Occurrence Of Atrial Arrhythmias Research Articles

ATrial arrhythmias in inhEriTed aRrhythmIa Syndromes: results from the TETRIS study.

Little is known about the distribution and clinical course of patients with inherited arrhythmia syndrome (IAS) and concomitant atrial arrhythmias (AAs). 1) to characterize the distribution of AAs in patients with IAS and 2) evaluate the long-term clinical course of these patients. An international multicenter study was performed and involved 28 centers in 16 countries. Inclusion criteria were: 1) IAS and 2) ECG documentation of AAs. The primary endpoint was a composite of sudden cardiac death, sustained VAs or appropriate ICD interventions. Strokes, inappropriate ICD shocks due to AAs, and the occurrence of sinus node dysfunction were assessed. A total of 522 patients with IAS and AAs were included. Most patients were diagnosed with Brugada syndrome (n=355, 68%) and long-QT syndrome (n=93, 18%). The remaining patients (n=71, 14%) presented with short-QT syndrome, early repolarization syndrome (ERS), catecholaminergic polymorphic ventricular tachycardia (CPVT), progressive cardiac conduction diseases, or idiopathic ventricular fibrillation. Atrial fibrillation (AF) was the most prevalent AA (82%), followed by atrial flutter (9%) and atrial tachycardia (9%). AA was the first clinical manifestation of IAS in 52% of patients. More than one type of AAs was documented in 23% of patients. Nine patients (3%) experienced VA before the diagnosis of IAS, due the use of anti-arrhythmic medications taken for the AA. The incidence of the primary endpoint was 1.4% per year, with a twofold increase observed in patients who experienced their first AA before the age of 20 (OR 2.2, p=0.043). This was consistent across the different forms of IAS. Inappropriate ICD shock due to AAs were reported in 2.8% of patients, strokes in 4.4% and sinus node dysfunction in 9.6%. Among patients with IAS and AAs, AA is the first clinical manifestation in about half of the cases, with more than one form of AAs present in one-fourth of the patients. The occurrence of AA earlier in life may be associated with a higher risk of ventricular arrhythmias. The occurrence of stroke and sinus node dysfunction is not-infrequently in this cohort.

Atrial arrhythmia in adults with sickle cell anemia: a missing link toward understanding and preventing strokes

AbstractAlthough patients with homozygous sickle cell anemia (SCA) carry both significant left atrial (LA) remodeling and an increased risk of stroke, the prevalence of atrial arrhythmia (AA) has never been prospectively evaluated. The aim of this study was to identify the prevalence and predictors of atrial arrhythmia in SCA. From 2018 to 2022, consecutive adult patients with SCA were included in the DREPACOEUR prospective registry and referred to the physiology department for cardiac evaluation, including a 24-hour electrocardiogram monitoring (ECG-Holter). The primary endpoint was the occurrence of AA, defined by the presence of excessive supraventricular ectopic activity (ESVEA) on ECG-Holter (ie >720 premature atrial contractions [PACs] or any run ≥ 20 PACs) or any recent history of atrial fibrillation. Overall, 130 patients with SCA (mean age: 45±12 years, 48% of male) were included. AA was found in 34 (26%) patients. Age (52±9 vs. 42±12 years, P=0,002), LA dilation (LAVi, 71±24 vs. 52±14 mL/m², P<0.001) and history of stroke without underlying cerebral vasculopathy (26% vs. 5%, P=0.009, OR=6.6 (95%CI 1.4-30.3]) were independently associated with AA. Age and LAVi correlated with PAC load per 24 hours on ECG-Holter. An age over 47 years or a LAVi >55mL/m² could predict AA with a PPV of 33% and a NPV of 92%. AAs are frequent in middle-aged patients with SCA and increase with age and LA remodeling, leading to a major additional risk factor for ischemic stroke. This study provides arguments and means to early screen for AA and potentially prevent cerebral complications.

HIPSC model reveals M1 macrophages cause atrial arrhythmia correlated to electrophysiological remodelling of atrial cardiomyocytes in 2D and 3D engineered heart tissue

Abstract Atrial fibrillation (AF) is the most common sustained arrhythmia with an estimated prevalence of 1.5–2%. Current treatments lack effectiveness and do not prevent recurrence. Inflammation is reported in AF patients, however, a causal connection remains elusive. In this study, we investigated the arrhythmic effects of pro-inflammatory macrophages (M1) on human induced pluripotent stem cell (hiPSC)-derived atrial cardiomyocytes (aCM), to better understand their role in AF. Macrophages are known to play a role in cardiac electrophysiology, but their role in arrhythmia is unclear. Three healthy hiPSC lines were differentiated to aCM and M1. Multi-electrode array recordings of isogenic, 2D cocultures of M1 and aCM showed a significant increase in beat rate irregularity compared to control conditions (P&amp;lt;0.001). Furthermore, spike amplitude of aCM and M1 cocultures was significantly decreased (P&amp;lt;0.001). Arrhythmias occurred only after activation of macrophages in the coculture. Addition of anti-inflammatory glucocorticoids significantly reduced beat irregularity in aCM and M1 cocultures compared to vehicle (1.9-fold decrease for Hydrocortisone, P&amp;lt;0.005) further supporting macrophage mediated inflammation to be the cause of the arrhythmia. RNA sequencing of aCM and M1 cocultures revealed aberrant expression of arrhythmia associated cardiac sodium and atrial potassium ion channels (SCN5A, KCNA5). Normal expression was restored through hydrocortisone addition. In addition, inflammation-induced arrhythmia was observed in 3D engineered heart tissues containing hiPSC derived aCM, M1 and cardiac fibroblasts. Tissues showed a significant increase in beating irregularity (P&amp;lt;0.005) compared to controls and had a significant, median reduction (&amp;gt;30%) of contraction amplitude (P&amp;lt;0.05). Our findings suggest a causal relationship between M1 and the occurrence of atrial arrhythmia. The reduction of arrhythmia using glucocorticoids correlates to clinical observations, that show their use being linked to reduced post operative AF burden. These results strongly support the relevance of the proposed hiPSC coculture model and elucidate a new potential AF mechanism.

Evaluation of right atrium structure and function in a rat model of monocrotaline-induced pulmonary hypertension: Exploring the possible antiarrhythmic properties of amiodarone.

Atrial arrhythmias (AA) are common in pulmonary hypertension (PH) and are closely associated with poor clinical outcomes. One of the most studied models to investigate PH is the rat model of monocrotaline (MCT) induced PH (MCT-PH). To date, little is known about right atrium (RA) function in the MCT-PH model and the propensity of RA to develop arrhythmias. Therefore, the aim of the study was to evaluate the function of the RA of control (CTRL) and MCT treated rats, and the ability of amiodarone, a classical antiarrhythmic, to prevent the occurrence of AA in the RA in MCT-PH rats. RA function was studied in MCT-PH rats 20 days after a single subcutaneous injection of MCT 50 mg/kg. The histological results indicated the presence of RA and right ventricular hypertrophy. Surface electrocardiogram demonstrated increased P wave duration, PR wave duration and QT interval in MCT rats. RA from MCT rats were more susceptible to develop ex vivo burst pacing arrhythmias when compared to CTRL. Intriguingly, amiodarone in clinical relevant concentration was not able to prevent the occurrence arrhythmias in RA from MCT-PH animals. Hence, we conclude that the rat model of MCT-PH impairs RA structure and function, and acute exposure of RA to amiodarone in clinical relevant concentration is not able to attenuate the onset of arrhythmias in the ex vivo RA preparation.

Incidence, Risk Factors, and Outcomes of Atrial Arrhythmias in Adult Patients With Atrioventricular Septal Defect.

This study aimed to assess the incidence, associated factors, and outcomes of atrial arrhythmias in adults with atrioventricular septal defect (AVSD). Data regarding atrial arrhythmias in adults with AVSD are particularly scarce. Data were analyzed from a multicentric cohort of adult patients with AVSD. Lifetime cumulative incidences of atrial arrhythmias were studied. Multiple logistic regression models were used to identify risk factors. A total of 391 patients (61.6% women) were enrolled with a mean age of 36.3 ± 16.3 years and a mean follow-up of 17.3 ± 14.2 years after initial surgical repair. Overall, 98 patients (25.1%) developed at least 1 episode of atrial arrhythmia at a mean age of 39.2 ± 17.2 years. The mean ages of patients at first episode of intra-atrial re-entrant tachycardia (IART)/ focal atrial tachycardia (FAT) and atrial fibrillation were 33.7 ± 15.3 and 44.3 ± 16.5 years, respectively. The lifetime risks for developing atrial arrhythmia to ages 20, 40, and 60 years were 3.7%, 17.8%, and 55.3%, respectively. IART/FAT was the leading arrhythmia until the age of 45, then atrial fibrillation surpassed IART/FAT. Age (odds ratio [OR]: 1.4; 95% confidence interval [CI]: 1.2-1.6), number of cardiac surgeries (OR: 4.1; 95%CI: 2.5-6.9), left atrial dilatation (OR: 3.1; 95%CI: 1.4-6.8), right atrial dilatation (OR: 4.1; 95%CI: 1.7-10.3), and moderate or severe left atrioventricular valve regurgitation (OR: 3.7; 95%CI: 1.2-11.7) were independently associated with a higher risk of atrial arrhythmias, whereas the type of AVSD and the age at repair were not. The occurrence of atrial arrhythmias was associated with pacemaker implantation (41.8% vs. 8.5%; P< 0.001), heart failure (24.5% vs. 1.0%; P< 0.001), and cerebrovascular accidents (11.2% vs. 3.4%; P = 0.007). The lifetime risk of atrial arrhythmias in patients with AVSD is considerable with more than half of patients developing≥1 atrial arrhythmia by the age of 60 and is associated with a significant morbidity. The risk in partial/intermediate AVSD is as high as in complete AVSD and is not impacted by age at repair.

Prevention of stroke and atrial arrhythmia consequences in hypertrophic cardiomyopathies: a clinical challenge that could be best managed by a better echocardiographic left atrial characterization

Abstract Funding Acknowledgements Type of funding sources: None. Background There is a need to better predict the risk of atrial arrhythmia (AA) and stroke in patients with hypertrophic cardiomyopathy (HCM). Purpose We sought to look at atrial remodeling and atrial function by echocardiography in a HCM-cohort to assess the association with occurrence of AA and stroke. Methods We retrospectively studied 216 patients diagnosed for HCM (mean age 52 ± 16 years) from 2015 to 2020. All patients underwent transthoracic echocardiography with the assessment of left atrial volume (LAV) and peak left atrial strain (PLAS). Patients were followed-up for 2,9 years for the development of a composite endpoint comprising occurrence of atrial arrhythmias and/or stroke. Results 78 patients had an event (24 stroke and 54 documented atrial arrhythmia). Univariate comparison analysis showed that LAV (37.2 ± 15.7 vs. 47 ± 20 ml/m², p = 0.0001) and anteroposterior LA diameter (41.7 ±7.58 vs. 45.8 ± 8.9 mm; p = 0.0006) were significantly higher in patients who met the composite endpoint, whereas PLAS was significantly impaired (27.1 ± 9.77 vs. 20.4 ± 10.5%; p &amp;lt; 0.0001). Other echographic parameters associated with the composite endpoint were mean E/e" ratio (0.65 [0.55-0.85] vs. 0.60 [0.45-0.75]; p = 0.0204) and tricuspid annular peak systolic velocity (S") (cm/s) (13.3 ± 2.92 vs. 12.2 ± 3.26; p = 0.0148). NTproBNP level (216 vs. 818 ; p &amp;lt; 0.0001), history of hypertension (42.3% vs. 62.3%; p = 0.005) and age at diagnosis (50.3 ± 16.7 vs. 57.1 ± 14.4; p = 0.0035) were the clinical parameters different between groups. In a multivariable analysis, PLAS was the only independent maker associated with the occurrence of AA and stroke, particularly for stroke with an odd ratio of 0.53 ([0.32-0.86]; p = 0.00097). Interestingly, 19 of 28 stroke patients (67%) did not experience any documented AA. Conclusion The decrease of PLAS is strongly associated with the risk of stroke, even in patients without documented atrial arrhythmia. Its use to guide the indication for an implantable holter monitoring and perhaps a prophylactic oral anticoagulation in HCM requires further investigation. Abstract Figure. Impaired PLAS in an HCM patient

Value of the left atrial size and function in hypertrophic cardiomyopathy for best understand who are the patients at risk for atrial arrhythmia and stroke

Patient with hypertrophic cardiomyopathy (HCM) are at high-risk for atrial arrhythmia (AA) and stroke. We sought to look at atrial remodeling and atrial function by echocardiography in a HCM-cohort to assess the association with the occurrence of AA and stroke. We retrospectively studied 216 patients diagnosed for HCM (mean age 52 ± 16 years) from 2015 to 2020. Complete echocardiography at baseline was performed including measurement of left atrial volume (LAV) and peak left atrial strain (PLAS). Patients were followed for development of the composite endpoint comprising history or occurrence of atrial arrhythmias and/or stroke during mean follow-up of 3 years. Seventy-eight patients had an event (24 stroke and 54 documented atrial arrhythmia). Univariable analysis showed that LAV (37.2 ± 15.7 mL/m 2 vs. 47 ± 20 mL/m 2 ; P = 0.0001), anteroposterior LA diameter (41.7 ±7.58 mm vs. 45.8 ± 8.9 mm; P = 0.0006) and PLAS (27.1 ± 9.77% vs. 20.4 ± 10.5%; P < 0.0001) were significantly associated with the occurrence of the endpoint. NTproBNP level (216 vs. 818 ng/L; P < 0.0001), history of hypertension (42.3% vs. 62.3%; P = 0.005) and age at diagnosis (50.3 ± 16.7 years vs. 57.1 ± 14.4 years; P = 0.0035) were the clinical parameters different between groups. In a multivariable analysis, PALS was the only independent maker associated with the occurrence of AA and stroke, particularly for stroke with an odd ratio of 0.51 ([0.36–0.69]; P ≤ 0,05). Interestingly, 19 of 28 stroke patients (67%) did not experience any documented atrial arrhythmias ( Table 1 , Fig. 1 ). The decrease of PLAS is strongly associated with the risk of stroke, even in patients without documented atrial arrhythmia. Its use to guide the indication for an implantable Holter monitoring and perhaps a prophylactic oral anticoagulation in HCM requires further investigation.

The Impact of Aorto-Mitral Angle on New-Onset Atrial Arrhythmia after Mitral Valve Repair in Patients with Mitral Regurgitation.

In this study, we hypothesized that post-operative aorto-mitral angle might be associated to the occurrence of post-operative atrial arrhythmia (AA), including atrial fibrillation and atrial tachycardia, after mitral valve repair in patients with mitral regurgitation (MR). Thus, this present study aims to determine the effects of post-operative aorto-mitral angle on new-onset AA after mitral valve repair with mitral annuloplasty for the treatment of MR.In total, 172 patients without any history of AA underwent mitral valve repair with mitral annuloplasty in our institution between 2008 and 2017. Patient information, including medical records and echocardiographic data, were retrospectively studied.As per our findings, AA occurred in 15 (8.7%) patients during the follow-up period (median, 35.7 months; range, 0.5-132 months). The patients with AA were noted to have a longer cardiopulmonary bypass time and a smaller aorto-mitral angle at post-operative TTE than the others (119 ± 6° versus 125 ± 10°, P = 0.003). No significant difference was noted in the degree of post-operative residual MR or functional MS between the groups. In a multivariate Cox proportional hazards analysis, the longer cardiopulmonary bypass time and the smaller post-operative aorto-mitral angle were independent predictors of the occurrence of AA during the follow-up period (odds ratio per 10 minutes 1.11; 95% CI 1.02-1.22, P = 0.019: odds ratio 0.91; 95% CI 0.85-0.98, P = 0.012).A small aorto-mitral angle at post-operative TTE was determined to be a predictor of new-onset AA after a mitral valve repair for treating MR.

A meta-analysis of the association of atrial septal abnormalities and atrial vulnerability.

Background:The mechanism of cryptogenic stroke (CS) in patients with atrial septal abnormalities remains unclear, and the increased incidence of atrial vulnerability may be one of the reasons. We performed this meta-analysis to clarify the association between atrial septal abnormalities and atrial vulnerability, and to provide evidence-based basis for the prevention and mechanism of CS.Methods:We systematically searched for studies on the association between atrial septal abnormalities and atrial vulnerability, and pooled available data on types of atrial septal abnormalities, types of atrial vulnerability, and methods of atrial vulnerability detection. The primary endpoints were the occurrence of atrial arrhythmias or P wave abnormalities. Random-effects models were used to calculate odds ratios (OR) and 95% confidence intervals (CI).Results:Twelve case-control studies were eligible. Compared with the control group, patients with atrial septal abnormalities had a higher risk of atrial vulnerability (OR: 1.93; 95% CI: 1.13-3.30, P = .02). Data based on stroke patients showed that the group with atrial septal abnormalities had a higher risk of atrial vulnerability than the control group (OR: 2.00; 95% CI: 1.13–3.53, P = .02). However, there was no significant difference in the incidence of atrial vulnerability between the 2 groups of nonstroke patients. Subgroup analysis showed that although atrial septal abnormality increased the risk of atrial vulnerability in the subgroup of atrial septal aneurysm (OR: 1.68; 95% CI: 0.47–5.95, P = .42), the subgroup of atrial fibrillation (AF)/atrial fluster (OR: 1.81; 95% CI: 0.94–3.46, P = .07) and the subgroup of subcutaneous recording system (OR: 1.33; 95% CI: 0.68–2.61, P = .41), the difference was not statistically significant.Conclusions:Atrial septal abnormalities can increase the risk of atrial vulnerability, and atrial arrhythmia caused by atrial septal abnormalities may be one of the mechanisms of CS.

Factors Determining Occurrence of Arrhythmias in Patients Post-closure of Atrial Septal Defects.

ObjectivesThis study aimed to determine the risk factors for the occurrence of arrhythmias after either transcatheter or surgical closure of atrial septal defect.MethodsThis prospective study included 150 patients admitted for transcatheter or surgical closure of atrial septal defect. Transthoracic echocardiography together with a twelve-leads ECG were done during 1 and 3 months follow up. The paired T, chi-square and Logistic regression tests were used to detect any association between any arrhythmias and factors that may affect its occurrence.ResultsOne-hundred and twenty-three patients had percutaneous device closure while the remaining 27 patients had surgical closure. The youngest and oldest of the studied patients being 3 & 50 years old respectively with female (108) over male (42) predominance in incidence. After closure, 8 patients at one month and another 3 patients at three months follow up out of the total 150 patients had supraventricular arrhythmias in the form of frequent premature atrial contractions (6 patients), atrioventricular nodal re-entrant tachycardia (2 patients), and paroxysmal Atrial fibrillation (3 patients). No conduction abnormalities nor ventricular arrhythmias occurred. Multivariate analysis showed that age, P wave dispersion, systolic myocardial velocity of right ventricle, and systolic pulmonary artery pressure were independently associated with the occurrence of atrial arrhythmia after atrial septal defect repair.ConclusionAge, P wave dispersion, Systolic pulmonary artery pressure, and systolic myocardial velocity of the right ventricle are independent risk factors to develop arrythmias in patients after atrial septal defect closure.

Left atrial morpho-functional changes in hypertrophic cardiomyopathy and Fabry disease: a CMR-feature tracking study

Abstract Funding Acknowledgements Type of funding sources: None. Background Left ventricular (LV) diastolic dysfunction (DD) is a hallmark of hypertrophic cardiomyopathy (HCM) and its phenocopies, such as Fabry disease (FD). Together with left atrial (LA) size, LA function is emerging as a sensitive marker of the adaptive changes to backward transmission of LV cardiac filling pressure, thus implementing DD assessment. Additionally, both HCM and FD are characterized by a primitive atrial myopathy, but LA morpho-functional changes in HCM and FD have never been directly compared. More recently, LA strain by Cardiovascular Magnetic Resonance Feature Tracking (CMR-FT) has been demonstrated to be a feasible and reproducible tool to explore LA function. Purpose To compare LA morpho-functional changes in HCM and FD and to explore their correlation with tissue alterations. Methods 15 HCM and 15 sex-, age- and LV mass index-matched FD patients underwent CMR (Magnetom Aera 1.5T, Siemens) and Doppler Echocardiography for LV diastolic function assessment (E/e’ and DD grading from 0 to 3). LA phasic function was evaluated by CMR-FT strain (Qstrain Medis). The software output included passive (εe, conduit function), active (εa, booster pump function) and total strain (εs, reservoir function), along with LA volumes and ejection fraction (EF). Late gadolinium enhancement (LGE) was quantified as a percentage of LV mass using the standard deviations (SDs) method (≥ 5 SDs). Interstitial fibrosis was assessed by extracellular volume (ECV) quantification in remote myocardium. All patients were in sinus rhythm. Results In the HCM group, the proportion of patients with DD grade 2-3 was only slightly higher than in FD (p 0.26). Accordingly, no significant difference was found in E/e’ value (p 0.78). Compared to FD, HCM patients showed more severe LA morpho-functional changes, including larger LA end-systolic volume (ESV) (113 ± 35 vs 84 ± 23 ml), lower LA EF (37 ± 7 vs 44 ± 9 %) and a greater reduction of εs (-20 ± 5 vs -25 ± 6 %) and εa (-10 ± 4 vs -15 ± 4 %) (all p &amp;lt; 0.05). LV size and function and the burden of fibrosis (LGE quantification and ECV) were comparable between the two groups. Interestingly, in HCM population, unlike in FD, LA morpho-functional measurements significantly correlated with tissue characterization parameters (LA ESV with LGE, r 0.56, p 0.03; εs and εa with ECV, r -0.51, p 0.05 and r -0.59, p 0.02, respectively). Conclusions LA morpho-functional alterations are much more severe in HCM compared to FD with similar degree of LV hypertrophy. A more severe atrial myopathy or different mechanisms of atrial damage in the two cardiomyopathies may explain these findings. LA CMR-FT analysis may represent a sensitive tool to discriminate between HCM and FD, although larger studies are needed to confirm this finding and the possible correlation with the occurrence of atrial arrhythmias and thromboembolic risk.

Chronic Obstructive Pulmonary Disease and Risk of Atrial Arrhythmias After ST-Segment Elevation Myocardial Infarction.

ST-segment elevation myocardial infarction (STEMI) and cardiac arrhythmias frequently occur in patients with chronic obstructive pulmonary disease (COPD). However, little is known about the association of COPD with the occurrence of atrial arrhythmias after STEMI. This retrospective analysis consisted of 320 patients with first STEMI without a history of atrial arrhythmias, with available 24-hour holter-ECG at 3- and/or 6 months follow-up. In total, 80 COPD patients were compared with 240 non-COPD patients, matched by age and gender (mean age 67±10 years, 74% male). Atrial arrhythmias were defined as: atrial fibrillation/flutter, atrial tachycardia (≥3 consecutive premature atrial contractions (PAC's)) and excessive supraventricular ectopy activity (ESVEA, ≥30 PAC's/hour or runs of ≥20 PAC's). Baseline characteristics were similar among COPD and non-COPD patients regarding infarct location, β-blocker use and cardiovascular risk profile except for smoking (69% vs. 49%, respectively, p=0.002). Additionally, atrial volumes, LVEF and TAPSE were comparable. During 1 year follow-up, a significantly higher prevalence of atrial tachycardia and ESVEA was observed in patients with COPD as compared to non-COPD patients (70% vs. 46%; p<0.001 and 21% vs. 11%; p=0.024, respectively). In multivariate analysis, COPD was independently associated with the occurrence of atrial arrhythmias (combined) during 1 year of follow-up (HR 3.59, 95% CI 1.78-7.22; p<0.001). COPD patients after STEMI have a significantly higher prevalence of atrial tachycardia and ESVEA within 1 year follow-up as compared to age- and gender matched patients without COPD. Moreover, COPD is independently associated with an increased prevalence of atrial arrhythmias after STEMI.

Association Between Flow Impairment in Dominant Coronary Atrial Branches and Atrial Arrhythmias in Patients With ST-Segment Elevation Myocardial Infarction

ObjectivesThe impact of atrial ischemia in the occurrence of atrial arrhythmias may vary based on the amount of jeopardized myocardium. We sought to determine the association between coronary flow impairment in dominant coronary atrial branches (CAB) and atrial arrhythmias at 1-year follow-up in ST-segment elevation myocardial infarction (STEMI) patients. MethodsPatients with STEMI involving the right or circumflex coronary artery were included. Dominant CAB was defined as the most developed CAB. Patients were followed-up during 1 year, including 24-h Holter ECG at 3 and 6 months. Atrial arrhythmias were defined as atrial fibrillation/flutter, atrial tachycardia (≥3 consecutive supraventricular ectopic beats) and excessive supraventricular ectopic activity (>30 supraventricular beats/h or runs ≥20 beats). ResultsA dominant CAB was identified in 897 of 900 patients STEMI (age 61 ± 12 years, 79% male). TIMI flow < 3 at the dominant CAB was present in 69 (8%) patients. Compared to those with dominant CAB preserved flow, patients with dominant CAB flow impairment presented with higher levels of troponin T (3.9 [2.2–8.2] vs. 3.1 [1.3–5.8], P = 0.008)and higher rates of atrial tachycardia at 3 months (68% vs. 37%, P = 0.007) and more supraventricular ectopic beats both at 3 months (58 [21–235] vs. 33 [12–119], P = 0.02) and at 6 months (62 [24–156] vs. 32 [12–115]; P = 0.04) on 24-h Holter ECG. Age and an impaired coronary flow at the dominant CAB were independently related to a higher risk of developing atrial arrhythmias at 1-year follow-up. ConclusionDominant CAB flow impairment is infrequent and is associated with the occurrence of atrial arrhythmias, in the form atrial tachycardia and supraventricular ectopic beats, at follow-up.

P1905Propofol suppresses atrial fibrillation in an experimental whole-heart model

Abstract Background Many clinical studies suggest an impact of propofol on the occurrence of atrial arrhythmias. Purpose Since experimental data is sparse, purpose of this study was to investigate the influence of propofol on atrial electrophysiology and the vulnerability to atrial fibrillation in a sensitive whole-heart model of atrial fibrillation. Methods 11 hearts of New Zealand white rabbits were isolated and Langendorff-perfused. Two catheters were placed on both atria to record atrial monophasic action potentials. Hearts were stimulated at three different cycle lengths (350ms, 250ms, 150ms), thereby obtaining cycle-length dependent atrial action potential durations (aAPD90) and effective refractory periods (aERP). Atrial post-repolarization (aPRR) refractoriness was defined as the difference between aERP and aAPD90. To increase the occurrence of atrial fibrillation, hearts were perfused with a combination of acetylcholine (ACh, 1μM) and isoproterenol (Iso, 1μM) after obtaining baseline data. Vulnerability to atrial fibrillation was tested by a standardized protocol consisting of several trains of burst pacing. Results Acetylcholine/isoproterenol infusion reduced aAPD90 (−3ms), aERP (−16ms) and aPRR (−14ms). Additional treatment with propofol prolonged aAPD90 (+5ms), aERP (+24ms) and aPRR (+20ms). Under baseline conditions, 13 episodes of atrial fibrillation lasting longer than 1s occurred. Additional treatment with acetylcholine/isoproterenol provoked more episodes of atrial fibrillation (33 episodes, p&lt;0.05). Infusion of propofol on top of acetylcholine/isoproterenol significantly suppressed atrial fibrillation (2 episodes, p&lt;0.05). Conclusion In this study, propofol prolonged aAPD90 and significantly reduced the occurrence of atrial fibrillation. Prolongation of effective refractory periods and especially of post-repolarization refractoriness protects the atrial myocardium against premature excitation and thereby prevents arrhythmias.

Procedural-related coronary atrial branch occlusion during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction and atrial arrhythmias at follow-up.

To evaluate the frequency of procedural-related atrial branch occlusion in ST-segment elevation myocardial infarction (STEMI) patients and its association with atrial arrhythmias at 1-year follow-up. Atrial ischemia due to procedural-related coronary atrial branch occlusion in elective percutaneous coronary intervention (PCI) has been associated with atrial arrhythmias. Its role in a STEMI scenario is unknown. STEMI patients treated with primary PCI were classified according to the loss or patency of an atrial branch at the end of the procedure. The occurrence of atrial arrhythmias was documented on 24-hr Holter-ECG at 3 and 6 months or on ECG during 1-year follow-up visits. Of 900 patients, 355 (age 61 ± 12 years, 79% male) underwent primary PCI involving the origin of an atrial branch. Procedural-related coronary atrial branch occlusion was observed in 18 (5%) individuals). During 1-year follow-up, 33% of patients with procedural-related atrial branch occlusion presented atrial arrhythmias, as compared with 55% in those with a patent atrial branch (p = .088). Age, no previous history of myocardial infarction, and a reduced flow in the culprit vessel were the only independent correlates of atrial arrhythmias. The frequency of procedural-related atrial branch occlusion during primary PCI is low (5%) and is not associated with increased frequency of atrial arrhythmias at 1-year follow-up.

Atrial Dysfunction in Arrhythmogenic Right Ventricular Cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy that is predominantly known to affect the ventricles. Evidence for atrial involvement remains limited. Therefore, we aimed to characterize atrial involvement in ARVC using functional cardiac magnetic resonance, define the extent of atrial size and function variation attributable to ventricular variables, and identify cardiac magnetic resonance-based predictors of atrial arrhythmias (AA) in ARVC. We analyzed cine cardiac magnetic resonance images of 66 definite ARVC patients without a history of AA or severe heart failure and 24 healthy controls. Using tissue tracking, we evaluated phasic biatrial volumes, ejection fractions (EFs), peak longitudinal strain, and strain rates (SRs). The primary outcome was the occurrence of AA during 6.8 years [3.0-10.8 years] of follow-up. Compared with controls, ARVC patients had higher biatrial volumes, reduced right atrial (RA) conduit function (passive EF [RAEFpassive] and peak early-diastolic SR), reduced RA and left atrial (LA) reservoir function (peak systolic SR), and reduced RA and LA pump function (peak late-diastolic SR; P<0.05). Using multivariable analysis, predictors of increased risk of AA during follow-up were higher atrial volumes (RAVmin and LAVmin), decreased LA reservoir function (total LAEF and LA peak longitudinal strain), and decreased RA conduit function (passive RAEF and RA early-diastolic SR). Compared with controls, patients with ARVC were found to have enlarged atria with decreased function on functional cardiac magnetic resonance examination. RA and LA parameters predict incident AA after adjusting for clinical and ventricular characteristics which suggests atrial involvement in ARVC.

Gene-Based Risk Stratification for Cardiac Disorders in LMNA Mutation Carriers.

Mutations in LMNA (lamin A/C), which encodes lamin A and C, typically cause age-dependent cardiac phenotypes, including dilated cardiomyopathy, cardiac conduction disturbance, atrial fibrillation, and malignant ventricular arrhythmias. Although the type of LMNA mutations have been reported to be associated with susceptibility to malignant ventricular arrhythmias, the gene-based risk stratification for cardiac complications remains unexplored. The multicenter cohort included 77 LMNA mutation carriers from 45 families; cardiac disorders were retrospectively analyzed. The mean age of patients when they underwent genetic testing was 45±17, and they were followed for a median 49 months. Of the 77 carriers, 71 (92%) were phenotypically affected and showed cardiac conduction disturbance (81%), low left ventricular ejection fraction (<50%; 45%), atrial arrhythmias (58%), and malignant ventricular arrhythmias (26%). During the follow-up period, 9 (12%) died, either from end-stage heart failure (n=7) or suddenly (n=2). Genetic analysis showed truncation mutations in 58 patients from 31 families and missense mutations in 19 patients from 14 families. The onset of cardiac disorders indicated that subjects with truncation mutations had an earlier occurrence of cardiac conduction disturbance and low left ventricular ejection fraction, than those with missense mutations. In addition, the truncation mutation was found to be a risk factor for the early onset of cardiac conduction disturbance and the occurrence of atrial arrhythmias and low left ventricular ejection fraction, as estimated using multivariable analyses. The truncation mutations were associated with manifestation of cardiac phenotypes in LMNA-related cardiomyopathy, suggesting that genetic analysis might be useful for diagnosis and risk stratification.

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OBJECTIVES/SPECIFIC AIMS: The morbidity and mortality in adults with single ventricular hearts who have undergone Fontan palliation is poorly defined. These patients have a high burden of arrhythmia, heart failure, and re-operation. We hypothesized that age and type of Fontan predict occurrence of arrhythmia. METHODS/STUDY POPULATION: In total, 205 patients aged 18 years who had undergone a Fontan procedure were identified. Those with incomplete data were excluded. Demographic, anatomic, pharmacologic, imaging, hemodynamic, and electrophysiologic data were collected. The χ2 and Mann-Whitney U tests were used to test significance defined as p&lt;0.05. RESULTS/ANTICIPATED RESULTS: Of the 205 patients identified, 59 had been lost to follow-up. Of the 146 patients (77, 53% female) actively followed 18 (12%) had died at a median (IQR) age of 27 (21–34.3); in patients alive as of 10/2016 the median age was 26 years (22–34). Fontan types were lateral tunnel (LT) (n=79, 54.1%), extracardiac (EC) (n=32, 22%), right atrial to pulmonary artery (RV-PA) (n=28, 19%), and Fontan with Bjork modification (n=4, 2.7%). Systemic left ventricle (n=96, 66%) was more common than systemic right ventricle (n=43, 30%). Of the 146 patients, 101 (69%) had significant morbidity or mortality: 86 (59%) were diagnosed with arrhythmia, 18 (12%) died, and 11 (8%) underwent heart transplants. Frequent procedures included: Fontan revisions/cryoablation in 28 (19%), electrophysiology studies with ablation in 73 (50%), and pacemakers in 53 (36%). Of the arrhythmia diagnoses, 57 (64%) were atrial tachyarrhythmias. RV-PA Fontan procedures were associated with significantly more atrial arrhythmia than all other Fontan types (70% vs. 30%; p&lt;0.01). There was no statistical difference in occurrence of atrial arrhythmia in adults with LT Versus EC Fontans (p=0.3). While patients who had undergone RV-PA and Bjork Fontans were older with median age 34 years, there was no significant difference in age between LT and EC (median 24.0 and 24.5). DISCUSSION/SIGNIFICANCE OF IMPACT: Adult survivors of the Fontan procedure suffer from significant morbidity and mortality. The single most prevalent morbidity is atrial arrhythmia. We conclude that RV-PA Fontans, now obsolete, have the highest prevalence of arrhythmia and that there is no difference in arrhythmia burden between LT and EC Fontans. Given the high prevalence of morbidity and mortality in this population, it is imperative that they be followed by cardiologists with expertise in congenital heart disease.

Influence of Genotype on Structural Atrial Abnormalities and Atrial Fibrillation or Flutter in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is associated with desmosomal mutations. Although desmosomal disruption affects both ventricles and atria, little is known about atrial involvement in ARVD/C. To describe the extent and clinical significance of structural atrial involvement and atrial arrhythmias (AA) in ARVD/C stratified by genotype. We included 71 patients who met ARVD/C Task Force Criteria and underwent cardiac magnetic resonance (CMR) imaging and molecular genetic analysis. Indexed atrial end-diastolic volume and area-length-ejection-fraction (ALEF) were evaluated on CMR and compared to controls with idiopathic right ventricular outflow tract tachycardia (n = 40). The primary outcome was occurrence of AA (atrial fibrillation or atrial flutter) during follow-up, recorded by 12-lead ECG, Holter monitoring or implantable cardioverter defibrillator (ICD) interrogation. Patients harbored a desmosomal plakophilin-2 (PKP2) (n = 37) or nondesmosomal phospholamban (PLN) (n = 14) mutation. In 20 subjects, no pathogenic mutation was identified. Compared to controls, right atrial (RA) volumes were reduced in PKP2 (P = 0.002) and comparable in PLN (P = 0.441) mutation carriers. In patients with no mutation identified, RA (P = 0.011) and left atrial (P = 0.034) volumes were increased. Bi-atrial ALEF showed no significant difference between the groups. AA were experienced by 27% of patients and occurred equally among PKP2 (30%) and no mutation identified patients (30%), but less among PLN mutation carriers (14%). Genotype influences atrial volume and occurrence of AA in ARVD/C. While the incidence of AA is similar in PKP2 mutation carriers and patients with no mutation identified, PKP2 mutation carriers have significantly smaller atria. This suggests a different arrhythmogenic mechanism.

Outcomes following the implantation of cardioverter-defibrillator for primary prevention in transposition of the great arteries after intra-atrial baffle repair: a single-centre experience.

Patients with D-loop transposition of the great arteries (D-TGA) status post intra-atrial baffling are at an increased risk for sudden cardiac arrest. The benefit of primary implantable cardioverter-defibrillator (ICD) implantation in these patients is questionable due to high burden of adverse events. We aimed to evaluate the incidence and causes of all types of device shocks, as well as of device-related complications among patients with D-TGA implanted with ICDs for primary prevention. Retrospective analysis of all patients with D-TGA who underwent atrial switch procedure and ICD implantation for primary prevention. Eighteen patients (83% males) were identified. Average age at atrial switch was 2.5 years (range 0.1-17) and at ICD implantation 26 years (15-41). During a median follow-up of 4 years, 10 patients (55%) received shocks for non-ventricular arrhythmic events, whereas 1 patient was shocked for ventricular tachycardia, for an annual rate of shock delivery of 7.1%. The most common cause for shock delivery was the occurrence of atrial arrhythmias, mostly in the form of atrial flutter. Elevated systemic ventricular end-diastolic pressures were found to be associated with an increased risk for inappropriate shocks. Five patients (28%) required lead extraction and three required generator change due to device recalls during follow-up. Atrial arrhythmias were the most common cause for ICD shocks in a primary prevention population, while ventricular tachycardia was infrequent. The association between elevated end-diastolic pressures and the occurrence of arrhythmias demonstrates the close mechano-electrical relationship in D-TGA and may be an important predictor of arrhythmic events.