Associations Between Atrial Arrhythmias and Brain Amyloid Deposition: The ARIC-PET Study

The aim of this study is to determine if there is an association between atrial arrhythmias and brain amyloid-β (Aβ), measured on florbetapir (FBP) PET. 346 nondemented participants from the Atherosclerosis Risk in Communities study underwent FBP-PET, 185 also wore Zio® XT Patch. The associations between global cortical Aβ (> 1.2 standardized uptake value ratio) and history of atrial fibrillation, zio-defined atrial tachycardia and premature atrial contractions, each, were evaluated. Among nondemented community-dwelling older adults, we did not find an association between atrial arrhythmias and Aβ. Other brain pathology may underlie the association described between atrial arrhythmias and cognition.

Arrhythmic Phenotypes Are a Defining Feature of Dilated Cardiomyopathy-Associated SCN5A Variants: A Systematic Review

Background: Variants in the SCN5A gene, that encodes the cardiac sodium channel, Nav1.5, are associated with a highly arrhythmogenic form of dilated cardiomyopathy (DCM). Our aim was to review the phenotypes, natural history, functional effects, and treatment outcomes of DCM-associated rare SCN5A variants. Methods: A systematic review of reported DCM-associated rare SCN5A variants was undertaken using PubMed and Embase. Results: Eighteen SCN5A rare variants in 29 families with DCM (173 affected individuals) were identified. Eleven variants had undergone experimental evaluation, with 7 of these resulting in increased sustained current flow during the action potential (eg, increased window current) and at resting membrane potentials (eg, creation of a new gating pore current). These variants were located in transmembrane voltage-sensing domains and had a consistent phenotype characterized by frequent multifocal narrow and broad complex ventricular premature beats (VPB; 72% of affected relatives), ventricular arrhythmias (33%), atrial arrhythmias (32%), sudden cardiac death (13%), and DCM (56%). This VPB-predominant phenotype was not seen with 1 variant that increased late sodium current, or with variants that reduced peak current density or had mixed effects. In the latter groups, affected individuals mainly showed sinus node dysfunction, conduction defects, and atrial arrhythmias, with infrequent VPB and VA. DCM did not occur in the absence of arrhythmias for any variant. Twelve studies (23 total patients) reported treatment success in the VPB-predominant cardiomyopathy using sodium channel-blocking drug therapy. Conclusions: SCN5A variants can present with a diverse spectrum of primary arrhythmic features. A majority of DCM-associated variants cause a multifocal VPB-predominant cardiomyopathy that is reversible with sodium channel blocking drug therapy. Early recognition of the distinctive phenotype and prompt genetic testing to identify variant carriers are needed. Our findings have implications for interpretation and management of SCN5A variants found in DCM patients with and without arrhythmias.

Influence of zones of low-amplitude activity on the mechanism and treatment of atrial arrhythmias.

A clinical case of interventional treatment of a patient with atypical atrial flutter who has not previously undergone surgical or interventional heart surgery. This clinical observation demonstrates the role of common zones of low-amplitude activity on the mechanism and treatment of atrial arrhythmias. Widespread areas of low-amplitude activity in the left atrium can create barriers to the propagation of excitation, which can cause atypical atrial flutter. High density mapping will help visualize the mechanism of this arrhythmia. Understanding the mechanism of atypical atrial flutter will help minimize RF exposure during treatment. Key words: high density mapping; atypical atrial flutter; atrial fibrosis; radiofrequency ablation.

423 Prevalence and prognostic significance of atrial arrhythmias in arrhythmogenic cardiomyopathy

Aims Limited data are available concerning atrial arrhythmias (AA) role in arrhythmogenic cardiomyopathy (AC). The aim of the present study was to assess the prevalence and incidence of AA in a large cohort of AC patients and to evaluate its association with clinical outcomes. Methods and results We retrospectively analysed 115 patients with definite diagnosis of ARVC, according to 2010 Task Force Criteria, enrolled in the Trieste Heart Muscle Disease Registry. Subjects were further classified into two phenotypic variants, based on ventricular involvement: right-dominant and biventricular form. Uni- and multivariable, extended Kaplan-Meier and cumulative incidence function analysis were performed, as appropriate, for the primary composite endpoint of death and heart transplant (HTx) and for the two distinct secondary endpoints of: (i) death, HTx and first heart failure (HF) hospitalization; (ii) first major ventricular arrhythmias (MVA). Mean age of patients at the time of enrollment was 39 ± 16 years and 80% were male. 73 patients (63%) had a right-dominant form, while 42 (37%) presented a biventricular involvement. AA occurred in the 26% of our study population at baseline or during a median follow-up of 214 months (IQR: 105–311), with a non-significant trend in higher cumulative incidence of AA in patients with biventricular form. At baseline, patients experiencing AA were older (44 ± 18 vs. 37 ± 15 years, P = 0.044) and had larger atrial dimensions, in particular of the right atrium (RA) (23, IQR: 19–27 vs. 18, IQR: 15–25 cm2, P < 0.007). AA emerged as independently associated to death/HTx (HR 2.68, 95% CI: 1.02–7.05, P = 0.046) along with NYHA class >2 (HR: 7.08, 95% CI: 2.50–20.1, P < 0.001) and RA area (HR: 1.05, 95% CI: 1.01–1.09, P = 0.011). Consistently, AA were also independently associated with the secondary endpoint of death/HTx/HF hospitalization (HR: 2.50, 95% CI: 1.06–5.88, P = 0.036), together with NYHA >2, the presence of biventricular involvement, higher RA and left atrium area. Finally, AA did not emerge as independently correlated to MVA during follow-up. Conclusions This observational long-term study suggests that AA were common in patients with AC and were independently associated with poor outcomes, mostly related to HF events. A prompt identification throughout the follow-up of AA appears relevant in improving the clinical management of AC patients.

Profibrillatory Structural and Functional Properties of the Atrial-Pulmonary Junction in the Absence of Remodeling

Background: Sole pulmonary vein (PV) isolation by ablation therapy prevents atrial fibrillation (AF) in patients with short episodes of AF and without comorbidities. Since incomplete PV isolation can be curative, we tested the hypothesis that the PV in the absence of remodeling and comorbidities contains structural and functional properties that are proarrhythmic for AF initiation by reentry.Methods: We performed percutaneous transvenous in vivo endocardial electrophysiological studies and quantitative histological analysis of PV from healthy sheep.Results: The proximal PV contained more myocytes than the distal PV and a higher percentage of collagen and fat tissue relative to myocytes than the left atrium. Local fractionated electrograms occurred in both the distal and proximal PVs, but a large local activation (>0.75 mV) was more often present in the proximal PV than in the distal PV (86 vs. 50% of electrograms, respectively, p = 0.017). Atrial arrhythmias (run of premature atrial complexes) occurred more often following the premature stimulation in the proximal PV than in the distal PV (p = 0.004). The diastolic stimulation threshold was higher in the proximal PV than in the distal PV (0.7 [0.3] vs. 0.4 [0.2] mA, (median [interquartile range]), p = 0.004). The refractory period was shorter in the proximal PV than in the distal PV (170 [50] vs. 248 [52] ms, p < 0.001). A linear relation existed between the gradient in refractoriness (distal-proximal) and atrial arrhythmia inducibility in the proximal PV.Conclusion: The structural and functional properties of the native atrial-PV junction differ from those of the distal PV. Atrial arrhythmias in the absence of arrhythmia-induced remodeling are caused by reentry in the atrial-PV junction. Ablative treatment of early paroxysmal AF, rather than complete isolation of focal arrhythmia, may be limited to inhibition of reentry.

Abstract 17083: Hunting For Clot: Strokes In Patients With Cardiac Amyloid

Case Presentation: A 76-year-old female with history of amyloid light chain (AL) cardiac amyloidosis and prior stroke presented with acute bilateral leg weakness. MRI of the brain revealed subacute infarcts in the right basal ganglia and precentral gyrus as well as chronic left cerebellar infarctions. CT angiogram of the head and neck did not show any significant intracranial or carotid artery disease. All current and previous admission ECGs and telemetry showed sinus rhythm with no atrial arrhythmias. Transthoracic echocardiogram with bubble study noted LV ejection fraction of 62%, normal left atrial size and no evidence of an intracardiac shunt. Despite the lack of traditional indicators, a cardioembolic source was feared given the high risk of intracardiac thrombi in AL amyloid patients. A TEE was performed and confirmed a large left atrial appendage (LAA) thrombus with severely reduced velocities and spontaneous echo contrast (Figure 1). The patient was started on apixaban for secondary stroke prevention. Discussion: Amyloid proteins deposit throughout heart tissue, distorting mechanical function and electric conduction resulting in reduced blood flow and a high risk of intracardiac thrombi that is 10 times that of nonamyloid patients. Patients with cardiac amyloidosis have a high prevalence of atrial arrhythmias, particularly atrial fibrillation, but remain at significant risk of thrombi even in the absence of these arrhythmias, ranging from 3-20%. Risk factors for clot include AL type amyloid and features of worsened hemodynamics such as LV systolic and diastolic dysfunction, elevated heart rates and lower systolic blood pressure. This case demonstrates the importance of aggressively “hunting” for intracardiac thrombi in amyloid patients presenting with stroke even without perceived risk factors, especially given the protective effect of starting anticoagulation.

Association of atrial arrhythmias with thrombospondin-1 in patients with acute myocardial infarction

Objectives Atrial remodeling is the main developmental cause of atrial arrhythmias (AA), which may induce atrial fibrillation, atrial flutter, atrial tachycardia, and frequent premature atrial beats in acute myocardial infarction (AMI) patients. Thrombospondin-1 (TSP-1) has been shown to play an important role in inflammatory and fibrotic processes, but its role in atrial arrhythmias is not well described. The purpose of this study was to investigate the role of TSP-1 in AMI patients with atrial arrhythmias. Methods A total of 219 patients with AMI who underwent percutaneous coronary intervention and with no previous arrhythmias were included. TSP-1 were analyzed in plasma samples. Patients were classified into 2 groups, namely, with and without AA during the acute phase of MI. Continuous electrocardiographic monitoring was used for AA diagnosis in hospital. Results Twenty-four patients developed AA. Patients with AA had higher TSP-1 levels (29.01 ± 25.87 μg/mL vs 18.36 ± 10.89 μg/mL, p < 0.001) than those without AA. AA patients also tended to be elderly (65.25 ± 9.98 years vs 57.47 ± 10.78 years, p < 0.001), had higher Hs-CRP (39.74 ± 43.50 mg/L vs 12.22 ± 19.25 mg/L, p < 0.001) and worse heart function. TSP-1 (OR 1.033; 95% CI 1.003–1.065, p = 0.034), Hs-CRP (OR 1.023; 95% CI 1.006–1.041, p = 0.008), age (OR 1.067; 95% CI 1.004–1.135, p = 0.038) and LVDd (OR 1.142; 95% CI 1.018–1.282, p = 0.024) emerged as independent risk factors for AA in AMI patients. Conclusion TSP-1 is a potential novel indicator of atrial arrhythmias during AMI. Graphical abstract