clinical presentation of leptospirosis: a retrospective study of 201 patients in a metropolitan city of Brazil

IntroductionLeptospirosis is a zoonosis of worldwide importance. The disease is endemic in Brazil. This study was conducted to describe the clinical and laboratory presentation of leptospirosis in a metropolitan city of Brazil.MethodsThis is a retrospective study including 201 consecutive patients with leptospirosis admitted to tertiary hospitals in Fortaleza, Brazil, between 1985 and 2006. All patients had clinical and epidemiological data suggestive of leptospirosis, and positive laboratorial test for leptospirosis (microscopic agglutination test, MAT, higher than 1:800).ResultsA total of 201 patients were included, with mean age of 38.9 ± 15.7 years; 79.1% were male. The mean length from onset of symptoms to admission was 7 ± 3 days. The main clinical signs and symptoms at admission were fever (96.5%), jaundice (94.5%), myalgia (92.5%), headache (74.6%), vomiting (71.6%) and dehydration (63.5%). Hemorrhagic manifestations were present in 35.8%. Acute kidney injury was found in 87% of the patients. Platelet count was less than 100,000/mm³ in 74.3%. Hematuria was found in 42.9%. Death occurred in 31 cases (15.4%).ConclusionsLeptospirosis is a globally relevant disease with potential fatal outcome. Signs and symptoms suggestive of leptospirosis must be known by any physician in order to institute early adequate treatment to improve outcome. Early indication and daily hemodialysis seems to be beneficial in this group of patients.     

Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal

AIM:To study the association between genetic ancestry,non-alcoholic fatty liver disease(NAFLD) metabolic characteristics in two cohorts of patients,from Brazil and Portugal. METHODS:We included 131 subjects from Brazil [(n = 45 with simple steatosis(S. Steatosis) and n = 86 with nonalcoholic steatohepatitis(NASH)] and 90 patients from Portugal(n = 66,S. Steatosis; n = 24,NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis:simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers(AT3-I/D,LPL,Sb19.3,APO,FYNull,PV92,and CKMM) with the greatest ethnicgeographical differential frequencies(≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP onlineand the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant(P 0.05). RESULTS:In the Brazilian sample,NASH was significantly more frequent among the elderly patients with diabetes(NASH 56 ± 1.1 years old vs S. Steatosis 51 ± 1.5 years old,P = 3.7 x 10-9),dyslipidemia(NASH 63% vs S. Steatosis 37%,P = 0.009),higher fasting glucose levels(NASH 124 ± 5.2 vs S. Steatosis 106 ± 5.3,P = 0.001) and Homeostatic Model of Assessment index 2.5 [NASH 5.3(70.8%) vs S. Steatosis 4.6(29.2%) P = 0.04]. In the Portuguese study population,dyslipidemia was present in all patients with NASH(P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group(P = 0.003,respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort(Brazilian cohort:P = 0.75; Portuguese cohort:P = 0.97). Nonetheless,the genetic ancestry contribution of the Brazilian and Portuguese population were different,and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH and S. Steatosis groups.CONCLUSION:There was no difference between the genetic ancestry contribution among Brazilian and Portuguese individuals with NASH and S. Steatosis from each cohort.     

Sudden Cardiac Death in Heart Failure: A 20-Year Perspective From a Mediterranean Cohort

BackgroundThe prediction of sudden cardiac death (SCD) in heart failure (HF) remains an unmet need. The aim of our study was to assess the prevalence of SCD over 20 years in outpatients with HF managed in a Mediterranean multidisciplinary HF Clinic, and to compare the proportion of SCD (SCD/all-cause death) to the expected proportional occurrence based on the validated Seattle Proportional Risk Model (SPRM) score.Methods and ResultsThis prospective observational registry study included 2772 outpatients with HF admitted between August 2001 and May 2021. Patients were included when the cause of death was known and SPRM score was available. Over the 20-year study period, 1351 patients (48.7%) died during a median follow-up period of 3.8 years (interquartile range 1.6–7.6). Among these patients, the proportion of SCD out of the total of deaths was 13.6%, whereas the predicted by SPRM was 39.6%. This lower proportion of SCD was observed independently of left ventricular ejection fraction, ischemic etiology, and the presence of an implantable cardiac defibrillator.ConclusionsIn a Mediterranean cohort of outpatients with HF, the proportion of SCD was lower than expected based on the SPRM score. Future studies should investigate to what extend epidemiological and guideline-directed medical therapy patterns influence SCD.     

DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease

Sickle cell disease (SCD) is a debilitating monogenic blood disorder with a highly variable phenotype characterized by severe pain crises, acute clinical events, and early mortality. Interindividual variation in fetal hemoglobin (HbF) expression is a known and potentially heritable modifier of SCD severity. High HbF levels are correlated with reduced morbidity and mortality. Common single nucleotide polymorphisms (SNPs) at the BCL11A and HBS1L-MYB loci have been implicated previously in HbF level variation in nonanemic European populations. We recently demonstrated an association between a BCL11A SNP and HbF levels in one SCD cohort [Uda M, et al. (2008) Proc Natl Acad Sci USA 105:1620–1625]. Here, we genotyped additional BCL11A SNPs, HBS1L-MYB SNPs, and an SNP upstream of ^Gγ-globin (HBG2; the XmnI polymorphism), in two independent SCD cohorts: the African American Cooperative Study of Sickle Cell Disease (CSSCD) and an SCD cohort from Brazil. We studied the effect of these SNPs on HbF levels and on a measure of SCD-related morbidity (pain crisis rate). We strongly replicated the association between these SNPs and HbF level variation (in the CSSCD, P values range from 0.04 to 2 × 10⁻⁴²). Together, common SNPs at the BCL11A, HBS1L-MYB, and β-globin (HBB) loci account for >20% of the variation in HbF levels in SCD patients. We also have shown that HbF-associated SNPs associate with pain crisis rate in SCD patients. These results provide a clear example of inherited common sequence variants modifying the severity of a monogenic disease.     

GSTT1 (rs4025935) null genotype is associated with increased risk of sickle cell disease in the populations of Tabuk—Northwestern region of Saudi Arabia

Background: Glutathione system plays an important role in the protection of cells and tissue against damage from oxidative stress. Impairment of the glutathione system due to genetic polymorphism of GST genes may increase the risk and severity of sickle cell disease (SCD). Present study was, therefore, undertaken to examine the relative impact of the genetic polymorphism of GSTT1 and GSTM1 (rs4025935 and rs71748309) on susceptibility and hematological aspects of the patients with SCD.

Methods: Present study included 100 patients with SCD and 200 healthy controls from northwestern region of Saudi Arabia. GSTM1 and GSTT1 (rs4025935 and rs71748309) genotypes were investigated by using single-tube multiplex PCR technique.

Results: It was observed that patients with SCD possessed significantly higher frequency of GSTT1 null genotype (26%) than healthy controls (15%), (P?=?0.00001). Compared to the presence of GSTT1 genotype, the OR for the GSTT1 null genotype were estimated to be 4.3 (2.17–8.64, P?=?0.00001). However, such association was not observed with respect to the presence of GSTM1 null genotype. In addition, it was observed that SCD in patients with GSTT1 genotype, the mean percentage levels for HbF and HbS were 0.48 and 35.4%, respectively; however, among SCD patients with GSTT1 null genotype, the mean percentage levels were significantly higher 1.62% (P?=?0.004) and 39.38% (P?=?0.02), respectively.

Conclusion: GSTT1 null genotype is significantly associated with increased risk of SCD among the population of northwestern region of Saudi Arabia. In addition, it may be one of the important factors responsible for hematological manifestations of SCD.     

Prognostic Significance of Nonischemic Myocardial Fibrosis in Patients With Normal LV Volumes and Ejection-Fraction

ObjectivesThis study aims to investigate the prognostic significance of late gadolinium enhancement (LGE) in patients without coronary artery disease and with normal range left ventricular (LV) volumes and ejection fraction.BackgroundNonischemic patterns of LGE with normal LV volumes and ejection fraction are increasingly detected on cardiovascular magnetic resonance, but their prognostic significance, and consequently management, is uncertain.MethodsPatients with midwall/subepicardial LGE and normal LV volumes, wall thickness, and ejection fraction on cardiovascular magnetic resonance were enrolled and compared to a control group without LGE. The primary outcome was actual or aborted sudden cardiac death (SCD).ResultsOf 748 patients enrolled, 401 had LGE and 347 did not. The median age was 50 years (interquartile range: 38-61 years), LV ejection fraction 66% (interquartile range: 62%-70%), and 287 (38%) were women. Scan indications included chest pain (40%), palpitation (33%) and breathlessness (13%). No patient experienced SCD and only 1 LGE+ patient (0.13%) had an aborted SCD in the 11th follow-up year. Over a median of 4.3 years, 30 patients (4.0%) died. All-cause mortality was similar for LGE+/- patients (3.7% vs 4.3%; P = 0.71) and was associated with age (HR: 2.04 per 10 years; 95% CI: 1.46-2.79; P < 0.001). Twenty-one LGE+ and 4 LGE- patients had an unplanned cardiovascular hospital admission (HR: 7.22; 95% CI: 4.26-21.17; P < 0.0001).ConclusionsThere was a low SCD risk during long-term follow-up in patients with LGE but otherwise normal LV volumes and ejection fraction. Mortality was driven by age and not LGE presence, location, or extent, although the latter was associated with greater cardiovascular hospitalization for suspected myocarditis and symptomatic ventricular tachycardia.     

Prevalência e Características Relacionadas de Pacientes com Eletrocardiograma com Padrão de Brugada em Santa Catarina,Brasil

Background:Brugada Syndrome is an inherited arrhythmogenic disorder characterized by the presence of specific electrocardiographic features with or without clinical symptoms. The patients present increased risk of sudden death due to ventricular fibrillation. The prevalence of this electrocardiographic pattern differs according to the studied region. However, epidemiological information including the Brazilian population is scarce.Objectives:To assess the prevalence of the electrocardiographic pattern of Brugada syndrome and the epidemiological profile associated with it.Methods:Cross-sectional study that included 846,533 ECG records of 716,973 patients from the electrocardiogram (ECG) database from the Santa Catarina Telemedicine Network over a 4-year period. All tests were 12-lead conventional ECG (without V1 and V2 in high positions). The tests revealing “Brugada Syndrome” diagnosis (Types 1 and 2) were reviewed by a cardiac electrophysiologist. The level of significance was set at p<0.05.Results:In total, 83 patients had a pattern potentially consistent with Brugada-type pattern ECG. Of these, 33 were confirmed having Brugada-type 1, and 22 with type 2 ECG after reevaluation. The prevalence of Brugada-type 1 ECG was 4.6 per 100,000 patients. Brugada-type 1 ECG was associated with the male gender (81.8% vs. 41.5%, p<0.001) and a lower prevalence of obesity diagnosis (9.1% vs. 26.4%, p=0.028).Conclusions:This study showed low prevalence of Brugada-type ECG in Southern Brazil. The presence of Brugada-type 1 ECG was associated with the male gender and lower prevalence of obesity diagnosis comparing to the general population.