Atrial Standstill Research Articles

Editorial to “Atrial standstill in a young patient with ischemic stroke associated with inheritance of a novel HCN4 mutation”

Editorial to “Atrial standstill in a young patient with ischemic stroke associated with inheritance of a novel HCN4 mutation”

Atrial standstill in a young patient with ischemic stroke associated with inheritance of a novel HCN4 mutation

Atrial standstill in a young patient with ischemic stroke associated with inheritance of a novel HCN4 mutation

Atrial standstill in a young patient treated with left bundle branch area pacing

Abstract Atrial standstill is a rare arrhythmogenic condition characterized by the absence of electrical and mechanical activity in the atria. The therapeutic options for these patients described in the current literature, in which no reversible cause is detected, are permanent cardiac pacing, anticoagulant, and heart failure treatment when the latter exists. We present a case of a young male with no personal or family history of cardiovascular disease, diagnosed with atrial standstill after multiple syncopal episodes, in whom, because of the high expected ventricular pacing percentage, we opted for conduction system pacing with left bundle branch area pacing.

Clinical presentation, management, and survival in dogs with persistent atrial standstill in the United Kingdom

ObjectivesTo investigate the clinical and echocardiographic presentation of dogs with persistent atrial standstill (PAS), identify variables measured at first presentation that could predict their survival, and document the progression of the disease after pacing. Materials and methodsRetrospective study of medical records of dogs diagnosed with PAS at three referral hospitals of the United Kingdom over seven years. ResultsTwenty-six dogs were diagnosed with PAS during the study period. Median age of the population was three years (range: seven months–12.5 years). The most common clinical sign was syncope (14/26). Twenty-four dogs received artificial pacemakers (PM). Major complications after PM implantation were observed in four dogs (four/24). Serial echocardiographic examinations showed that cardiac dimensions of PAS dogs with left atrial or left ventricular dilation at first presentation did not return to reference range after pacing. Further dilation of the cardiac chambers, recurrence of congestive heart failure (CHF), or development of new episodes of CHF were documented in seven, four, and 10 PAS dogs, respectively, despite pacing. Median survival time for cardiac-related deaths after PM implantation was 1512 days (18–3207). Neither CHF nor echocardiographic variables at presentation predicted survival after PM implantation in PAS dogs. ConclusionsPersistent atrial standstill (PAS) is an uncommon bradyarrhythmia, occurring in young adult dogs. Affected dogs were often presented with syncope. Whilst syncope resolved, cardiac remodeling persisted after PM implantation. Long-term survival was favorable after PM implantation and was not predicted by congestive status or cardiac chamber size at first presentation.

Novel pathogenic variant in LMNA gene identified in a six-generation family causing atrial cardiomyopathy and associated right atrial conduction arrhythmias.

To characterize the cardiac phenotype associated with the novel pathogenic variant (c.1526del) of LMNA gene, which we identified in a large, six-generation family. A family tree was constructed. The clinical data of living and deceased family members were collected. DNA samples from 7 family members were analyzed for LMNA mutations using whole-exome high-throughput sequencing technology. The clinical presentation of pathogenic variant carriers was evaluated. In this six-generation family (n = 67), one member experienced sudden death at the age of 40-years-old. Three pathogenic variant carriers were identified to possess a novel heterozygous deletion mutation in LMNA gene (HGVS: NM_170707.4, c.1526del) located at exon 9 of LMNA chr1:156137145, which creates a premature translational stop signal (p.Pro509Leufs*39) in the LMNA gene and results in an mutant lamin A protein product. The main symptoms of the pathogenic variant carriers were palpitation, fatigue, and syncope, which typically occurred around 20-years-old. AV-conduction block and non-sustained ventricular tachycardia were the first signs of disease and would rapidly progress to atrial standstill around 30-years-old. Significant right atrial enlargement and bicuspid aortic valve malformation was also commonly seen in patients who carried this pathogenic variant. The pathogenic variant of c.1526del p.P509Lfs*39 was a frameshift deletion located at exon 9 of LMNA chr1:156137145 and causes severe right atrial enlargement, sick sinus syndrome, atrial standstill, ventricular tachycardia, and bicuspid aortic valve malformation. Our findings expand the phenotypic spectrum of novel LMNA gene mutations.

Myosin light-chain 4 gene-transfer attenuates atrial fibrosis while correcting autophagic flux dysregulation

ObjectivesTo determine the role of MYL4 regulation of lysosomal function and its disturbance in fibrotic atrial cardiomyopathy. BackgroundWe have previously demonstrated that the atrial-specific essential light chain protein MYL4 is required for atrial contractile, electrical, and structural integrity. MYL4 mutation/dysfunction leads to atrial fibrosis, standstill, and dysrhythmia. However, the underlying pathogenic mechanisms remain unclear. Methods and resultsRats subjected to knock-in of a pathogenic MYL4 mutant (p.E11K) developed fibrotic atrial cardiomyopathy. Proteome analysis and single-cell RNA sequencing indicate enrichment of autophagy pathways in mutant-MYL4 atrial dysfunction. Immunofluorescence and electron microscopy revealed undegraded autophagic vesicles accumulated in MYL4p.E11K rat atrium. Next, we identified that dysfunctional MYL4 protein impairs autophagy flux in vitro and in vivo. Cardiac lysosome positioning and mobility were regulated by MYL4 in cardiomyocytes, which affected lysosomal acidification and maturation of lysosomal cathepsins. We then examined the effects of MYL4 overexpression via adenoviral gene-transfer on atrial cardiomyopathy induced by MYL4 mutation: MYL4 protein overexpression attenuated atrial structural remodeling and autophagy dysfunction. ConclusionsMYL4 regulates autophagic flux in atrial cardiomyocytes via lysosomal mobility. MYL4 overexpression attenuates MYL4 p.E11K induced fibrotic atrial cardiomyopathy, while correcting autophagy and lysosomal function. These results provide a molecular basis for MYL4-mutant induced fibrotic atrial cardiomyopathy and identify a potential biological-therapy approach for the treatment of atrial fibrosis.

Electrocardiographic changes associated with hyperkalaemia in domestic cats

Hyperkalaemia is a life-threatening electrolyte imbalance because it affects cardiac conduction and can lead to fatal arrhythmias if left untreated. The present study describes the occurrence of hyperkalaemia in cats and the electrocardiographic changes associated with this electrolyte imbalance. Hyperkalaemia was identified in 83.33 per cent of the study group subjects. Acute kidney injury and obstructive uropathy were the main clinical conditions associated with it. Electrocardiographic findings in hyperkalaemia in different cats under study included peaked T waves in lead II and the precordial lead CV6LL, atrial standstill and sino-ventricular rhythm, normal sinus rhythm, ventricular tachycardia, first-degree atrio-ventricular block, bradycardia, sinus tachycardia, and atrio-ventricular dissociation. Electrocardiography should always be performed in cases suspected of electrolyte imbalances, particularly hyperkalaemia, so as to identify any fatal arrhythmias and initiate treatment at the earliest.

Time to Move Forward on Pediatric Atrial Standstill

Time to Move Forward on Pediatric Atrial Standstill

Permanent transvenous pacemaker placement in a Terrier with sick sinus syndrome

Pacemaker therapy is generally considered necessary in patients with symptomatic bradycardia that does not respond to medical management. Common arrhythmias requiring implantation of a permanent pacemaker include third degree atrioventricular (AV) block, high grade second degree AV block, sick sinus syndrome and persistent atrial standstill. This patient care report discusses the diagnosis and treatment of a tTrrier with sick sinus syndrome.

Rare and potential pathogenic mutations of LMNA and LAMA4 associated with familial arrhythmogenic right ventricular cardiomyopathy/dysplasia with right ventricular heart failure, cerebral thromboembolism and hereditary electrocardiogram abnormality

BackgroundArrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is associated with ventricular arrhythmia, heart failure (HF), and sudden death. Thromboembolism is also an important and serious complication of ARVC/D. However, the etiology of ARVC/D and thromboembolism and their association with genetic mutations are unclear.MethodsGenomic DNA samples of peripheral blood were conducted for whole-exome sequencing (WES) and Sanger sequencing in the ARVC/D family. Then, we performed bioinformatics analysis for genes susceptible to cardiomyopathies and arrhythmias. Further, we analyzed how the potential pathogenic mutations were affecting the hydrophobicity and phosphorylation of amino acids and their joint pathogenicity by ProtScale, NetPhos and ORVAL algorisms.ResultsWe discovered a Chinese Han family of ARVC/D with right ventricular HF (RVHF), cerebral thromboembolism, arrhythmias (atrial fibrillation, atrial standstill, multifocal ventricular premature, complete right bundle block and third-degree atrioventricular block) and sudden death. Based on the WES data, the variants of LMNA p.A242V, LAMA4 p.A225P and RYR2 p.T858M are highly conserved and predicated as “deleterious” by SIFT and MetaSVM algorithms. Their CADD predicting scores are 33, 27.4 and 25.8, respectively. These variants increase the hydrophobicity of their corresponding amino acid residues and their nearby sequences by 0.378, 0.266 and 0.289, respectively. The LAMA4 and RYR2 variants lead to changes in protein phosphorylation at or near their corresponding amino acid sites. There were high risks of joint pathogenicity for cardiomyopathy among these three variants. Cosegregation analysis indicated that LMNA p.A242V might be an important risk factor for ARVC/D, electrocardiogram abnormality and cerebral thromboembolism, while LAMA4 p.A225P may be a pathogenic etiology of ARVC/D and hereditary electrocardiogram abnormality.ConclusionsThe LMNA p.A242V may participate in the pathogenesis of familial ARVC/D with RVHF and cerebral thromboembolism, while LAMA4 p.A225P may be associated with ARVC/D and hereditary electrocardiogram abnormality.

PO-642-07 ATRIAL STANDSTILL: A RARE COMPLICATION OF CORONARY VASOSPASM FOLLOWING SURGICAL AORTIC VALVE REPLACEMENT

Atrial standstill is a phenomenon characterized by the absence of both electrical and mechanical atrial activity, resulting in complete lack of excitability. Identified causes include drugs, electrolyte abnormalities, hypoxia, and myocardial infarction.

Clinical Profile, Arrhythmias, and Adverse Cardiac Outcomes in Emery-Dreifuss Muscular Dystrophies: A Systematic Review of the Literature.

Simple SummaryCardiolaminopathies portend an augmented risk of atrial and ventricular arrhythmias, thromboembolic events, ventricular dysfunction, and mortality. A high level of evidence on the clinical management of cardiac involvement in this setting is still lacking, and strong recommendations cannot be formulated. Our systematic review reported the incidence rates for the main cardiovascular outcomes in 1070 LMNA mutation carriers and 40 EMD mutation carriers, with a minimum follow-up of one-year. Our results stressed the importance of a structured follow-up aiming at the early recognition of atrial arrhythmias and the prevention of thromboembolic events. In patients with a need for pacing, cardioverter–defibrillator implantation should be considered due to the high burden of malignant ventricular arrhythmias.Cardiolaminopathies are a heterogeneous group of disorders which are due to mutations in the genes encoding for nuclear lamins or their binding proteins. The whole spectrum of cardiac manifestations encompasses atrial arrhythmias, conduction disturbances, progressive systolic dysfunction, and malignant ventricular arrhythmias. Despite the prognostic significance of cardiac involvement in this setting, the current recommendations lack strong evidence. The aim of our work was to systematically review the current data on the main cardiovascular outcomes in cardiolaminopathies. We searched PubMed/Embase for studies focusing on cardiovascular outcomes in LMNA mutation carriers (atrial arrhythmias, ventricular arrhythmias, sudden cardiac death, conduction disturbances, thromboembolic events, systolic dysfunction, heart transplantation, and all-cause and cardiovascular mortality). In total, 11 studies were included (1070 patients, mean age between 26–45 years, with follow-up periods ranging from 2.5 years up to 45 ± 12). When available, data on the EMD-mutated population were separately reported (40 patients). The incidence rates (IR) were individually assessed for the outcomes of interest. The IR for atrial fibrillation/atrial flutter/atrial tachycardia ranged between 6.1 and 13.9 events/100 pts–year. The IR of atrial standstill ranged between 0 and 2 events/100 pts-year. The IR for malignant ventricular arrhythmias reached 10.2 events/100 pts–year and 15.6 events/100 pts–year for appropriate implantable cardioverter–defibrillator (ICD) interventions. The IR for advanced conduction disturbances ranged between 3.2 and 7.7 events/100 pts–year. The IR of thromboembolic events reached up to 8.9 events/100 pts–year. Our results strengthen the need for periodic cardiological evaluation focusing on the early recognition of atrial arrhythmias, and possibly for the choice of preventive strategies for thromboembolic events. The frequent need for cardiac pacing due to advanced conduction disturbances should be counterbalanced with the high risk of malignant ventricular arrhythmias that would justify ICD over pacemaker implantation.

Lack of authentic atrial fibrillation in commonly used murine atrial fibrillation models.

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 establish an atrial filtration (AF) model in our laboratory, 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-LKB1 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 may not reflect human AF well, and raise a cautionary note for use of those murine models to study AF.

Post-COVID myocarditis diagnosed by endomyocardial biopsy and/or magnetic resonance imaging 2–9 months after acute COVID-19

Abstract Purpose To study clinical features of myocarditis and its possible mechanisms (including persistence of SARS-Cov-2 in the myocardium) in the long-term period after acute COVID-19. Methods Fifteen patients (8 male and 7 female, mean age 47.8±13.4, 24–65 years) diagnosed with postcovid myocarditis were included in the study. The diagnosis of COVID-19 was confirmed by positive PCR results in 40%, and seroconversion in all patients. The average time of admission after COVID-19 was 4 [3; 7] months, from 2 to 9 months. The diagnosis of myocarditis was confirmed by cardiac MRI in 10 patients and by right ventricular endomyocardial biopsy (EMB) in 6 patients. The PCR for cardiotropic viruses and PCR with immunohistochemical study for SARS-Cov2 detection were used. All patients had study for anti-heart antibodies (AHA), EchoCG, and Holter ECG. Coronary atherosclerosis was excluded in all patients over 40 years (7 coronary angiography, 4 cardiac CT). Results A clear association of the cardiac symptoms with a previous new coronavirus infection was noted in all patients. The symptoms started 1–5 months following COVID-19. MRI showed subepicardial and intramyocardial LGE, signs of hyperemia, increased T1 relaxation time, edema. AHA levels were increased 3–4-fold in 73%. Two variants of postcovid myocarditis were observed. 1. Arrhythmic variant (n=6) – newly developed frequent supraventricular or ventricular extrasystole, recurrent atrial fibrillation in the absence of systolic dysfunction. 2. Decompensated variant with biventricular heart failure (n=9): the mean LV EF was 34.1±7.8% (23 to 46%), LV EDD 5.8±0.7 cm, EDV 153.8±46.1 ml, pulmonary artery systolic pressure 40.7±11.2 mmHg. In one case, myocarditis was accompanied by IgG4- and ANCA-negative aortitis. SARS-Cov-2 RNA was detected in 4 of 5 myocardial biopsies (in one case the material in the study). The longest period of virus persistence after COVID-19 was 9 months. By using spike and nucleocapsid antibodies, coronavirus was detected in cardiomycytes and macrophages. Data of patients with morphologically proved myocarditis are presented in Table 1. Lymphocytic myocarditis was diagnosed and confirmed immunohistochemically (n=5); giant cell myocarditis with atrial standstill was detected in one more case (Fig. 1). Three patients had also signs of endocarditis, in two cases with parietal thrombosis. Conclusions COVID-19 can lead to the subacute and chronic myocarditis of varying severity. Post-COVID myocarditis manifests itself in two main clinical forms - isolated arrhythmias and systolic dysfunction with heart failure. Post-COVID myocarditis is characterized by prolonged persistence of coronavirus (up to 9 months in this study, in most patients with decompensated variant) in combination with high immune activity (high titers of AHA), which should be considered as the main mechanisms of its long-term course. Treatment approaches for such myocarditis require investigation. Funding Acknowledgement Type of funding sources: None. Table 1. Patients with EMB proved myocarditisFigure 1. The EMB in postcovide myocarditis

Atrial standstill in the newborn: a case report

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.

Left atrial mechanical standstill after electrical cardioversion for atrial flutter: a case report

Left atrial mechanical standstill after electrical cardioversion for atrial flutter: a case report

Hypoxaemia and bradyarrhythmia in a foal undergoing surgical bladder repair

AbstractA five‐day‐old female Thoroughbred foal was diagnosed with uroperitoneum and ruptured bladder. Prior to general anaesthesia mild hyperkalaemia (5.2 mmol L−1) and respiratory distress were noticed. Under general anaesthesia urine was drained rapidly by free flow through an abdominal incision. During abdominal drainage heart rate declined from 80 to 40 beats per minute and atrial standstill was suspected on the electrocardiogram. Arterial blood gas analysis revealed worsening hyperkalaemia (6 mmol L−1) and severe hypoxaemia (PaO2 31 mmHg). Calcium gluconate, 23% 4 mg kg−1 diluted 1:4 with sodium chloride 0.9%, was administer over 20 minutes to restoring the resting membrane potential. To treat hypoxaemia, mechanical ventilation was started and salbutamol 100 μg was administered through the endotracheal tube. Atrial standstill resolved and heart rate increased. General anaesthesia ended without further complications. Careful pre‐operative preparation is required in foals with uroperitoneum to avoid the exacerbation of relatively mild alterations in electrolyte balance.

Cardiac Arrhythmias in Muscular Dystrophies Associated with Emerinopathy and Laminopathy: A Cohort Study.

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 < 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.

Life-threatening hyperkalaemia during general anaesthesia in a domestic short-haired cat

There are an increasing number of reports describing the development of hyperkalaemia in healthy veterinary patients during general anaesthesia. While the majority of cases are dogs, it has also been...

An SCN1B Variant Affects Both Cardiac-Type (NaV1.5) and Brain-Type (NaV1.1) Sodium Currents and Contributes to Complex Concomitant Brain and Cardiac Disorders.

Voltage-gated sodium (NaV) channels are transmembrane proteins that initiate and propagate neuronal and cardiac action potentials. NaV channel β subunits have been widely studied due to their modulatory role. Mice null for Scn1b, which encodes NaV β1 and β1b subunits, have defects in neuronal development and excitability, spontaneous generalized seizures, cardiac arrhythmias, and early mortality. A mutation in exon 3 of SCN1B, c.308A>T leading to β1_p.D103V and β1b_p.D103V, was previously found in a patient with a history of proarrhythmic conditions with progressive atrial standstill as well as cognitive and motor deficits accompanying structural brain abnormalities. We investigated whether β1 or β1b subunits carrying this mutation affect NaV1.5 and/or NaV1.1 currents using a whole cell patch-clamp technique in tsA201 cells. We observed a decrease in sodium current density in cells co-expressing NaV1.5 or NaV1.1 and β1D103V compared to β1WT. Interestingly, β1bD103V did not affect NaV1.1 sodium current density but induced a positive shift in the voltage dependence of inactivation and a faster recovery from inactivation compared to β1bWT. The β1bD103V isoform did not affect NaV1.5 current properties. Although the SCN1B_c.308A>T mutation may not be the sole cause of the patient’s symptoms, we observed a clear loss of function in both cardiac and brain sodium channels. Our results suggest that the mutant β1 and β1b subunits play a fundamental role in the observed electrical dysfunction.