Johannes Steinfurt

The Diagnosis, Risk Stratification, and Treatment of Brugada Syndrome

BACKGROUND Brugada syndrome (BrS) is among the more common familial arrhythmia syndromes, with an estimated prevalence of 1 to 5 per 10 000 persons. It is characterized by a right ventricular conduction delay, dynamic or persistent ST-segment elevations in the precordial leads V1-3 , and an elevated risk of syncope and sudden cardiac death in young adults without structural heart disease. METHODS This article is based on original and review articles on BrS that appeared in English from 2010 onward and were retrieved by a selective search in PubMed, with special attention to international consensus publications on inherited arrhythmogenic diseases. RESULTS According to the new diagnostic criteria, the diagnosis of BrS requires typical ECG changes in only one precordial lead. This will likely increase sensitivity, but may also lead to an increase in asymptomatic patients. Established risk markers include sudden cardiac arrest and a spontaneous type 1 ECG with arrhythmic syncope. Patients with these findings benefit from the implantation of a cardioverter-defibrillator. There is no validated algorithm for risk stratification of asymptomatic patients. Because of the low prevalence of BrS, there have been no randomized controlled trials (RCTs) in this disease, and all recommendations are based on expert opinion. BrS is usually inherited in an autosomal dominant manner. Recently discovered gene polymorphisms modify the risk of BrS, challenging the conception of BrS as a monogenetic disease. Electro-anatomic mapping studies have revealed, for the first time, an arrhythmogenic substrate over the right ventricular outflow tract in BrS patients. CONCLUSION BrS is one important differential diagnosis to consider in patients presenting with syncope or sudden cardiac arrest. The goal of current research is to achieve a deeper understanding of the genetic and electrophysiological changes underlying BrS. Further insights in these areas will probably enable better risk stratification of asymptomatic BrS patients in the future.

High-dose flecainide with low-dose β-blocker therapy in catecholaminergic polymorphic ventricular tachycardia: A case report and review of the literature

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by recurrent syncopes and sudden cardiac death triggered by sympathetic activation in young individuals without structural heart disease and a normal baseline electrocardiogram. There is reason to question whether the current expert consensus treatment recommendation, maximal tolerated β-blockade alone or in combination with low-dose flecainide, is the optimal antiarrhythmic treatment strategy in CPVT, as high doses of β-blockers may eventually lead to adverse side effects and β-blocker discontinuation. Indeed, β-blocker non-compliance accounts for around 5% of sudden cardiac deaths in CPVT patients. Case report Differing from the current recommendation, we present the first report of a CPVT patient successfully treated with high-dose flecainide and minimal β-blockade. This combination resulted in complete suppression of ventricular arrhythmias during exercise stress tests and Holter monitoring and was well tolerated without any side effects. We review the current literature on β-blocker non-compliance-related sudden cardiac death in CPVT, summarize the in vitro and in vivo data on flecainide therapy in CPVT, and discuss the rationale of our antiarrhythmic approach.<Learning objective: This case illustrates typical features of CPVT including the therapeutic management of a young CPVT patient with poor β-blocker tolerance at normal dosages. In this setting, high-dose flecainide combined with minimal β-blockade may (1) result in complete antiarrhythmic response and may (2) improve the antiarrhythmic drug-compliance thereby reducing the risk of non-compliance-related sudden cardiac death.>.

Avoiding sports-related sudden cardiac death in children with congenital channelopathy : Recommendations for sports activities

For the past few years, children affected by an inherited channelopathy have been counseled to avoid (recreational) sports activities and all competitive sports so as to prevent exercise-induced arrhythmia and sudden cardiac death. An increased understanding of the pathophysiological mechanisms, better anti-arrhythmic strategies, and, in particular, more epidemiological data on exercise-induced arrhythmia in active athletes with channelopathies have changed the universal recommendation of “no sports,” leading to revised, less strict, and more differentiated guidelines (published by the American Heart Association/American College of Cardiology in 2015). In this review, we outline the disease- and genotype-specific mechanisms of exercise-induced arrhythmia; give an overview of trigger-, symptom-, and genotype-dependent guidance in sports activities for children with long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), or short QT syndrome (SQTS); and highlight the novelties in the current guidelines compared with previous versions. While it is still recommended for patients with LQT1 and CPVT (even when asymptomatic) and all symptomatic LQTS patients (independent of genotype) to avoid any competitive and high-intensity sports, other LQTS patients successfully treated with anti-arrhythmic therapies and phenotype-negative genotype-positive patients may be allowed to perform sports at different activity levels – provided they undergo regular, sophisticated evaluations to detect any changes in arrhythmogenic risk.ZusammenfassungBis vor Kurzem wurde Kindern mit angeborenen Ionenkanalerkrankungen die Teilnahme am Freizeit- oder Wettkampfsport meist strikt untersagt, um sportinduzierte Arrhythmien und den plötzlichen Herztod zu vermeiden. Verbesserte pathophysiologische Erkenntnisse über die zugrunde liegenden Erkrankungen, Fortschritte in der antiarrhythmischen Therapie und insbesondere epidemiologische Erfahrungen mit Rhythmusereignissen bei aktiven Athleten mit Ionenkanalerkrankungen haben zu weniger strengen, individualisierten Empfehlungen in den neuen amerikanischen Leitlinien der American Heart Association/des American College of Cardiology von 2015 geführt. Für die Beratung von Kindern mit Long-QT-Syndrom (LQTS), Brugada-Syndrom (BrS), katecholaminerger polymorpher ventrikulärer Tachykardie (CPVT) oder Short-QT-Syndrom (SQTS) beschreiben die Autoren die krankheits- und genotypspezifischen Mechanismen sportinduzierter Arrhythmien, geben einen Überblick über die Neuerungen im Vergleich zu älteren Leitlinien und erörtern die differenzierteren, trigger-, symptom- bzw. mutationsabhängigen Empfehlungen zu den einzelnen Krankheitsentitäten. Neben dem fortbestehenden Sportverbot im kompetitiven und hochintensiven Bereich für alle CPVT- und LQT1-Patienten sowie generell für alle symptomatischen LQTS-Patienten gibt es vor allem beim LQTS Patientengruppen, deren Sportverbot unter bestimmten Voraussetzungen gelockert werden kann. So können z. B. erfolgreich antiarrhythmisch behandelte und darunter asymptomatische LQTS-Patienten sowie mutations-positive phänotyp-negative LQTS-Patienten, die unter regelmäßiger Reevaluation ihres Risikoprofils von Spezialisten begleitet werden, durchaus zu sportlichen Aktivitäten zurückkehren.

Avoiding sports-related sudden cardiac death in children with congenital channelopathy

For the past few years, children affected by an inherited channelopathy have been counseled to avoid (recreational) sports activities and all competitive sports so as to prevent exercise-induced arrhythmia and sudden cardiac death. An increased understanding of the pathophysiological mechanisms, better anti-arrhythmic strategies, and, in particular, more epidemiological data on exercise-induced arrhythmia in active athletes with channelopathies have changed the universal recommendation of “no sports,” leading to revised, less strict, and more differentiated guidelines (published by the American Heart Association/American College of Cardiology in 2015). In this review, we outline the disease- and genotype-specific mechanisms of exercise-induced arrhythmia; give an overview of trigger-, symptom-, and genotype-dependent guidance in sports activities for children with long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), or short QT syndrome (SQTS); and highlight the novelties in the current guidelines compared with previous versions. While it is still recommended for patients with LQT1 and CPVT (even when asymptomatic) and all symptomatic LQTS patients (independent of genotype) to avoid any competitive and high-intensity sports, other LQTS patients successfully treated with anti-arrhythmic therapies and phenotype-negative genotype-positive patients may be allowed to perform sports at different activity levels – provided they undergo regular, sophisticated evaluations to detect any changes in arrhythmogenic risk.ZusammenfassungBis vor Kurzem wurde Kindern mit angeborenen Ionenkanalerkrankungen die Teilnahme am Freizeit- oder Wettkampfsport meist strikt untersagt, um sportinduzierte Arrhythmien und den plötzlichen Herztod zu vermeiden. Verbesserte pathophysiologische Erkenntnisse über die zugrunde liegenden Erkrankungen, Fortschritte in der antiarrhythmischen Therapie und insbesondere epidemiologische Erfahrungen mit Rhythmusereignissen bei aktiven Athleten mit Ionenkanalerkrankungen haben zu weniger strengen, individualisierten Empfehlungen in den neuen amerikanischen Leitlinien der American Heart Association/des American College of Cardiology von 2015 geführt. Für die Beratung von Kindern mit Long-QT-Syndrom (LQTS), Brugada-Syndrom (BrS), katecholaminerger polymorpher ventrikulärer Tachykardie (CPVT) oder Short-QT-Syndrom (SQTS) beschreiben die Autoren die krankheits- und genotypspezifischen Mechanismen sportinduzierter Arrhythmien, geben einen Überblick über die Neuerungen im Vergleich zu älteren Leitlinien und erörtern die differenzierteren, trigger-, symptom- bzw. mutationsabhängigen Empfehlungen zu den einzelnen Krankheitsentitäten. Neben dem fortbestehenden Sportverbot im kompetitiven und hochintensiven Bereich für alle CPVT- und LQT1-Patienten sowie generell für alle symptomatischen LQTS-Patienten gibt es vor allem beim LQTS Patientengruppen, deren Sportverbot unter bestimmten Voraussetzungen gelockert werden kann. So können z. B. erfolgreich antiarrhythmisch behandelte und darunter asymptomatische LQTS-Patienten sowie mutations-positive phänotyp-negative LQTS-Patienten, die unter regelmäßiger Reevaluation ihres Risikoprofils von Spezialisten begleitet werden, durchaus zu sportlichen Aktivitäten zurückkehren.

Staphylococcus aureus bacteremia with iliac artery endarteritis in a patient receiving ustekinumab

BackgroundUstekinumab (Stelara®), a human monoclonal antibody targeting the p40-subunit of interleukin (IL)-12 and IL-23, is indicated for moderate to severe plaque psoriasis and psoriatic arthritis. In large multicenter, prospective trials assessing efficacy and safety of ustekinumab increased rates of severe infections have not been observed so far.Case presentationHere, we report the case of a 64-year old woman presenting with chills, pain and swelling of her right foot with dark maculae at the sole, and elevated inflammatory markers. She had received a third dose of ustekinumab due to psoriatic arthritis three days before admission. Blood cultures revealed growth of Staphylococcus aureus and imaging showed a thickening of the aortic wall ventral the bifurcation above the right internal iliac artery, resembling an acute bacterial endarteritis. Without the evidence of aneurysms and in absence of foreign bodies, the decision for conservative management was made. The patient received four weeks of antibiotic therapy with intravenous flucloxacillin, followed by an oral regime with levofloxacin and rifampicin for an additional four weeks. Inflammatory markers resolved promptly and the patient was discharged in good health.ConclusionTo our knowledge, this is the first report of a severe S. aureus infection in a patient receiving ustekinumab. Albeit ustekinumab is generally regarded as a safe drug, severe bacterial infections should always be included in the differential diagnosis of elevated inflammatory markers in patients receiving biologicals as these might present with nonspecific symptoms and fever might be absent. Any effort to detect deep-seated or metastatic infections should be made to prevent complications and to secure appropriate treatment. Although other risk factors for an invasive staphylococcal infection like psoriasis, recent corticosteroid injection, or prior hospitalisations were present, and therefore a directive causative link between the S. aureus bacteraemia and ustekinumab can not be drawn, we considered the reporting of this case worthwhile to alert clinicians as we believe that ongoing pharmacovigilance to detect increased risks for rare but severe infections beyond phase II and phase III trials in patients treated with biologicals is essential.

Fascicular parasystole and recurrent syncope – a case report

Abstract Introduction Parasystole refers to an ectopic pacemaker that discharges with a constant rate competing with the primary pacemaker of the heart the sinus node. Parasystolic pacemakers have been described in the atrium, atrioventricular node, His bundle, and in the ventricle. Ventricular parasystole usually carries a benign prognosis, but there are a few reports of ventricular tachyarrhythmia initiated by parasystolic beats. Case presentation We present a case of a 15-year-old otherwise healthy teenager with recurrent most likely arrhythmic syncope who was diagnosed with ventricular parasystole from the left posterior fascicle. After exclusion of structural and primary electrical heart disease, the patient was deemed at increased risk of parasystole-induced tachyarrhythmia, and thus catheter ablation of the ectopic focus was performed. Since catheter ablation the patient continues to be free of any symptoms. Discussion This report highlights the potential risks of parasystole in context of recurrent syncope and reviews the available literature on parasystole and ventricular tachyarrhythmia.

Avoiding sports-related sudden cardiac death in children with congenital channelopathy@@@Vermeidung des sportbezogenen plötzlichen Herztods bei Kindern mit angeborenen Ionenkanalerkrankungen: Recommendations for sports activities@@@Empfehlungen für sportliche Aktivitäten

For the past few years, children affected by an inherited channelopathy have been counseled to avoid (recreational) sports activities and all competitive sports so as to prevent exercise-induced arrhythmia and sudden cardiac death. An increased understanding of the pathophysiological mechanisms, better anti-arrhythmic strategies, and, in particular, more epidemiological data on exercise-induced arrhythmia in active athletes with channelopathies have changed the universal recommendation of “no sports,” leading to revised, less strict, and more differentiated guidelines (published by the American Heart Association/American College of Cardiology in 2015). In this review, we outline the disease- and genotype-specific mechanisms of exercise-induced arrhythmia; give an overview of trigger-, symptom-, and genotype-dependent guidance in sports activities for children with long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), or short QT syndrome (SQTS); and highlight the novelties in the current guidelines compared with previous versions. While it is still recommended for patients with LQT1 and CPVT (even when asymptomatic) and all symptomatic LQTS patients (independent of genotype) to avoid any competitive and high-intensity sports, other LQTS patients successfully treated with anti-arrhythmic therapies and phenotype-negative genotype-positive patients may be allowed to perform sports at different activity levels – provided they undergo regular, sophisticated evaluations to detect any changes in arrhythmogenic risk.ZusammenfassungBis vor Kurzem wurde Kindern mit angeborenen Ionenkanalerkrankungen die Teilnahme am Freizeit- oder Wettkampfsport meist strikt untersagt, um sportinduzierte Arrhythmien und den plötzlichen Herztod zu vermeiden. Verbesserte pathophysiologische Erkenntnisse über die zugrunde liegenden Erkrankungen, Fortschritte in der antiarrhythmischen Therapie und insbesondere epidemiologische Erfahrungen mit Rhythmusereignissen bei aktiven Athleten mit Ionenkanalerkrankungen haben zu weniger strengen, individualisierten Empfehlungen in den neuen amerikanischen Leitlinien der American Heart Association/des American College of Cardiology von 2015 geführt. Für die Beratung von Kindern mit Long-QT-Syndrom (LQTS), Brugada-Syndrom (BrS), katecholaminerger polymorpher ventrikulärer Tachykardie (CPVT) oder Short-QT-Syndrom (SQTS) beschreiben die Autoren die krankheits- und genotypspezifischen Mechanismen sportinduzierter Arrhythmien, geben einen Überblick über die Neuerungen im Vergleich zu älteren Leitlinien und erörtern die differenzierteren, trigger-, symptom- bzw. mutationsabhängigen Empfehlungen zu den einzelnen Krankheitsentitäten. Neben dem fortbestehenden Sportverbot im kompetitiven und hochintensiven Bereich für alle CPVT- und LQT1-Patienten sowie generell für alle symptomatischen LQTS-Patienten gibt es vor allem beim LQTS Patientengruppen, deren Sportverbot unter bestimmten Voraussetzungen gelockert werden kann. So können z. B. erfolgreich antiarrhythmisch behandelte und darunter asymptomatische LQTS-Patienten sowie mutations-positive phänotyp-negative LQTS-Patienten, die unter regelmäßiger Reevaluation ihres Risikoprofils von Spezialisten begleitet werden, durchaus zu sportlichen Aktivitäten zurückkehren.