Sudden Death In Young Patients Research Articles

Clinical findings and outcomes of Brugada syndrome in women

Abstract Introduction Brugada syndrome (BrS) is a genetic disorder characterized by typical ECG changes and association with spontaneous ventricular tachyarrhythmia (VTA) and sudden death in young patients. BrS has been widely established to be particularly prevalent in men, however less information exists regarding female patients and their long-term risk. Objectives The purpose of this study was to investigate the clinical characteristics and long-term prognosis of women with BrS. Methods This study includes a retrospective analysis of a single-center cohort of patients followed and observed for relevant clinical outcomes. The data collected included demographic data, severity of symptoms (e.g. syncope, VTA), cardioverter-defibrillator logs and occurrence of sudden cardiac death. Results 317 patients were diagnosed with BrS between 1998 and 2023. Among those, 112 (36%) were female. At presentation, 5 patients (4%) were symptomatic with history of survived cardiac arrest and/or documented VTA. 29 (26%) had history of unexplained syncope and 78 (70%) were asymptomatic. The average age at diagnosis was 42.1±15.1 yrs. as opposed to 40.1±14.2 yrs. in men. Females presented less frequently with a type 1 ECG pattern (5% vs 21%; p<0.01), had a trend to a higher rate of family history of sudden cardiac death (31% vs 25%; p=n.s.), and had less sustained VTA during programmed ventricular stimulation (4% vs 19%; p<0.01). Genetic testing was performed in 89 females (79% of the sample) and pathogenic variants were present in 36 (40%) women. An implantable cardioverter defibrillator was inserted in 24 (31%) females for primary prevention. During mean follow-up of 138±72 months, 11 women had cardiovascular events (syncope, VT/VF or death). Syncope was most common and occurred in 8 cases. No VTA were documented in any female patient. In the group of ICD patients, 8 shocks have occurred. None of these were deemed appropriate by medical controls. There were 3 deaths. Two were considered non-arrhythmic due to pulmonary embolism and breast carcinoma. One ICD patient died suddenly during sleep. Unfortunately, no device interrogation data was available. Conclusion Women typically present less symptomatic and demonstrate a reduced incidence of life-threatening arrhythmias during follow-up , often experiencing a frequent occurrence of inappropriate implantable defibrillator therapy. The less frequent prevalence of the BrS ECG pattern in women adds complexity to the diagnostic process. Further studies are still needed to elucidate gender differences for risk stratification of BrS.

Prediction and Prevention of Sudden Death in Young Patients (

Highly reliable identification of adults with hypertrophic cardiomyopathy (HC) at risk for sudden death (SD) has been reported. A significant controversy remains, however, regarding the most reliable risk stratification methodology for children and adolescents with HC. The present study assesses the accuracy of SD prediction and prevention with prophylactic implantable cardioverter-defibrillators (ICDs) in young HC patients. The study group is comprised of 146 HC patients <20 years of age evaluated consecutively over 17 years with prospective risk stratification and ICD decision-making. We relied on ≥1 established individual risk markers considered major within each patient's clinical profile, based on an enhanced American College of Cardiology /American Heart Association (ACC/AHA) guidelines algorithm. Of the 60 largely asymptomatic patients implanted with primary prevention ICDs at age 15 ± 4 years, 9 (15%) experienced device therapy terminating potentially lethal ventricular tachyarrhythmias and restoring sinus rhythm at 19 ± 6 years (range 9 to 29), 5.1 ± 6.0 years after implant; 3 patients had multiple appropriate ICD discharges. The individual risk marker algorithm was associated with 100% sensitivity in predicting SD events (95%CI: 69, 100) and 63% specificity for identifying patients without events (95%CI: 54, 71). Of these patients with device therapy, massive left ventricular hypertrophy (absolute wall thickness ≥30 mm) was the most common predictor, present in 70% of patients either alone or in combination with other risk markers. Each of the 146 study patients have survived to date at 22 ± 5 years, including all 86 without ICD recommendations. In conclusion, an enhanced ACC/AHA risk stratification strategy, based on established individual risk markers, was highly reliable in prospectively predicting SD events in children and adolescents with HC, and preventing arrhythmia-based catastrophes in this susceptible high risk population.

La mort par infarctus du myocarde chez le sujet jeune : étude de 312 cas de mort subite

Sudden cardiac death in young is seen as a dramatic phenomenon requiring knowledge of its impact. We aim to study the epidemiological characteristics of sudden cardiac ischemic death in young, and to discuss his involvement in the occurrence of death. We performed a retrospective cohort study using autopsy data from the department of forensic medicine of the University Hospital of Fattouma Bourguiba, Monastir-Tunisia. A review of all autopsies performed during 23 years was done. In each case, clinical information and circumstances of death were obtained. We have included all sudden death in persons aged between 1 year and 35 years for the male and from one year to 45 years for female. We collected 312 cases of sudden death during the studied period. The collected data were processed using SPSS 20. The significance level was set at 0.05. Thirty-two cases of cardiac ischemic sudden death have been collected. Myocardial infarction was the second cause of sudden death in young patients. There was a male predominance. The most affected subjects were aged between 25–45 years. The death occurred more frequently at rest. Coronary artery disease has been discovered in twenty-four cases (75%). The myocardial infarction occurred on healthy coronary arteries in eight cases. An anomalous course of coronary arteries, in particular myocardial bridging, was found in eight cases (25%). Toxicological screening was negative in all cases. Identifying epidemiological characteristics of sudden cardiac ischemic death in this population is important for guiding approaches to prevention that must be based on dietary hygienic measures and the control of cardiovascular risk factors.

A Rare Cause of Supraventricular Ectopic Beats and Angina in a Young Patient

Abstract Introduction: We present the case of a young man with multiple atherosclerotic risk factors and a rare cause of angina and supraventricular ectopic beats. Case presentation: A 35-year-old man with one-year history of stable angina pectoris and supraventricular ectopic beats, without any medication, presented to the emergency room complaining of anterior chest pain that occurs at moderate physical exertion. The rest electrocardiogram, transthoracic echocardiography, and chest X-ray were normal; the exertion stress test was also normal, except for supraventricular ectopic beats (trigeminal rhythm). Due to the intermediate pre-test probability of coronary artery disease, he was evaluated using coronary computed tomography angiography. An anomalous origin of the right coronary artery from the left coronary sinus, with an inter-arterial course and without any atheroma plaques, was observed. During hospitalization the evolution was stable, without complications. The patient was further referred to a cardiac surgery clinic to evaluate the possibility of surgical treatment of this anomaly. Conclusions: Coronary artery anomalies are very rare; however, they present multiple implications in current practice. The most severe complication of this condition is represented by sudden death in young patients due to malignant ventricular arrhythmias. Imaging diagnostic techniques allow for a rapid, noninvasive diagnosis of this rare cause of angina.

Clinical Yield of Familial Screening After Sudden Death in Young Subjects: The French Experience.

After sudden cardiac death with negative autopsy, clinical screening of relatives identifies a high proportion of inherited arrhythmia syndrome. However, the efficacy of this screening in families not selected by autopsy has never been assessed. We aim to investigate the value of clinical screening in relatives of all subjects who died suddenly before 45 years of age. One hundred and three consecutive families who experienced unexplained sudden cardiac death before 45 years of age were included from May 2009 to December 2014 in a prospective multicenter registry. Clinical screening was provided to all relatives and performed in 64 families (230 relatives, 80 unexplained sudden cardiac death). Diagnosis was established in 16 families (25%), including Brugada syndrome (7), long QT syndromes (5), dilated cardiomyopathy (2), and hypertrophic cardiomyopathy (2). The diagnostic yield was mainly dependent on the number of screened relatives (3.8±3.4 screened relatives in diagnosed families versus 2.0±1.5; P<0.005) rising to 47% with at least 3 relatives. It additionally increased from 3 of 32 (9%) to 9 of 22 (41%) when both parents were screened (P=0.01). Diagnostic performance was also dependent on the exhaustiveness of screening (70% of complete screening in the diagnosed families versus 25%; P<0.0001) with 17 Brugada syndromes and 15 long QT syndromes diagnosed based on pharmacological tests. Even without autopsy, familial screening after sudden death in young patients is effective. Broad screening of relatives and systematic tests, including pharmacological challenges, greatly increases the likelihood of diagnosis in families.

Sudden Death in a Young Patient with Atrial Fibrillation

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.

Anomalous Aortic Origin of Left Coronary Artery Leading to Sudden Cardiac Arrest in Young Female

Purpose: Anomalous aortic origin of the coronary artery(AAOCA) is an uncommon but important cause of sudden death in young patients. Vigilance is required to ascertain a prompt diagnosis and expedite surgery to prevent further fatal events. We describe a case of a 20-year-old female with an anomalous left coronary artery origin, whose presentation and path to diagnosis and treatment is outlined. Methodology: A 20-year-old female presented following an out of hospital cardiac arrest (OOHCA) whilst swimming. ROSC was achieved with CPR and a single defibrillation from an AED. History revealed recurrent episodes of chest pain and syncope over the previous 4 years. She was evaluated 3 years prior by cardiology; TTE and EST were found to be normal and EP review for prolonged QTS stratified her as a low risk for QTS. She was discharged without further investigations. CTCA performed following her arrest revealed an anomalous left coronary artery, arising from the right coronary sinus, passing intramurally between the aortic root and pulmonary trunk. This was repaired by deroofing the left coronary artery across the top of the left and right commisure of the aortic valve. The aortic valve commisure was re-suspended with good outcome. Results: Surgery provided excellent immediate results and exercise stress test at 6 months was negative. She remained asymptomatic with no further episodes of chest pain or syncope and is now able to perform strenuous activities. Conclusion: The AAOCA arising from the opposite sinus of Valsalva is a rare but an important condition which targets children and adolescents with an often fatal outcome if diagnosis is missed.

The Italian subcutaneous implantable cardioverter-defibrillator survey: S-ICD, why not?

AimsA recommendation for a subcutaneous-implantable cardioverter-defibrillator (S-ICD) has been added to recent European Society of Cardiology Guidelines. However, the S-ICD is not ideally suitable for patients who need pacing. The aim of this survey was to analyse the current practice of ICD implantation and to evaluate the actual suitability of S-ICD.Methods and resultsThe survey ‘S-ICD Why Not?’ was an independent initiative taken by the Italian Heart Rhythm Society (AIAC). Clinical characteristics, selection criteria, and factors guiding the choice of ICD type were collected in consecutive patients who underwent ICD implantation in 33 Italian centres from September to December 2015. A cardiac resynchronization therapy (CRT) device was implanted in 39% (369 of 947) of patients undergoing de novo ICD implantation. An S-ICD was implanted in 12% of patients with no CRT indication (62 of 510 with available data). S-ICD patients were younger than patients who received transvenous ICD, more often had channelopathies, and more frequently received their device for secondary prevention of sudden death. More frequently, the clinical reason for preferring a transvenous ICD over an S-ICD was the need for pacing (45%) or for antitachycardia pacing (36%). Nonetheless, only 7% of patients fulfilled conditions for recommending permanent pacing, and 4% of patients had a history of monomorphic ventricular tachycardia that might have been treatable with antitachycardia pacing.ConclusionThe vast majority of patients needing ICD therapy are suitable candidates for S-ICD implantation. Nevertheless, it currently seems to be preferentially adopted for secondary prevention of sudden death in young patients with channelopathies.

Cardiac Magnetic Resonance and Computed Tomography in Hypertrophic Cardiomyopathy: an Update.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease and represents the main cause of sudden death in young patients. Cardiac magnetic resonance (CMR) and cardiac computed tomography (CCT) are noninvasive imaging methods with high sensitivity and specificity, useful for the establishment of diagnosis and prognosis of HCM, and for the screening of patients with subclinical phenotypes. The improvement of image analysis by CMR and CCT offers the potential to promote interventions aiming at stopping the natural course of the disease. This study aims to describe the role of RCM and CCT in the diagnosis and prognosis of HCM, and how these methods can be used in the management of these patients.

The role of cardiovascular magnetic resonance in sudden death risk stratification in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death in young patients, but current risk stratification strategies do not identify all patients at risk. Contrast-enhanced cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) can identify areas of abnormal myocardial substrate comprising fibrosis, the structural nidus for potentially life-threatening ventricular arrhythmias. More recently, follow-up studies have demonstrated a strong relationship between extent of LGE in patients with HCM and increased risk of adverse disease-related events, including sudden death.

Family History of Sudden Death Should Be a Primary Indication for Implantable Cardioverter Defibrillator in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden death in young patients. A number of noninvasive clinical markers, including family history, have formed the basis for a risk stratification strategy aimed at identifying high-risk patients with HCM. The observation that sudden death can occur in multiple relatives of the same family, and clinical studies in which a family history of HCM-related sudden death emerges as an independent predictor of sudden death, support the principle that family history should be considered a risk factor which, in the appropriate clinical scenario, can form the basis for recommending prophylactic implantable cardioverter defibrillator therapy.

Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: disease mechanisms and pharmacological rescue.

Jervell and Lange-Nielsen syndrome (JLNS) is one of the most severe life-threatening cardiac arrhythmias. Patients display delayed cardiac repolarization, associated high risk of sudden death due to ventricular tachycardia, and congenital bilateral deafness. In contrast to the autosomal dominant forms of long QT syndrome, JLNS is a recessive trait, resulting from homozygous (or compound heterozygous) mutations in KCNQ1 or KCNE1. These genes encode the α and β subunits, respectively, of the ion channel conducting the slow component of the delayed rectifier K(+) current, IKs. We used complementary approaches, reprogramming patient cells and genetic engineering, to generate human induced pluripotent stem cell (hiPSC) models of JLNS, covering splice site (c.478-2A>T) and missense (c.1781G>A) mutations, the two major classes of JLNS-causing defects in KCNQ1. Electrophysiological comparison of hiPSC-derived cardiomyocytes (CMs) from homozygous JLNS, heterozygous, and wild-type lines recapitulated the typical and severe features of JLNS, including pronounced action and field potential prolongation and severe reduction or absence of IKs. We show that this phenotype had distinct underlying molecular mechanisms in the two sets of cell lines: the previously unidentified c.478-2A>T mutation was amorphic and gave rise to a strictly recessive phenotype in JLNS-CMs, whereas the missense c.1781G>A lesion caused a gene dosage-dependent channel reduction at the cell membrane. Moreover, adrenergic stimulation caused action potential prolongation specifically in JLNS-CMs. Furthermore, sensitivity to proarrhythmic drugs was strongly enhanced in JLNS-CMs but could be pharmacologically corrected. Our data provide mechanistic insight into distinct classes of JLNS-causing mutations and demonstrate the potential of hiPSC-CMs in drug evaluation.

Arteria coronaria única y arco aórtico derecho

Coronary anomalies are mostly asymptomatic and diagnosed incidentally during coronary angiography or echocardiography. However, they must be taken into account in the differential diagnosis of angina, dyspnea, syncope, acute myocardial infarction or sudden death in young patients. The case is presented of two rare anomalies, single coronary artery originating from right sinus of Valsalva and right aortic arch, in a 65 year-old patient with atherosclerotic coronary artery disease treated percutaneously.

Successful neo-ostium creation using pulmonary artery tissue in a case of anomalous origin of the left coronary artery from the right sinus of Valsalva

Anomalous origin of the left coronary artery (LCA) from the right sinus of Valsalva is rare and is known to cause sudden death in young patients. A 17-year old male patient experienced syncopal episodes after intense exercise. No abnormal findings were noted on brain magnetic resonance imaging, electroencephalography or Holter monitoring. Contrast-enhanced coronary computed tomography revealed the anomalous origin of the LCA from the right sinus of Valsalva. Considering the positional relationship with the aortic valve and the morphology of the left main trunk, a neo-ostium was created in the left coronary sinus, and patch angioplasty was performed using pulmonary arterial wall tissue. The postoperative course of the patient was uneventful, and the patient remains asymptomatic 2 years after surgery. Here, we describe this case and review the literature on the different surgical techniques for this anomaly. We believe that our technique would be useful in cases of anomalous origin of the LCA from the right sinus of Valsalva, regardless of morphological variations.

Origem anômala da artéria coronária esquerda do seio de Valsalva direito

Trazemos neste artigo a descricao de uma peca anatomica especificamente preparada para demonstrar uma rara anomalia da origem da arteria coronaria esquerda do seio de Valsalva direito, com incidencia de 0,15% em pacientes submetidos a cinecoronariografia. Trata-se de um subgrupo de anomalias das arterias coronarias que tem o maior potencial para repercussoes clinicas, em especial a morte subita em jovens. Discutimos, a luz dos conhecimentos atuais, os mecanismos fisiopatologicos, o diagnostico e as opcoes de tratamento das variacoes anatomicas da origem anomala da arteria coronaria do seio contralateral.

Anomalous Origin of the Left Coronary Artery from the Right Sinus of Valsalva

This article reports an anatomic specimen specifically prepared to demonstrate a rare anomaly of the origin of the left coronary artery from the right sinus of Valsalva, with an incidence of 0.15% in patients undergoing coronary angiography. This is a subgroup of coronary artery anomalies with the greatest potential for clinical repercussions, especially sudden death in young patients. Based on current knowledge, pathophysiologic mechanisms, diagnosis and treatment options of anatomical variations of the anomalous origin of a coronary artery from the contralateral sinus are discussed. Origem Anômala da Artéria Coronária Esquerda do Seio de Valsalva Direito Trazemos neste artigo a descrição de uma peça anatômica especificamente preparada para demonstrar uma rara anomalia da origem da artéria coronária esquerda do seio de Valsalva direito, com incidência de 0,15% em pacientes submetidos a cinecoronariografia. Trata-se de um subgrupo de anomalias das artérias coronárias que tem o maior potencial para repercussões clínicas, em especial a morte súbita em jovens. Discutimos, à luz dos conhecimentos atuais, os mecanismos fisiopatológicos, o diagnóstico e as opções de tratamento das variações anatômicas da origem anômala da artéria coronária do seio contralateral.

Molekulargenetische Diagnostik bei hereditären Arrhythmiesyndromen heute und in Zukunft

Genetic testing already has a substantial impact in identifying hereditary arrhythmia syndromes after sudden death in young patients. This report provides information on current developments, available options and reasonable approaches in the clinical setting. In addition the limitations of genetic testing are discussed. Genetic testing is only useful for patients in the context of clinical findings interpreted by an experienced cardiogenetics team.

Spontaneous Coronary Artery Dissection in a 27-Year-Old Woman

BackgroundSpontaneous coronary artery dissection (SCAD) causes acute coronary syndromes or sudden death in young patients who are often lacking classic coronary disease risk factors. Systemic inflammatory and connective tissue diseases have been suggested as risk factors for SCAD. ObjectiveTo review the risk factors, diagnosis, and management of this uncommon but life-threatening disease. Case ReportWe report a case of a 27-year-old woman with a history of an ill-defined inflammatory arthropathy who presented with an acute ST-elevation myocardial infarction. SCAD was diagnosed by coronary angiography. Percutaneous coronary intervention was attempted but was unsuccessful. The patient recovered uneventfully with medical management and was ultimately diagnosed with systemic lupus erythematosus. ConclusionsSCAD is a rare but important cause of acute coronary syndromes and sudden death. It commonly occurs in young women. Although pregnancy is the most well-established risk factor, systemic inflammatory and connective tissue diseases have also been suggested as risk factors.

The Phenotype of a CASQ2 Mutation in a Saudi Family with Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) manifests with episodic syncope or sudden death in young patients following physical activity or emotional stress. The autosomal recessive form of CPVT is caused by mutations in the CASQ2 gene. In a consanguineous family, a novel homozygous CASQ2 mutation (p.L77P) was identified in a child with CPVT who required implantation of a cardioverter defibrillator due to episodes of syncope while on medical therapy. Genetic testing found the younger sibling, who had normal initial clinical screening, to be affected. Our cases underscore the importance of family screening through genetic testing to preemptively apply the appropriate medical intervention in CPVT.

Cardiac arrest associated with sildenafil ingestion in a patient with an abnormal origin of the left coronary artery: case report

BackgroundLeft coronary artery arising from the right sinus of Valsalva is an uncommon congenital coro-nary anomaly that seems to be associated with sudden death in young patients.Case presentationWe report a case of cardiac arrest in a 59-year-old patient after sexual intercourse and Silde-nafil ingestion. A coronary arteriography and an angiographic computed tomography scan subsequently revealed a LCA origin from the right aortic sinus along with an intramural course of the left main stem. In addition a distal stenosis of the right coronary artery was detected. After successful resuscitation without neurological deficits coronary artery bypass surgery was performed.ConclusionTo our knowledge, this is the first report demonstrating sudden cardiac arrest associated with Sildenafil ingestion in a patient with this type of coronary anomaly. The question arises, whether a cardiac screening is necessary before a Sildenafil therapy is initiated.