Left atrial remodeling and voltage-guided ablation outcome in persistent atrial fibrillation patients according to CHA2DS2-VASc score.

BACKGROUND: CHA2DS2-VASc score-related differences have been reported in atrial fibrotic remodeling and prognosis of atrial fibrillation (AF) patients after ablation. There are currently no data on the efficacy of low voltage zone (LVZ)-guided ablation in persistent AF patients according to CHA2DS2-VASc score. We assessed in a cohort of persistent AF patients the extent of LVZ, the regional distribution of LA voltage and the outcome of LA voltage-guided substrate ablation in addition to PVI according to CHA2DS2-VASc score. METHODS: 138 consecutive persistent AF patients undergoing a first voltage-guided catheter ablation were enrolled. 58 patients with CHAD2DS2-VASc score ≥ 3 and 80 patients with CHAD2DS2-VASc score ≤ 2 were included. LA voltage maps were obtained using 3D-electroanatomical mapping system in sinus rhythm. LVZ was defined as < 0.5 mV. RESULTS: In the high CHAD2DS2-VASc score group, LA voltage was lower (1.5 [1.1-2.5] vs. 2.3 [1.5-2.8] mV, p = 0.02) and LVZs were more frequently identified (40% vs. 18%), p < 0.01). Female with CHA2DS2-VASc score ≥ 3 (p = 0.031), LA indexed volume (p = 0.009) and P-wave duration ≥ 150 ms (p = 0.001) were predictors of LVZ. After a 36-month follow-up, atrial arrhythmia-free survival was similar between the two groups (logrank test, P = 0.676). CONCLUSIONS: AF patients with CHAD2DS2-VASc score ≥ 3 display more LA substrate remodeling with lower voltage and more LVZs compared with those with CHAD2DS2-VASc score ≤ 2. Despite this atrial remodeling, they had similar and favorable 36 months results after one single procedure. Unlike male with CHAD2DS2-VASc score ≥ 3, female with CHAD2DS2-VASc score ≥ 3 was predictor of LVZ occurrence.

Impact of left ventricular diastolic function and direct oral anticoagulant use for predicting embolic events in patients with heart failure and atrial fibrillation.

Background: Patients with atrial fibrillation (AF) and heart failure (HF) have high stroke risk owing to left atrial dysfunction. However, anticoagulation is a concern in patients with high bleeding risk. We aimed to identify independent predictors of stroke in HF patients with AF. Methods: We retrospectively examined 320 patients (mean age 79 ± 12 years, 163 women) hospitalized with acute HF complicated by AF between January 2014 and December 2018. Patients were followed from admission until ischemic stroke or systemic embolism (SSE) onset or death or were censored at the last contact date or September 2023. Results: SSE occurred in 40 patients (median follow-up of 528 days). Multivariate Cox regression analysis identified age (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.00-1.07, p = .034), direct oral anticoagulant (DOAC) use (HR 0.26, 95% CI 0.11-0.60, p = .002), and early diastolic peak flow velocity to early diastolic peak annular velocity (E/e'; HR 1.05, 95% CI 1.02-1.08, p < .001) to be independent predictors of SSE, whereas left atrial reservoir strain was not. After determining an appropriate E/e' cutoff by receiver-operating characteristic curve analysis and adjusting the multivariate Cox model, E/e' ≥17.5 (HR 3.30, 95% CI 1.56-6.83, p = .001) independently predicted SSE. The results were consistent with no interaction in the subanalysis except for gender. Conclusion: Elderly patients not on DOACs with elevated E/e' may be at higher risk of stroke, suggesting that DOACs should be the first choice for patients with elevated E/e' and aggressive additional prophylaxis and careful follow-up are needed.

Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights.

Metformin is an orally effective anti-hyperglycemic drug that despite being introduced over 60 years ago is still utilized by an estimated 120 to 150 million people worldwide for the treatment of type 2 diabetes (T2D). Metformin is used off-label for the treatment of polycystic ovary syndrome (PCOS) and for pre-diabetes and weight loss. Metformin is a safe, inexpensive drug with side effects mostly limited to gastrointestinal issues. Prospective clinical data from the United Kingdom Prospective Diabetes Study (UKPDS), completed in 1998, demonstrated that metformin not only has excellent therapeutic efficacy as an anti-diabetes drug but also that good glycemic control reduced the risk of micro- and macro-vascular complications, especially in obese patients and thereby reduced the risk of diabetes-associated cardiovascular disease (CVD). Based on a long history of clinical use and an excellent safety record metformin has been investigated to be repurposed for numerous other diseases including as an anti-aging agent, Alzheimer's disease and other dementias, cancer, COVID-19 and also atrial fibrillation (AF). AF is the most frequently diagnosed cardiac arrythmia and its prevalence is increasing globally as the population ages. The argument for repurposing metformin for AF is based on a combination of retrospective clinical data and in vivo and in vitro pre-clinical laboratory studies. In this review, we critically evaluate the evidence that metformin has cardioprotective actions and assess whether the clinical and pre-clinical evidence support the use of metformin to reduce the risk and treat AF.

Changes in left atrial function following two regimens of combined exercise training in patients with ischemic cardiomyopathy: a pilot study.

Purpose: Left atrial dysfunction has shown to play a prognostic role in patients with ischemic cardiomyopathy (ICM) and is becoming a therapeutic target for pharmacological and non-pharmacological interventions. The effects of exercise training on the atrial function in patients with ICM have been poorly investigated. In the present study, we assessed the effects of a 12-week combined training (CT) program on the left atrial function in patients with ICM. Methods: We enlisted a total of 45 clinically stable patients and randomly assigned them to one of the following three groups: 15 to a supervised CT with low-frequency sessions (twice per week) (CTLF); 15 to a supervised CT with high-frequency sessions (thrice per week) (CTHF); and 15 to a control group following contemporary preventive exercise guidelines at home. At baseline and 12 weeks, all patients underwent a symptom-limited exercise test and echocardiography. The training included aerobic continuous exercise and resistance exercise. The analysis of variance (ANOVA) was used to compare within- and inter-group changes. Results: At 12 weeks, the CTLF and CTHF groups showed a similar increase in the duration of the ergometric test compared with the control (ANOVA p < 0.001). The peak atrial longitudinal strain significantly increased in the CTHF group, while it was unchanged in the CTLF and control groups (ANOVA p = 0.003). The peak atrial contraction strain presented a significant improvement in the CTHF group compared with the CTLF and control groups. The left ventricular global longitudinal strain significantly increased in both the CTHF and the CTLF groups compared with the control group (ANOVA p = 0.017). The systolic blood pressure decreased in the CTHF and CTLF groups, while it was unchanged in the control group. There were no side effects causing the discontinuation of the training. Conclusions: We demonstrated that a CT program effectively improved atrial function in patients with ICM in a dose-effect manner. This result can help with programming exercise training in this population.

The SK4 channel allosteric blocker, BA6b9, reduces atrial fibrillation substrate in rats with reduced ejection fraction.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is strongly associated with several comorbidities including heart failure (HF). AF in general, and specifically in the context of HF, is progressive in nature and associated with poor clinical outcomes. Current therapies for AF are limited in number and efficacy and do not target the underlying causes of atrial remodeling such as inflammation or fibrosis. We previously identified the calcium-activated SK4 K+ channels, which are preferentially expressed in the atria relative to the ventricles in both rat and human hearts, as attractive druggable target for AF treatment. Here, we examined the ability of BA6b9, a novel allosteric inhibitor of SK4 channels that targets the specific calmodulin-PIP2 binding domain, to alter AF susceptibility and atrial remodeling in a systolic HF rat postmyocardial infarction (post-MI) model. Daily BA6b9 injection (20 mg/kg/day) for 3 weeks starting 1-week post-MI prolonged the atrial effective refractory period, reduced AF induction and duration, and dramatically prevented atrial structural remodeling. In the post-MI left atrium (LA), pronounced upregulation of the SK4 K+ channel was observed, with corresponding increases in collagen deposition, α-SMA levels, and NLRP3 inflammasome expression. Strikingly, BA6b9 treatment reversed these changes while also significantly reducing the lateralization of the atrial connexin Cx43 in the LA of post-MI rats. Our findings indicate that the blockade of SK4 K+ channels using BA6b9 not only favors rhythm control but also remarkably reduces atrial structural remodeling, a property that is highly desirable for novel AF therapies, particularly in patients with comorbid HF.

Coronary Sinus Metabolite 12,13-diHOME Is a Novel Biomarker for Left Atrial Remodeling in Patients With Atrial Fibrillation.

BACKGROUND: 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) has shown potential in protecting against heart disease, but its relationship with atrial fibrillation (AF) remains unknown. METHODS: Coronary sinus (CS) and femoral vein blood samplings were synchronously collected from AF and non-AF subjects (paroxysmal supraventricular tachycardia or idiopathic premature ventricular complexes) who underwent catheter ablation. First, untargeted metabolomic profiling was performed in a discovery cohort (including 12 AF and 12 non-AF subjects) to identify the most promising CS or femoral vein metabolite. Then, the selected metabolite was further measured in a validation cohort (including 119 AF and 103 non-AF subjects) to confirm its relationship with left atrium remodeling and 1-year postablation recurrence of AF. Finally, the biological function of the selected metabolite was validated in a rapid-paced cultured HL-1 atrial cardiomyocytes model. RESULTS: Metabolomic analysis identified CS 12,13-diHOME as the most pronounced change metabolite correlated with left atrium remodeling in the discovery cohort. In the validation cohort, CS 12,13-diHOME was significantly lower in patients with AF than non-AF controls (84.32±20.13 versus 96.24±23.56 pg/mL; P<0.01), and associated with worse structural, functional, and electrical remodeling of left atrium. Multivariable regression analyses further demonstrated that decreased CS 12,13-diHOME was an independent predictor of 1-year postablation recurrence of AF (odds ratio, 0.754 [95% CI, 0.648-0.920]; P=0.005). Biological function validations showed that 12,13-diHOME treatment significantly protect the cell viability, improved the expression of MHC (myosin heavy chain) and Cav1.2 (L-type calcium channel α1c), and attenuated mitochondrial damage in the rapid-paced cultured HL-1 cardiomyocytes model. CONCLUSIONS: CS metabolite 12,13-diHOME is decreased in patients with AF and can serve as a novel biomarker for left atrium remodeling.

Understanding the Electrical Substrates Contributing to "Ablation-Resistant" Atrial Fibrillation?

Atrial fibrillation (AF) was largely ignored by cardiac electrophysiologists until it was first suggested in 1998 that it might be amenable to catheter ablation. In the 25 years since then, a vast body of knowledge has emerged, initially reporting the "hypes and hopes" that ablation was appropriate for all but more recently acknowledging that not all patients benefit from this approach. The AF "epidemic" and more holistic understanding of the complex contributors to its development question whether it is even meaningful to consider AF a single condition that is always responsive to ablation management. In this issue, Masuda et al11 provide novel insights into the electrophysiologic "footprints" that they found in the body of the left atrium of patients who underwent a second ablation procedure after achieving pulmonary vein isolation. In conclusion, the findings require prospective validation but may show a way of achieving antiarrhythmic success in a cohort of patients responding unpredictably to current ablation strategies.

Left atrial remodeling and voltage-guided ablation outcome in obese patients with persistent atrial fibrillation.

Background: Obesity is a risk factor for atrial fibrillation (AF). Data regarding left atrial (LA) remodeling in obese patients are scarce. Whether obesity favors AF recurrence after catheter ablation (CA) is still controversial. We assessed the distribution of epicardial atrial fat on computed tomography (CT), LA bipolar voltage, low-voltage zone (LVZ) extent, and the outcome of voltage-guided ablation of persistent AF in obese and non-obese patients. Methods: A total of 139 patients with persistent AF undergoing a first voltage-guided ablation were enrolled and divided into two groups: 74 were non-obese and 65 were obese. Epicardial adipose tissue (EAT) was assessed on a CT scanner. LA endocardial voltage maps were obtained using a 3D mapping system in sinus rhythm. LVZ was defined as a bipolar peak-to-peak voltage amplitude <0.5 mV. Results: LA volume, voltage, and EAT amount were similar in the two groups. LVZ was less frequent in obese patients [12 (18.8%) vs. 26 (35.1%), p = 0.05], particularly on the anterior wall. The posterior and lateral EATs were correlated with posterior and lateral LVZ extent, respectively, in obese patients. After 36 months of follow-up, the AF-free survival rate was similar. Lateral EAT [odds ratio (OR) 1.21, 95% confidence interval (CI) 1-1.4, p = 0.04] and P-wave duration (OR 1.03, 95% CI 1-1.05, p = 0.03), but not body mass index (BMI), were predictors of AF recurrence after CA. Conclusion: In obese patients, LVZ was less marked than in non-obese patients with similar LA volumes, voltage, and EAT amounts. In obese patients, posterior and lateral EATs were correlated with posterior and lateral LVZ extents. Obese patients had a similar and favorable 36-month outcome after AF ablation. BMI was not predictive of AF recurrence.

Association Between Atrial Fibrillation Symptoms and Clinical Outcomes: A Prospective Multicenter Registry Study.

The presence of symptoms plays an important role in determining whether to focus on rhythm control or rate control when treating atrial fibrillation (AF). Previous comparative studies on the clinical outcomes of symptomatic and asymptomatic AF have yielded inconsistent results, and a link between AF symptoms and left atrial (LA) remodeling is not established. Patients selected from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, which is a prospective, multicenter study consisting of patients with non-valvular AF, were grouped into 2 groups: symptomatic and asymptomatic. The primary outcome was a composite of the following cardiovascular outcomes: all-cause death, ischemic stroke, transient ischemic attack, systemic embolism, myocardial infarction, and heart failure hospitalization. Of 10,210 patients with AF, 4,327 (42%) had symptomatic AF. The asymptomatic group had an older mean age, more men, and more patients with hypertension and diabetes mellitus than the symptomatic group. The asymptomatic group had a larger left atrium (LA) diameter (43.6 vs 42.2 mm, p <0.001) than the symptomatic group. During a median follow-up of 32.9 (29.5 to 36.4) months, the asymptomatic and symptomatic groups showed similar incidences of the primary outcome (1.44 vs 1.45 per 100 person-years; log-rank, p = 0.8). In conclusion, the absence of AF symptoms is associated with increased LA. However, symptomatic and asymptomatic patients with AF have a similar risk of cardiovascular outcomes. This suggests that beneficial treatment for AF may be considered regardless of whether patients have symptomatic or asymptomatic AF.

Cardiac Structural and Functional Remodeling After Transcatheter Mitral Valve in Valve Implantation: Early Changes and Prognostic Significance.

Background: Transcatheter mitral valve-in-valve (MViV) replacement has emerged as an alternative to redo mitral valve (MV) surgery for the management of failed bioprosthetic MVs. The degree of cardiac remodeling assessed by echocardiography has been shown to have prognostic implications in degenerative mitral regurgitation patients undergoing MV surgery. The impact of transcatheter MViV in patients with degenerative bioprosthetic MV failure on cardiac remodeling and its associated prognosis remains undescribed. Objectives: The aim of this study is to describe the early anatomic and functional changes of the left-sided chambers and right ventricle by echocardiography posttranscatheter MViV intervention and their impact on mortality outcomes. Additionally, we sought to analyze the outcome of heart failure in bioprosthetic MV failure patients undergoing transcatheter MViV replacement. Methods: We analyzed consecutive patients undergoing MViV intervention for symptomatic bioprosthetic MV failure. Echocardiograms before intervention and within 100 days postintervention were analyzed. A chart review was performed to obtain baseline characteristics, follow-up visits, 30-day heart failure and 1-year all-cause mortality outcomes. Results: A total of 62 patients (mean age 69 ± 13 years, 61% male) were included in the study. Most patients were undergoing MViV intervention for prosthetic mitral stenosis n = 48 (77.4%) and the rest for mitral regurgitation or mixed disease. Compared with baseline, significant reductions were observed in median left atrial volume (LAV; 103 [81-129] ml vs. 95.2 [74.5-117.5] ml, p < 0.01) and mean (SD) left atrial conduit strain (9.1% ± 5.2% vs. 10.8% ± 4.8%, p = 0.039) within 100 days postintervention. Early reduction in right ventricular free wall global longitudinal strain and fractional area change also occurred postintervention. No significant change in left ventricular chamber dimensions or ejection fraction was observed. During the 1-year follow up period, 5 (8%) patients died. While baseline LAV was not associated with 1-year all-cause mortality (OR 0.98 CI 0.95-1.01; p = 0.27), a change in LAV in the follow up period was associated with all-cause mortality at 1 year (OR 1.06 CI 1.01-1.12; p = 0.023). At 30 days postintervention, 65% of patients had an improvement in their New York Heart Association functional class. Conclusion: In this retrospective study of patients undergoing transcatheter MViV intervention for failed bioprosthetic MVs, early reverse remodeling of the left atrium occurs within 100 days postintervention and reduction in LAV is associated with reduced all-cause mortality at 1 year. In addition, there is significant improvement in heart failure symptoms at 30 days following intervention but further investigation into the longitudinal remodeling changes and long-term outcomes is needed.

Practical approach for atrial cardiomyopathy characterization in patients with atrial fibrillation.

Atrial fibrillation (AF) causes progressive structural and electrical changes in the atria that can be summarized within the general concept of atrial remodeling. In parallel, other clinical characteristics and comorbidities may also affect atrial tissue properties and make the atria susceptible to AF initiation and its long-term persistence. Overall, pathological atrial changes lead to atrial cardiomyopathy with important implications for rhythm control. Although there is general agreement on the role of the atrial substrate for successful rhythm control in AF, the current classification oversimplifies clinical management. The classification uses temporal criteria and does not establish a well-defined strategy to characterize the individual-specific degree of atrial cardiomyopathy. Better characterization of atrial cardiomyopathy may improve the decision-making process on the most appropriate therapeutic option. We review current scientific evidence and propose a practical characterization of the atrial substrate based on 3 evaluation steps starting with a clinical evaluation (step 1), then assess outpatient complementary data (step 2), and finally include information from advanced diagnostic tools (step 3). The information from each of the steps or a combination thereof can be used to classify AF patients in 4 stages of atrial cardiomyopathy, which we also use to estimate the success on effective rhythm control.

Impact of nocturnal blood pressure dipping on recurrence of atrial fibrillation after pulmonary vein isolation.

Lack of the typical nocturnal blood pressure (BP) fall, i.e non-dipper, has been known as a cardiovascular risk. However, the influence of non-dipper on atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) has been unclear. We investigated the clinical impact of non-dipping as evaluated by 24-hour ambulatory BP monitoring on the long-term outcome of AF recurrence post-PVI in 76 AF patients with a history of increased BP. The PVI procedure was successful in all 76 patients (mean age, 66±9years; antihypertensive medication, 89%; non-paroxysmal AF, 24%). Twenty patients had AF recurrence during a median follow-up of 1138 days. There was no difference in BP levels between the AF recurrence and non-recurrence groups (average 24 h systolic BP:126 ± 17 vs.125 ± 14 mmHg; P = 0.84). On the other hand, the patients with non-dipper had a higher AF recurrence than those with dipper (38.9% vs.15.0%; P = 0.018). In Cox hazard analysis adjusted by age, non-paroxysmal AF and average 24-hr systolic BP level, the non-dipper was an independent predictor of AF recurrence (HR 2.78 [95%CI:1.05-7.34], P = 0.039). Non-dipper patients had a larger left atrial (LA) volume index than the dipper patients (45.9 ± 17.3 vs.38.3 ± 10.2 ml/m2, P = 0.037). Among the 58 patients who underwent high-density voltage mapping in LA, 11 patients had a low-voltage area (LVA) defined as an area with a bipolar voltage < 0.5 mV. However, there was no association of LVA with non-dipper or dipper (22.2% vs.16.1%, P = 0.555). Non-dipper is an independent predictor of AF recurrence post-PVI. Management of abnormal diurnal BP variation post-PVI may be important.

Quantitative analysis of fractionated electrogram area of left atrium during right atrial pacing as an indicator of left atrial electrical remodeling in patients with atrial fibrillation.

Background: The clinical significance of left atrial local electrogram fractionation after restoration of sinus rhythm in patients with atrial fibrillation (AF) has not been elucidated. Methods: We evaluated ultrahigh-resolution maps of the left atrium (LA) during RA pacing acquired after pulmonary vein isolation in 40 patients with AF. The association between low-voltage area (LVA, <0.5 mV), fractionated electrogram area (FEA, the highlighted area with LUMIPOINT™ Complex Activation), the interval from onset of LA activation to wavefront collision at the mitral isthmus (LA activation time), and wave propagation velocity (WPV) was evaluated quantitatively. Results: The total LVA, total FEA with ≥5.0 peaks or ≥7.0 peaks were 7.0 ± 7.9 cm2, 15.9 ± 12.9 cm2, and 5.2 ± 7.5 cm2, respectively. These areas were predominantly observed in the anteroseptal region. Total LVA, total FEA with ≥5.0 peaks, and total FEA with ≥5.0 peaks in the normal voltage area (NVA: ≥0.5 mV) correlated with LA activation time (R = 0.69, 0.75, and 0.71; each p < .0001). In the anterior wall, these areas correlated with regional mean WPV (R = -0.75, -0.83, and - 0.55; each p < .0001) and the extent of slow conduction area (SCA) with WPV <0.3 m/s (R = 0.89, 0.84, 0.33; p < .0001 for LVA and FEA, p < .05 for FEA located in NVA). The anterior wall FEA with ≥7.0 peaks and that in the NVA showed a better correlation in predicting anterior wall SCA (R = 0.92 and 0.86, each p < .0001). Conclusion: Quantitative analysis of FEA together with LVA may facilitate the assessment of LA electrical remodeling.

Association between left atrial low-voltage area and induction and recurrence of macroreentrant atrial tachycardia in pulmonary vein isolation for atrial fibrillation.

BACKGROUND: The relationship between induction and recurrence due to atrial tachycardia (AT) and left atrial (LA) matrix progression after atrial fibrillation (AF) ablation remains unclear. METHODS: One hundred fifty-two consecutive patients with paroxysmal and persistent AF who underwent pulmonary vein isolation (PVI) and cavo-tricuspid isthmus (CTI) ablation and achieved sinus rhythm before the procedure were classified into three groups according to the AT pattern induced after the procedure: group N (non-induced), F (focal pattern), and M (macroreentrant pattern) in 3D mapping. RESULTS: The total rate of AT induction was 19.7% (30/152) in groups F (n = 13) and M (n = 17). Patients in group M were older than those in groups N and F, with higher CHADS2/CHA2DS2-VASc values, left atrial enlargement, and low-voltage area (LVA) size of LA. The receiver operating characteristic curve determined that the cut-off LVA for macroreentrant AT induction was 8.8 cm2 (area under the curve [AUC]: 0.86, 95% confidence interval [CI]: 0.75-0.97). The recurrence of AT at 36 months in group N was 4.1% (5/122), and at the second ablation, all patients had macroreentrant AT. Patients with AT recurrence in group N had a wide LVA at the first ablation, and the cut-off LVA for AT recurrence was 6.5 cm2 (AUC 0.94, 95%CI 0.88-0.99). Adjusted multivariate analysis showed that only LVA size was associated with the recurrence of macroreentrant AT (odds ratio 1.21, 95%CI 1.04-1.51). CONCLUSIONS: It is important to develop a therapeutic strategy based on the LVA size to suppress the recurrence of AT in these patients.

Atrial Proteomic Profiling Reveals a Switch Towards Profibrotic Gene Expression Program in CREM-IbΔC-X Mice with Persistent Atrial Fibrillation.

Background: Overexpression of the CREM (cAMP response element-binding modulator) isoform CREM-IbΔC-X in transgenic mice (CREM-Tg) causes the age-dependent development of spontaneous AF. Purpose: To identify key proteome signatures and biological processes accompanying the development of persistent AF through integrated proteomics and bioinformatics analysis. Methods: Atrial tissue samples from three CREM-Tg mice and three wild-type littermates were subjected to unbiased mass spectrometry-based quantitative proteomics, differential expression and pathway enrichment analysis, and protein-protein interaction (PPI) network analysis. Results: A total of 98 differentially expressed proteins were identified. Gene ontology analysis revealed enrichment for biological processes regulating actin cytoskeleton organization and extracellular matrix (ECM) dynamics. Changes in ITGAV, FBLN5, and LCP1 were identified as being relevant to atrial fibrosis and remodeling based on expression changes, co-expression patterns, and PPI network analysis. Comparative analysis with previously published datasets revealed a shift in protein expression patterns from ion-channel and metabolic regulators in young CREM-Tg mice to profibrotic remodeling factors in older CREM-Tg mice. Furthermore, older CREM-Tg mice exhibited protein expression patterns that resembled those of humans with persistent AF. Conclusions: This study uncovered distinct temporal changes in atrial protein expression patterns with age in CREM-Tg mice consistent with the progressive evolution of AF. Future studies into the role of the key differentially abundant proteins identified in this study in AF progression may open new therapeutic avenues to control atrial fibrosis and substrate development in AF.

Right Atrial Remodeling and Outcome in Patients with Secondary Tricuspid Regurgitation.

BACKGROUND: In patients with secondary tricuspid regurgitation (STR), right atrial remodeling (RAR) is a proven marker of disease progression. However, the prognostic value of RAR, assessed by indexed right atrial volume (RAVi) and reservoir strain (RAS), remains to be clarified. Accordingly, the aim of our study is to investigate the association with outcome of RAR in patients with STR. METHODS: We enrolled 397 patients (44% men, 72.7 ± 13 years old) with mild to severe STR. Complete two-dimensional and speckle-tracking echocardiography analysis of right atrial and right ventricular (RV) size and function were obtained in all patients. The primary end point was the composite of death from any cause and heart failure hospitalization. RESULTS: After a median follow-up of 15 months (interquartile range, 6-23), the end point was reached by 158 patients (39%). Patients with RAS <13% and RAVi >48 mL/m2 had significantly lower survival rates compared to patients with RAS ≥13% and RAVi ≤48 mL/m2 (log-rank P < .001). On multivariable analysis, RAS <13% (hazard ratio, 2.11; 95% CI, 1.43-3.11; P < .001) and RAVi > 48 mL/m2 (hazard ratio, 1.49; 95% CI, 1.01-2.18; P = .04) remained associated with the combined end point, even after adjusting for RV free-wall longitudinal strain, significant chronic kidney disease, and New York Heart Association class. Secondary tricuspid regurgitation excess mortality increased exponentially with values of 18.2% and 51.3 mL/m2 for RAS and RAVi, respectively. In nested models, the addition of RAS and RAVi provided incremental prognostic value over clinical, conventional echocardiographic parameters of RV size and function and RV free-wall longitudinal strain. CONCLUSIONS: In patients with STR, RAR was independently associated with mortality and heart failure hospitalization. Assessment of RAR could improve risk stratification of patients with STR, potentially identifying those who may benefit from optimization of medical therapy and a closer follow-up.

Predictors of first pass isolation of the pulmonary veins in real world ablations: An analysis of 2671 patients from the REAL-AF registry.

INTRODUCTION: During atrial fibrillation ablation (AFA), achievement of first pass isolation (FPI) reflects effective lesion formation and predicts long-term freedom from arrhythmia recurrence. We aim to determine the clinical and procedural predictors of pulmonary vein FPI. METHODS: We reviewed AFA procedures in a multicenter prospective registry of AFA (REAL-AF). A multivariate ordinal logistic regression, weighted by inverse proceduralist volume, was used to determine predictors of FPI. RESULTS: A total of 2671 patients were included with 1806 achieving FPI in both vein sides, 702 achieving FPI in one, and 163 having no FPI. Individually, age, left atrial (LA) scar, higher power usage (50 W), greater posterior contact force, ablation index >350 posteriorly, Vizigo™ sheath utilization, nonstandard ventilation, and high operator volume (>6 monthly cases) were all related to improved odds of FPI. Conversely sleep apnea, elevated body mass index (BMI), diabetes mellitus, LA enlargement, antiarrhythmic drug use, and center's higher fluoroscopy use were related to reduced odds of FPI. Multivariate analysis showed that BMI > 30 (OR 0.78 [0.64-0.96]) and LA volume (OR per mL increase = 1.00 [0.99-1.00]) predicted lower odds of achieving FPI, whereas significant left atrial scarring (>20%) was related to higher rates of FPI. Procedurally, the use of high power (50 W) (OR 1.32 [1.05-1.65]), increasing force posteriorly (OR 2.03 [1.19-3.46]), and nonstandard ventilation (OR 1.26 [1.00-1.59]) predicted higher FPI rates. At a site level, high procedural volume (OR 1.89 [1.48-2.41]) and low fluoroscopy centers (OR 0.72 [0.61-0.84]) had higher rates of FPI. CONCLUSION: FPI rates are affected by operator experience, patient comorbidities, and procedural strategies. These factors may be postulated to impact acute lesion formation.