Thomas Wichter - Academia.edu (original) (raw)

Papers by Thomas Wichter

Research paper thumbnail of Pregnancy in arrhythmogenic cardiomyopathy

Herzschrittmachertherapie & Elektrophysiologie, 2021

Arrhythmogenic cardiomyopathy (AC) is a rare heart muscle disease with a genetic background and a... more Arrhythmogenic cardiomyopathy (AC) is a rare heart muscle disease with a genetic background and autosomal dominant mode of transmission. The clinical manifestation is characterized by ventricular arrhythmias (VA), heart failure (HF) and the risk of sudden cardiac death (SCD). Pregnancy in young female patients with AC represents a challenging condition for the life and family planning of young affected women. In addition to genetic mechanisms that influence the complex pathophysiology of AC, experimental and clinical data have confirmed the pathogenetic role of strenuous exercise and competitive sports in the early onset and rapid progression of AC symptoms and complications. Pregnancy and exercise share a number of physiological aspects of adaptation. In AC, both result in ventricular volume overload and myocardial stretch. Therefore, pregnancy has been postulated as a potential risk factor for HF, VA, SCD, and pregnancy-related obstetric complications in patients with AC. However,...

Research paper thumbnail of Arrhythmogenic right ventricular cardiomyopathy: an update

Research paper thumbnail of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Korean Circulation Journal, Oct 1, 2008

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by progressiv... more Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by progressive, fibrofatty replacement of the myocardium, ventricular arrhythmia, sudden death, and progressive heart failure. ARVC/D may be an important cause of syncope, ventricular arrhythmias, electrocardiogram (ECG) abnormalities and/or non-ischemic wall motion abnormalities. Some patients, however, do not have a typical clinical presentation. Thus, a high clinical suspicion and extensive studies may be needed to establish the diagnosis of ARVC/D. Recent progress in diagnostic modalities and a better understanding of the clinical manifestations of ARVC/D may lead to optimal management of affected patients.

Research paper thumbnail of Abnormalities of Cardiac Sympathetic Innervation in

The online version of this article, along with updated information and services, is located on the

Research paper thumbnail of Antiarrhythmic Treatment of Arrhythmogenic Right Ventricular Cardiomyopathy : Drugs , Catheter Ablation , or ICD ?

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of sudden cardiac death a... more Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of sudden cardiac death and ventricular tachyarrhythmias in young, apparently healthy individuals and athletes. Myocardial atrophy with subsequent fibrofatty replacement predominantly affects right ventricular myocardium and results in global and regional dysfunction as well as areas of slow conduction and dispersion of refractoriness which are prerequisites for reentrant ventricular tachyarrhythmias. Patients affected with ARVC should be excluded from competitive sports and vigorous training. To provide optimal treatment, a detailed diagnostic evaluation and risk stratification is mandatory. Tailored treatment strategies aim at the suppression or effective termination of recurrent ventricular tachyarrhythmias and prevention of sudden death by antiarrhythmic drug therapy, catheter ablation, or implantation of a cardioverter-defibrillator (ICD). Antiarrhythmic drugs may be used as a stand-alone treatment to suppress VT recurrences in patients with ARVC and low risk of sudden death. Sotalol (preferred) or amiodarone in combination with β-blockers showed the highest efficacy rates. In patients at higher risk, an ICD should be implanted and antiarrhythmic drugs be used only as an adjunct to prevent or suppress frequent VT recurrences and ICD discharges. Catheter ablation using conventional or electroanatomic mapping techniques yields good acute results for eliminating the targeted arrhythmia substrate. However, during the progressive long-term course of ARVC, VT recurrences from new arrhythmia foci are frequent and therefore limit the curative value of catheter ablation. In patients with frequent VT recurrences and ICD discharges however, catheter ablation plays an important role as a palliative and adjunctive treatment option for arrhythmia suppression. ICD implantation has been increasingly used for secondary and also primary prevention of sudden death in patients with ARVC. In secondary prevention, the ICD has shown to improve the long-term prognosis of patients at high risk of sudden death by effective termination of life-threatening recurrences of ventricular tachyarrhythmias. However, adequate lead placement may be difficult and lead-related complications during longterm follow-up must be taken into account. The role of ICD therapy for primary prevention of sudden death in ARVC is not yet adequately defined. Ongoing international registries will provide important additional data to improve risk stratification and refine treatment algorithms in order to select the best individual treatment for arrhythmia suppression and prevention of sudden death in patients with ARVC.

Research paper thumbnail of Implantable Cardioverter/Defibrillator Therapy in Arrhythmogenic Right Ventricular Cardiomyopathy: Single-Center Experience of Long-Term Follow-Up and Complications in 60 Patients

Background—Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of ventricular... more Background—Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of ventricular tachycardia (VT) and cardiac arrest in young patients. We hypothesized that treatment with implantable cardioverter/defibrillators (ICDs) is safe and improves the long-term prognosis of ARVC patients at high risk of sudden death. Methods and Results—Sixty patients with ARVC (aged 43±16 years) were treated with transvenous ICD systems. Despite a higher number of right ventricular sites tested for adequate lead positions (P <0.05), lower R-wave amplitudes (P <0.001) were achieved in ARVC patients compared with other entities. During follow-up of 80±43 months (396 patient-years), event-free survival was 49%, 30%, 26%, and 26% for appropriate ICD therapies and 79%, 64%, 59%, and 56% for potentially fatal VT (>240 bpm) after 1, 3, 5, and 7 years, respectively. Multivariate analysis identified extensive right ventricular dysfunction as an independent predictor of appropriate ICD disc...

Research paper thumbnail of Arrhythmogenic right ventricular cardiomyopathy

Circulation. Arrhythmia and electrophysiology, 2012

Research paper thumbnail of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Research paper thumbnail of Arrhythmogene rechtsventrikuläre Kardiomyopathie : Ätiologie, Diagnostik und Therapie (Übersicht)

Medizinische Klinik, 1998

~Die arrhythmogene rechtsventrikul~e Kardiomyopathie (AKVC) ist charakterisiert durch regional be... more ~Die arrhythmogene rechtsventrikul~e Kardiomyopathie (AKVC) ist charakterisiert durch regional betonte Degeneration und Atrophie des rechtsventrikuliren Myokards mit nachs Ersatz durch Fett-und Bindewebe. Die Erkrankung manifestiert sich ira Jugend-oder ]ungen Erwachsenenalter, MGnner sind Niufiger betroffen. Leitsymptome der ARVG sind ventrikul~re Tachyarrhythmien mit linksschenkelblockartiger Konfiguration. Auch pl6tzliche Herztodesf~Ue kSnnen die p¡ Manifestation der ARVC darstellen. ~l Charakteristische Befunde sind Repolarisationsst6rungen und eine Verl2ingerung des QRS-Komplexes in den rechtspr~kordialen Ableitungen des Oberfl~ichen-EKG sowie regional betonte St6rungen der Struktur und Funktion des rechten Ventrikels. Eme lmksventrikul~re Beteiligung wird erst in fortgeschrittenen Krankheitsstadien beobachtet und kann in seltenen F/illen zu einer biventrikul~iren Herzinsuftizienz f'ª El Ira Vordergrund der Therapie stehen die Behandlung der Kammertachykardien und die Prophylaxe des pl6tzlichen Herztodes. Der individueUe Einsatz von antiarrhythmischer Pharmakotherapie, Katheterablation und Defibrillatorimplantation kann zur Verbesserung der Langzeitprognose von Patienten mit ARVC beitragen.

Research paper thumbnail of Arrhythmogene rechtsventrikul�re Kardiomyopathie (ARVC)

Notfall Rettungsmed, 2009

Research paper thumbnail of Arrhythmogenic right ventricular cardiomyopathy (ARVC): Risk stratification and therapy

Notfall Rettungsmed, 2009

Research paper thumbnail of Arrhythmogene rechtsventrikuläre Kardiomyopathie

Medizinische Klinik, 1998

~Die arrhythmogene rechtsventrikul~e Kardiomyopathie (AKVC) ist charakterisiert durch regional be... more ~Die arrhythmogene rechtsventrikul~e Kardiomyopathie (AKVC) ist charakterisiert durch regional betonte Degeneration und Atrophie des rechtsventrikuliren Myokards mit nachs Ersatz durch Fett-und Bindewebe. Die Erkrankung manifestiert sich ira Jugend-oder ]ungen Erwachsenenalter, MGnner sind Niufiger betroffen. Leitsymptome der ARVG sind ventrikul~re Tachyarrhythmien mit linksschenkelblockartiger Konfiguration. Auch pl6tzliche Herztodesf~Ue kSnnen die p¡ Manifestation der ARVC darstellen. ~l Charakteristische Befunde sind Repolarisationsst6rungen und eine Verl2ingerung des QRS-Komplexes in den rechtspr~kordialen Ableitungen des Oberfl~ichen-EKG sowie regional betonte St6rungen der Struktur und Funktion des rechten Ventrikels. Eme lmksventrikul~re Beteiligung wird erst in fortgeschrittenen Krankheitsstadien beobachtet und kann in seltenen F/illen zu einer biventrikul~iren Herzinsuftizienz f'ª El Ira Vordergrund der Therapie stehen die Behandlung der Kammertachykardien und die Prophylaxe des pl6tzlichen Herztodes. Der individueUe Einsatz von antiarrhythmischer Pharmakotherapie, Katheterablation und Defibrillatorimplantation kann zur Verbesserung der Langzeitprognose von Patienten mit ARVC beitragen.

Research paper thumbnail of Arrhythmogenic right ventricular cardiomyopathy/dysplasia: risk stratification and therapy

Progress in cardiovascular diseases

Research paper thumbnail of Arrhythmogenic right ventricular cardiomyopathy: clinical registry and database, evaluation of therapies, pathology registry, DNA banking

European heart journal, 2004

Research paper thumbnail of Idiopathic Right Ventricular Outflow Tract Tachycardia

Arrhythmogenic RV Cardiomyopathy/Dysplasia, 2007

Research paper thumbnail of Implantable cardioverter-defibrillator therapy in arrhythmogenic right ventricular cardiomyopathy**Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology

Journal of the American College of Cardiology, 2005

Research paper thumbnail of Efficacy and Safety of d,l-Sotalol in Patients With Ventricular Tachycardia and in Survivors of Cardiac Arrest

Journal of the American College of Cardiology, 1997

The aim of this study was to assess the antiarrhythmic efficacy and safety of d,l-sotalol in pati... more The aim of this study was to assess the antiarrhythmic efficacy and safety of d,l-sotalol in patients with ventricular tachycardia (VT) or ventricular fibrillation (VF) and in survivors of cardiac arrest and to identify the factors that are associated with arrhythmia suppression and therefore might be helpful in predicting drug efficacy. Background. Despite increasing use of the class III antiarrhythmic agent d,l-sotalol, data on its short-and long-term efficacy in a large patient cohort are lacking. Information on its long-term tolerability and safety is limited. Methods. A total of 396 patients with inducible sustained VT or VF (VT/VF) underwent programmed stimulation before and after receiving oral d,l-sotalol (240 to 640 mg/day). Patients in whom VT/VF was rendered either noninducible or more difficult to induce (more extrastimuli or faster drive cycle length needed for VT/VF induction) were discharged on a regimen of oral d,l-sotalol. Results. d,l-Sotalol suppressed VT/VF in 151 patients (38.1%) and rendered the arrhythmia more difficult to induce in 76 patients (19.2%). The extent of drug-induced prolongation of right ventricular refractoriness and a shorter VT cycle length at baseline were independent predictors of immediate drug efficacy. Torsade de pointes developed in seven patients (1.8%). Two hundred ten patients (53%) continued to receive d,l-sotalol and were followed up for 34 ؎ 18 months (mean ؎ SD). The actuarial rates for the absence of arrhythmic recurrence (either VT/VF or sudden death) at 1 and 3 years were 89% and 77%, respectively. Actuarial rates for overall survival at 1 and 3 years were 94% and 86%, respectively. VT/VF suppression by d,l-sotalol was an independent discriminant variable that separated patients with and without arrhythmia recurrence. However, noninducibility of VT/VF did not predict freedom from sudden death. Conclusions. Oral d,l-sotalol is effective and safe in patients with VT/VF. However, sudden cardiac death develops in a significant proportion of patients, and programmed stimulation seems to be of limited value for its prediction.

Research paper thumbnail of Impaired myocardial blood flow and flow reserve associated with increased coronary resistance in persistent idiopathic atrial fibrillation

Journal of Nuclear Cardiology, 2005

Background: Abnormalities in myocardial metabolism and mechanical performance are known to charac... more Background: Abnormalities in myocardial metabolism and mechanical performance are known to characterize hypertrophic cardiomyopathy (HCM). This study evaluated myocardial perfusion, oxidative and substrate metabolism in genetically homogenous HCM patients with different phenotypic expressions. Methods: Eight patients with HCM caused by the Asp175Asn substitution in the alpha-tropomyosin gene underwent in fasting state myocardial blood flow, oxygen consumption (Kmono) and free fatty acid (FFA) uptake measurements using positron emission tomography and [15O]H20, [11C]acetate and [18F]FTHA respectively. Echocardiographic measurements were used to assess myocardial function and work. Efficiency of forward work was calculated. Results: As compared to normal values, patients with HCM were characterised with normal global perfusion but increased oxygen consumption and reduced efficiency. Myocardial FFA uptake was within the normal range. Global perfusion and Kmono as well as efficiency were inversely correlated with LV mass and were significantly lower in patients with LV mass Ͼ 180g (nϭ 4) than LV mass Ͻ 180 g (nϭ 4) (p Ͻ 0.05). Global myocardial FFA uptake was not associated with degree of hypertrophy. Typical for HCM, hypertrophy was heterogenous affecting more commonly septal wall. At individual level, regional FFA uptake and Kmono correlated nicely in patients with mild LV hypertrophy (Rϭ 0.73-0.99, avg 0.85) whereas the correlation was mainly inverse in patients with more advanced hypertrophy (Rϭ Ϫ0.88-0.68, avg Ϫ0.24). Conclusions: Genetically defined homogenous HCM patients with Asp175Asn mutation in the alpha-tropomyosin gene are characterized with increased oxygen consumption and reduced efficiency of forward work but normal perfusion and FFA uptake. However, cardiac phenotypic expression is also associated with changes in perfusion, oxygen consumption and efficiency. The patients with advanced LV hypertrophy are characterised with uncoupling of regional oxidative metabolism and FFA utilization indicating switch in cardiac substrate metabolism not attributable to genetic factors.

Research paper thumbnail of Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy

Human Molecular Genetics, 2012

Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric left ventricular hypertrophy, di... more Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric left ventricular hypertrophy, diastolic dysfunction and myocardial disarray. HCM is caused by mutations in sarcomeric genes, but in >40% of patients, the mutation is not yet identified. We hypothesized that FHL1, encoding four-and-a-half-LIM domains 1, could be another disease gene since it has been shown to cause distinct myopathies, sometimes associated with cardiomyopathy. We evaluated 121 HCM patients, devoid of a mutation in known disease genes. We identified three novel variants in FHL1 (c.134delA/K45Sfs, c.459C>A/C153X and c.827G>C/ C276S). Whereas the c.459C>A variant was associated with muscle weakness in some patients, the c.134delA and c.827G>C variants were associated with isolated HCM. Gene transfer of the latter variants in C2C12 myoblasts and cardiac myocytes revealed reduced levels of FHL1 mutant proteins, which could be rescued by proteasome inhibition. Contractility measurements after adeno-associated virus transduction in rat-engineered heart tissue (EHT) showed: (i) higher and lower forces of contraction with K45Sfs and C276S, respectively, and (ii) prolonged contraction and relaxation with both mutants. All mutants except one activated the fetal hypertrophic gene program in EHT. In conclusion, this study provides evidence for FHL1 to be a novel gene for isolated HCM. These data, together with previous findings of proteasome impairment in HCM, suggest that FHL1 mutant proteins may act as poison peptides, leading to hypertrophy, diastolic dysfunction and/or altered contractility, all features of HCM.

Research paper thumbnail of Arrhythmogenic right ventricular cardiomyopathy/dysplasia clinical presentation and diagnostic evaluation: Results from the North American Multidisciplinary Study

Research paper thumbnail of Pregnancy in arrhythmogenic cardiomyopathy

Herzschrittmachertherapie & Elektrophysiologie, 2021

Arrhythmogenic cardiomyopathy (AC) is a rare heart muscle disease with a genetic background and a... more Arrhythmogenic cardiomyopathy (AC) is a rare heart muscle disease with a genetic background and autosomal dominant mode of transmission. The clinical manifestation is characterized by ventricular arrhythmias (VA), heart failure (HF) and the risk of sudden cardiac death (SCD). Pregnancy in young female patients with AC represents a challenging condition for the life and family planning of young affected women. In addition to genetic mechanisms that influence the complex pathophysiology of AC, experimental and clinical data have confirmed the pathogenetic role of strenuous exercise and competitive sports in the early onset and rapid progression of AC symptoms and complications. Pregnancy and exercise share a number of physiological aspects of adaptation. In AC, both result in ventricular volume overload and myocardial stretch. Therefore, pregnancy has been postulated as a potential risk factor for HF, VA, SCD, and pregnancy-related obstetric complications in patients with AC. However,...

Research paper thumbnail of Arrhythmogenic right ventricular cardiomyopathy: an update

Research paper thumbnail of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Korean Circulation Journal, Oct 1, 2008

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by progressiv... more Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by progressive, fibrofatty replacement of the myocardium, ventricular arrhythmia, sudden death, and progressive heart failure. ARVC/D may be an important cause of syncope, ventricular arrhythmias, electrocardiogram (ECG) abnormalities and/or non-ischemic wall motion abnormalities. Some patients, however, do not have a typical clinical presentation. Thus, a high clinical suspicion and extensive studies may be needed to establish the diagnosis of ARVC/D. Recent progress in diagnostic modalities and a better understanding of the clinical manifestations of ARVC/D may lead to optimal management of affected patients.

Research paper thumbnail of Abnormalities of Cardiac Sympathetic Innervation in

The online version of this article, along with updated information and services, is located on the

Research paper thumbnail of Antiarrhythmic Treatment of Arrhythmogenic Right Ventricular Cardiomyopathy : Drugs , Catheter Ablation , or ICD ?

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of sudden cardiac death a... more Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of sudden cardiac death and ventricular tachyarrhythmias in young, apparently healthy individuals and athletes. Myocardial atrophy with subsequent fibrofatty replacement predominantly affects right ventricular myocardium and results in global and regional dysfunction as well as areas of slow conduction and dispersion of refractoriness which are prerequisites for reentrant ventricular tachyarrhythmias. Patients affected with ARVC should be excluded from competitive sports and vigorous training. To provide optimal treatment, a detailed diagnostic evaluation and risk stratification is mandatory. Tailored treatment strategies aim at the suppression or effective termination of recurrent ventricular tachyarrhythmias and prevention of sudden death by antiarrhythmic drug therapy, catheter ablation, or implantation of a cardioverter-defibrillator (ICD). Antiarrhythmic drugs may be used as a stand-alone treatment to suppress VT recurrences in patients with ARVC and low risk of sudden death. Sotalol (preferred) or amiodarone in combination with β-blockers showed the highest efficacy rates. In patients at higher risk, an ICD should be implanted and antiarrhythmic drugs be used only as an adjunct to prevent or suppress frequent VT recurrences and ICD discharges. Catheter ablation using conventional or electroanatomic mapping techniques yields good acute results for eliminating the targeted arrhythmia substrate. However, during the progressive long-term course of ARVC, VT recurrences from new arrhythmia foci are frequent and therefore limit the curative value of catheter ablation. In patients with frequent VT recurrences and ICD discharges however, catheter ablation plays an important role as a palliative and adjunctive treatment option for arrhythmia suppression. ICD implantation has been increasingly used for secondary and also primary prevention of sudden death in patients with ARVC. In secondary prevention, the ICD has shown to improve the long-term prognosis of patients at high risk of sudden death by effective termination of life-threatening recurrences of ventricular tachyarrhythmias. However, adequate lead placement may be difficult and lead-related complications during longterm follow-up must be taken into account. The role of ICD therapy for primary prevention of sudden death in ARVC is not yet adequately defined. Ongoing international registries will provide important additional data to improve risk stratification and refine treatment algorithms in order to select the best individual treatment for arrhythmia suppression and prevention of sudden death in patients with ARVC.

Research paper thumbnail of Implantable Cardioverter/Defibrillator Therapy in Arrhythmogenic Right Ventricular Cardiomyopathy: Single-Center Experience of Long-Term Follow-Up and Complications in 60 Patients

Background—Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of ventricular... more Background—Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of ventricular tachycardia (VT) and cardiac arrest in young patients. We hypothesized that treatment with implantable cardioverter/defibrillators (ICDs) is safe and improves the long-term prognosis of ARVC patients at high risk of sudden death. Methods and Results—Sixty patients with ARVC (aged 43±16 years) were treated with transvenous ICD systems. Despite a higher number of right ventricular sites tested for adequate lead positions (P <0.05), lower R-wave amplitudes (P <0.001) were achieved in ARVC patients compared with other entities. During follow-up of 80±43 months (396 patient-years), event-free survival was 49%, 30%, 26%, and 26% for appropriate ICD therapies and 79%, 64%, 59%, and 56% for potentially fatal VT (>240 bpm) after 1, 3, 5, and 7 years, respectively. Multivariate analysis identified extensive right ventricular dysfunction as an independent predictor of appropriate ICD disc...

Research paper thumbnail of Arrhythmogenic right ventricular cardiomyopathy

Circulation. Arrhythmia and electrophysiology, 2012

Research paper thumbnail of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Research paper thumbnail of Arrhythmogene rechtsventrikuläre Kardiomyopathie : Ätiologie, Diagnostik und Therapie (Übersicht)

Medizinische Klinik, 1998

~Die arrhythmogene rechtsventrikul~e Kardiomyopathie (AKVC) ist charakterisiert durch regional be... more ~Die arrhythmogene rechtsventrikul~e Kardiomyopathie (AKVC) ist charakterisiert durch regional betonte Degeneration und Atrophie des rechtsventrikuliren Myokards mit nachs Ersatz durch Fett-und Bindewebe. Die Erkrankung manifestiert sich ira Jugend-oder ]ungen Erwachsenenalter, MGnner sind Niufiger betroffen. Leitsymptome der ARVG sind ventrikul~re Tachyarrhythmien mit linksschenkelblockartiger Konfiguration. Auch pl6tzliche Herztodesf~Ue kSnnen die p¡ Manifestation der ARVC darstellen. ~l Charakteristische Befunde sind Repolarisationsst6rungen und eine Verl2ingerung des QRS-Komplexes in den rechtspr~kordialen Ableitungen des Oberfl~ichen-EKG sowie regional betonte St6rungen der Struktur und Funktion des rechten Ventrikels. Eme lmksventrikul~re Beteiligung wird erst in fortgeschrittenen Krankheitsstadien beobachtet und kann in seltenen F/illen zu einer biventrikul~iren Herzinsuftizienz f'ª El Ira Vordergrund der Therapie stehen die Behandlung der Kammertachykardien und die Prophylaxe des pl6tzlichen Herztodes. Der individueUe Einsatz von antiarrhythmischer Pharmakotherapie, Katheterablation und Defibrillatorimplantation kann zur Verbesserung der Langzeitprognose von Patienten mit ARVC beitragen.

Research paper thumbnail of Arrhythmogene rechtsventrikul�re Kardiomyopathie (ARVC)

Notfall Rettungsmed, 2009

Research paper thumbnail of Arrhythmogenic right ventricular cardiomyopathy (ARVC): Risk stratification and therapy

Notfall Rettungsmed, 2009

Research paper thumbnail of Arrhythmogene rechtsventrikuläre Kardiomyopathie

Medizinische Klinik, 1998

~Die arrhythmogene rechtsventrikul~e Kardiomyopathie (AKVC) ist charakterisiert durch regional be... more ~Die arrhythmogene rechtsventrikul~e Kardiomyopathie (AKVC) ist charakterisiert durch regional betonte Degeneration und Atrophie des rechtsventrikuliren Myokards mit nachs Ersatz durch Fett-und Bindewebe. Die Erkrankung manifestiert sich ira Jugend-oder ]ungen Erwachsenenalter, MGnner sind Niufiger betroffen. Leitsymptome der ARVG sind ventrikul~re Tachyarrhythmien mit linksschenkelblockartiger Konfiguration. Auch pl6tzliche Herztodesf~Ue kSnnen die p¡ Manifestation der ARVC darstellen. ~l Charakteristische Befunde sind Repolarisationsst6rungen und eine Verl2ingerung des QRS-Komplexes in den rechtspr~kordialen Ableitungen des Oberfl~ichen-EKG sowie regional betonte St6rungen der Struktur und Funktion des rechten Ventrikels. Eme lmksventrikul~re Beteiligung wird erst in fortgeschrittenen Krankheitsstadien beobachtet und kann in seltenen F/illen zu einer biventrikul~iren Herzinsuftizienz f'ª El Ira Vordergrund der Therapie stehen die Behandlung der Kammertachykardien und die Prophylaxe des pl6tzlichen Herztodes. Der individueUe Einsatz von antiarrhythmischer Pharmakotherapie, Katheterablation und Defibrillatorimplantation kann zur Verbesserung der Langzeitprognose von Patienten mit ARVC beitragen.

Research paper thumbnail of Arrhythmogenic right ventricular cardiomyopathy/dysplasia: risk stratification and therapy

Progress in cardiovascular diseases

Research paper thumbnail of Arrhythmogenic right ventricular cardiomyopathy: clinical registry and database, evaluation of therapies, pathology registry, DNA banking

European heart journal, 2004

Research paper thumbnail of Idiopathic Right Ventricular Outflow Tract Tachycardia

Arrhythmogenic RV Cardiomyopathy/Dysplasia, 2007

Research paper thumbnail of Implantable cardioverter-defibrillator therapy in arrhythmogenic right ventricular cardiomyopathy**Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology

Journal of the American College of Cardiology, 2005

Research paper thumbnail of Efficacy and Safety of d,l-Sotalol in Patients With Ventricular Tachycardia and in Survivors of Cardiac Arrest

Journal of the American College of Cardiology, 1997

The aim of this study was to assess the antiarrhythmic efficacy and safety of d,l-sotalol in pati... more The aim of this study was to assess the antiarrhythmic efficacy and safety of d,l-sotalol in patients with ventricular tachycardia (VT) or ventricular fibrillation (VF) and in survivors of cardiac arrest and to identify the factors that are associated with arrhythmia suppression and therefore might be helpful in predicting drug efficacy. Background. Despite increasing use of the class III antiarrhythmic agent d,l-sotalol, data on its short-and long-term efficacy in a large patient cohort are lacking. Information on its long-term tolerability and safety is limited. Methods. A total of 396 patients with inducible sustained VT or VF (VT/VF) underwent programmed stimulation before and after receiving oral d,l-sotalol (240 to 640 mg/day). Patients in whom VT/VF was rendered either noninducible or more difficult to induce (more extrastimuli or faster drive cycle length needed for VT/VF induction) were discharged on a regimen of oral d,l-sotalol. Results. d,l-Sotalol suppressed VT/VF in 151 patients (38.1%) and rendered the arrhythmia more difficult to induce in 76 patients (19.2%). The extent of drug-induced prolongation of right ventricular refractoriness and a shorter VT cycle length at baseline were independent predictors of immediate drug efficacy. Torsade de pointes developed in seven patients (1.8%). Two hundred ten patients (53%) continued to receive d,l-sotalol and were followed up for 34 ؎ 18 months (mean ؎ SD). The actuarial rates for the absence of arrhythmic recurrence (either VT/VF or sudden death) at 1 and 3 years were 89% and 77%, respectively. Actuarial rates for overall survival at 1 and 3 years were 94% and 86%, respectively. VT/VF suppression by d,l-sotalol was an independent discriminant variable that separated patients with and without arrhythmia recurrence. However, noninducibility of VT/VF did not predict freedom from sudden death. Conclusions. Oral d,l-sotalol is effective and safe in patients with VT/VF. However, sudden cardiac death develops in a significant proportion of patients, and programmed stimulation seems to be of limited value for its prediction.

Research paper thumbnail of Impaired myocardial blood flow and flow reserve associated with increased coronary resistance in persistent idiopathic atrial fibrillation

Journal of Nuclear Cardiology, 2005

Background: Abnormalities in myocardial metabolism and mechanical performance are known to charac... more Background: Abnormalities in myocardial metabolism and mechanical performance are known to characterize hypertrophic cardiomyopathy (HCM). This study evaluated myocardial perfusion, oxidative and substrate metabolism in genetically homogenous HCM patients with different phenotypic expressions. Methods: Eight patients with HCM caused by the Asp175Asn substitution in the alpha-tropomyosin gene underwent in fasting state myocardial blood flow, oxygen consumption (Kmono) and free fatty acid (FFA) uptake measurements using positron emission tomography and [15O]H20, [11C]acetate and [18F]FTHA respectively. Echocardiographic measurements were used to assess myocardial function and work. Efficiency of forward work was calculated. Results: As compared to normal values, patients with HCM were characterised with normal global perfusion but increased oxygen consumption and reduced efficiency. Myocardial FFA uptake was within the normal range. Global perfusion and Kmono as well as efficiency were inversely correlated with LV mass and were significantly lower in patients with LV mass Ͼ 180g (nϭ 4) than LV mass Ͻ 180 g (nϭ 4) (p Ͻ 0.05). Global myocardial FFA uptake was not associated with degree of hypertrophy. Typical for HCM, hypertrophy was heterogenous affecting more commonly septal wall. At individual level, regional FFA uptake and Kmono correlated nicely in patients with mild LV hypertrophy (Rϭ 0.73-0.99, avg 0.85) whereas the correlation was mainly inverse in patients with more advanced hypertrophy (Rϭ Ϫ0.88-0.68, avg Ϫ0.24). Conclusions: Genetically defined homogenous HCM patients with Asp175Asn mutation in the alpha-tropomyosin gene are characterized with increased oxygen consumption and reduced efficiency of forward work but normal perfusion and FFA uptake. However, cardiac phenotypic expression is also associated with changes in perfusion, oxygen consumption and efficiency. The patients with advanced LV hypertrophy are characterised with uncoupling of regional oxidative metabolism and FFA utilization indicating switch in cardiac substrate metabolism not attributable to genetic factors.

Research paper thumbnail of Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy

Human Molecular Genetics, 2012

Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric left ventricular hypertrophy, di... more Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric left ventricular hypertrophy, diastolic dysfunction and myocardial disarray. HCM is caused by mutations in sarcomeric genes, but in >40% of patients, the mutation is not yet identified. We hypothesized that FHL1, encoding four-and-a-half-LIM domains 1, could be another disease gene since it has been shown to cause distinct myopathies, sometimes associated with cardiomyopathy. We evaluated 121 HCM patients, devoid of a mutation in known disease genes. We identified three novel variants in FHL1 (c.134delA/K45Sfs, c.459C>A/C153X and c.827G>C/ C276S). Whereas the c.459C>A variant was associated with muscle weakness in some patients, the c.134delA and c.827G>C variants were associated with isolated HCM. Gene transfer of the latter variants in C2C12 myoblasts and cardiac myocytes revealed reduced levels of FHL1 mutant proteins, which could be rescued by proteasome inhibition. Contractility measurements after adeno-associated virus transduction in rat-engineered heart tissue (EHT) showed: (i) higher and lower forces of contraction with K45Sfs and C276S, respectively, and (ii) prolonged contraction and relaxation with both mutants. All mutants except one activated the fetal hypertrophic gene program in EHT. In conclusion, this study provides evidence for FHL1 to be a novel gene for isolated HCM. These data, together with previous findings of proteasome impairment in HCM, suggest that FHL1 mutant proteins may act as poison peptides, leading to hypertrophy, diastolic dysfunction and/or altered contractility, all features of HCM.

Research paper thumbnail of Arrhythmogenic right ventricular cardiomyopathy/dysplasia clinical presentation and diagnostic evaluation: Results from the North American Multidisciplinary Study