Resolution of left atrial appendage thrombi: No difference between phenprocoumon and non-vitamin K-dependent oral antagonists.

BACKGROUND: Atrial fibrillation is the most important risk factor for left atrial appendage (LAA) thrombi, a potentially life-threatening condition. Thrombus resolution may prevent embolic events and allow rhythm-control strategies, which have been shown to reduce cardiovascular complications. HYPOTHESIS: There is no significant difference between phenprocoumon and non-Vitamin K-dependent oral anticoagulants (NOACs) in the resolution of LAA-thrombi in a real-world setting. METHODS: Consecutive patients with LAA-thrombi from June 2013 to June 2017 were included in an observational single-center analysis. The primary endpoint was defined as the resolution of the thrombus. The observational period was 1 year. Resolutions rates in patients on phenprocoumon or NOACs were compared and the time to resolution was analyzed. RESULTS: We identified 114 patients with LAA-thrombi. There was no significant difference in the efficacy of resolution between phenprocoumon and NOACs (p = .499) at the time of first control which took place after a mean of 58 ± 42.2 (median 48) days. At first control most thrombi were dissolved (74.6%). The analysis after set-time intervals revealed a resolution rate of 2/3 of LAA-thrombi after 8-10 weeks in the phenprocoumon and NOAC groups. After 12 weeks a higher number of thrombi had resolved in the presence of NOAC (89.3%) whereas in the presence of phenprocoumon 68.3% had resolved (p = .046). CONCLUSION: In this large observational study NOACs were found to be potent drugs for the resolution of LAA-thrombi. In addition, the resolution of LAA-thrombi was found to be faster in the presence of NOAC as compared to phenprocoumon.

[Sudden-onset dyspnea, cough and hemoptysis in a previously healthy 46-year-old female swimmer]. / Akut einsetzende Dyspnoe, Husten und Hämoptysen bei einer 46-jährigen bisher gesunden Schwimmerin.

This case report describes the case of a patient that developed suddenly dyspnea, cough and hemoptysis while swimming. Under the clinical presentation of pulmonary edema she required short-term invasive ventilation. Initially, echocardiography showed globally highly reduced systolic left ventricular function, which rapidly normalized. After exclusion of other pulmonary or cardiac causes swimming-induced pulmonary edema was diagnosed. This should be considered in cases of pulmonary edema, particularly in patients practicing sports with contact to water.

Epileptic seizure in a patient with an implantable cardioverter-defibrillator: Quo vadis right ventricular lead?

The case of a 77-year-old man admitted for suspected epileptic seizure is reported. Patient history showed implantation of a single-chamber implantable cardioverter-defibrillator (ICD) after cardiac arrest in 2007 with replacement in 2012 due to battery depletion; the patient reported no previous syncope, unconsciousness or seizures. Interrogation records of the ICD showed five ventricular tachyarrhythmia episodes that corresponded to the "seizure". Further examination revealed incorrect position of the RV-lead. Diagnosis was a provoked epileptic seizure due to undersensing of ventricular tachycardia because of improper ICD lead implantation in the coronary sinus. Treatment consisted of implantation of a new device with an additional ICD lead into the right ventricle.

A fatal combination in an old lady: Tako-Tsubo cardiomyopathy, long QT syndrome, and cardiac hypertrophy.

Tako-Tsubo cardiomyopathy (TT-CM), also called stress-induced cardiomyopathy or transient left ventricular (LV) apical ballooning syndrome, is characterized by transient apical or midventricular LV dysfunction that mimics myocardial infarction, but in the absence of significant coronary artery disease. The onset of TT-CM is typically triggered by an acute medical illness or by intense emotional, psychological, or physical stress. During the acute phase, a disturbed repolarization with QT prolongation in the surface ECG is frequently obvious. Despite the generally good prognosis of TT-CM, severe clinical courses have been reported due to the depressed LV function with cardiogenic shock or malignant tachyarrhythmias. We report an unusual presentation of a patient with TT-CM and recurrent episodes of torsades de pointes tachyarrhythmias. In this patient, we identified pre- and coexisting congenital long QT syndrome and severe cardiac hypertrophy--all of them associated with disturbed myocardial repolarization and predisposed the patient to malignant tachyarrhythmias.

Cardiac arrhythmias and sudden death in infancy: implication for the medicolegal investigation.

Genetically transmitted diseases are an important cause of juvenile sudden cardiac death (SCD). In a considerable proportion of individuals in which a medicolegal investigation is performed, structural heart disease is absent, and the medical examiner fails to discover an adequate cause of death. In such cases, an inherited arrhythmogenic disease should be considered, which manifests with life-threatening ventricular tachycardia or SCD. Molecular diagnosis is progressively becoming an important tool for these questions. Therefore, postmortem genetic testing ("molecular autopsy") should be considered as a part of the comprehensive medicolegal investigation in SCD cases without apparent structural heart disease. It will have implications not only for the deceased individual but also for living family members in preventing (further) cardiac events by expert counseling, appropriate lifestyle adjustment, and adequate treatment, if available.

Electrocardiographic risk stratification in families with congenital long QT syndrome.

AIMS: The QT interval in the surface ECG is one of the most often used risk stratifiers in families with congenital long QT syndrome (LQTS). The best ECG lead for clinical management of LQTS families remains unclear. METHODS AND RESULTS: The predictive power of the QTc interval in all ECG leads was studied in 200 consecutive genotyped LQTS family members to identify mutation carriers (n = 103; age: 35+/-19 years) and high-risk LQTS patients (n = 16 with survived sudden cardiac arrest) using receiver operating curve (ROC) analysis (ROC = area under curve). Additionally, the risk for events (syncope and sudden cardiac arrest) was calculated for QTc decile in all individuals. The predictive power was highest in lead II and lead V5 for identifying carriers in LQTS families. These ECG leads were optimal for risk stratification (ROC range 0.83-0.87). In these leads, positive predictive value (PPV) and negative predictive value (NPV) were highest for suggested QTc cut-offs (440 and 500 ms) for identification of LQTS mutation carriers and high-risk patients (PPV between 78-81 and 73-80%, respectively). The risk for events in QTc deciles increased exponentially from 10 to 80% and was 40% for QTc > 500 ms. CONCLUSION: On the basis of these data, QTc is the best diagnostic and prognostic ECG parameter in LQTS families. A single measurement should be obtained in lead II if measurable and then in left precordial leads (preferably V5) as a second choice.

[Tako-tsubo cardiomyopathy. Incidence in patients with acute coronary syndrome]. / Tako-Tsubo-Kardiomyopathie. Inzidenz bei Patienten mit akutem Koronarsyndrom.

BACKGROUND AND METHODS: In 2005, an emergency coronary angiography was performed at the authors' clinic in 215 patients (148 men, 67 women) with troponin-positive acute coronary syndrome. RESULTS: In five of these patients (exclusively women, mean age [+/- SD] 61 +/- 12 years), tako-tsubo cardiomyopathy was identified. This represents a frequency of 2.3% (5/215 patients) of all investigated patients and of 7.5% (5/67 patients) within the group of women. In these patients, levocardiography revealed severe left ventricular dysfunction with apical wall motion abnormality known as "apical ballooning". At angiography, a significant coronary artery disease could be excluded. Chest pain was present in all patients, combined with ST segment elevation in one (20%) and T-wave inversion in four (80%). Elevated cardiac markers were found in all cases. All patients experienced psychologically stressful circumstances preceding the onset of symptoms. The patients all survived, showing normalized ejection fraction and rapid restoration of previous cardiovascular function within a mean (+/- SD) of 15 +/- 11 days. CONCLUSION: Tako-tsubo cardiomyopathy is a distinctive form of regional left ventricular dysfunction triggered by psychologically stressful events, which has a favorable clinical outcome. With a remarkable frequency of 7.5% especially in women, tako-tsubo cardiomyopathy should be included in the differential diagnosis of acute myocardial infarction.

Sudden infant death syndrome and long QT syndrome: an epidemiological and genetic study.

Sudden infant death syndrome (SIDS) is a frequent cause of death among infants. The etiology of SIDS is unknown and several theories, including fatal ventricular arrhythmias, have been suggested. We performed an epidemiological and genetic investigation of SIDS victims to estimate the presence of inherited long QT syndrome (LQTS) as a contributor for SIDS. Forty-one consecutively collected and unrelated SIDS cases were characterized by clinical and epidemiological criteria. We performed a comprehensive gene mutation screening with single-strand conformation polymorphism analysis and sequencing techniques of the most relevant LQTS genes to assess mutation frequencies. In vitro characterization of identified mutants was subsequently performed by heterologous expression experiments in Chinese hamster ovary cells and in Xenopus laevis oocytes. A positive family history for LQTS was suspected by mild prolonged Q-T interval in family members in 2 of the 41 SIDS cases (5%). In neither case, a family history of sudden cardiac death was present nor a mutation could be identified after thorough investigation. In another SIDS case, a heterozygous missense mutation (H105L) was identified in the N-terminal region of the KCNQ1 (LQTS 1) gene. Despite absence of this mutation in the general population and a high conservational degree of the residue H105 during evolution, electrophysiological investigations failed to show a significant difference between wild-type and KCNQ1(H105L)/minK-mediated I(Ks) currents. Our data suggest that a molecular diagnosis of SIDS related to LQTS genes is rare and that, even when an ion channel mutation is identified, this should be regarded with caution unless a pathophysiological relationship between SIDS and the electrophysiological characterization of the mutated ion channel has been demonstrated.

Substitution of a conserved alanine in the domain IIIS4-S5 linker of the cardiac sodium channel causes long QT syndrome.

OBJECTIVE: Congenital long QT syndrome type 3 (LQT3) is an inherited cardiac arrhythmia disorder due to mutations in the cardiac sodium channel gene, SCN5A. Although most LQT3 mutations cause a persistent sodium current, increasing diversity in the disease mechanism is shown. Here we present the electrophysiological properties of the A1330T sodium channel mutation (DIIIS4-S5 linker). Like the A1330P, LQT3 mutation, A1330T, causes LQT3 in the absence of a persistent current. METHODS: A1330T, A1330P and wild-type sodium channels were expressed in HEK-293 cells and characterized using the whole-cell configuration of the patch-clamp technique. RESULTS: The A1330T mutation shifts positively the voltage-dependence of inactivation and speeds recovery from inactivation. Measurements of sodium window (I(Na, window)) currents revealed a positive shift of the I(Na, window) voltage range for both 1330 mutants, with in addition an increase in I(Na, window) magnitude for the A1330P mutant. Action potential (AP) clamp experiments revealed that these changes in I(Na, window) properties cause an increased inward current during the initial part of phase 4 repolarization of the AP. CONCLUSIONS: Our findings indicate that the alanine at position 1330 in the DIIIS4-S5 linker of the cardiac sodium channel has a role in channel fast inactivation. Substitution by a threonine shifts the voltage range of I(Na, window) activity to more positive potentials. Here the counter-acting effect of outward K+ current is reduced and may delay AP repolarization, explaining the LQT3 phenotype.

Implantable cardioverter-defibrillator therapy in patients with congenital long-QT syndrome: a long-term follow-up.

OBJECTIVES: The purpose of this study was to evaluate retrospectively a single-center experience with the use of ICDs in patients with long QT syndrome (LQTS) concerning outcome, complications, and optimal programming. BACKGROUND: Use of implantable cardioverter-defibrillator (ICD) in patients with congenital LQTS is controversial but is generally accepted in high-risk patients. METHODS: We enrolled 27 symptomatic patients with LQTS undergoing ICD therapy (QTc 540 +/- 64 ms(1/2); 85% female, 63% cardiac arrest; 33% syncope despite beta-blockers; 4% with severe phenotype) and 81 genotyped patients with LQTS undergoing conventional drug therapy (28 LQT1, 39 LQT2, 1 LQT3, 13 LQT5). During a mean follow-up of 65 +/- 34 months, one death occurred in the ICD group that was not LQTS related. A total of 178 appropriate shocks were observed in 10/27 patients (37%), mostly in survivors of cardiac arrest (in 58% of cardiac arrest patients vs. in 20% of non-cardiac arrest patients). RESULTS: In a logistic regression analysis, only QTc interval (121/178 shocks (68%) for QTc > 500 ms(1/2)) and "survived cardiac arrest" were prognostic for ICD shocks. In 30% of patients in the ICD group, multiple shocks occurred and could be reduced after increase of antibradycardia pacing rate, adding beta-blocker therapy, or starting the rate-smoothing algorithm (average 7.1 shocks before to 0.75 shocks after additional intervention annually). CONCLUSION: ICD therapy is a safe and useful tool in high-risk patients with LQTS. QTc interval and cardiac arrest survivors were prognostic factors for appropriate ICD shocks. The results of this large single-center experience suggest that beta-blockers should always be added to ICD therapy. In addition, some patients might benefit from additional antibradycardia pacing, prolonged detection time, and a rate-smoothing algorithm to prevent recurrent episodes.

Prolonged atrial action potential durations and polymorphic atrial tachyarrhythmias in patients with long QT syndrome.

UNLABELLED: Atrial APD and Polymorphic AT in LQTS. INTRODUCTION: Prolongation of the QT interval and torsades de pointes tachycardias due to altered expression or function of repolarizing ion channels are the hallmark of congenital long QT syndrome (LQTS). The same ion channels also contribute to atrial repolarization, and familial atrial fibrillation may be associated with a mutated KVLQT1 gene. We therefore assessed atrial action potential characteristics and atrial arrhythmias in LQTS patients. METHODS AND RESULTS: Monophasic action potentials (MAPs) were simultaneously recorded from the right atrial appendage and the inferolateral right atrium in 10 patients with LQTS (8 with identifiable genotype) and compared to 7 control patients. Atrial arrhythmias also were compared to MAPs recorded in patients with persistent (n = 10) and induced (n = 4) atrial fibrillation. Atrial action potential durations (APD) and effective refractory periods (ERP) were prolonged in LQTS patients at cycle lengths of 300 to 500 msec (APD prolongation 30-41 msec; ERP prolongation 26-52 msec; all P < 0.05). Short episodes of polymorphic atrial tachyarrhythmias (polyAT, duration 4-175 sec) occurred spontaneously or during pauses after pacing in 5 of 10 LQTS patients, but not in controls (P < 0.05). P waves showed undulating axis during polyAT. Cycle lengths of polyAT were longer than during persistent and induced atrial fibrillation. Afterdepolarizations preceded polyAT in 2 patients. The electrical restitution curve was shifted to longer APD in LQTS patients and to even longer APD in LQTS patients with polyAT. CONCLUSION: This group of LQTS patients has altered atrial electrophysiology: action potentials are prolonged, and polyAT occurs. PolyAT appears to be a specific arrhythmia of LQTS reminiscent of an atrial form of "torsades de pointes".

The long QT syndrome: considerations in the athletic population.

In athletes, ventricular arrhythmias and sudden cardiac death are rare and unpredictable events. Often, an underlying heart disease is present, but pre-existing clinical signs or symptoms may not be recognized. Primary electrical disorders (such as the long QT syndrome) are rarely present in athletes but, so far, are a considerable reason for disqualification from sport activity. These disorders are mostly inherited, and patients should be referred to a cardiologist with special experience. Through the efforts of molecular genetics and cellular electrophysiology, an increasing understanding of the underlying mechanisms of arrhythmogenesis is being gathered. During the past decade, evidence has grown that establishing accurate genetic diagnoses and dissection of molecular disease mechanisms can have an impact on prognosis, and help direct therapy in a range of cardiovascular diseases. Further achievements in the areas of clinical and molecular research, improvement of medical education, and expansion of genotyping facilities will facilitate the correct and immediate identification of affected patients.

[Long QT-syndromes: diagnosis and genetics]. / Angeborene QT-Syndrome : Diagnostik und Genetik.

The long-QT syndrome (LQTS) is a familiar disease characterized by abnormal myocardial repolarization and a high risk of sudden cardiac death. As a hallmark of the disease, the heart-rate corrected QT interval is intrinsically prolonged. Recent advances in molecular genetics have elicited that various inborn defects in cardiac ion channel genes regulating cardiac ion currents underlie this propensity to develop malignant ventricular arrhythmias. Meanwhile, a widespread locus and allelic genetic heterogeneity in LQTS is evident, thus, complicating the power of DNA diagnostic tools. The following review will briefly summarize clinical and genetic aspects of LQTS.