scholarly journals Sudden death in a young patient with atrial fibrillation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
María Tamargo ◽  
María Ángeles Espinosa ◽  
Víctor Gómez-Carrillo ◽  
Miriam Juárez ◽  
Francisco Fernández-Avilés ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiac Arrest ◽  
Genetic Testing ◽  
Sudden Death ◽  
Clinical Data ◽  
Molecular Mechanisms ◽  
Young Patients ◽  
Structural Heart Disease ◽  
Polymorphic Ventricular Tachycardia ◽  
Qt Syndrome

Sudden cardiac death (SCD) in young patients without structural heart disease is frequently due to inherited channelopathies such as long QT syndrome (LQTS), Brugada syndrome or Catecholaminergic polymorphic ventricular tachycardia. Accordingly, the addition of genetic testing to clinical data may be useful to identify the cause of the sudden death in this population. Mutations in the KCNQ1 encoded Kv7.1 channel are related to type 1 LQTS, familial atrial fibrillation (AF), short QT syndrome, and SCD. We present a clinical case where the presence of AF after resuscitation in a young man with cardiac arrest was the key clinical data to suspect an inherited disorder and genetic testing was the main determinant for identifying the cause of the cardiac arrest. The KCNQ1 p.Arg231His mutation explained the combined phenotype of AF and susceptibility to ventricular arrhythmias. The case highlights the importance of continued research in genetics and molecular mechanisms of channelopathies.

P4797Genetic testing in 101 consecutive lone atrial fibrillation patients is able to identify a subgroup with increased severity

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G D'Arezzo Pessente ◽  
F D Darrieux ◽  
L S Sacilotto ◽  
N O Olivetti ◽  
F W Wulkan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Genetic Testing ◽  
Family History ◽  
Sudden Death ◽  
Genetic Variants ◽  
Family Members ◽  
Young Patients ◽  
National Council ◽  
Severe Phenotype ◽  
History Of

Abstract Introduction Atrial fibrillation (AF) is the most common arrhythmia and the cause of 15% of all strokes and up to 6% of medical admissions. It is estimated that currently about 2.0 million Brazilians, and 30 million individuals worldwide, are affected by the disease. It is a complex and multifactorial disease, and the mechanisms are still not well understood. Between 10–20% of AF patients do not have any known predisposing factors, a condition once called “lone AF”. The role of genetic testing still remains controversial in this clinical scenario. Purpose The aim of this study was to identify the occurrence of pathogenic genetic variants in patients with atrial fibrillation without known risk factors. Methods In a tertiary hospital, 101 young patients with apparent “lone AF” were screened with genetic testing by NGS using a custom genetic panel with 159 channelopathy and cardiomyopathy related genes. Variants found were classified according to the American College of Genetic and Genomic (ACMG) criteria. Subjects were evaluated with clinical and familial history, electrocardiogram, 24 hours Holter monitoring, echocardiogram, cardiac MRI and treatment response. Multivariate analyses were performed by logistic linear regression model. Results During an inclusion period of 4 years, 101 consecutive patients, with mean age of 38.6 years old, were classified as “lone AF” (78% male); 76% presented paroxysmal AF and 24% persistent/permanent AF. Family history of early sudden death (bellow 60 years old) was reported in 37% of cases (78% below 50 years old); 10% had family members with pacemakers; and 44% reported having family members with early AF onset. Genetic testing demonstrated that 14/101 (13.8%) of patients presented genetic variants classified as pathogenic or likely pathogenic (P/LP) according to ACMG criteria. The genes most frequently affected were LMNA (3/101), ANK2 (3/101) and truncating variants in TTN (3/101). Two variables were significantly associated with harboring a pathogenic mutation: family history of sudden death (OR: 5.58; 1,19–26,12 CI; p=0.029) and pacemaker reported in the family history (OR: 6.83; 1.11–42.04 CI; p=0.038). Conclusion Our data showed that approximately 15% of “lone AF” patients are carriers of known pathogenic mutations in genes associated with inherithed cardiomyopathy. In addition, we show that being a carrier is potentially associated with a more severe phenotype. These findings suggest that genetic testing in “lone AF” patients may be able to identify a subgroup with a more severe phenotype are for whom a different management strategy might be indicated. Acknowledgement/Funding National Council for Scientific and Technological Development (CNPq)

The Postmortem Interpretation of Cardiac Genetic Variants of Unknown Significance in Sudden Death in the Young: A Case Report and Review of the Literature

2020 ◽  
Vol 10 (3-4) ◽  
pp. 166-175
Author(s):  
Saleh Fadel ◽  
Alfredo E. Walker
Keyword(s):  
Genetic Testing ◽  
Sudden Death ◽  
Traumatic Event ◽  
Screening Tests ◽  
Polymorphic Ventricular Tachycardia ◽  
Unique Challenge ◽  
Variants Of Unknown Significance ◽  
Prophylactic Measures ◽  
Unknown Significance ◽  
Qt Syndrome

Sudden cardiac death (SCD) in adolescents and young adults is a major traumatic event for families and communities. In these cases, it is not uncommon to have a negative autopsy with structurally and histologically normal heart. Such SCD cases are generally attributed to channelopathies, which include long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. Our understanding of the causes for SCDs has changed significantly with the advancements in molecular and genetic studies, where many mutations are now known to be associated with certain channelopathies. Postmortem analysis provides great value in informing decision-making with regard to screening tests and prophylactic measures that should be taken to prevent sudden death in first degree relatives of the decedent. As this is a rapidly advancing field, our ability to identify genetic mutations has surpassed our ability to interpret them. This led to a unique challenge in genetic testing called variants of unknown significance (VUS). VUSs present a diagnostic dilemma and uncertainty for clinicians and patients with regard to next steps. Caution should be exercised when interpreting VUSs since misinterpretation can result in mismanagement of patients and their families. A case of a young adult man with drowning as his proximate cause of death is presented in circumstances where cardiac genetic testing was indicated and undertaken. Eight VUSs in genes implicated in inheritable cardiac dysfunction were identified and the interpretation of VUSs in this scenario is discussed.

Indications for genetic testing in athletes and its application in daily practice

2019 ◽  
pp. 166-176
Author(s):  
Andrea Mazzanti ◽  
Katherine Underwood ◽  
Silvia G. Priori
Keyword(s):  
Cardiovascular Disease ◽  
Genetic Testing ◽  
Genetic Information ◽  
Cardiac Death ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Daily Practice ◽  
Polymorphic Ventricular Tachycardia ◽  
Molecular Testing ◽  
Long Qt ◽  
Qt Syndrome

Genetic information is fundamental for the management of patients with primary arrhythmia syndromes (e.g. long QT syndrome or catecholaminergic polymorphic ventricular tachycardia) and cardiomyopathies (e.g. arrhythmogenic right ventricular cardiomyopathy or hypertrophic cardiomyopathy) which increase the risk of sudden cardiac death. Importantly, molecular testing can play a pivotal role in establishing a clinical diagnosis of an inherited cardiovascular disease, particularly when the phenotype in unclear and overlaps with the normal adaptations induced in the heart by chronic exercise. However, the decision to undergo genetic testing needs to be justified on a clinical basis and handled by professionals who are capable of framing the results in the correct perspective. In this chapter we will answer the following questions. When should genetic testing be performed in athletes? Which genetic tests should be requested for athletes? What impact should a positive genetic result have on sports eligibility?

scholarly journals Acquired Long QT Syndrome: A Review of the Literature

2020 ◽  
Vol 3 (1) ◽  
pp. 67-70
Author(s):  
Rajendram R
Keyword(s):  
Cardiac Arrest ◽  
Long Qt Syndrome ◽  
Qt Interval ◽  
Torsade De Pointes ◽  
Polymorphic Ventricular Tachycardia ◽  
Beta Blockade ◽  
Illustrative Case ◽  
Long Qt ◽  
Life Threatening ◽  
Qt Syndrome

The QT interval represents the duration of ventricular depolarization and repolarization. It is measured from the beginning of the QRS complex to the end of the T wave. Prolongation of the QT interval may be congenital or acquired. This increases the risk of polymorphic ventricular tachycardia (i.e torsades de pointes) and cardiac arrest. To increase the awareness of this life-threatening phenomenon I outline an illustrative case in which acquired prolongation of the QT interval due to electrolyte derangement and administration of ciprofloxacin resulted in cardiac arrest due to torsade de pointes. Management of a patient with a long QT syndrome includes Immediate cessation of drugs that prolong the QT interval; cardiac monitoring, serial 12 lead ECGs and transthoracic echocardiography; measurement of serum electrolytes; intravenous potassium replacement; intravenous magnesium replacement; beta-blockade. Causes of acquired prolongation of the QT interval are common in critically ill patients. It is important to recognize this and consider screening with 12 lead ECG to reduce the risk of life-threatening ventricular arrhythmias.

Abstract 2194: Predictors of RyR2 Genotype Among Patients Referred for Long QT Syndrome Genetic Testing

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
David J Tester ◽  
Melissa L Will ◽  
Michael J Ackerman
Keyword(s):  
Cardiac Arrest ◽  
Genetic Testing ◽  
Mutational Analysis ◽  
Age At Diagnosis ◽  
Polymorphic Ventricular Tachycardia ◽  
Cardiac Events ◽  
Blocker Therapy ◽  
Targeted Analysis ◽  
Lqts Gene

Introduction : Type 1 catecholaminergic polymorphic ventricular tachycardia (CPVT1) is pursuant to mutations in the RyR2- encoded cardiac ryanodine receptor. Recently, we discovered nearly as many CPVT1-causing mutations as LQT3-causing mutations in a large cohort of unrelated LQTS referral patients. Here, we examine potential predictors of RyR2 genotype (CPVT1) among LQTS referral patients. Methods : Previously, comprehensive mutational analysis of the LQT1–10 susceptibility genes was completed for 541 unrelated patients (358 females, average age at diagnosis = 24 years, average QTc = 482 ms) referred for LQTS genetic testing. Using PCR, DHPLC, and DNA sequencing, we performed targeted analysis of RyR2 involving 44 exons (8–15, 37–49, 83–105) for the 260 unrelated referrals (172 females, average age at diagnosis = 25 years, average QTc = 470 ms) that remained “genotype-negative” following LQTS genetic testing. Results : Overall, 22 distinct RyR2 mutations (19 novel) were seen in 23 (8.8%, 12 females, average age at diagnosis = 22 ±14 years) unrelated “genotype-negative” LQTS individuals. Compared to patients with either genetically proven LQTS or the remaining genotype negative cohort, the RyR2 -positive cohort had significantly lower average QTc (419 ms vs 494 ms, p =2.4 ×10 −6 ; vs 472 ms, p = 0.005) and was more likely to experience either syncope (88% vs 66%, p = 0.06 vs 53%, p = 0.008) or cardiac arrest (56% vs 23%, p = 0.006 vs 17%, p = 0.001). Overall, 123 of the 541 LQTS referrals (23%) exhibited exertion-induced cardiac events (68 LQTS gene positive; 42 gene negative, and 13 RyR2-positive). Every RyR2 -positive case with an exertionally-triggered event had a QTc ≤ 460 ms, compared to only 17% of LQTS gene positive cases (p = 0.1 × 10 −8 ) and 24% of LQT1 cases. None of the exertion-induced LQTS gene positive cases had a QTc ≤ 420 ms. Conclusions: Failure to distinguish CPVT from LQTS can be a fatal mistake, as individuals with CPVT1 have a more severe phenotype and are much less protected by beta blocker therapy than those with LQT1. CPVT1, rather than concealed LQT1, should lead the differential diagnosis in the setting of syncope/cardiac arrest during exercise and a normal resting QTc.

Abstract 3091: The Clinical and Electrocardiographic Phenotype of Unrelated Patients with Genotype-Negative Long QT Syndrome

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Malek M El Yaman ◽  
David J Tester ◽  
Argelia Medeiros Domingo ◽  
Carla M Haglund ◽  
Michael J Ackerman
Keyword(s):  
Cardiac Arrest ◽  
Genetic Testing ◽  
Family History ◽  
Long Qt Syndrome ◽  
Susceptibility Genes ◽  
Long Qt ◽  
Diagnostic Score ◽  
Minor Genes ◽  
History Of ◽  
Qt Syndrome

Long QT syndrome (LQTS) is a heterogeneous group of channelopathies characterized by increased risk of potentially lethal ventricular arrhythmias. LQT1, LQT2, and LQT3 comprise 95% of genetically proven cases and exhibit a number of established genotype-phenotype correlations. The study aimed at examining the phenotypes of genotype-negative LQTS, accounting for ~25% of LQTS cases. An IRB-approved retrospective analysis was conducted on 56 patients (39 female, 25 ± 17 years) who, after genetic testing either in our sudden death genomics laboratory or with the commercially available Familion test, were negative for mutations in the 3 principal LQTS-susceptibility genes ( KCNQ1, KCNH2, and SCN5A), and the minor genes underlying LQT5 and LQT6. All had been diagnosed with LQTS, with a clinical diagnostic score of ≥ 3.5 or QTc ≥ 480 ms. The mean diagnostic score was 4.4 (95% CI 4.2 – 4.7); mean QTc was 525 ms (95% CI 508 – 543 ms). Two-thirds were symptomatic (syncope, cardiac arrest, and/or seizures) with exercise-triggered events in 10 (26%). Twenty-one (38%) had a family history of sudden cardiac arrest. ECG showed a T wave pattern suggestive of LQT1 in 32%, LQT2 in 43%, and LQT3 in 18%. In those with exercise-induced symptoms, the ECG was LQT2-like in 50% and LQT1-like in 30%. One patient had post-partum syncope with an LQT2-like ECG. None had an auditory trigger, but 3 patients, all with an LQT2-like ECG, had a family history of auditory-triggered events. One-third of the patients had received an ICD, 58% as secondary prevention. Over 2/3 were on beta-blockers. Among the 45 patients so far tested for mutations in minor LQTS-susceptibility genes, 2 had LQTS-causing mutations in ANKB (LQT4), 1 in SCN4B (LQT10), 1 in AKAP9 (LQT11) and 2 in SNTA1 (LQT12). Genotype-negative patients with a firm LQTS diagnosis show marked phenotypic heterogeneity, suggesting multiple underlying pathogenic pathways. Only a few patients have LQTS-causing mutations in minor genes after complete LQT1–12 genetic testing. Classifying genotype negative patients into LQT1-, LQT2-, or LQT3-like profiles may guide the discovery of novel genes encoding channel interacting proteins corresponding to those specific signaling pathways.

scholarly journals Electrocardiographic Assessment and Genetic Analysis in Neonates: a Current Topic of Discussion

2018 ◽  
Vol 15 (1) ◽  
pp. 30-37 ◽  
Author(s):  
Georgia Sarquella-Brugada ◽  
Sergi Cesar ◽  
Maria Dolores Zambrano ◽  
Anna Fernandez-Falgueras ◽  
Victoria Fiol ◽  
...  
Keyword(s):  
Sudden Death ◽  
Genetic Analysis ◽  
Screening Program ◽  
Cost Effective ◽  
Polymorphic Ventricular Tachycardia ◽  
Clinical Value ◽  
Unexpected Death ◽  
Technological Advances ◽  
Qt Syndrome ◽  
Low Prevalence

Background: Sudden death of a newborn is a rare entity, which may be caused by genetic cardiac arrhythmias. Among these diseases, Long QT syndrome is the most prevalent arrhythmia in neonates, but other diseases such as Brugada syndrome, Short QT syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia also cause sudden death in infants. All these entities are characterized by well-known alterations in the electrocardiogram and the first symptom of the disease may be an unexpected death. Despite the low prevalence of these diseases, the performance of an electrocardiogram in the first hours or days after birth could help identify these electrical disruptions and adopt preventive measures. In recent years, there has been an important impulse by some experts in the scientific community towards the initiation of a newborn electrocardiogram-screening program, for the detection of these electrocardiographic abnormalities. In addition, the use of genetic analysis in neonates could identify the cause of these heart alterations. Identification of relatives carrying the genetic alteration associated with the disease allows adoption of measures to prevent lethal episodes. Conclusion: Recent technological advances enable a comprehensive genetic screening of a large number of genes in a cost-effective way. However, the interpretation of genetic data and its translation into clinical practice are the main challenges for cardiologists and geneticists. However, there is important controversy as to the clinical value, and cost-effectiveness of the use of electrocardiogram as well as of genetic testing to detect these cases. Our review focuses on these current matters of argue.

Abstract 15884: Life-threatening Arrhythmias With Autosomal Recessive TECRL Variants

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Gregory Webster ◽  
Elhadi H Aburawi ◽  
Marie Chaix ◽  
Stephanie Chandler ◽  
Roger Foo ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Sudden Death ◽  
Long Qt Syndrome ◽  
Catecholaminergic Polymorphic Ventricular Tachycardia ◽  
Polymorphic Ventricular Tachycardia ◽  
Long Qt ◽  
Long Term Follow Up ◽  
Qt Syndrome

Introduction: Sudden death and aborted sudden death have been observed in patients with biallelic variants in TECRL . Phenotypes have only begun to be described and no data are available on medical therapy after long-term follow-up. Methods: An international, multicenter retrospective review was conducted. We report new cases associated with TECRL variants and long-term follow-up from previously published cases. Results: We present 10 cases and 37 asymptomatic heterozygous carriers. Median age at onset of cardiac symptoms was 8 years (range 1-22 years) and cases were followed for an average of 10.3 years (SD 8.3), right censored by death in 3 cases. All patients on metoprolol, bisoprolol or atenolol were transitioned to nadolol or propranolol due to failure of therapy. Phenotypes typical of both long QT syndrome and catecholaminergic polymorphic ventricular tachycardia were observed. We also observed divergent phenotypes in some cases despite identical homozygous variants. None of 37 heterozygous family members had a cardiac phenotype. Conclusions: Patients with biallelic pathogenic TECRL variants present with variable cardiac arrhythmia phenotypes, including those typical of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia. Nadolol and propranolol may be superior beta-blockers in this setting. No cardiac disease or sudden death was present in patients with a heterozygous genotype.

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