Presence Of Atrial Arrhythmias Research Articles

Abstract 16625: Frameshift Mutation in LMNA Gene Causes Atrial Arrhythmogenesis via Epigenetic Inhibition of KCNA5 Expression

Introduction: Cardiolaminopathy is a genetic heart disease caused by LMNA mutations, often leading to atrial tachycardia, AV block, ventricular arrhythmia and eventually dilated cardiomyopathy. While performing WES on pedigrees with primary atrial myopathy, we identified that nearly half of them possess mutations on the LMNA gene. However, previous studies on laminopathy have mainly focused on ventricular lesions, leaving the mechanism of how LMNA mutation leads to the atrial myopathy yet to be elucidated. Methods: To better understand the role of the LMNA gene in atrial cardiomyopathy, we employed the CRISPR/Cas9 to establish a heterozygous KI mouse model with a frameshift mutation ( lmna c.1249delA, p.K418Sfs) identified from a pedigree of atrial cardiomyopathy. Results: The heterozygous mice displayed progressive and spontaneous atrial arrhythmia, along with increased fibrosis, without any involvement of the ventricles, which was consistent with the affected individuals in the pedigree. Electrophysiological measurements showed prolonged APD90, an increased occurrence of EAD events, and augmented atrial conduction heterogeneity compared to the control mice. Bioinformatics analysis of mouse atrium indicated KCNA5 , which specifically expressed in the atrium, was significantly down-regulated. This reduction was further corroborated through Western blotting and immunofluorescence. Additionally, ChIP qPCR analysis revealed an enhanced binding of KCNA5 with lamin A/C and reduced binding with the promoting histone H3K4me3 in the mutant atrium. Notably, the presence of atrial arrhythmia and the downregulation of KCNA5 were also observed in another lmna frameshift mutation mouse model, suggesting that these mechanisms may be universal in LMNA -related atrial cardiomyopathy. Conclusions: Laminopathy causing atrial cardiomyopathy has long been underestimated. Our study validates the pathogenicity of LMNA frameshift mutation for the atrium and highlights epigenetic changes leading to KCNA5 expression downregulation and consequential phenotypic alterations. These results broaden the current knowledge of laminopathy beyond its previous emphasis on ventricular lesions, offering potential therapeutic targets for the disease.

979 ARRHYTHMOGENIC CARDIOMYOPATHY: LONG-TERM FOLLOW-UP OF A PROSPECTIVE MULTICENTRE COHORT

Abstract Background Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disease characterized by fibro-fatty replacement of predominantly right, left or biventricular myocardium. The clinical course of ACM is characterized by high risk of abrupt arrhythmic ventricular events, potentially leading to sudden cardiac death (SCD), and by progressive impairment of biventricular systolic function, which may lead to heart failure (HF)-related death, with an estimated overall yearly mortality ranging from 0.08% to 3.6% among studies. Aim This study sought to assess the long-term follow-up of a cohort of ACM patients from the Piedmont region of Italy, specifically evaluating the cumulative incidence of SCD, HF-related death and heart transplantat. Methods Patients who received a definite ACM diagnosis according to the latest available International Task Force Criteria (ITFC) at three different institutions in Piedmont (“Cardinal Massaia” Hospital of Asti, “Azienda Ospedaliera Ordine Mauriziano” of Turin and “Città della Salute e della Scienza” Hospital of Turin) between 1982 and March 2022 were prospectively enrolled. Clinical, electrocardiographic and imaging data were collected at baseline and during follow-up. The occurrence of two coprimary composite endpoints was evaluated, namely the arrhythmic composite endpoint of SCD or aborted SCD and the HF-related composite endpoint, including heart transplant for end-stage HF or cardiac death due to pump failure. Independent predictors of the coprimary composite endpoints were also assessed by means of multivariable analysis. Results The overall population included 97 patients; mean age at diagnosis was 38.2 ± 14.3 years; 66 (68%) patients were male. Median follow-up was 12.9 years (interquartile range 0-38 years). The composite arrhythmic outcome occurred in 10 (10.3%) patients and the composite HF outcome occurred in 13 (13.5%) patients. Overall, 19 (19.6%) patients died: seven (37%) patients died from SCD, four (21%) patients died of end-stage HF and eight (42%) patients died from non-cardiac causes. The cumulative incidence of cardiac death was 1.65% per year. Aborted SCD occurred in 3 (3%) patients, sustained ventricular tachycardias in 51 (52%), HF in 17 (18%) and atrial fibrillation in 21 (22%); forty-seven (48%) underwent an implantable cardioverter defibrillator implantation (ICD) and 8 (8%) patients underwent heart transplant. Mean interval between ACM diagnosis and heart transplant was 130.4 ± 75.3 months. At univariable analysis, the presence at baseline of terminal activation duration (TAD) ≥ 55 ms on surface electrocardiogram (p value 0.037), right atrium dilatation at transthoracic echocardiography (p value 0.021) and cardiac magnetic resonance imaging (p value 0.031) and palpitations as main clinical presentation (p value 0.017) were associated with the occurrence of the arrhythmic endpoint. At multivariable analysis, baseline TAD ≥ 55 msec was the only predictor of the composite arrhythmic endpoint (odds ratio 12.5, 95% confidence interval 1.29 to 121.26, p value 0.029). At univariable analysis, the presence of epsilon waves (p value 0.017), TAD ≥ 55 ms (p value 0.020) and T wave inversion in leads V1-V3 (p value 0.022) on surface electrocardiogram, HF (p value 0.018) or atrial arrhythmias (p value < 0.001) at presentation and New York Heart Association (NYHA) class III to IV at diagnosis (p value 0.002) were significantly associated with the composite HF-related endpoint. At multivariable analysis, the presence of atrial arrhythmias at presentation was the only predictor of the HF-related composite endpoint (odds ratio 10.8, 95% confidence interval 1.29 to 90.32, p value 0.028). Conclusions In this multicenter cohort of 97 ACM patients, the cumulative incidence of cardiac death was 1.65% per year at long-term follow-up. Arrhythmic death accounted for the majority of cardiac fatal events (64%), confirming the peculiar predisposition to SCD of ACM patients. Evolution towards end-stage HF and cardiac death due to pump failure were common.

Abstract 14185: Higher Rates of Heart Failure Hospitalizations for V142I ATTR-CM Patients With Atrial Arrhythmias and Conduction Disease

Introduction: TTR cardiac amyloidosis (ATTR-CM) is a progressive, infiltrative cardiomyopathy that is characterized by the deposition of amyloid fibril extracellularly in the myocardium. Patients with ATTR-CM are known to be at higher risk for arrhythmias and conduction disease, likely due to changes in the cardiac anatomy and disruption of the conduction system by amyloid fibrils. Our study aims to determine whether presence of an arrhythmia or conduction disease is associated with mortality and heart failure hospitalizations in patients with ATTR-CM and V142I mutation. Hypothesis: Patients with arrhythmia or conduction disease will have higher rates of heart failure hospitalizations (HFH) and mortality than those without it. Methods: We conducted a retrospective chart review of patients diagnosed with ATTR-CM with V142I mutations enrolled in Emory University's Cardiac Amyloidosis Clinic between January 2014 and April 2022. Kaplan-Meier (KM) curves stratified by presence of atrial arrhythmia, ventricular arrhythmia, or conduction disease were generated for mortality and first HFH within 2 years of initial diagnosis. Log-rank test was used to compare KM curves. A p-value < 0.05 was considered significant. Results: 111 patients were identified to have ATTR-CM with V142I mutation. 51.4% (57) of the patients had an atrial arrhythmia (fibrillation or flutter), 46.8% (52) had conduction abnormalities (defined as second or third degree heart block). 44.1% (49) had ventricular arrhythmias (including NSVT, sustained VT, and/or VF). Patients who had atrial arrhythmia and conduction disease were more likely to have HFH within 2 years compared to those who did not (p = 0.0011, p = 0.044 respectively). Patients with atrial arrhythmia, ventricular arrhythmia, or conduction disease were not at higher risk of mortality within 2 years (p=0.21, p=0.71, p=0.66 respectively). Conclusions: For patients with ATTR-CM with V142I mutation, atrial arrhythmia and conduction disease were risk factors for HFH within 2 years. Atrial and ventricular arrhythmia and conduction disease were not associated with higher mortality within 2 years.

Comparison of DOS and Windows version of the MwPharm - a pharmacokinetic software for PK/PD monitoring of digoxin

Background and objectives: Digoxin is the oldest drug indicated for the treatment of systolic heart failure (HF). It is also useful in controlling excessive ventricular rate in the presence of atrial arrhythmias. Therapeutic drug monitoring (TDM) has become an integral part of its prescription, allowing to optimize therapy and to reduce the incidence of toxicity. Since 1991, the MwPharm software package (Mediware, Groningen, The Netherlands / Prague, Czech Republic) has been used for pharmacokinetic and pharmacodynamic (PK/PD) modelling in TDM, including digoxin. First Windows version with a broader spectrum was released in 2014, as a reaction of worse support of the DOS background on later versions of Windows. After its release, the company had decided to not develop DOS versions anymore, even though they are globally used with success. The aim of this study was to compare the usefulness of DOS and Windows version (WIN) of the MwPharm, and their prediction quality in TDM of digoxin.

Atrial arrhythmias and thromboembolic complications in adults post Fontan surgery

ObjectivePatients with Fontan surgery experience late complications in adulthood. We studied the factors associated with the development and maintenance of atrial arrhythmias and thromboembolic complications in an adult population with...

298Atrioventricular synchronous pacing in leadless ventricular pacemaker is safe and effective in patients with paroxysmal AV block and atrial arrhythmias

Abstract Funding Acknowledgements Medtronic, Inc. Background/Introduction Accelerometer (ACC)-based AV synchronous pacing by tracking atrial activity is feasible using a leadless ventricular pacemaker. Patients may experience variable AV conduction (AVC) and/or atrial arrhythmias during the lifetime of their device. ACC-based AV synchronous pacing should facilitate AVC and pace appropriately in those two common rhythms. Purpose To characterize the behavior of ACC-based AV synchronous pacing algorithms during paroxysmal AV block (AVB) and atrial arrhythmias. Methods The MARVEL2 (Micra Atrial tRacking using a Ventricular accELerometer) was a 5-hour acute study to assess the efficacy of atrial tracking with a temporarily downloaded algorithm into a Micra leadless pacemaker. Patients with a history of AVB were eligible for inclusion. The MARVEL2 algorithm included a mode-switching algorithm that switched between VDD and VVI-40 depending upon AVC status. The AVC algorithm requires 2 ventricular paces (VP) at 40 bpm out of 4 pacing cycles to switch to VDD. Results Overall, 75 patients (age 77.5 ± 11.8 years, 40% female, median time from Micra implant 9.7 months) from 12 centers worldwide were enrolled. During study procedures, 40 patients (53%) had normal sinus rhythm with complete AVB, 18 (24%) had 1:1 AVC, 5 (7%) had varying AVC status, 8 (11%) had atrial arrhythmias, and 2 other rhythms. Two patients with complete AVB had the AVC mode switch feature disabled due to an idioventricular rate >40 bpm. Among the 40 subjects with a predominant 3rd degree AVB and normal sinus function the median %VP was 99.9% compared to 0.2% among those with 1:1 AVC (Figure). In the patients with 1:1 AVC, there were 64 opportunities to AVC mode switch with 48 switching to VDI-40. In the other 16 cases (2 patients) the mode remained VDD due to sinus bradycardia varying between 40-45 bpm. High %VP was observed in 2 patients with 1:1 AVC and sinus bradycardia <40 bpm. The AVC mode switch minimized %VP (<1%) in patients with PR intervals > 300 ms (N = 2). Among patients with varying AVC, the algorithm appropriately switched to VDD when the ventricular rate was paced at 40 bpm. During infrequent AVB or AF with ventricular response >40 bpm, VVI-40 mode was maintained. In patients with AF, the ACC signal was of low amplitude and there was infrequent sensing, resulting in VP at the lower rate (50 bpm). In the one patient with atrial flutter, the ACC was intermittently detected, resulting in VP at 67 bpm (IQR 66-67 bpm). Conclusion(s) The mode switching algorithm in the MARVEL2 reduced %VP in patients with 1:1 AVC and appropriately switched to VDD during complete AVB. If greater AV synchrony or rate support is required, disabling the AVC algorithm may be appropriate for low grade AVB or idioventricular rhythms. In the presence of atrial arrhythmias, the algorithm paced near the lower rate. Abstract Figure. Distribution of VP% by heart rhythm

Abstract 13086: The Impact of Glycemic Variability on Mortality in Patients With Diabetes Hospitalized With Acute Heart Failure

Hypothesis: Acute heart failure (AHF) in patients with diabetes is associated with increased mortality, however the impact of glycemic variability is unclear. Methods: We screened our database within 1 year to identify patients with AHF and diabetes. The glucose variables of interest were: hypoglycemia (glucose blood level <70 mg/dl); glycated haemoglobin (HbA1c); admission glycemia; mean glycemia index (MGI), defined as mean of all fasting glucose blood levels measured during hospitalization; and glycemic lability index (GLI), calculated by a validated formula, using successive glucose measurements and times between measurements. All these parameters were added to conventional potential prognostic markers: left ventricular ejection fraction (LVEF), admission systolic/diastolic blood pressure (SBP/DBP) and mean of all measurements during hospitalization (SBPm/DBPm), presence of respiratory failure, mechanical ventilation, atrial arrhythmias, troponin I and NTproBNP values, admission renal function (GRF) and mean of all measurements during hospitalization (GRFm). The outcome was in-hospital mortality. Results: 113 patients (70±10yrs, 56% men) were identified. 13 patients (12%) died. Admission glycemia (341±81 vs 228±105 mg/dl), MGI (287±108 vs 164±38 mg/dl), GLI (18161±24774 vs 6408±18108 mg/dl 2 /h) were higher in non-survivors, whereas LVEF (22±12 vs 34±12%), SBP (102±43 vs 154±43 mmHg), SBPm (92±37vs127±25 mmHg), DBPm (76±11vs.56±24), and GRFm (37±22 vs 57±27 ml/min) were lower (all p<0.01). Presence of atrial arrhythmias, respiratory failure, but not mechanical ventilation was higher in non-survivors; hypoglicemia, HbA1c, troponin I, NTproBNP, and GRF were similar. Only MGI≥188 mg/dl and LVEF≤28% were independently associated with in-hospital mortality (Figure). Conclusions: Parameters of glycemic variability and LVEF are associated with in-hospital mortality in patients with diabetes hospitalized with AHF.

Brugada syndrome in the young: an assessment of risk factors predicting future events.

To investigate the clinical characteristics, prognoses, and presence of risk factors in young patients with Brugada syndrome (BS). A consecutive cohort of 128 young BS patients (≤25 years old at diagnosis) was analysed. Eighty-eight patients (69%) were asymptomatic, whereas 40 (31%) presented with clinical manifestations of BS. Markers of prognosis and risk were identified upon comparison of these two groups. A history of malignant syncope was strong predictors of ventricular arrhythmic events. Family history of sudden cardiac death (SCD) and mutations in the SCN5A gene did not associate with increased risk. Symptomatic patients presented with significantly abnormal baseline electrical characteristics when compared with the asymptomatic cohort, including spontaneous type I electrocardiograph (ECG) patterns, sinus node dysfunction (SND), first-degree atrioventricular (AV) block, and intra-ventricular conduction delay. The symptomatic group more frequently exhibited atrial arrhythmias. Electrophysiological studies resulted positive more frequently in symptomatic patients, but no risk association for future events could be determined. During the follow-up period (mean: 65 months), 10 arrhythmic events occurred in nine symptomatic patients (event rate: 4.5% per year). No events occurred in the asymptomatic group. Variables significantly associated with arrhythmic events during follow-up were presence of symptoms at diagnosis and spontaneous type I ECG. The presence of atrial arrhythmias and conduction abnormalities was also associated with the risk of arrhythmic events during follow-up. Symptomatic BS in the young age is a rare but malignant condition that can manifest with a spectrum of electrical abnormalities (i.e. SND, atrial tachycardias, AV block, and infra-nodal conduction delay) and result in the extreme cases in lethal arrhythmic events and SCD.

PROLONGED P WAVE DURATION IS NOT ASSOCIATED WITH SUBCLINICAL ATRIAL ARRHYTHMIAS IN MIDDLE-AGED ENDURANCE ATHLETES

PROLONGED P WAVE DURATION IS NOT ASSOCIATED WITH SUBCLINICAL ATRIAL ARRHYTHMIAS IN MIDDLE-AGED ENDURANCE ATHLETES

Is IBD in the Elderly a Manifestation of Ischemia Precipitated by Underlying Cardiac Arrhythmias?

Purpose: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the bowel, comprising ulcerative colitis (UC) and Crohn's disease (CD). It is thought that IBD has a bimodal peak of incidence, often occurring in the 2nd decade of life and again after the 5th decade of life; interestingly, over 15% of atrial arrhythmias are also estimated as being diagnosed over age 65. While both UC and CD have distinct characteristics, their pathogenesis remains poorly understood. We questioned whether late-onset IBD was actually a marker of vascular ischemic disease rather than a primary disease of the intestine, and whether the focus of attention should be on underlying cardiovascular co-morbidities that predispose these patients to ischemic events. The goal of this study was 1.) to determine the prevalence of atrial arrhythmias in patients diagnosed with IBD, 2.) to compare the rates in CD and UC, 3.) to compare the rates in late-onset IBD to those with early-onset IBD, and 4.) to determine whether the presence of atrial arrhythmias in IBD influences long-term survival. Methods: We reviewed in detail the medical records of all patients at Hines VA who underwent a complete GI investigation between 1996 and 2011, and were diagnosed with UC or CD. All IBD patients had biopsyproven colitis. Late-onset and early-onset was defined as IBD diagnosed after and before age 50, respectively. Results: A total of 447 patients were diagnosed with IBD during the 15-year study period. Of the 447 pts, 11% had documented atrial arrhythmias, of which: 9% of CD and 13% of UC patients (P=NS). Atrial arrhythmias were present in 17% of the late-onset IBD patients, compared to 5% of the earlyonset IBD patients (Diff: 12%; CI: 6% to 18%). IBD patients with atrial arrhythmias had significantly worse survivals than those without (at 33 years post diagnosis, 50% vs. 80% [HR: 2.5; CI: 1.2 to 5.0]). Conclusion: Compared to IBD patients without atrial arrhythmias, the IBD cohort with them have a significantly increased mortality that may not be due to underlying bowel disease. “Late-onset IBD” in patients with concurrent atrial arrhythmias may actually serve as a warning for underlying cardiovascular disease.Figure

Arrhythmogenic right ventricular cardiomyopathy: Arrhythmias upstream and downstream

By using a large research registry, Camm et al examined the prevalence and characteristics of atrial arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and their relationship to demographics and disease severity. The results are reported in the current issue of the journal. All patients had been genotyped and fulfilled the 2010 Task Force Criteria. Atrial arrhythmia was defined as a narrow complex arrhythmia lasting at least 30 seconds, and it was subclassified into atrial fibrillation, atrial flutter, and other atrial arrhythmias. More than 90% (230 of 248) of the studied patients had an implantable cardioverter-defibrillator (ICD). In brief, 14% (35 of 248) of the studied patients exhibited atrial arrhythmia during follow-up (median 5.8 years). Atrial fibrillation was the most common arrhythmia. Only a third of the arrhythmic episodes were detected by using conventional electrocardiography (ECG; the remainder being detected through ICD interrogation or Holter studies). The authors conclude that atrial arrhythmias are common in patients with ARVC, that atrial arrhythmias occur in younger patients compared to the general population, and that the presence of atrial arrhythmias was associated with atrial enlargement, increasing age and male sex. Atrial arrhythmias have previously been reported with ARVC. The primary contribution of this article is the large number of patients (n = 248) in the registry and the relatively unselected population. The first data indicating that atrial arrhythmia occasionally may be a part of the

Abstract 351: Downregulation of Connexin43 by MicroRNA-130a Results in Cardiac Arrhythmias

MicroRNAs (miRs) are endogenous ~22 nucleotide RNA molecules that are now recognized as critical regulators of diverse physiological and pathological processes; however, studies of miRs and arrhythmogenesis remain sparse. Connexin43 (Cx43), a major cardiac gap junction protein, is critical for maintaining normal cardiac electrical conduction. One aspect of arrhythmia pathogenesis that has elicited great interest has been changes in Cx43 expression. Computational analysis of messenger RNAs predicted Cx43 to be a target for miR-130a. We hypothesized that overexpression of miR-130a in adult cardiomyocytes would result in cardiac arrhythmias. To study this, we used an inducible (tetracycline-off) bigenic system to study miR-130a overexpression in the adult mouse heart. 12 weeks after induction of miR-130a, 100% (16/16) of transgenic mice demonstrated a loss of sinus rhythm and irregular ventricular activity suggestive of atrial fibrillation on surface electrocardiograms (ECG). Nonsustained ventricular tachycardia was also observed during ECG recordings. Atrial contractions could not be detected by pulse wave Doppler. Intracardiac electrocardiography confirmed the presence of atrial arrhythmias. Western blot analysis demonstrated a 90% reduction in Cx43 levels and immunofluorescent staining confirmed a near complete loss of Cx43 in transgenic compared to littermate control hearts (n=12). Morphology of the intercalated disc was evaluated by electron microscopy and showed a loss of gap junctions in transgenic hearts. To validate Cx43 as a direct target of miR-130a, we performed in vitro target assays in 3T3 fibroblasts, known to express miR-130a. Using a luciferase reporter fused to the 3’UTR of Cx43 compared to a control (SV40) 3’UTR, we found a 55% ± 6% reduction in luciferase activity with the Cx43 3’UTR (p<0.01, n=9). Addition of an antisense miR-130a inhibitor resulted in a dose dependent loss of inhibitory activity of the Cx43 3’UTR reporter, with no changes seen in the control vector. In conclusion, we have identified an unappreciated role of miR-130a as a direct regulator of Cx43. Overexpression of miR-130a results in the development of a variety of important cardiac arrhythmias including atrial fibrillation and ventricular tachycardia.

Determinants of reduced tricuspid annular plane systolic excursion in patients with severe systolic left ventricular dysfunction

Objective Right ventricular (RV) dysfunction is associated with poor exercise tolerance and prognosis, regardless of left ventricular (LV) function. Tricuspid annular plane systolic excursion (TAPSE) is a non-invasive parameter of RV longitudinal function which can predict outcome in heart failure (HF) patients (pts). Our aim was to investigate the relation of TAPSE to clinical and echocardiographic parameters in severe LV dysfunction.Methods and results The study included 119 pts with non-ischaemic dilated cardiomyopathy (n = 46) and ischaemic heart disease (n = 73) in stable HF with severe LV systolic dysfunction (LV ejection fraction (EF) < 30%). In pts with diff erent LV dysfunction severity the higher NYHA class correlated with lower TAPSE dimensions: NYHA class IV 12.7 ± 2.9 mm vs. NYHA class III 15.9 ± 4.2 mm and NYHA class II 18.8 ± 4.2 mm, P< 0.001. The presence of atrial arrhythmias in 16% of pts was related to lower values of TAPSE (12.9 ± 3.6 mm vs. 15.4 ± 4.2 mm, P< 0.05). Pts with non-ischaemic HF aetiology were found to have lower values of TAPSE compared to ischaemic aetiology (12.5 ± 2.8 mm vs. 16.6 ± 4.1 mm, P= 0.001) and increased odds of low TAPSE (≤ 14 mm) – odds ratio (OR) [95% confi dence interval] = 9.8 [3.8-25.6], P< 0.001. Multivariate analysis revealed that LVEF, deceleration time (DT) of early mitral infl ow E wave and the RV end-diastolic diameter are independent determinants of reduced TAPSE (≤ 14 mm) in pts with severe LV systolic dysfunction.Conclusion The lower TAPSE values are related to higher NYHA functional class, presence of atrial arrhythmias and non-ischaemic aetiology in HF pts. The LVEF, DT of LV fi lling and RV end-diastolic diameter are independent predictors of reduced TAPSE (≤ 14 mm) in pts with severe systolic LV dysfunction.

Predictive model for late atrial arrhythmia after closure of an atrial septal defect

ObjectivesTo develop a quantitative event-free prediction model of late atrial arrhythmia after atrial septal defect (ASD) repair. BackgroundThe clinical management of ASD is driven by risk factors that determine the occurrence of late atrial arrhythmia. MethodsData from ASD type secundum patients, included in the Belgian Congenital Heart Disease Registry, were analyzed. Based on review of the literature, age at repair, gender, pulmonary hypertension, atrial arrhythmia before and within one month after repair were included in the model. Using Cox-regression analysis, a weighted risk score was derived, which was validated using the Brier score. ResultsA total of 155 patients (117 women; median age at follow-up 53.9years, range 18.0–78.8) having 349 follow-up years was included. Thirty-nine patients (25.2%) presented with late atrial arrhythmia. Multivariate analysis showed that a mPAP≥25mmHg (HR 4.39; 95%CI 2.17–9.09; P<0.0001), the presence of atrial arrhythmia before (HR 3.52; 95%CI 1.75–7.14; P=0.002) and≤1month after repair (HR 6.62; 95%CI 2.38–20.00; P<0.0001) and gender (HR 2.18 95%CI 1.11–4.35) were associated with late atrial arrhythmia. A risk score (0 to 28 points) to predict atrial arrhythmia free survival was derived for follow-up times ranging from one to 5years. Mean Brier score for the model was 0.10. ConclusionsWe formulated a well validated risk model to predict arrhythmia-free survival in ASD patients undergoing ASD repair. Further research is needed whether this model can be used for individual clinical risk stratification and whether the model can be adapted for application in other congenital heart defects.

Identifying High Risk in Adults With Congenital Heart Disease and Atrial Arrhythmias

Atrial arrhythmias are associated with an increased mortality risk in adults with congenital heart disease (CHD). However, little is known about risk stratification in the specific group of adult patients with CHD and atrial arrhythmias. We sought to identify predictors of mortality in adult with CHD and atrial arrhythmias and to establish a risk score. The study involved 378 adult patients with CHD (mean age 39 ± 13 years) and atrial arrhythmias who had serial follow-up in a tertiary referral center from 1999 through 2009. During a median follow-up of 5.2 years, there were 40 deaths (11%). Overall mortality rate was 2.0% per patient-year. Common modes of death included heart failure-related death (35%), sudden cardiac death (20%), and perioperative death (18%). Independent predictors of mortality were poor functional class (hazard ratio 3.69, 95% confidence interval [CI] 1.69 to 8.03, p = 0.001), single-ventricle physiology (hazard ratio 3.33, 95% CI 1.51 to 7.35, p = 0.003), pulmonary hypertension (hazard ratio 2.96, 95% CI 1.41 to 6.19, p = 0.004), and valvular heart disease (hazard ratio 2.73, 95% CI 1.33 to 5.59, p = 0.006). A risk score was constructed using these predictors in which patients were assigned 1 point for the presence of each risk factor. Mortality rates in the low-risk (no risk factor), moderate-risk (1 risk factor), and high-risk (>1 risk factor) groups were 0.5%, 1.9%, and 6.5% per patient-year, respectively (log-rank p <0.001). In conclusion, in adult with CHD and atrial arrhythmias specific clinical variables identify patients at high risk for death. Importantly, the absence of any of these risk factors is associated with an excellent survival despite the presence of atrial arrhythmias.

The importance of pulmonary artery pressures on late atrial arrhythmia in transcatheter and surgically closed ASD type secundum

AimsAtrial fibrillation and flutter remain an important cause of morbidity in adults with atrial septal defect (ASD). This study aimed at investigating predictors for late (≥1month after repair) atrial arrhythmia. MethodsPatients who underwent ASD closure after the age of 18years, were selected through the databases of three medical centres in Belgium. Preprocedural, periprocedural and follow-up data were extracted. Univariate and multivariate Cox-regression analysis was performed. Kaplan–Meier analysis was performed for any independent predictor of late atrial arrhythmia. ResultsA total of 155 patients (38 men and 117 women) was included. Twenty-four patients (median age 48.3years, range 19.9–79.8) underwent surgical and 131 (median age 57.6years, range 18.2–86.9) underwent transcatheter closure. Thirty-nine patients (25.2%) presented with late atrial arrhythmia. Male gender (P=0.008), creatinine (P=0.002), atrial arrhythmia before (P<0.0001) and within 1month after repair (P=0.001) and a mean pulmonary artery pressure (mPAP) ≥25mmHg (P<0.0001) correlated with late atrial arrhythmia in univariate Cox-regression analysis. Multivariate analysis showed that mPAP ≥25mmHg (HR 3.72; 95%CI 1.82–7.59; P<0.0001) and the presence of atrial arrhythmia before (HR 3.22; 95%CI 1.56–6.66; P=0.002) and within 1month after repair (HR 2.08; 95%CI 2.08–15.92; P=0.001) were predictive of late atrial arrhythmia. Kaplan–Meier analysis showed that patients with a mPAP ≥25mmHg had a higher risk at developing late atrial arrhythmia (P<0.0001). ConclusionIn patients with ASD type secundum, a mPAP ≥25mmHg is an independent predictor of late atrial arrhythmia. The presence of pulmonary hypertension before repair should raise awareness for atrial arrhythmias and may be used to guide therapy.