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Giant cell myocarditis (GCM) is a rare condition. Its association with SARS‐CoV‐2 has not been described before. The 46‐year‐old female patient was admitted to the clinic on September 2020. She had 7 year adrenal insufficiency history and infarct‐like debut of myocardial disease in November 2019. After COVID‐19 in April 2020, cardiac disease progressed. The examination showed low QRS voltage, QS complexes in V1–V5 leads, atrial standstill, left ventricular systolic and restrictive dysfunction, elevated anti‐heart antibodies, and subepicardial late gadolinium enhancement by magnetic resonance imaging. Endomyocardial biopsy and pacemaker implantation were performed, but the patient died suddenly due to ventricular tachycardia or ventricular fibrillation (the resuscitation was ineffective). The autopsy revealed GCM, SARS‐CoV‐2, and Parvovirus B19 were detected in the myocardium. The role of SARS‐CoV‐2 in the pathogenesis of autoimmune myocarditis is discussed.

The mouse is a useful preclinical species for evaluating disease etiology due to the availability of a wide variety of genetically modified strains and the ability to perform disease-modifying manipulations. In order to better characterize atrial fibrillation (AF), we profiled several commonly used murine AF models. We initially evaluated a pharmacological model of acute carbachol (CCh) treatment plus atrial burst pacing in C57BL/6 mice. In an effort to observe micro-reentrant circuits indicative of authentic AF, we employed optical mapping imaging in isolated mouse hearts. While CCh reduced atrial refractoriness and increased atrial tachyarrhythmia vulnerability, the left atrial (LA) excitation patterns were rather regular without reentrant circuits or wavelets. Therefore, the atrial tachyarrhythmia resembled high frequency atrial flutter, not typical AF per se. We next examined both a chronic angiotensin II (Ang II) infusion model and the surgical model of transverse aortic constriction (TAC), which have both been reported to induce atrial and ventricular structural changes that serve as a substrates for micro-reentrant AF. Although we observed some extent of atrial remodeling such as fibrosis or enlarged LA diameter, burst pacing-induced atrial tachyarrhythmia vulnerability did not differ from control mice in either model. This again suggested that an AF-like pathophysiology is difficult to demonstrate in the mouse. To continue searching for a valid murine AF model, we studied mice with a cardiac-specific deficiency (KO) in liver kinase B1 (Cardiac-LKB1), which has been reported to exhibit spontaneous AF. Indeed, the electrocardiograms (ECG) of conscious Cardiac-LKB1 KO mice exhibited no P waves and had irregular RR intervals, which are characteristics of AF. Histological evaluation of Cardiac-LKB1 KO mice revealed dilated and fibrotic atria, again consistent with AF. However, atrial electrograms and optical mapping revealed that electrical activity was limited to the sino-atrial node area with no electrical conduction into the atrial myocardium beyond. Thus, Cardiac-LKB KO mice have severe atrial myopathy or atrial standstill, but not AF. In summary, the atrial tachyarrhythmias we observed in the four murine models were distinct from typical human AF, which often exhibits micro- or macro-reentrant atrial circuits. Our results suggest that the four murine AF models we examined are poor representations of human AF, and raise a cautionary note about the use of any murine model to study AF.

Atrial standstill (AS) is a rare condition characterized by the absence of electrical and mechanical atrial activity,1 first described by Cushny.2 The absence of P waves and bradycardia, along with a wide QRS complex, are seen on the electrocardiogram (ECG). The clinical course of AS varies greatly; the timeline can be persistent or transient, and the spatial distribution of the atrial lesion can be diffuse or partial.3, 4 In many cases, the AS appears initially in the right atrium (RA) and progresses to the entire left atrium. It occasionally complicates symptomatic sick sinus syndrome.5 We hereby describe a case of AS where a dual-chamber permanent pacemaker implantation was necessary owing to symptomatic sick sinus syndrome. An electrophysiological study (EPS) revealed inactivity throughout almost the entire RA, with the exception of the coronary sinus (CS). A permanent atrial lead was therefore placed in the CS.

Pacemaker implantation is considered as a standard procedure for treatment of symptomatic bradycardia in both dogs and cats. Advanced second-degree and third-degree atrioventricular blocks, sick sinus syndrome, persistent atrial standstill, and vasovagal syncope are the most common rhythm disturbances that require pacing to either alleviate clinical signs or prolong survival. Most pacemakers are implanted transvenously, using endocardial leads, but rarely epicardial leads may be necessary. To decide whether a patient is a candidate for pacing, as well as which pacing modality should be used, the clinician must have a clear understanding of the etiology, the pathophysiology, and the natural history of the most common bradyarrhythmias, as well as what result can be achieved by pacing patients with different rhythm disturbances. The goal of this review was, therefore, to describe the indications for pacing by evaluating the available evidence in both human and veterinary medicine. We described the etiology of bradyarrhythmias, clinical signs and electrocardiographic abnormalities, and the choice of pacing modality, taking into account how different choices may have different physiological consequences to selected patients. It is expected that this review will assist veterinarians in recognizing arrhythmias that may require permanent pacing and the risk-benefit of each pacing modality and its impact on outcome.

Emery-Dreifuss muscular dystrophy (EDMD) is a group of hereditary muscular dystrophy syndrome caused by deficiency of genes encoding nuclear envelope proteins. Patients having EDMD show the triad of muscle dystrophy, joint contracture, and cardiac disease. In almost all patients, cardiac involvement is prevalent and is the most severe aspect of EDMD. Cardiac disease is predominantly shown by conduction defects, atrial fibrillation/flutter, and atrial standstill. Sudden death and heart failure because of left ventricular dysfunction are important causes of mortality, particularly in those patients that have the LMNA mutation. Medical treatment of EDMD is limited to addressing symptoms and ambulation support; moreover, pacemaker implantation is necessary when there are severe conduction defects and bradycardia occurs. Note that automated defibrillation devices may be considered for those patients who have a high risk of sudden death, rate, or rhythm control. Also, anticoagulation should be initiated in those patients who have atrial fibrillation/flutter. Thus, for optimal management, a multidisciplinary approach is required.

The use of leadless trans-catheter pacemakers is increasing particularly in the elderly population. However, its indication for those with anatomical anomaly remains unknown. We had a 75-year-old woman with atrial standstill and ventricular escape. Micra leadless pacemaker (Medtronic, Inc, Minneapolis, MN, USA) failed to be deployed due to too enlarged right atrium accompanied by atrial septal deficiency, followed by successful implantation of transvenous pacemaker lead by using SelectSecure lead (Medtronic) with a C315 delivery catheter that enhanced back-up force toward the ventricular septum against significant tricuspid regurgitation. The Micra is a promising system, but we should understand its limitations as well as alternative systems particularly for such an anatomical anatomy.

Introduction: Cardiac involvement in patients with muscular dystrophy associated with Lamin A/C mutations (LMNA) is characterized by atrioventricular conduction abnormalities and life-threatening cardiac arrhythmias. Little is known about cardiac involvement in patients with emerin mutation (EMD). The aim of our study was to describe and compare the prevalence and time distribution of cardiac arrhythmias at extended follow-up. Patients and methods: 45 consecutive patients affected by muscular dystrophy associated to laminopathy or emerinopathy were examined. All patients underwent clinical evaluation, 12-lead surface electrocardiogram (ECG), 24 h electrocardiographic monitoring, and cardiac implanted device interrogation. Results: At the end of 11 (5.0–16.6) years of follow-up, 89% of the patients showed cardiac arrhythmias. The most prevalent was atrial standstill (AS) (31%), followed by atrial fibrillation/flutter (AF/Afl) (29%) and ventricular tachycardia (22%). EMD patients presented more frequently AF/AFl compared to LMNA (50% vs. 20%, p = 0.06). Half of the EMD patients presented with AS, whilst there was no occurrence of such in the LMNA (p = 0.001). Ventricular arrhythmias were found in 60% of patients with laminopathy compared to 3% in patients with emerinopathy (p &lt, 0.001). The age of AVB occurrence was higher in the LMNA group (32.8 +/− 10.6 vs. 25.1 +/− 9.1, p = 0.03). Conclusions: Atrial arrhythmias are common findings in patients with muscular dystrophy associated with EMD/LMNA mutations, however, they occurred earlier in EMD patients. Ventricular arrhythmias were very common (60%) in LMNA and occurred definitely earlier compared to the EMD group.

Background We examined the genetic background of a Chinese Han family in which some members presented with complex arrhythmias including sick sinus syndrome, progressive conduction block, atrial fibrillation, atrial standstill and Brugada syndrome. The possible underlying mechanism associated with the genetic mutation was explored. Methods Targeted capture sequencing was conducted in the probands in the coding and splicing regions of genes implicated in inherited arrhythmias. Stable cell lines overexpressing wild type (WT) or mutant SCN5A were generated in HEK293T cells. Whole‐cell recording was performed to evaluate the functional changes in sodium channels. Results The rare heterozygous linkage mutations, SCN5A R965C and R1309H, were found in these patients with complex familial arrhythmias. Compared to WT, R965C or R1309H, the peak current of sodium channel was dramatically reduced in HEK293T cell with linkage R965C‐R1309H mutation when testing potentials ranging from −45 to 15 mV. Notably, the maximum peak current of sodium channels with R1309H and linkage R965C‐R1309H displayed significant decreases of 31.5% and 73.34%, respectively, compared to WT. Additionally, compared to R965C or R1309H alone, the linkage mutation R965C‐R1309H demonstrated not only a more obvious depolarisation‐shifted activation and hyperpolarisation‐shifted inactivation, but also a more significant alteration in the time constant, V1/2 and the slope factor of activation and inactivation. Conclusions The linkage mutation SCN5A R965C‐R1309H led to a more dramatically reduced current density, as well as more significant depolarisation‐shifted activation and hyperpolarisation‐shifted inactivation in sodium channels than R965C or R1309H alone, which potentially explain this complex familial arrhythmia syndrome., The rare hereditary disease with complex arrhythmia syndrome resulted from the heterozygous linkage SCN5A R965C‐R1309H mutation, detected by targeted capture sequencing. The linkage mutation SCN5A R965C‐R1309H led to a more dramatic reduction in the current density of sodium channel, more depolarisation‐shifted activation and more hyperpolarisation‐shifted inactivation than either single mutation, R965C or R1309H, indicating synergistic effects on the pore‐gating properties of sodium channels, as detected by whole‐cell recordings.

Introduction: Atrial mechanical standstill is a rare phenomenon. Electrical function is preserved but atrial contraction is absent. Standard 2D transthoracic echocardiography evaluates isolated left atrial standstill by analyzing pulsed-wave Doppler imaging of mitral valve (MV) inflows and tissue Doppler imaging (TDI) at MV annulus. Case report: In a 65-year old patient with arterial hypertension and hyperlipidaemia electrical conversion of persistent atrial flutter to sinus rhythm was achieved. The patient has had atrial flutter for about a year. He also suffered from COVID- 19 pneumonia infection 2 months before being admitted to the hospital. In spite of sinus rhythm after the electrical conversion that was seen on twelve-lead electrocardiography, 48 hours after conversion no mechanical left atrial activity was restored. MV inflow demonstrated normal E wave (passive filling in early diastole) but absent A wave (atrial contraction during late diastole). TDI at the MV annulus also confirmed isolated mechanical LA standstill. There was absence of a’ at the MV annulus. Conclusion: Atrial standstill is condition that may involve impairment of electrical function (electrical silence or an inability to pace or capture), or mechanical function (based on imaging). The pathophysiologic mechanism can be the underlying presence of atrial fibrosis, myopathy or it may include interatrial block. The absence of mechanical LA contraction has potential hemodynamic consequences, also there could be the possibility for the thrombus formation within the atria leading to thromboembolism. That is why anticoagulation should be continued.

Background: Mutations in the nuclear envelope genes encoding LMNA and EMD are responsible for Emery-Dreifuss muscular dystrophy. However, LMNA mutations often manifest dilated cardiomyopathy with conduction disturbance without obvious skeletal myopathic complications. On the contrary, the phenotypic spectrums of EMD mutations are less clear. Our aims were to determine the prevalence of nonsyndromic forms of emerinopathy, which may underlie genetically undefined isolated cardiac conduction disturbance, and the etiology of thromboembolic complications associated with EMD mutations. Methods: Targeted exon sequencing was performed in 87 probands with familial sick sinus syndrome (n=36) and a progressive cardiac conduction defect (n=51). Results: We identified 3 X-linked recessive EMD mutations (start-loss, splicing, missense) in families with cardiac conduction disease. All 3 probands shared a common clinical phenotype of progressive atrial arrhythmias that ultimately resulted in atrial standstill associated with left ventricular noncompaction (LVNC), but they lacked early contractures and progressive muscle wasting and weakness characteristic of Emery-Dreifuss muscular dystrophy. Because the association of LVNC with EMD has never been reported, we further genetically screened 102 LVNC patients and found a frameshift EMD mutation in a boy with progressive atrial standstill and LVNC without complications of muscular dystrophy. All 6 male EMD mutation carriers of 4 families underwent pacemaker or defibrillator implantation, whereas 2 female carriers were asymptomatic. Notably, a strong family history of stroke observed in these families was probably due to the increased risk of thromboembolism attributable to both atrial standstill and LVNC. Conclusions: Cardiac emerinopathy is a novel nonsyndromic X-linked progressive atrial standstill associated with LVNC and increased risk of thromboembolism.

Background Atrial standstill is an arrhythmogenic condition characterized by the absence of spontaneous electrical and mechanical atrial activity or in response to stimulation. There are few reported familial cases which have been associated with SCN5A mutations cosegregating with GJA5 or RYR2; however, isolated SCN5A mutations are rare. Objective The purpose of this study was to determine the clinical and biophysical consequence of a novel SCN5A mutation identified in a family with progressive atrial standstill and sudden death. Methods The family of a sporadic case of congenital atrial standstill underwent genetic screening. Human Embryonic Kidney 293 cells were transfected with wild-type (WT) or mutant SCN5A cDNAs. Biophysical properties were studied using whole-cell using patch clamp methods. Results A novel homozygous SCN5A mutation, p.V1340L, was identified in the proband and her sister. The proband had complete atrial standstill whereas the sister had partial atrial standstill. Heterozygous mutations were identified in the mother, father, and brother. All three had normal sinus rhythm and were asymptomatic. The mutant Nav1.5(V1340L) reduced Nav1.5 current density as well as showed a depolarizing shift in the voltage-dependent steady-state activation (WT: -35.3 ± 1.62 mV; V1340L: -22.4 ± 2.59 mV; P = 0.001). Conclusions A homozygous loss-of-function SCN5A mutation likely results in atrial standstill and sudden death due to suppression of initiation of action potential.

Aims Unexplained scar-related atrial tachycardia (AT) has been frequently encountered in clinical practice. We hypothesized that idiopathic, isolated fibrotic atrial cardiomyopathy (ACM) underlies this rhythm disorder. This study was aimed to characterize the underlying substrate and to explore the aetiology of this unexplained scar-related AT. Methods and results Twenty-six (11 men, aged 46 ± 13 years) of 52 non-surgical scar-related AT patients identified by three-dimensional voltage mapping were enrolled in this prospective observational study. Multimodality image examinations (echocardiography, cardiac magnetic resonance, 99Tc single-photon emission computed tomography), ventricular voltage mapping, and intracardiac pressure curve recording ruled out ventricular involvement. Catheter ablation was acutely successful for all the patients, and pacemaker implantation was performed in seven patients who presented sinus node dysfunction or atrial standstill after termination of the AT. In three patients with multiple AT recurrences, the diseased areas of the right atrium were resected and dechannelled via mini-invasive surgical interventions. Histological examinations revealed profound fibrosis without amyloidosis or adipose deposition. Viral and familial investigations yielded negative results. Fibrosis progression over a median of 45 (5-109) months of follow-up manifested as atrial arrhythmia recurrence in seven patients and atrial lead non-capture due to newly developed atrial standstill in two patients. Two patients suffered four ischaemic stroke events before receiving anticoagulation treatment. Conclusion Isolated, fibrotic ACM may underlie the idiopathic scar-related ATs. This novel cardiomyopathy has unique clinical characteristics with high morbidity including stroke and warrants specific therapeutic strategies. Further investigations are required to determine the aetiology and mechanism.

Introduction. Persistent atrial standstill is a rare syndrome characterized by absence of mechanical and electrical atrial activity. The article presents a unique case of atrial standstill in the newborn patient with tachyarrhythmia.Brief description. The first manifestation of atrial standstill in the patient was heart failure (HF) manifestations and wide-complex tachycardia according to electrocardiography, which was identified as ventricular tachycardia. At the local outpatient clinic, the child was prescribed with antiarrhythmic therapy (AAT), which decreased heart rate. Three months later, a transesophageal electrophysiological study was carried out in our center in order to determine the arrhythmia origin. A multiform idioventricular rhythm with a heart rate of 46-119 beats per min was diagnosed, atrial pacing spike (A waves) was not recorded. Given bradyarrhythmia, hemodynamic abnormalities on echocardiography (significant atrial enlargement, decreased contractility), the patient, in order to prevent the risk of sudden cardiac death, underwent implantation of single chamber pacemaker in VVIR mode and bipolar ventricular lead. Anticoagulant therapy was prescribed. After 6-month follow-up, relief of HF symptoms and an increase in left ventricular contractile function was noted.Discussion. Timely diagnosis and implantation of pacemakers allowed avoiding AAT and minimizing the HF symptoms. Continuous ventricular pacing and anticoagulant therapy are important in HF prevention.

Objective Supraventricular arrhythmias are commonly detected in patients with anti-mitochondrial antibody M2 (AMA-M2)-associated myopathy. However, the prevalence of supraventricular arrhythmias in unselected AMA-M2-positive patients and the impact of AMA-M2 on supraventricular arrhythmias have yet to be fully investigated. Methods We analyzed 384 patients (116 men; age, 60 [48-69] years), who underwent AMA-M2 testing following the detection of elevated hepatobiliary enzymes. Supraventricular arrhythmias involving atrial fibrillation, atrial flutter, atrial tachycardia, sick sinus syndrome, and atrial standstill were confirmed by a 12-lead electrocardiogram, 24-hour ambulatory monitoring, and physician-assigned diagnoses within the three years before and two years after the AMA-M2 test. Results Seventy-seven (20%) patients were positive for AMA-M2. The prevalence of supraventricular arrhythmias among AMA-M2-positive patients was higher than that among AMA-M2-negative patients (14% vs. 6%, p=0.008). A univariate analysis showed that supraventricular arrhythmias were associated with AMA-M2 positivity, aging, congestive heart failure, and the CHADS2 score. The multivariate analysis determined that AMA-M2 positivity was an independent risk factor for supraventricular arrhythmias (odds ratio 3.52, p=0.011). Among the AMA-M2-positive patients, the AMA-M2 titer did not differ to a statistically significant extent, regardless of the presence or absence of supraventricular arrhythmias. Multiple supraventricular arrhythmias with extremely low atrial deflections was a characteristic finding in AMA-M2-positive patients with supraventricular arrhythmias. Conclusion AMA-M2 enhances the risk of supraventricular arrhythmias, indicating the possible involvement of the atrial myocardium and the formation of an arrhythmogenic substrate. The results highlight the need for clinical attention to supraventricular arrhythmias in AMA-M2-positive patients.

Atrial standstill is an uncommon but serious clinical entity that is often unrecognised in the clinical setting. Its diagnosis and treatment should be swift as malignant arrhythmias and thromboembolic complications can arise. We present a 79-year-old man brought to our emergency department with acute confusion, heart failure and severe bradycardia in the context of diabetic ketoacidosis, and discuss the diagnosis and management of this arrhythmic condition.

Atrial standstill is one of the important clinical consequences on the heart in severe hyperkalemia, but it occurs even at modest potassium ion elevation. The extent to which other factors might potentiate the electrocardiographic changes induced by hyperkalemia remains unclear.This was a retrospective review of the data on 12,639 hospital admissions over a 15-year period. A total of 778 patients with hyperkalemia were identified, 28 of whom had atrial standstill, and had several parameters measured prior to any treatment of hyperkalemia. Patients with atrial standstill were older (P=0.036), had lower diastolic blood pressure (DBP; P0.0001) and serum sodium concentration (P0.0001), higher serum potassium (P0.0001), and high prevalence of angiotensin converting-enzyme inhibitor (ACEI; P=0.009) or mineral corticoid receptor (MR)-blocker (P=0.006), compared with those without atrial standstill. On multivariate logistic regression, DBP67 mmHg (P=0.006), serum sodium ion135 mmol/L (P=0.006) and serum potassium ion6.1 mmol/L (P=0.018) were identified as independent indicators of atrial standstill, after adjusting for sex, age, chronic maintenance hemodialysis, diuretics use or ACEI/angiotensin receptor blocker and MR blocker.Hyponatremia and decline in DBP are associated with atrial standstill in patients with hyperkalemia. (Circ J 2016; 80: 1781-1786).

An 1 year old intact male mixed dog (weighing 20 kg) was presented with primary complaints of abdominal distension and severe exercise intolerance. Electrocardiogram found profound bradycardia (46-79 beats/min) with atrial standstill. Laboratory studies found no particular abnormalities. Serum cortisol and T4 concentration were within normal range. Diagnostic imaging studies revealed generalized cardiomegaly, ascites, dilation in all cardiac chambers, absence of atrial contraction, absence of transmitral A-peak, mitral and tricuspid valve insufficiency and normal left ventricular systolic dimension. Based on diagnostic findings, the case was diagnosed as idiopathic atrial standstill. The dog was treated with conventional therapy for heart failure.

Isolated left ventricular noncompaction (LVNC) is a rare cardiomyopathy with morphologic characteristics of two distinct myocardial layers i.e., thin compacted epicardial and thick noncompacted endocardial layers. The noncompacted myocardium consists of prominent ventricular trabeculae and deep intertrabecular recesses. It can lead to arrhythmias, heart failure or systemic embolisms. Electrocardiographic patterns of patients with LVNC are various and non-specific; however, the most common findings are intraventricular conduction delay, left ventricular hypertrophy, and repolarization abnormalities. We reported the first case, to the best of our knowledge, of a 29-year-old man who had recent cerebral infarction and incidental LVNC with spontaneous left atrial standstill.

Aims Cardiac atrial arrhythmias are the most common type of heart rhythm disorders. Its genetic elucidation remains challenging with poor understanding of cellular and molecular processes. These arrhythmias usually affect elderly population but in rare cases, young children may also suffer from such electrical diseases. Severe complications, including stroke, are commonly age related. This study aims to identify a genetic link between electro-mechanic atrial dysfunction and stroke in children. Methods and results In two unrelated boys of 11 and 14 years with both stroke and atrial arrhythmias, the clinical phenotype was determined through a complete physical examination, electrocardiogram (ECG), Holter ECG, and computed tomography. The genetic testing was performed on a large 95 genes panel implicated in myocardial electrical imbalance, using the next generation sequencing method. The panel also includes the genes usually associated with the development of cardiomyopathies. In one child, a left atrial dilation was observed. The 2nd boy suffered from atrial standstill. Both suffered from atrial bradycardia, flutter, and fibrillation. The complete genetic testing revealed the SCN5A c.3823G>A (p.D1275N) mutation in the first family, c.1141-2A>G and c.3157G>A (p.E1053K) mutations in the second family. Conclusion Our results strengthen the association between Nav1.5 mutations and the occurrence of stroke in young patients. It emphasizes the need to look for atrial myopathy in the decision process for anticoagulation in young patients with atrial arrhythmic events.

International audience; BACKGROUND: Inherited cardiac conduction disease is a rare bradyarrhythmia associated with mutations in various genes that affect action potential propagation. It is often characterized by isolated conduction disturbance of the His-Purkinje system, but it is rarely described as a syndromic form. OBJECTIVES: The authors sought to identify the genetic defect in families with a novel bradyarrhythmia syndrome associated with bone malformation. METHODS: The authors genetically screened 15 European cases with genotype-negative de novo atrioventricular (AV) block and their parents by trio whole-exome sequencing, plus 31 Japanese cases with genotype-negative familial AV block or sick sinus syndrome by targeted exon sequencing of 457 susceptibility genes. Functional consequences of the mutation were evaluated using an in vitro cell expression system and in vivo knockout mice. RESULTS: The authors identified a connexin-45 (Cx45) mutation (p.R75H) in 2 unrelated families (a de novo French case and a 3-generation Japanese family) who presented with progressive AV block, which resulted in atrial standstill without ventricular conduction abnormalities. Affected individuals shared a common extracardiac phenotype: a brachyfacial pattern, finger deformity, and dental dysplasia. Mutant Cx45 expressed in Neuro-2a cells showed normal hemichannel assembly and plaque formation. However, Lucifer yellow dye transfer and gap junction conductance between cell pairs were severely impaired, which suggested that mutant Cx45 impedes gap junction communication in a dominant-negative manner. Tamoxifen-induced, cardiac-specific Cx45 knockout mice showed sinus node dysfunction and atrial arrhythmia, recapitulating the intra-atrial disturbance. CONCLUSIONS: Altogether, the authors showed that Cx45 mutant p.R75H is responsible for a novel disease entity of progressive atrial conduction system defects associated with craniofacial and dentodigital malformation.

Atrial standstill (AS) is a rare condition defined by a lack of active atrial contraction caused by an inability of the atrial myocardium to create or perpetuate electrical activity. Drugs (e.g. quinidine or digitalis), electrolyte disorder as well as structural heart diseases (hypertensive heart disease, dilated cardiomyopathy, valvular heart disease and myocarditis) and genetic predispositions may contribute to this condition [1–6]. Obstructive sleep apnea with consecutively increased right atrial pressure, underlying hypertension and paroxysms of atrial fibrillation might be further synergistically interacting contributing factors. According to the reports of Nakazato and Zipes AS seems to be a progressive disease which initially involves the high right atrium (RA) and then progresses towards the lower RA. Just the vicinity of the tricuspid valve, the lower interatrial septum and the region of the ostium of the coronary sinus remain excitable [5, 7]. As the main right atrium is not excitable, patients with AS and symptomatic bradycardia were often treated by implantation of a VVI pacemaker [5]. We present the case of a patient suffering from severe palpitations despite AS. We saw a 62-year-old male DDDR pacemaker (PM) patient, implanted due to intermittent AV-Block III in another hospital. Currently the patient suffered from severe palpitations during his atrial driven tachycardia with a heart rate of 105 bpm with 1:1 ventricular stimulation (cycle length 575 ms) for 8 weeks (Fig. 1a). Coronary heart disease had already been ruled out previously via coronary angiogram. Echocardiographic examination showed an only slightly reduced systolic left ventricular function (EF 48 %) without any major valvular dysfunction. Cardiac risk factors were hypertension, hyperlipidemia and diabetes mellitus. Additionally, the patient suffered from obstructive sleep apnea and paroxysmal atrial fibrillation. To better study tachycardia during the EP Study, PM was programmed from DDDR to VVI 30/min followed by a drop in ventricular rate to 53 bpm due to 2:1 atrioventricular block (Fig. 1c). Figure 2a depicts the catheter positioning with an electrical silent right atrium (RA) along the 20 polar halo catheter which could neither sense nor evoke electrical signals even under high output stimulation (Fig. 2a). Exclusively in the coronary sinus (CS) and directly adjacent areas a remnant strand of vital right atrial myocardium displayed rapid centrifugal activity (Fig. 2b). We performed entrainment stimulation along the coronary sinus electrodes where we achieved similar post-pacing intervals (PPI) at the most proximal pair of electrodes and consecutively longer PPIs while stimulating more distally. Atrial ectopy from the pulmonary veins was excluded after transseptal puncture with a 20-polar Lasso Catheter. A CS anomaly or a CS diverticle was ruled out by CS phlebography. 3-D electroanatomical mapping was employed after pacing manoeuvres including entrainment and post-pacing H. Bogossian (&) B. Lemke M. Zarse Department of Cardiology and Angiology, Klinikum Ludenscheid, Markische Kliniken GmbH, Paulmannshoherstr. 14, 58515 Ludenscheid, Germany e-mail: bogossian@t-online.de; Harilaos.bogossian@klinikumluedenscheid.de

Evaluation of the Substrate in Genetic Atrial Arrhythmias Introduction Although atrial arrhythmias may have genetic causes, very few data are available on evaluation of the arrhythmic substrate in genetic atrial diseases in humans. In this study, we evaluate the nature and evolution of the atrial arrhythmic substrate in a genetic atrial cardiomyopathy. Methods and Results Repeated electroanatomic mapping and tomographic evaluations were used to investigate the evolving arrhythmic substrate in 5 patients with isolated arrhythmogenic atrial cardiomyopathy, caused by Natriuretic Peptide Precursor A (NPPA) gene mutation. Atrial fibrosis was assessed using late gadolinium enhancement magnetic resonance imaging (LGE-MRI). The substrate of atrial tachycardia (AT) and atrial fibrillation (AF) was biatrial dilatation with patchy areas of low voltage and atrial wall scarring (in the right atrium: 68.5% ± 6.0% and 22.2% ± 10.2%, respectively). The evolution of the arrhythmic patterns to sinus node disease with atrial standstill (AS) was associated with giant atria with extensive low voltage and atrial scarring areas (in the right atrium: 99.5% ± 0.7% and 57.5% ± 33.2%, respectively). LGE-MRI-proven biatrial fibrosis (Utah stage IV) was associated with AS. Atrial conduction was slow and heterogeneous, with lines of conduction blocks. The progressive extension and spatial distribution of the scarring/fibrosis were strictly associated with the different types of arrhythmias. Conclusion The evolution of the amount and distribution of atrial scarring/fibrosis constitutes the structural substrate for the different types of atrial arrhythmias in a pure genetic model of arrhythmogenic atrial cardiomyopathy.

Atrial standstill is a rare arrhythmia defined by the absence of mechanical and electrical activity in the atria. Few cases of atrial standstill have been described in children, none of which have presented with cerebral infarction confirmed by imaging. We report a unique case of a 7-year-old girl presenting with expressive aphasia, central facial palsy and irregular pulse with cerebral infarction secondary to atrial standstill. This case illustrates that cardiogenic cerebral embolism in children can be caused by rare conditions like atrial standstill and should be considered in paediatric patients undergoing evaluation for stroke. There are no established treatment guidelines for atrial standstill. We recommend that treatment be directed towards any potential underlying cause. All patients with atrial standstill should receive long-term oral anticoagulation treatment and a permanent cardiac pacemaker implant to reduce the risk of further strokes or other cardiac events.

Partial atrial standstill (AS) is a rare disease of the atrial myocardium characterised by a lack of active contraction caused by a failure to create or perpetuate electrical activity. This condition can be a result of drug treatment (e.g. quinidine or digitalis), electrolyte disorders, structural heart diseases (hypertensive heart disease, dilated cardiomyopathy, valvular heart disease and myocarditis) or genetic predispositions [1–6]. Previous reports describe AS as a progressive disease which initially commences in the high right atrium (RA) and progresses towards the lower RA. Only the vicinity of the tricuspid valve, the lower interatrial septum and the region of the ostium of the coronary sinus remain excitable [5, 7]. Patients with AS and symptomatic bradycardia are frequently treated by implantation of a VVI pacemaker because identifying a stimulation site in the for the most part non-excitable atrium remains challenging [5]. However, despite AS supraventricular tachycardias may still originate in the in other respects ‘‘silent’’ right atrium and therefore can be targeted by catheter ablation [8]. We present the case of a patient suffering from palpitations due to superior vena cava (SVC) atrial flutter despite AS. A 61-year-old male patient reported to our hospital due to severe palpitations. Surface ECG suggested typical atrial flutter with a cycle length of 380 ms and initial 1:1 conduction. Oral beta-blocker treatment resulted in 2:1 conduction. Coronary heart disease had previously been ruled out by coronary angiography. Echocardiographic examination showed a normal left ventricular function (LVEF 60 %) with signs of hypertensive heart disease. Besides hypertension no further cardiac risk factors were present. Figure 1a shows the 20 polar halo-catheter positioning displaying electrical silence along the right free atrial wall. The bipolar signals 3–10 did neither sense nor evoke electrical signals even under high output stimulation (Fig. 1b). Entrainment mapping in the distal coronary sinus revealed a long post-pacing interval (PPI) of 100 ms ? cycle length while the PPI in the proximal CS shortened to 30 ms ? cycle length. Entrainment mapping in the septal part of the right atrium (Halo 15/16) showed an only slightly longer PPI of 15 ms ? cycle length. Simultaneous 3-D electroanatomical voltage mapping as well as local activation mapping (NAVX, St. Jude Medical, Minneapolis, USA) was employed to more precisely define the area of interest (Fig. 2). Voltage map revealed a scar region in the high right atrium and the free atrial wall up to the medial right atrial appendage region (Fig. 2a). We employed this map as surrogate parameter for lack of atrial contraction, refraining from additional echocardiographic proof. Local activation map displayed a re-entry circuit around the superior vena cava (SVC) (Fig. 2b). Early activation meeting late activation was observed at the ridge between right atrial appendage and SVC. Conventional & Harilaos Bogossian harilaos.bogossian@klinikum-luedenscheid.de

Atrial standstill (AS) is a very rare condition characterized by complete loss of electrical and mechanical activity and excitability of the atria. Absence of P waves, bradycardia and junctional escape rhythm may suggest AS on surface ECG. In nearly half of the reported cases, the condition manifested with syncope [1, 2]. AS must be differentiated from common sinus node disease with sinus arrest or highgrade sinoatrial block that may have similar symptoms and surface ECG presentation [3]. AS has been rarely described to be primary with familial clustering and/or associated cardiac ion channel mutations [2, 4]. More commonly, it has been linked to heart disorders such as myocarditis, ischemic heart disease, or dilated cardiomyopathy [5–7]. AS occurring in the context of structural myocardial disease may indicate a poor prognosis [1, 8]. A 48-year-old female patient was referred to our emergency department due to fatigue, progressive dyspnoea on exertion and recurring syncope since a few months. Three years earlier she had presented to our outpatient clinic for recurrent pulmonary infections, where a normal ECG had been registered (Fig. 1a). Four months before she had been hospitalized at an external institution for ascites and pleural effusion of unknown origin and atrial fibrillation was diagnosed on surface ECG. A diuretic as well as oral anticoagulation were initiated. At presentation, the patient reported no family history of syncope or sudden death, and physical examination revealed cachexia (BMI 18.6 kg/m), but no obvious cardiopulmonary pathologies. Shortly after admission, the patient exhibited rapid polymorphic ventricular tachycardia (VT), requiring CPR and defibrillation. Twelve-lead surface ECG, recorded prior the arrhythmic event, showed absence of P waves with an escape rhythm of 48/min, a QRS duration of 70 ms, constant R–R intervals, and a prolonged QT interval of 600 ms (QTc 536 ms) (Fig. 1b). Laboratory findings revealed mild hypokalemia (3.2 mmol/ L), slightly elevated liver enzymes, an INR value of 2.1, N-terminal pro-BNP of 1,465 pg/mL (7.39 of normal value) and an ANP of 2.89 nmol/L (1.59 of normal value), whereas normal values were found for calcium, blood cell count, CRP, renal and thyroid functional parameters and CK. Chest X-ray revealed marked cardiomegaly, and the echocardiogram showed a dilated left ventricle with a severely reduced left ventricular ejection fraction (LVEF) of 20 %. Of note, LVEF had been reported to be 45 and 60 %, 2 and 3 months earlier, respectively. Furthermore, echocardiography showed dilated right and left atria along with moderate to severe tricuspid and moderate mitral regurgitation. A transesophageal echocardiogram revealed a thrombus in the left atrial appendage, where no significant flow was identifiable with Doppler imaging (Fig. 1c, d). Few hours after admission, the patient again developed recurrent polymorphic VT with syncope and need for defibrillation despite normalization of potassium levels (Fig. 1e). Coronary artery disease was ruled out angiographically and a temporary transvenous pacemaker was inserted. Myocardial biopsies were taken from the right ventricle, but provided no evidence for acute myocarditis [9], arrhythmogenic right ventricular dysplasia [10], amyloidosis or hemosiderosis. This was in line with findings from cardiac MRI, so that idiopathic dilated cardiomyopathy was diagnosed. With ventricular overdrive pacing at 80 bpm and initiation of beta-blocker medication VT did M. R. Schroeter (&) G. Hasenfus M. Zabel D. Vollmann Abt. Kardiologie und Pneumologie, Universitatsmedizin Gottingen, Herzzentrum, Robert-Koch-Str. 40, 37099 Gottingen, Germany e-mail: mschroeter@med.uni-goettingen.de

Atrial standstill is a rare disorder of cardiac rhythm that is characterized by total absence of electrical activity in one or both atria. We report herein the case of a patient with atrial fibrillation and symptomatic 4.0 s pauses who received a ventricular demand pacemaker. The patient later underwent mitral valve replacement with a pericardial tissue valve and the Cox-maze III procedure for symptomatic mitral stenosis and atrial fibrillation. Following surgery, he developed atrial standstill and became pacemaker dependent. The pacemaker was later revised to an atrioventricular sequential pacemaker. Twelve hours after revision, atrioventricular sequential pacing was noted and mechanical function of the atria was confirmed by Doppler echocardiography.

Persistent atrial standstill is a rare arrhythmia in both human and veterinary patients. In recent decades, cases of partial atrial standstill have been recognized in humans. We describe a case of presumptive partial atrial standstill in a Greyhound, in which there was disparate left and right atrial electromechanical function and rapid progression to congestive heart failure over the span of fourteen weeks. An atrial cardiomyopathy characterized by severe, diffuse, fibrofatty replacement of the atrial myocardium was identified histologically.

Although sinus node dysfunction (SND) and atrial arrhythmias frequently coexist and interact, the putative mechanism linking the 2 remain unclear. Although SND is accompanied by atrial myocardial structural changes in the right atrium, atrial fibrillation (AF) is a disease of variable interactions between left atrial triggers and substrate most commonly of left atrial origin. Significant advances have been made in our understanding of the genetic and pathophysiologic mechanism underlying the development and progression of SND and AF. Although some patients manifest SND as a result of electric remodeling induced by periods of AF, others develop progressive atrial structural remodeling that gives rise to both conditions together. The treatment strategy will thus vary according to the predominant disease phenotype. Although catheter ablation will benefit patients with predominantly AF and secondary SND, cardiac pacing may be the mainstay of therapy for patients with predominant fibrotic atrial cardiomyopathy. This contemporary review summarizes current knowledge on sinus node pathophysiology with the broader goal of yielding insights into the complex relationship between sinus node disease and atrial arrhythmias.

Background— The arrhythmogenesis of ventricular myocardial ischemia has been extensively studied, but models of atrial ischemia in humans are lacking. This study aimed at describing the electrophysiological alterations induced by acute atrial ischemia secondary to atrial coronary branch occlusion during elective coronary angioplasty. Methods and Results— Clinical data, 12-lead ECG, 12-hour Holter recordings, coronary angiography, and serial plasma levels of high-sensitivity troponin T and midregional proatrial natriuretic peptide were prospectively analyzed in 109 patients undergoing elective angioplasty of right or circumflex coronary arteries. Atrial coronary branches were identified and after the procedure patients were allocated into two groups: atrial branch occlusion (ABO, n=17) and atrial branch patency (non-ABO, n=92). In comparison with the non-ABO, patients with ABO showed: (1) higher incidence of periprocedural myocardial infarction (20% versus 53%, P =0.01); (2) more frequent intra-atrial conduction delay (19% versus 46%, P =0.03); (3) more marked PR segment deviation in the Holter recordings; and (4) higher incidence of atrial tachycardia (15% versus 41%, P =0.02) and atrial fibrillation (0% versus 12%, P =0.03). After adjustment by a propensity score, ABO was an independent predictor of periprocedural infarction (odds ratio, 3.4; 95% confidence interval, 1.01–11.6, P P =0.02). Conclusions— Selective atrial coronary artery occlusion during elective percutaneous transluminal coronary angioplasty is associated with myocardial ischemic damage, atrial arrhythmias, and intra-atrial conduction delay. Our data suggest that atrial ischemic episodes might be considered as a potential cause of atrial fibrillation in patients with chronic coronary artery disease.

Thiamine-responsive megaloblastic anemia (TRMA) syndrome is an uncommon autosomal recessive disorder. The disease is caused by mutations in the gene, SLC19A2, encoding a high-affinity thiamine transporter, which disturbs the active thiamine uptake into cells. Major features include megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Cardiac malformations with conduction defects and/or dysrhythmias, have also been described in some patients. To our knowledge, only 13 TRMA patients with cardiac defects have been reported. Here, we describe the first case of TRMA syndrome with atrial standstill, probably caused by a 2 base-pair deletion in exon 4 (1147delGT) of the gene SLC19A2.

Objectives To quantify cardiac troponin-I (cTnI) concentration in dogs with symptomatic bradyarrhythmias before and after artificial pacing and to correlate cTnI concentration with diagnosis, echocardiographic parameters, serology, and outcome. Animals, materials and methods Medical records from the University of Pennsylvania from 2006 to 2009 were reviewed, and 14 dogs with cTnI assay results before and after pacemaker were identified. The ECG diagnosis included complete atrioventricular block (AVB), sick sinus syndrome, 2nd degree AVB, and atrial standstill. Serology, presence of premature beats, echocardiographic measurements, and pacing modality were recorded. Results Mean cTnI concentration was elevated both pre- and post-pacing, and was significantly higher pre-pacing vs. post-pacing. Post-pacing cTnI concentration in 9 of 14 dogs (64%) remained above the reference range. Four dogs yielded high serum titers for Bartonella spp. Four dogs with markedly increased cTnI concentration had progressive left ventricular enlargement and myocardial failure as compared to pre-pacing examination. Conclusions Elevated cTnI concentration suggests that cardiac injury persists after artificial pacing in dogs with bradyarrhythmias. Myocarditis secondary to Bartonella spp. or other causes may be an important cause of AVB in dogs. Prospective studies investigating the correlation of cTnI to potential etiology and development of post-pacing LV dysfunction and outcome are needed.

Atrial septal defects of the ostium secundum variety are typically asymptomatic in infancy and early childhood. Congestive heart failure (CHF) may occur in the presence of significant mitral valve disease, pulmonary artery hypertension, or other diseases that lead to elevated filling pressures of the ventricles. Atrial standstill, a rare disease, was the probable cause of CHF in the 3-year-old child discussed in this report.

We present the first form of laminopathy connected with a new mutation of the lamin A/C gene expressed by dilated cardiomyopathy and partial atrial standstill associated with Charcot-Marie-Tooth type 2 axonal neuropathy. The rapid development of the cardiac disease was controlled by medical treatment and resynchronization therapy associated with a defibrillator.

Partial atrial standstill is characterized by the failure of atrial activity either spontaneously or in response to electrical stimulation in restricted site of atria. In this case with bradycardia, atrial standstill was restricted to the lateral and posterior right atrium. The markedly prolonged intraatrial conduction delay was observed in the superior to septal region of the right atrium. The electroanatomical mapping was successfully utilized to estimate atrial activity and to find a suitable site for atrial lead placement. The electroanatomical mapping may become an innovated strategy to estimate atrial electrical status in partial atrial standstill.

Cardiac sodium channel dysfunction caused by mutations in the SCN5A gene is associated with a number of relatively uncommon arrhythmia syndromes, including long-QT syndrome type 3 (LQT3), Brugada syndrome, conduction disease, sinus node dysfunction, and atrial standstill, which potentially lead to fatal arrhythmias in relatively young individuals. Although these various arrhythmia syndromes were originally considered separate entities, recent evidence indicates more overlap in clinical presentation and biophysical defects of associated mutant channels than previously appreciated. Various SCN5A mutations are now known to present with mixed phenotypes, a presentation that has become known as "overlap syndrome of cardiac sodium channelopathy." In many cases, multiple biophysical defects of single SCN5A mutations are suspected to underlie the overlapping clinical manifestations. Here, we provide an overview of current knowledge on SCN5A mutations associated with sodium channel overlap syndromes and discuss a possible role for modifiers in determining disease expressivity in the individual patient.

An 85-year-old man with persistent atrial flutter (AFL) with slow ventricular rate of 44/min, causing fatigue and presyncope, was referred for urgent treatment. In spite of thromboembolic risk scale value 4, he had not been treated with anticoagulants because of high risk of bleeding. The decision was made to perform urgent catheter ablation to interrupt and cure AFL. Intracardiac echocardiography probe was placed in the pulmonary artery and visualized left atrial appendage free from thrombus with its proper function. Heparin was administered and AFL stopped during energy application. Intracardiac echocardiography showed immediate thrombus formation in left atrial appendage owing to complete atrial standstill and no retrograde conduction during hemodynamically effective escape nodal rhythm. This case report shows that in patients with sinus node disease effective ablation of AFL with escape rhythm without retrograde conduction to the atria may result in complete 'electrically induced' atrial standstill and immediate thrombus formation.

Two young Labrador retriever dogs with bradycardia-induced syncope resulting from atrial myopathy underwent permanent transvenous pacemaker implantation. Both dogs developed heart failure 3–5 years after pacemaker implantation. Both were managed medically for approximately 7 years after pacemaker implantation and, ultimately, were humanely euthanized due to refractory heart failure signs and quality of life concerns. Long-term management of dogs with atrial myopathy and secondary atrial standstill with pacemaker implantation and medical therapy for heart failure is feasible and prognosis may be better than previously reported or speculated.

Congenital atrial standstill has been linked to SCN5A. Incomplete penetrance observed in atrial standstill has been attributed in part to the digenic inheritance of polymorphisms in the atrial-specific gap junction connexin 40 (Cx40) in conjunction with an SCN5A mutation.The purpose of this study was to determine the clinical and biophysical characteristics of a novel SCN5A mutation identified in a family with atrial standstill.Family members of an apparently sporadic case of atrial standstill underwent genetic screening of SCN5A and atrial-specific genes including Cx40. Biophysical properties of the wild-type (WT) and mutant SCN5A channels in a heterologous expression system were studied using the whole-cell patch clamp technique.The novel SCN5A mutation L212P was identified in the proband (age 11 years) and his father. The father was in normal sinus rhythm. The proband had no P waves on surface ECG, and his right atrium could not be captured by pacing. The recombinant L212P Na channel showed a large hyperpolarizing shift in both the voltage dependence of activation (WT: -48.1 +/- 0.9 mV; L212P: -63.5 +/- 1.5 mV; P.001) and inactivation (WT: -86.6 +/- 0.9 mV; L212P: -95.6 +/- 0.8 mV; P.001) and delayed recovery from inactivation. Further screenings for genetic variations that might mitigate L212P dysfunction revealed that the proband, but not his father, carries Cx40 polymorphisms inherited from his asymptomatic mother.These results suggest that genetic defects in SCN5A most likely underlie atrial standstill. Coinheritance of Cx40 polymorphisms is a possible genetic factor that modifies the clinical manifestation of this inherited arrhythmia.

A 71-year-old male was referred to another hospital for dizziness. A bradycardia -tachycardia syndrome and Cor triatriatum were detected, and an operation to resect the membrane in the left atrium and implant a pacemaker epicardially was performed. However, no suitable site could be found on either atria and therefore, a single chamber ventricular pacemaker was implanted. In the electrophysiological study performed in our hospital, we could not detect any atrial potentials in either atria, excluding the region close to the His bundle (HB) and within coronary sinus (CS), in spite of extensive catheter mapping. A regular atrial rhythm with a cycle length of 820 ms, which was synchronous with the rate of the QRS complex on the surface ECG, was recorded only at the HB. Meanwhile, the CS catheter recording exhibited regular focal activity with a cycle length of 150 ms, and this focal activity did not conduct to the atrium close to the HB. Furthermore, this activity was dissociated from the ventricular activity recorded from the CS catheter. During an isoproterenol infusion, an atrial tachycardia with a cycle length of 380 ms was recorded only at the HB, and the twelve-lead ECG exhibited a regular tachycardia with the same cycle length as this tachycardia. Meanwhile, the focal activity within the CS persisted without any change in the cycle length. These findings suggested that there was dissociation between the right atrium (RA) and CS. Furthermore, partial atrial standstill was observed in both atria, excluding the RA close to the atrio-ventricular (AV) node and area within the CS. These rare electrophysiological features were considered to play an important role in the genesis of a simultaneous combination of the two tachycardias at their respective sites.

Takehara N, Makita N, Kawabe J, Sato N, Kawamura Y, Kitabatake A, Kikuchi K (Asahikawa Medical College, Asahikawa; Hokkaido University Graduate School of Medicine, Sapporo, Japan; and Cardiovascular Research Institute, Newark, NY, USA). A cardiac sodium channel mutation identified in Brugada syndrome associated with atrial standstill (Case Report). J Intern Med 2004; 255: 137–142. Mutations in the cardiac Na+ channel gene SCN5A are responsible for multiple lethal ventricular arrhythmias including Brugada syndrome and congenital long QT syndrome. Here we report a case of Brugada syndrome with ST elevation in the right precordial and inferior leads accompanied by atrial standstill and spontaneous ventricular fibrillation. Atrial standstill and J wave elevation were provoked by procainamide. Genetic analysis revealed a missense mutation (R367H) in SCN5A. The resultant mutant Na+ channel was nonfunctional when expressed heterologously in Xenopus oocytes. Our study suggests that genetic defects in SCN5A may be associated with atrial standstill in combination with ventricular arrhythmias.

Background and Purpose— Emery-Dreifuss muscular dystrophy (EDMD) is a rare inherited disorder associated with cardiac involvement. We investigated the spectrum and relevance of the cardiac manifestations of EDMD, focusing on bradyarrhythmias and tachyarrhythmias (including atrial fibrillation/flutter), embolic stroke, and heart failure. Methods and Results— Eighteen patients (age 42.8±19.6 years) with genetically confirmed X-linked (n=10, including 3 carriers) or autosomal dominant (n=8) EDMD were followed for a period ranging from 1 to 30 years in a research center for neuromuscular diseases and in a university cardiological department. Pacemakers were required by 10 of 18 (56%) patients for bradyarrhythmia, and related complications occurred in 3 of 10 (30%) cases. Atrial fibrillation/flutter developed in 11 of 18 (61%) patients, with atrial standstill subsequently occurring in 5 of 11 (45%) cases and embolic stroke (most often disabling) in 4 of 11 (36%). Heart failure requiring transplantation occurred in 1 of 18 (6%) patients, and asymptomatic left ventricular dysfunction in a further 3 (17%). No relationship was evident between neuromuscular impairment and cardiac involvement. Conclusions— Both X-linked and autosomal dominant EDMD patients risk not only bradyarrhythmia (requiring pacemaker implant) but also atrial fibrillation/flutter, which often anticipates atrial standstill and can cause disabling embolic stroke at a relatively young age. Antithromboembolic prophylaxis has to be recommended in EDMD patients with atrial fibrillation/flutter or atrial standstill. With careful monitoring, survival after pacemaker implant may be long. Heart failure, which seems to occur only in a minority of patients, may be severe.

We report here the case of a 22-year-old female patient with an incomplete Ebstein's anomaly, complete heart block and atrial standstill. Atrial paralysis associated with Ebstein's anomaly is the most important feature, since there is a report of familial Ebstein's anomaly associated with atrial standstill but isolated cases have not been described. The patient presented with atypical chest pain and a symptomatic bradycardia of 37 beats per minute. A VVIR pacemaker was implanted. She has subsequently been symptom free.

Introduction: Early phase CT contrast defects in the left atriium (LA) and left atrial appendage (LAA) are often observed in atrial fibrillation (AF) or atrial flutter (AFL) despite absence of thrombi. However their clinical significance is unclear. Hypothesis: In order to investigate this correlation we compared CT, transesophageal echocardiology (TEE), CHADS2 score, and occurrence of embolism (including cerebral infarction). Methods: A total of 32 AF or AFL subjects who underwent CT and TEE within 3 months were enrolled. 5 subjects with LAA thrombi by TEE were excluded. A total of 27 subjects were retrospectively analyzed (persistent AFL 10, persistent AF 9, chronic AF 3, paroxysmal AF 3, permanent atrial standstill 2, 22 male, 61±11 years, occurrence of embolism 26%, median CHADS2 score 1). We measured velocity in the LAA by TEE. We also measured CT attenuations in the LAA and LA, and calculated LAA/LA ratios. Results: CT LAA/LA ratios were significantly lower in subjects with embolism than without (0.44±0.30 vs 0.74±0.24). CT LAA/LA ratios were smaller when CHADS2 score was ≥2 (0.57±0.31 vs 0.75±0.24). CT LAA/LA ratios correlated with TEE LAA velocity (R=0.44). According to receiver operating characteristic (ROC) curves, at a best cutoff of 24.3m/sec (TEE LAA velocity), sensitivity and specificity for occurrence of embolism were 70% and 86%, respectively (Area under the curve (AUC) 0.69). Another ROC curve, at a best cutoff of 0.41 (CT LAA/LA ratio), produced a sensitivity and specificity for occurrence of embolism of 90% and 71%, respectively (AUC 0.78). In logistic regression models using LA diameter, left ventricular ejection fraction, presence of moderate to severe mitral valve stenosis or regurgitation measured by TEE, the odds ratio for CT LAA/LA ratios was 0.017 (P=0.043) for prediction of embolism. Conclusion: CT LAA/LA ratio correlates with TEE LA velocity and is a prognostic indicator for the occurrence of embolism in AF or AFL subjects without LAA thrombosis.

We describe an elderly case of idiopathic dilatation of the right atrium in which right-sided heart failure was exacerbated by drug-induced bradyarrhythmia. An 84-year-old man, who had a 10-year history of episodic edema, was treated with proscillaridin and verapamil hydrochloride at another hospital. He had experienced a poor appetite and general malaise 2 months previously, and exertional dyspnea 10 days previously. On admission, he had jugular venous dilatation, systemic edema, and hepatomegaly. On auscultation, a third heart sound originating from the right ventricle and systolic murmur of tricuspid regurgitation were heard. An admission electrocardiogram showed an atrial standstill and junctional escape rhythm with a QRS rate of 31 beats/minute. Chest roentgenogram revealed a bilateral pleural effusion and cardiomegaly with a cardiothoracic ratio of 76%, but no pulmonary congestion. Echocardiogram disclosed idiopathic dilatation of the right atrium and secondary tricuspid regurgitation. He was given a diagnosis of right-sided heart failure due to idiopathic dilatation of the right atrium exacerbated by bradyarrhythmia, which was suspected to derive from the side effects of proscillaridin and verapamil hydrochloride. Thus, these agents were withheld. In addition, the patient reduced sodium intake and was treated with diuretics and beta-adrenergic agonist. Thereafter, right-sided heart failure markedly improved. At the time of the last follow-up 16 months after discharge, he felt well.