Left Atrial Area Research Articles

Left atrial strain after paroxysmal atrial fibrillation linac-based cardiac radioablation in elderly population.

Catheter ablation of atrial fibrillation (AF) may increase the risk of complication in aged patients. Stereotactic arrhythmia radioablation (STAR) is a non-invasive therapeutic alternative for cardiac arrhythmia. This sub-study evaluated left atrial strain (LAS) in elderly AF patients underwent STAR. Symptomatic paroxysmal AF patients aged > 70 years, with antiarrhythmic drugs failure or intolerance, enrolled in a phase II trial that have demonstrated the feasibility of LINAC-based STAR (total dose of 25Gy single fraction delivered in 3min), performed a 15-day electrocardiogram Holter monitoring to detect AF episodes (≥ 30s) and an echocardiographic LAS evaluation before and after STAR (at 1-, 3-, 6- and 12-month). Out 18 patients underwent STAR in the trial, 16 (7 males, 78 ± 5 years) completed the follow-up for LAS study. No baseline difference in echocardiographic and LAS parameters was observed between the 9 patients with AF recurrence during follow-up and those who maintained sinus rhythm. At 6- and 12-month after STAR, LAS reservoir was lower in patients with AF episodes than those without (respectively, p = 0.039 and p = 0.001). Values of left atrial area and volume as well as LAS conduit and contractile phase were not statistically significant different by patient's outcome across evaluations. Although no baseline LAS parameter before STAR seems predict AF recurrence after treatment in elderly patients, lower values of reservoir phase were observed during follow-up in those experiencing AF episodes. More research is needed to better assess the value of LAS monitoring in paroxysmal AF patients underwent Stereotactic cardiac radioablation.

Left Ventricular Diastolic Function in Children with Atrial Septal Defects Improves After Closure by Means of Increased Hydraulic Force

AbstractHydraulic force aids diastolic filling of the left ventricle (LV) by facilitating basal movement of the atrioventricular plane. The short-axis atrioventricular area difference (AVAD) determines direction and magnitude of this force. Patients with atrial septal defect (ASD) have reduced LV filling due to the left-to-right shunt across the atrial septum and thus potentially altered hydraulic force. The aims were therefore to use cardiac magnetic resonance images to assess whether AVAD and thus the hydraulic force differ in children with ASD compared to healthy children, and if it improves after ASD closure. Twenty-two children with ASD underwent cardiac magnetic resonance before ASD closure. Of these 22 children, 17 of them repeated their examination also after ASD closure. Twelve controls were included. Left atrial and ventricular areas were delineated in short-axis images, and AVAD was defined as the largest ventricular area minus the largest atrial area at each time frame and normalized to body height (AVADi). At end diastole AVADi was positive in all participants, suggesting a force acting towards the atrium assisting the diastolic movement of the atrioventricular plane; however, lower in children both before (6.3 cm2/m [5.2–8.0]; p < 0.0001) and after ASD closure (8.7 cm2/m [6.6–8.5]; p = 0.0003) compared to controls (12.2 cm2/m [11.3–13.9]). Left ventricular diastolic function improves after ASD closure in children by means of improved hydraulic force assessed by AVAD. Although AVADi improved after ASD closure, it was still lower than in controls, indicating diastolic abnormality even after ASD closure. In patients where AVADi is low, ASD closure may help avoid diastolic function deterioration and improve outcome. This could likely be important also in patients with small shunt volumes, especially if they are younger, who currently do not undergo ASD closure. Changes in clinical routine may be considered pending larger outcome studies.

Left atrial low voltage areas and heart failure in patients with atrial fibrillation: Implication of the atrial myopathy.

Atrial fibrillation (AF) and heart failure (HF) affect each other and are often co-morbid. The fact that HF development is not uncommon even after ablation suggests that we need a deeper understanding of the pathology of these conditions. Atrial myocardial degeneration is an underlying factor in AF patients and may be associated with HF development after ablation. This study aimed to investigate the impact of low-voltage areas (LVAs) on HF prognosis after AF ablation. This observational study included 1481 consecutive patients undergoing initial ablation for AF. Left atrial LVAs were defined as regions with a bipolar peak-to-peak voltage of <0.50mV. Patients were divided into three groups: no LVA (LVA size indexed to body surface area <3cm2/m2, n=1129), small LVA (3-10cm2/m2, n=217), and extensive LVA (≥10cm2/m2, n=135). A composite endpoint of HF hospitalization or death occurred more frequently in patients with larger LVAs (3.3% vs. 6.5% vs. 13.3%, P<0.0001) during the 3-year follow up period. The extent of LVAs was independently related to the risk of the composite endpoint with an adjusted hazard ratio of 1.55 (95% confidence interval, 1.16-2.10) for each additional step of LVA classification (P=0.003). LVA presence and its extent were associated with frequent HF hospitalization and death. Underlying atrial myopathy appears to define a poor HF prognosis after AF ablation.

A novel endocardial activation–derived predictor for focal paraseptal atrial tachycardias: Evidence from a multicenter cohort study

BackgroundThe electrocardiogram-based algorithm for predicting paraseptal atrial tachycardia (PSAT) is limited by the significant overlaps in P-wave morphology originating from various paraseptal sites. ObjectivesThe goals of this study were to investigate the endocardial activation characteristics of PSAT and to seek an endocardial activation–derived predictor for the ablation site. MethodsForty-four patients [11 men (25%); mean age 62.6 ± 14.7 years] with PSAT ablation in 4 tertiary medical centers were assigned to 3 groups according to the ablation site: right atrial (RA) para-Hisian region (group 1, n = 10), noncoronary cusp (NCC) (group 2, n = 13), and left atrial (LA) paraseptal area (group 3, n = 21). Multiple-chamber activation mapping was performed guided by a 3-dimensional navigation system. The discrepancies in the earliest activation time between 2 of 3 chambers (ΔRA-LA, ΔRA-NCC, and ΔLA-NCC) were calculated in each group and used for pairwise comparisons. ResultsThere was a significant difference in ΔRA-LA, ΔRA-NCC, and ΔLA-NCC among the 3 groups. ΔRA-LA was the only parameter that could consistently predict the ablation site of PSAT with good accuracy (area under the curve 1.000, sensitivity 100% and specificity 100%, and cutoff value 7 ms for predicting right para-Hisian or NCC ablation; area under the curve 0.974, sensitivity 92.3% and specificity 95.2%, and cutoff value −4 ms for predicting NCC or left paraseptal ablation). Based on 2 cutoff values, a 2-step algorithm was developed to predict the ablation site of PSAT with a positive predictive value of 95.4% and a negative predictive value of 97.0%. ConclusionΔRA-LA is a useful endocardial activation–derived parameter for predicting the successful ablation site of PSAT.

Female Alms1-deficient mice develop echocardiographic features of adult but not infantile Alström syndrome cardiomyopathy.

Alström syndrome (AS), a multisystem disorder caused by biallelic ALMS1 mutations, features major early morbidity and mortality due to cardiac complications. The latter are biphasic, including infantile dilated cardiomyopathy and distinct adult-onset cardiomyopathy, and poorly understood. We assessed cardiac function of Alms1 knockout (KO) mice by echocardiography. Cardiac function was unaltered in Alms1 global KO mice of both sexes at postnatal day 15 (P15) and 8 weeks. At 23 weeks, female - but not male - KO mice showed increased left atrial area and decreased isovolumic relaxation time, consistent with early restrictive cardiomyopathy, as well as reduced ejection fraction. No histological or transcriptional changes were seen in myocardium of 23-week-old female Alms1 global KO mice. Female mice with Pdgfra-Cre-driven Alms1 deletion in cardiac fibroblasts and in a small proportion of cardiomyocytes did not recapitulate the phenotype of global KO at 23 weeks. In conclusion, only female Alms1-deficient adult mice show echocardiographic evidence of cardiac dysfunction, consistent with the cardiomyopathy of AS. The explanation for sexual dimorphism remains unclear but might involve metabolic or endocrine differences between sexes.

Role of NOD1 in atrial myopathy associated with heart failure

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Funding: Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (ISCIII [PI17/01344 and PI20/01482]), Ministry of Education (FPU19/01973), SEC, Proyecto Traslacional 2019, FEDER, FSE, CIBER-CV, a network funded by ISCIII Introduction Heart failure (HF) is a complex syndrome that constitutes one of the leading causes of cardiovascular death worldwide. Although multifactorial mechanisms appear to be responsible of atrial and ventricular HF-myopathy, the innate immune system and the derived inflammatory response have gained much attention in the last years. Previous studies from our group have demonstrated that the nucleotide-binding oligomerization domain 1 (NOD1), a receptor of the innate immune system, plays a role in HF left ventricular (LV) dysfunction. However, its role in HF-atrial myopathy remains completely unknown. The main purpose of our study is to determine the role of NOD1 in human and experimental HF-atrial myopathy. Methods and Results The study was performed in two cohorts of individuals who underwent heart valve repair surgery, 51 non-failing individuals (NF) with LV ejection fraction (LVEF)&amp;gt;50% and NT-ProBNP levels&amp;lt;200pg/mL and 41 subjects with medium to severe reduced EF (HF)&amp;lt;50% and NT-ProBNP levels&amp;gt;200pg/mL. An informed consent was signed by all patients. Atrial myocardial tissue was excised from the atrial appendage and prepared for biochemical and histological studies. Echocardiography analysis showed that left and right atrial areas (LA and RA) were significantly increased in the HF group compared to NF, while LA and RA reservoir functions were significantly decreased in HF. Immunostaining demonstrated NOD1 location in atrial cardiomyocytes, being the protein levels of NOD1 and its specific adaptor RIP2 significantly increased in atrial tissue obtained from HF vs. NF. Although the prevalence of atrial fibrillation (AF) was significantly higher in the HF group compared to NF, the upregulation of NOD1 was not conditioned by the presence of AF. Similarly, pigs that underwent transverse aortic constriction (TAC) or proximal left circumflex coronary artery occlusion involving the LA branch (LAI), showed an upregulation of NOD1 pathway in atrial tissue, compared with the sham operated animals. Interestingly, an atrial upregulation of NOD1 axis was also observed in wild-type TAC mice, whereas Nod1-/- knockout mice showed a prevention in both structural and functional atrial remodelling induced by TAC, mainly by a prevention of intracellular calcium mishandling in isolated atrial cardiomyocytes. Finally, wild-type mice injected i.p. for 3 days with 3.3 mg/kg with a selective activator of NOD1, showed increased structural atrial remodelling and intracellular calcium mishandling compared to the vehicle-treated group. Conclusions Our results demonstrate that NOD1 axis is upregulated in human, swine and murine atrial failing myocardium. Genetic deletion of NOD1 prevented HF-atrial structural and functional remodelling, mainly by avoiding intracellular calcium mishandling, whereas its pharmacological activation induced atrial dilation and intracellular Ca2+ mishandling. All these data uncover NOD1 as a new player in atrial HF-remodelling.

Atrioventricular Area Difference Aids Diastolic Filling in Patients with Repaired Tetralogy of Fallot.

A hydraulic force aids diastolic filling of the left ventricle (LV) and is proportional to the difference in short-axis area between the left ventricle and atrium; the atrioventricular area difference (AVAD). Patients with repaired Tetralogy of Fallot (rToF) and pulmonary regurgitation (PR) have reduced LV filling which could lead to a negative AVAD and a hydraulic force impeding diastolic filling. The aim was to assess AVAD and to determine whether the hydraulic force aids or impedes diastolic filling in patients with rToF and PR, compared to controls. Twelve children with rToF (11.5 [9-13] years), 12 pediatric controls (10.5 [9-13] years), 12 adults with rToF (21.5 [19-27] years) and 12 adult controls (24 [21-29] years) were retrospectively included. Cine short-axis images were acquired using cardiac magnetic resonance imaging. Atrioventricular area difference was calculated as the largest left ventricular short-axis area minus the largest left atrial short-axis area at beginning of diastole and end diastole and indexed to height (AVADi). Children and adults with rToF and PR had higher AVADi (0.3 cm2/m [-1.3 to 0.8] and -0.6 [-1.5 to -0.2]) at beginning of diastole compared to controls (-2.7 cm2/m [-4.9 to -1.7], p = 0.015) and -3.3 cm2/m [-3.8 to -2.8], p = 0.017). At end diastole AVADi did not differ between patients and controls. Children and adults with rToF and pulmonary regurgitation have an atrioventricular area difference that do not differ from controls and thus a net hydraulic force that contributes to left ventricular diastolic filling, despite a small underfilled left ventricle due to pulmonary regurgitation.

Outcome after cryoballoon ablation of persistent atrial fibrillation in patients with heart failure with preserved ejection fraction versus tachycardiomyopathy: a propensity score-matched analysis

Abstract Introduction Atrial fibrillation (AF) often coexists with heart failure (HF). The aim of the study was to detect differences in outcome between patients with arrhythmia induced cardiomyopathy (AIC)/tachycardiomyopathy and HFpEF undergoing cryoballoon pulmonary vein isolation (cryo-PVI) using a propensity score-based model. Methods In this retrospective observational study, we analysed persistent AF patients with HFpEF and AIC undergoing cryoballoon ablation between 2014 and 2020. AIC was diagnosed ex juvantibus during the first year after ablation at the 3- and 12-month follow-up when LVEF recovered to &amp;gt; 50% and by more than 10% after ablation and a different aetiology for reduced LVEF was excluded. Propensity score matching was used to pair patients based on their age, sex, CHA2DS2-VASc score and left atrial (LA) area. The primary endpoint was the first documented &amp;gt; 30-s recurrence of atrial arrhythmia after a 3-month blanking period during the one-year follow-up. The secondary endpoints were improvements in NYHA class and reduction of LA area. For identification of independent predictors of atrial arrhythmia recurrence after ablation, univariate and multivariate Cox regression analyses were performed. Results Out of 1293 consecutive patients who underwent cryo-PVI, 148 persistent AF patients with HFpEF and 66 patients with AIC were identified. Propensity score matching yielded 46 patients in each group. HFpEF patients were more symptomatic than AIC patients (NYHA: 2.4 +/- 0.5 vs. 2.0 +/- 0,8; p = 0.002). Other baseline characteristics did not differ between the two groups, except LVEF (57 % [IQR: 52-62%] vs. 41% [QR: 35%-45%]; p= 0.002). Kaplan-Meier curves (Figure 1) demonstrated no difference in recurrence-free survival rate between the groups during the 12-month follow-up (71.7 % vs. 56.5%, log-rank P = 0.16). After the 12-month follow-up, the median LA area decreased significantly in the HFpEF group from 25.8 cm2 (IQR: 23.4-29.5 cm2) to 24.6cm2 (IQR: 22.0-29.6 cm2; p = 0.045) and in the AIC group from 26.6 cm2 (IQR: 22.9-31.1 cm2) to 23.0 cm2 (IQR: 18.3-25.2 cm2; p=0.024). At the 12-month follow-up the median LA-area was significantly higher in the HFpEF than in the AIC cohort (p= 0.007). NYHA class improved significantly in both groups from baseline. At the 1-year follow-up NYHA class was similar between both groups (1.6 +/- 0.8 vs. 1.4 +/- 0,6; p = 0.206). After univariate and multivariate analysis, the following predictors of atrial arrhythmia recurrence were identified: body-mass-index (BMI; HR = 1.082, p = 0.015) and LA area (HR = 1.079, p = 0.003). Conclusions Cryoballoon catheter ablation of persistent AF seems to have similar effectiveness on arrhythmia free survival in patients with HFpEF and AIC. NYHA class and LA enlargement improved after ablation in both groups although LA area in HFpEF was higher than in AIC patients at follow-up. BMI and LA area were identified as predictors of arrhythmia recurrence.

J-curved phenomenon between the prevalence of left atrial low-voltage areas and body mass index existed in patients with atrial fibrillation ablation

Abstract Background Left atrial low-voltage areas (LVAs) were known to be associated with atrial fibrosis and atrial fibrillation (AF) recurrence after catheter ablation. However, the association between body mass index (BMI) and prevalence of LVAs has not been fully elucidated. We hypothesized that LVAs were more frequently found in patients with abnormal BMI than in those with normal BMI. Purpose The purpose of this study was to clarify the association between body mass index (BMI) and the prevalence of LVAs in patients with AF ablation. Methods Between December 2014 and March 2022, 1,479 (age, 68±10 years; female, 500 [34%]) consecutive patients who underwent initial AF ablation were enrolled. BMI was divided into four groups, namely &amp;lt;18.5 kg/m², 18.5-25 kg/m², 25-30 kg/m², ≥30 kg/m². LVAs was defined as areas with bipolar voltage of &amp;lt;0.5 mV covered ≥5 cm² of left atrium. Rhythm outcome following the catheter ablation procedure was also followed for 24 months. Results LVAs were found in 349 (24%) patients. J-curved phenomenon existed between BMI and the prevalence of LVAs (Figure 1). In particular, BMI &amp;lt;18.5 kg/m² was an independent predictor of LVAs on multivariate analysis (odds ratio, 1.9; 95% confidence interval: 1.01–3.5; p=0.046). As for rhythm outcome, there was significant difference in freedom from AF recurrence among groups stratified by BMI (Figure 2). Conclusions Between BMI and the prevalence of LVAs, J-curved phenomenon existed in patients with AF ablation. There was significant difference in rhythm outcome following AF ablation among groups stratified by BMI.Figure 1Figure 2

Left ventricular wall thickening predicts left atrial low voltage areas in patients undergoing catheter ablation for atrial fibrillation

Abstract Background The success rate of circumferential pulmonary vein isolation (CPVI) remains suboptimal in patients with paroxysmal and persistent atrial fibrillation; moreover, the detection of low voltage areas (LVA) in the left atrium does predict an even higher recurrence rate of atrial tachyarrhythmias after the procedure. Left ventricular wall thickening (LVWT) is known to correlate with left atrial volume; however, no data is available whether LVWT is predictive of the presence of left atrial LVA. Purpose The aim of this study was to investigate whether LVWT is predictive of left atrial LVA and to verify that the presence of LVA confer a higher arrhythmia recurrence rate after catheter ablation for atrial fibrillation. Methods A total of 374 patients who undervent CPVI with the use of 3D electroanatomical mapping system as a primary procedure were enrolled in the study. Transthoracic echocardiography was performed in all patients prior the procedure with measurement of the thickness of the septum and the posterior wall. Patients were classified based on LVWT as normal (females:≤9mm, males:≤10mm), borderline (females:10-11mm, males: 11-12mm) and increased (females:≥12mm, males:≥13mm). A detailed left atrial voltage map was obtained in all patients prior to ablation with the identification of LVA (bipolar voltage &amp;lt;0.5mV with an area &amp;gt;5cm2). Arrhythmia recurrence was defined as documented atrial fibrillation or atrial tachycardia lasting for at least 30 seconds. Results Among 374 patients (mean age: 59.0±10.2 years, 131 females) 94, 195 and 85 were considered to be normal, borderline and increased based on LVWT, respectively. LVA were found in 29.9% (112/374) of patients. According to LVWT, LVA were detected in 16.0% (15/94), 31.3% (61/195) and 42.4% (36/85) in patients with normal, borderline and increased wall thickness, respectively, p=0.005. Patients with left atrial LVA had a higher [60.7% (68/112)] arrhythmia recurrence compared to those without low voltage areas [35.1% (92/262)] during a mean follow-up of 2.1±1.9 years, p&amp;lt;0.0001. Conclusions Left ventricular wall thickening predicts the presence of left atrial low voltage areas in patients undergoing catheter ablation for atrial fibrillation. Low voltage areas confer a higher arrhyhtmia recurrence rate during follow-up.

Left atrial low-voltage areas, but not volume, predict the recurrence of atrial fibrillation in repeat ablation procedures

Abstract Background Left atrial (LA) low voltage areas (LVA) are a controversial target in atrial fibrillation ablation procedures. However, LVA and LA volume are good predictors of arrhythmia recurrence in ablation-naïve patients. Their predictive value in pre-ablated, myopathic atria is uncertain. Purpose Patient selection for repeat ablations is sometimes difficult. Predicting factors of rhythm outcome might help with the decision. Methods Consecutive patients with recurrent atrial fibrillation (AF) or atrial tachycardia (AT) scheduled for repeat LA ablation were included in the prospective Bernau ablation registry between 2016 and 2020. All patients received a complete LA ultra-high-density map before ablation. Maps were analyzed for LA size, LVA percentage and distribution. The predictive value of demographic, anatomic and mapping variables on AF recurrence was analyzed in univariate logistic regression and integrated in a multivariate Cox regression if the p-value was &amp;lt;0.250. Results 160 patients (50.6% male, 1.3 pre-ablations, 60% persistent AF) with complete LA voltage maps were included. Mean follow-up time was 16 ± 11 months. Mean recorded electrograms (EGMs) per map were 9754 ± 5808, mean LA volume was 176.1 ± 35.9 ml and mean rate of LVAs &amp;lt; 0.5 mV was 30.6% ± 23.1%. Baseline characteristics are depicted in table 1. During follow-up recurrence rate of AF or AT &amp;gt; 30 seconds was 55.6%. Patients with recurrence had a significant higher percentage of LVAs (40.0% vs. 18.8%, p&amp;lt;.001) but no relevant difference in LA volume (172 vs. 178 ml, p=.299). ROC curves revealed a cut-off of 22% LVAs with highest sensitivity (73.0%) and specificity (71.8%). Based on this cut-off event free survival was significantly higher in the Low LVA group (p&amp;lt;0.01), Figure 1. Other relevant clinical, anatomic or laboratory predictors could not be found in multivariate Cox regression analysis. Conclusion The amount of left atrial LVA is a good predictor for arrhythmia recurrence, even in a cohort of repeat ablations with progressively diseased atria. EAM derived left atrial volume has minor impact on recurrence in this group and should not solely guide the decision in favor or against further invasive treatment. Accomplishing a thorough 3D map of the left atrium to account for LVA should be mandatory in all repeat procedures.Baseline CharacteristicsKaplan-Meier for recurrence and voltage

Associations between stroke risk factors and left atrial low-voltage areas in patients with atrial fibrillation undergoing catheter ablation from the REAL-AF registry

Abstract Background Prior research indicates that increased left atrial low-voltage areas (LA LVA) are linked to comorbidities and CHA2DS2-VASc score in patients with persistent atrial fibrillation (PerAF) undergoing catheter ablation. However, given the heterogeneity of AF where patients may transition between paroxysmal AF (PAF) and PerAF types, it is biologically plausible that these associations span all forms of AF. Purpose To investigate the relationship of stroke demographics and comorbidities to LA LVA and AF type in a multicenter registry of patients undergoing catheter ablation. Methods The Real-world Experience of Catheter Ablation for the Treatment of Symptomatic PAF and PerAF Using Novel Contact Force Technologies registry (REAL-AF) is a prospective, observational multicenter registry of patients undergoing catheter ablation. We evaluated 6053 patients undergoing first-time catheter ablation for both PAF and PerAF to identify associations between stroke risk factors and LA LVA. LA LVA was determined in contact maps as bipolar voltage &amp;lt;0.50 mV. Mapping was completed using 5-spline high-density catheters before ablation. LA LVA was categorized into low (&amp;lt;5%) vs. high (≥5%) based on preliminary data. Analyses were conducted using independent samples t-test and Chi-square test. Results LA LVA was associated with greater CHA2DS2-VASc score (3.2 vs. 2.5, p &amp;lt;0.001). Age 75+ (Odds ratio (OR): 2.22, p&amp;lt;0.001), congestive heart failure (CHF) (OR: 2.01, p&amp;lt;0.001), female sex (OR): 1.51, p&amp;lt;0.001), vascular disease (OR: 1.50, p&amp;lt;0.001), age 65-74 (OR: 1.20, p=0.001), hypertension (OR: 1.38, p&amp;lt;0.001), history of stroke (OR: 1.29, p=0.004) and diabetes (OR: 1.25, p=0.001) were also associated with LA LVA (Table 1). These associations remained significant among a subgroup of those presenting in normal sinus rhythm (N = 3546). Patients with CHF (OR: 2.09, p&amp;lt;0.001), hypertension (OR: 1.89, p&amp;lt;0.001) and male sex (OR: 0.60, p&amp;lt;0.001) were more likely to have PerAF in the LVA ≥5% subgroup (n=1594) (Table 2). All other components of the CHA2DS2-VASc score were not significantly associated with AF type in this subgroup. While there was a significant association between AF type and CHA2DS2-VASc score (PAF: 3.15, PerAF: 3.42, p&amp;lt;0.001) in the LA LVA ≥5% subgroup, the effect size was small (Cohen’s d = -0.179). Conclusion LA LVA ≥5% was associated with all separate components and overall CHA2DS2-VASc score. In patients with LA LVA ≥5%, there were only associations between PerAF and CHF, hypertension, and male sex, implying a special role in substrate progression. Our findings suggest that LA LVA may represent a more sensitive clinical phenotyping tool of AF rather than current duration-based ones. This is the largest study to our knowledge in elucidating the relationship between increased LA LVA and stroke risk factors in the AF population.

Ultra-high density mapping for the evaluation of the antral scar extension after ablation with a radiofrequency balloon catheter in atrial fibrillation patients

Abstract Background The Heliostar radiofrequency (RF) balloon ablation catheter enables one-shot pulmonary veins isolation (PVI). The RF balloon by occluding the PV ostia creates an antral scar. Purpose We sought to investigate the extension of the antral scar by mean of ultra-high density mapping. Methods Paroxysmal and persistent atrial fibrillation (AF) patients undergoing first PVI ablation with the Heliostar catheter across 4 European centers were enrolled. Ultra-high density mapping of left atrium was performed with the Octaray catheter, a octa-spline mapping catheter before and after the ablation. All maps were acquired in sinus rhythm, patients in AF underwent electrical cardioversion before mapping. The bipolar voltage maps from each patients were analysed: the left atrial area &amp;lt; 0.2 mV was considered scar and was calculated before and after the ablation and the distance between left and right antral lesions at upper and inferior posterior wall were also calculated. Results Overall, 49 patients were enrolled, 82% were male, the mean age was 60±9 years, 66% had paroxysmal AF. PVI was achieved in 100% patients. The mean left atrial area was 209±44 cm2, the scar after the ablation was 9±4.6 %, with 49±11% of the posterior wall still viable (bipolar voltage &amp;gt; 0.5mV). The distance between left and right antral lesions at the upper posterior wall was 26.57 mm whereas at the inferior aspect was 29.59 mm. Conclusions The RF balloon catheter creates a wide antral scar during AF ablation although without compromising the integrity of the posterior wall.

Intermittent hypoxia is significantly associated with low-voltage areas in patients with atrial fibrillation complicated by obstructive sleep apnea

Abstract Background Obstructive sleep apnea (OSA) is one of risk factors for atrial fibrillation (AF); however, how OSA affects the structural and electrical atrial remodeling is not well described. This study aimed to determine the association of OSA with left atrial (LA) size and LA low-voltage area (LVA), a known arrhythmogenic substrate for AF. Methods Eighty-three patients undergoing catheter ablation of AF (forty-nine with OSA [apnea–hypopnea index: AHI ≥ 5/h] and thirty-four control patients without OSA by full polysomnography or portable monitor) were studied. In all cases, LA maps were created using a three-dimensional electro-anatomical mapping system in sinus rhythm or pacing from the right atrium. LVA was defined as a bipolar voltage &amp;lt; 0.5 mV. %LVA is defined as ratio of LVA to LA area. Results LVA and %LVA were larger in OSA group as compared to Control group (6.0 ± 6.6 vs. 2.6 ± 3.2 cm2, P = 0.003 and 7.5 ± 8.5 vs. 3.5 ± 4.6 %, P = 0.008, respectively). On the other hand, there was no difference in LA size between the two groups. In addition, 3% oxygen desaturation index (ODI) was significantly correlated with %LVA (r = 0.282, P = 0.010), but not with LA size (r = 0.053, P = 0.637). Multiple regression analysis demonstrated that 3%ODI ≥ 30 (3.088, 1.078-8.851, P = 0.036) was significantly associated with %LVA after adjustment. Conclusion In patients with AF complicated by OSA, significant enlargement of the LVA was observed, but there was no evidence of enlargement in LA size. Intermittent hypoxia may be one of the mechanisms of this atrial electro-anatomical remodeling.figure 1figure 2

Left atrial low-voltage area is associated with poor rhythm outcome and poor efficacy of left atrial additional ablation in patients with long-standing persistent atrial fibrillation ablation

Abstract Background Although left atrial additional ablation other than pulmonary vein (PV) isolation is often performed in order to modify arrhythmogenic substrate, rhythm outcome in patients with long-standing persistent atrial fibrillation (LS-PerAF) is still challenging. Left atrial low-voltage areas (LVAs) is correlated with degeneration of atrial myocardium, and atrial fibrillation (AF) recurrence following catheter ablation. However, in patients with LS-PerAF, the association between the prevalence of LVAs and rhythm outcome has not been clarified. We hypothesized that AF recurrence after AF ablation more frequently occurred in patients with LVAs than in those without, and that the prevalence of LVAs was associated with the efficacy of left atrial additional ablation. Purpose The purpose of this study was to investigate the association between the prevalence of LVAs and rhythm outcome or efficacy of left atrial additional ablation in patients with LS-PerAF ablation. Methods In total, 123 (age, 66 ± 9 years; female, 28 [23%]) consecutive patients who underwent initial ablation for LS-PerAF were included. Left atrial additional ablation was defined as an ablation for left atrium other than PV isolation and ablation for non-PV foci. The definition of LVAs was sites with a bipolar voltage of &amp;lt;0.5 mV covering ≥5 cm² of left atrium. Rhythm outcome after the catheter ablation was followed for 24 months. Results LVAs was found in 31 (25%) patients, and left atrial additional ablation was performed for 31 (25%) patients. Freedom from AF recurrence was significantly lower in patients with LVAs than in those without (Figure 1A). In contrast, freedom from AF recurrence was similar between patients with left atrial additional ablation and those without (Figure 1B). In patients without LVAs, freedom from AF recurrence was significantly higher in patients with left atrial additional ablation than in those without (Figure 2A). On the contrary, in patients with LVAs, freedom from AF recurrence during was similar between patients with left atrial additional ablation and those without (Figure 2B). Conclusions In patients undergoing LS-PerAF ablation, AF recurrence more frequently occurred in patients with LVAs than in those without. Only in patients without LVAs, freedom from AF recurrence was significantly higher in patients with left atrial additional ablation than in those without.Figure 1Figure 2

First-time catheter ablation outcomes for atrial fibrillation are dependent on low-voltage areas rather than paroxysmal vs. persistent classifications: a REAL-AF study

Abstract Background Left atrial low-voltage areas (LA LVA) measured at time of catheter ablation for atrial fibrillation (AF) have been increasingly recognized as an indicator of atrial fibrosis [1]. However, little is known whether first-time catheter ablation outcomes differ between paroxysmal AF (PAF) and persistent AF (PerAF) in patients with higher LA LVA, which may indicate a more advanced substrate independent of clinical subtype. Purpose To evaluate whether outcomes of first-time catheter ablation for AF are dependent on LA LVA rather than PAF vs. PerAF types in a multicenter registry of patients. Methods The Real-world Experience of Catheter Ablation for the Treatment of Symptomatic PAF and PerAF Using Novel Contact Force Technologies registry (REAL-AF) is a prospective, observational multicenter registry of patients undergoing catheter ablation. We evaluated 4181 patients undergoing first-time catheter ablation for both PAF and PerAF to determine AF recurrence within 12 months. Contact maps were created using a 5-spline high-density catheter. LA LVA was calculated using these contact maps based on a bipolar voltage of &amp;lt;0.50 mV. LA LVA was categorized into low (&amp;lt;5%) vs. high (≥5%) based on preliminary data. Risk of recurrence was analyzed using Cox proportional hazard models. Results Patients with LA LVA ≥5% who underwent first-time catheter ablation for AF (both PAF and PerAF) experienced a higher risk of AF recurrence within 12 months (Hazard ratio (HR): 1.95, p&amp;lt;0.001), see Figure 1. Overall, 82.0% of patients were free of AF in the LA LVA &amp;lt;5% group compared to 69.1% in the LA LVA ≥5% group. This association remained significant in a subpopulation of patients presenting in normal sinus rhythm (N = 2463) at time of ablation (HR: 1.90, p&amp;lt;0.001). 12-month ablation outcomes between PAF and PerAF in patients with LA LVA ≥5% (N = 1590) were not statistically significant (71.0% vs 67.3% respectively, HR: 1.15, p=0.30), see Figure 2. Finally, in the LA LVA &amp;lt;5% group (N = 2591), patients with PerAF had a 1.42 times higher risk for AF recurrence within 12 months after catheter ablation (p=0.04). Conclusion This is the largest real-world registry to date demonstrating that LA LVA ≥5% is associated with a higher risk of AF recurrence within 12 months in patients undergoing first-time catheter ablation for AF. Among patients with LA LVA ≥5%, AF recurrence was not associated with AF type. These findings motivate further studies into using LA LVA as a prognostic tool for patients undergoing first-time catheter ablation for AF and using non-invasive methods to assess this in order to stratify patients further.

Conduction velocity-based functional substrate mapping during atrial fibrillation (AF) enhances identification of AF drivers compared to mapping during sinus rhythm

Abstract Background Conduction velocity (CV) heterogeneity is known to play a role in the initiation and maintenance of atrial fibrillation (AF) [1,2]. CV has been shown to decrease with cycle lengths (CLs) &amp;lt;600ms in low voltage areas (LVAs) [3,4], and with CLs &amp;lt;300ms in non-LVAs [4]. Yet, the impact of rhythm and CL on voltage-independent, CV-based atrial substrate mapping remains uncertain. Purpose This study evaluates CV differences based on mapping protocol and explores the relationship between CV and AF pathologic conduction patterns (PCPs) identified through global, non-contact, charge density mapping (CDM) [5]. Methods CDM was performed in twelve patients with persistent AF, presenting for de novo ablation. All mapping was performed prior to any ablation. Sinus rhythm (SR) CV was assessed during atrial pacing at two CLs (380ms and 800ms). To mitigate the impact of wavefront direction, pacing was performed at three sites: mid coronary sinus, left atrial appendage, and right atrial appendage. AF CV was determined from a 20-second continuous recording of global propagation. PCPs were identified as: focal firing (FF), rotational propagation (Localised Rotational Activation [LRA]), and pivoting propagation (Localised Irregular Activity [LIA]) [5]. Patients’ left atrial geometries consisted of approximately 3000 vertices, facilitating paired comparisons of spatial data. At each vertex, values for median CV dependent on mapping protocol and frequency of PCPs were utilised for analysis. Variables are presented as mean±standard deviation, median (interquartile range), and count (percentage) as appropriate. All analyses were performed using R (version 4.1.2). CV distributions were compared using the Analysis of Variance test. Results Mean age was 64±12 years, eight (67%) were male, median time since AF diagnosis was 3.1 (2-3.5) years, and median CHA2DS2-VASc score was 2 (2-4). Median CV across our cohort was significantly lower during AF than SR with either long or short CL pacing (0.37mm/ms vs 0.66mm/ms vs 0.61mm/ms, p&amp;lt;0.001). Histograms of CV vs left atrial surface area demonstrated similar distributions for both CLs. However, there was poor overlap with AF, which was prominently skewed towards slower CVs (Figure 1). Slower CVs during AF were associated with an increased frequency of PCPs (Figure 2), particularly FF with CVs &amp;lt;0.2mm/ms, and LRA and LIA with CVs &amp;lt;0.4mm/ms. This association was absent during SR. Conclusions Rhythm has a significant impact on CV-based functional substrate mapping. Slower CVs observed during AF likely result from the presence of CLs shorter than 300ms, which impact both LVA and non-LVA areas. Crucially, areas of slow CV during AF were associated with the location of PCPs. Mapping performed during AF may improve identification of areas where functional remodelling has preceded structural. Such areas, characterised by CV heterogeneity, may serve as promising targets for catheter ablation.Figure 1.Figure 2.

Pulsed-field ablation of atrial fibrillation in patients with multiple cardiovascular comorbidities: acute safety and efficacy from a large nationwide multicenter experience

Abstract Background Patients with multiple cardiovascular (CV) comorbidities are increasing users of health care globally. The decision to perform ablation of atrial fibrillation (AF) may be challenging in this population, due to the difficulty in evaluating their life expectancy and the associated procedural risk. In addition, no data have been reported on the efficiency, effectiveness, and safety outcomes for non-thermal ablation, such as electroporation with pulsed-field ablation (PFA). Purpose To evaluate procedural workflow and safety for AF ablation in these patients through a novel PFA technology (Farapulse) in a large, nationwide clinical practice. Methods Consecutive patients who had undergone PFA of AF from 10 Italian centers were included. Patients were stratified according to the numbers of several comorbidities, assigning 1 point each, including: advanced age (≥80 years), LVEF≤35%, structural heart disease, coronary artery disease, chronic kidney disease, chronic obstructive pulmonary disease, previous stroke/TIA, hyperthyroidism, cancer history, cancer ongoing, severe sleep apnea, diabetes, hypertension, dyslipidemia. Results We included 634 patients (age 62±9 years, 73% male, 67% paroxysmal AF, 88% de novo ablation procedure, LVEF 57±8%). Two-hundred-nine (33%) patients had no risk-factors, 179 (28.2%) patients had at least 1, 137 (21.6%) two, 63 (9.9%) patients 3 risk-factors and 46 (7.3%) patients more than 4 comorbidities. Patients with accumulated risk factors (≥4) had a higher percentage of long-standing AF (17.4% vs 5.4%, p=0.005) and more often underwent de novo ablation procedure (93.5% vs 81.3%, p=0.04). In these cases, operators decided to adopt more frequently, albeit not significantly, advanced diagnostic such as 3D mapping system (30.4% vs 21.9%, p=0.20) or intracardiac echocardiography (41.3% vs 29.8%, p=0.13), a general anesthesia sedation strategy (41.3% vs 32.1%, p=0.88) and a more extensive lesion set beyond PVI (i.e. left atrial posterior wall area, 32.6% vs 23.1%, p=0.15). Procedures in which patients with accumulated risk factors are involved required longer support (preparation plus skin-to-skin) time (90[65-120] min vs 72[60-100] min, p=0.02) and skin-to-skin time (70[60-100] min vs 60[55-85] min, p=0.03) compared to patients with &amp;lt;4 risk factors, whereas time to PVI (19[14-25] min vs 20[14-25] min, p=0.81) and total number of PFA deliveries to achieve PVI (32[32-38] vs 32[32-36], p=0.55) were similar. PVI was achieved in all patients. No major procedure-related adverse events were reported. Conclusion In this preliminary experience, the use of Farapulse PFA system for AF ablation in patients with accumulated risk factors was safe and effective and resulted in similar and fast time to PVI.

Predictive value of guideline-referred risk scores in estimating left atrial low voltage areas and recurrence of atrial fibrillation in repeat ablation procedures

Abstract Background Despite advances in mapping and ablation techniques, atrial fibrillation (AF) recurrence remains a challenge after pulmonary vein isolation. Low voltage areas (LVA) in the left atrium are associated with higher recurrence rates after left atrial ablation. Risk scores for evaluating post-ablation recurrences are not well established, although a better patient selection for repeat procedures would be of great help in clinical practice. Purpose Risk scores for prediction of AF recurrence have not been tested in a cohort of repeat ablations. Methods This single-center study includes consecutive patients from the prospective Bernau ablation registry undergoing ultra-high-density (UHD) mapping and repeat ablation for AF/AT recurrence between 2016 and 2020. The potential of seven guideline mentioned risk scores (APPLE, DR-FLASH, MB-LATER, ATLAS, CAAP-AF, BASE-AF 2, ALARMEc) to predict (1) AF/AT recurrence beyond a three-months blanking period after repeat left atrial ablation (Re-PVI ± further LA ablation) and (2) the percentage of left atrial LVA in UHD mapping was investigated. LVA were defined as sites with a bipolar peak-to-peak voltage of &amp;lt;0.5 mV with an extent of &amp;gt;1cm². Optimal cutoff for sensitivity and specificity for LVA and AF/AT recurrence as endpoint was chosen using C statistics with receiver-operator characteristics (ROC). Further ROCs were performed to illustrate the predictive ability of the scores. Pearson correlation was used to test associations between variables. Results 160 patients (mean age 67.9 ± 9.1 years, 60.6% persistent AF, mean AF duration 4.6 ± 3.8 years) with complete left atrial UHD mappings (mean EGMs 9754 ± 5808) were included. Overall recurrence rate over a mean follow-up time of 16 ± 11 months was 55.6%. The predictive value of the investigated risk scores on AF/AT recurrence in our cohort was low (Table 1), with the highest power for CAAP-AF (p = 0.015, AUC = 0.615) and DR-FLASH score (p = 0.040, AUC = 0.594), Figure 1. With respect to left atrial LVA we found a better predictive power for the CAAP-AF (p &amp;lt; 0.001, AUC 0.702), APPLE (p &amp;lt; 0.001, AUC 0.687), DR-FLASH (p &amp;lt; 0.001, AUC 0.688), ATLAS (p = 0.005, AUC 0.634) and ALARMEc (p = 0.007, AUC 0.608) score to predict low voltage based on a calculated cut-off of 22% of total left atrial surface (Figure 1). Conclusion The predictive value of guideline-referred risk scores in estimating AF/AT recurrence after repeat ablation is low and does not seem to be of relevant help in patient selection for further interventional treatment. Some scores demonstrate a fairly good prediction for the amount of left atrial LVA and therefore might help in choosing the right mapping and ablation regime beforehand.

Arrhythmia-induced versus arrhythmia-superimposed cardiomyopathy: outcome in patients with atrial fibrillation and heart failure undergoing cryoballoon pulmonary vein isolation

Abstract Introduction The outcome in patients with arrhythmia-induced cardiomyopathy (AIC) compared with that in patients with arrhythmia-mediated/superimposed cardiomyopathy (AMC) undergoing cryoballoon pulmonary vein isolation (cryo-PVI) is also poorly defined. Methods In this retrospective observational study, we analysed patients with AF and reduced left ventricular ejection fraction (LVEF &amp;lt; 50%) who underwent cryoballoon ablation between 2014 and 2020. Patients with LVSD were divided into AIC and AMC. AIC was diagnosed ex juvantibus during first year after ablation at 3- and 12-month follow-up when LVEF recovered to &amp;gt; 50% and by more than 10% after ablation and a different aetiology for reduced LVEF was excluded. AMC was diagnosed when structural heart disease was responsible for LVSD and AF had likely exacerbated pre-existing LVSD. For identification of independent predictors of LVEF non-improvement after ablation, univariate and multivariate logistic regression analyses were performed. LVEF non-improvement was defined when LVEF neither increased by more than 10% nor increased over absolute 50% at 12-month follow-up. The first documented &amp;gt; 30-s atrial arrhythmia recurrence after a 3-month blanking period during the one-year follow-up was compared by Kaplan-Meier analysis. Results Out of 1293 consecutive patients who underwent cryoballoon ablation, 113 AF patients with reduced LVEF (&amp;lt;50%) were identified. After 1-year follow-up these patients were divided into AIC (N= 77) and AMC (N = 36) groups. The prevalence of persistent AF was comparable in both groups (85.7% vs. 77.8 %, p = 0.435). LVEF, left atrial (LA) enlargement, and left ventricular end diastolic diameter (LVEDD) were similar between the groups. After one year, the median LVEF improved significantly in the AIC group from 42% (IQR: 35-45%) to 60% (IQR: 58-63%; p &amp;lt; 0.0001) and in the AMC group from 42% (IQR: 33-45%) to 47.5% (IQR= 43-53%; p=0.015). At follow-up LVEF was significantly higher in the AIC than in the AMC cohort (p &amp;lt; 0,001). After univariate and multivariate analysis, the following parameters were associated with non-LVEF improvement: LVEDD (OR = 1.12, p = 0.012) and atrial arrhythmia recurrence (OR = 5.87, p = 0.031; Figure 1). In the AIC group LA area decreased from 25.6 cm2 (IQR: 22.4-29.5 cm2) to 21.8 cm2 (IQR: 18.3-25.2 cm2; p = 0.012). In AMC patients LA enlargement did not change with respect to baseline. Kaplan-Meier curves demonstrated no difference in recurrence-free survival rate between the groups during the 12-month follow-up (75.3% vs. 75%, log-rank P = 0.89; Figure 2). Conclusions LVEDD and arrhythmia recurrence were identified as predictors of non-LVEF improvement after cryo-PVI. The LVEF increased in both groups after ablation, but in AIC group more than in AMC group. In the AIC group LA atrial area decreased compared to the AMC group. Atrial arrhythmia recurrence rates were comparable between AIC and AMC groups after 12 months.Figure 1Figure 2