Performance of Different Risk Scores for the Detection of Atrial Fibrillation Among Patients With Cryptogenic Stroke.

BACKGROUND: Atrial fibrillation (AF) is a frequent underlying cause of cryptogenic stroke (CS) and its detection can be increased using implantable cardiac monitoring (ICM). We sought to evaluate different risk scores and assess their diagnostic ability in identifying patients with CS with underlying AF on ICM. METHODS: Patients with CS, being admitted to a single tertiary stroke center between 2017 and 2022 and receiving ICM, were prospectively evaluated. The CHA2DS2-VASc, HAVOC, Brown ESUS-AF, and C2HEST scores were calculated at baseline. The primary outcome of interest was the detection of AF, which was defined as at least 1 AF episode on ICM lasting for 2 consecutive minutes or more. The diagnostic accuracy measures and the net reclassification improvement were calculated for the 4 risk scores. Stroke recurrence was evaluated as a secondary outcome. RESULTS: A total of 250 patients with CS were included, and AF was detected by ICM in 20.4% (n=51) during a median monitoring period of 16 months. Patients with CS with AF detection were older compared with the rest (P=0.045). The median HAVOC, Brown ESUS-AF, and C2HEST scores were higher among the patients with AF compared with the patients without AF (all P<0.05), while the median CHA2DS2-VASc score was similar between the 2 groups. The corresponding C statistics for CHA2DS2-VASc, HAVOC, Brown ESUS-AF, and C2HEST for AF prediction were 0.576 (95% CI, 0.482-0.670), 0.612 (95% CI, 0.523-0.700), 0.666 (95% CI, 0.587-0.746), and 0.770 (95% CI, 0.699-0.839). The C2HEST score presented the highest diagnostic performance based on C statistics (P<0.05 after correction for multiple comparisons) and provided significant improvement in net reclassification for AF detection (>70%) compared with the other risk scores. Finally, stroke recurrence was documented in 5.6% of the study population, with no difference regarding the 4 risk scores between patients with and without recurrent stroke. CONCLUSIONS: The C2HEST score was superior to the CHA2DS2-VASc, HAVOC, and Brown ESUS-AF scores for discriminating patients with CS with underlying AF using ICM.

Early arrhythmia recurrence after cryoballoon ablation in atrial fibrillation: A systematic review and meta-analysis.

INTRODUCTION: Early arrhythmia recurrence within the 3-month blanking period is a common event that historically has been attributed to reversible phenomena. While its mechanistic links remain obscure, accumulating evidence support the argument of shortening the blanking period. We aimed to elucidate the association between early and late arrhythmia recurrence after atrial fibrillation cryoablation. METHODS: The MEDLINE database, ClinicalTrials. gov, medRxiv, and Cochrane Library were searched for studies evaluating early and late arrhythmia recurrence rates in patients undergoing cryoablation for atrial fibrillation. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was late arrhythmia recurrence. RESULTS: Early arrhythmia recurrence was found predictive of decreased arrhythmia-free survival after evaluating 3975 patients with paroxysmal or persistent atrial fibrillation who underwent cryoablation (odds ratio [OR]: 5.31; 95% confidence interval [CI]: 3.75-7.51). This pattern remained unchanged after subanalyzing atrial fibrillation type (paroxysmal; OR: 7.16; 95% CI: 4.40-11.65 and persistent; OR: 7.63; 95% CI: 3.62-16.07) as well as cryoablation catheter generation (first generation; OR: 5.15, 95% CI: 2.39-11.11 and advanced generation; OR: 5.83, 95% CI: 3.68-9.23). Studies permitting antiarrhythmic drug utilization during the blanking period or examining early recurrence as a secondary outcome were found to be a significant source of statistical heterogeneity. CONCLUSION: Our findings suggest that early arrhythmia recurrence is predictive of late outcomes after cryoablation for atrial fibrillation. Identifying which patients deserve earlier reintervention is an open research avenue.

Different venous approaches for implantation of cardiac electronic devices. A network meta-analysis.

OBJECTIVES: Many of the complications arising from cardiac device implantation are associated to the venous access used for lead placement. Previous analyses reported that cephalic vein cutdown (CVC) is safer but less effective than subclavian vein puncture (SVP). However, comparisons between these techniques and axillary vein puncture (AVP) - guided either by ultrasound or fluoroscopy - are lacking. Thus, we aimed to compare safety and efficacy of these approaches. METHODS: We searched for articles assessing at least two different approaches regarding the incidence of pneumothorax and/or lead failure (LF). When available, bleeding and infectious complications as well as procedural success were analyzed. A frequentist random effects network meta-analysis model was adopted. RESULTS: Thirty-six studies were analyzed. Most articles assessed SVP versus CVC. Compared to SVP, both CVC and AVP were associated with reduced odds of pneumothorax (OR: 0.193, 95%CI: 0.136-0.275 and OR: 0.128, 95%CI: 0.050-0.329; respectively) and LF (OR: 0.63, 95%CI: 0.406-0.976 and OR: 0.425, 95%CI: 0.286-0.632; respectively). No significant differences between AVP and CVC were demonstrated. Limited data suggests no major impact of different approaches on infectious and bleeding complications. Initial CVC approach required significantly more often an alternate/additional venous access for lead placement, compared to both AVP and SVP. No differences between these two were identified. CONCLUSION: Both AVP and CVC seem to decrease incident pneumothorax and LF, compared to SVP. Initial AVP approach seems to decrease the need of alternate venous access, compared to CVC. These results suggest that AVP should be further clinically tested.

Implantable Cardiac Monitoring in the Secondary Prevention of Cryptogenic Stroke.

OBJECTIVE: In this study, we sought to evaluate the impact of implantable cardiac monitoring (ICM) in the prevention of stroke recurrence after a cryptogenic ischemic stroke or transient ischemic attack (TIA). METHODS: We evaluated consecutive patients with cryptogenic ischemic stroke or TIA admitted in a comprehensive stroke center during an 8-year period. We compared the baseline characteristics and outcomes between patients receiving conventional cardiac monitoring with repeated 24-hour Holter-monitoring during the first 5 years in the outpatient setting and those receiving continuous cardiac monitoring with ICM during the last 3 years. Associations on the outcomes of interest were further assessed in multivariable regression models adjusting for potential confounders. RESULTS: We identified a total of 373 patients receiving conventional cardiac monitoring and 123 patients receiving ICM. Paroxysmal atrial fibrillation (PAF) detection was higher in the ICM cohort compared to the conventional cardiac monitoring cohort (21.1% vs 7.5%, p < 0.001). ICM was independently associated with an increased likelihood of PAF detection during follow-up (hazard ratio [HR] = 1.94, 95% confidence interval [CI] = 1.16-3.24) in multivariable analyses. Patients receiving ICM were also found to have significantly higher rates of anticoagulation initiation (18.7% vs 6.4%, p < 0.001) and lower risk of stroke recurrence (4.1% vs 11.8%, p = 0.013). ICM was independently associated with a lower risk of stroke recurrence during follow-up (HR = 0.32, 95% CI = 0.11-0.90) in multivariable analyses. INTERPRETATION: ICM appears to be independently associated with a higher likelihood of PAF detection and anticoagulation initiation after a cryptogenic ischemic stroke or TIA. ICM was also independently related to lower risk of stroke recurrence in our cryptogenic stroke / TIA cohort. ANN NEUROL 2020;88:946-955.

Effect of cryoballoon and radiofrequency ablation for pulmonary vein isolation on left atrial function in patients with nonvalvular paroxysmal atrial fibrillation: A prospective randomized study (Cryo-LAEF study).

BACKGROUND: Isolation of the pulmonary veins (PVI) has become a mainstay in atrial fibrillation (AFib) therapy. Lesions in left atrial tissue lead to scar formation and this may affect left atrial function. METHODS: Patients with paroxysmal AFib were randomly assigned in a 1:2 allocation scheme to radiofrequency (RF) ablation or cryoballoon. Real-time three-dimensional echocardiography was performed (under sinus rhythm in all cases) before ablation and at 1 and 3 months to evaluate the left atrial functional indices. The primary outcome measure was change in left atrial ejection fraction (LAEF) at 1 month. RESULTS: 120 patients were randomized (80 to cryoballoon, 40 to RF). The absolute change in LAEF at 1 month was 4.0 (Q1-Q3, -0.1to 7.6)% in the cryoballoon group and -0.8 (Q1-Q3, -1.9 to 0.9)% in the RF group (P < 0.001 for the comparison between groups). At 3 months, the corresponding changes were 6.7 (Q1-Q3, 3.4-11.2)% and 0.7 (Q1-Q3, -0.7 to 3.5)%, respectively (P < 0.001). Overall, the rate of patients with lower LAEF at 3 months compared to baseline was 2.5% in the cryoballoon group and 32.5% in the RF group (P < 0.001). AFib recurrence rate at 6 months was higher in patients with decreased LAEF (odds ratio, 6.2; 95% confidence interval, 2.0-19.5; P = 0.002). CONCLUSION: The Cryo-LAEF study prospectively compared the effects of RF and cryoballoon ablation on left atrial function. Both at 1 and 3 months postablation, LAEF was either improved or stable in both ablation groups.

Effect of Postablation Statin Treatment on Arrhythmia Recurrence in Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: Statins have been proposed as a means to prevent postablation atrial fibrillation (AF) recurrences, mainly on the basis of their pleiotropic effects. The objective of this subanalysis of a prospectively randomized controlled study population of patients undergoing radiofrequency ablation for paroxysmal AF was to test the hypothesis that statin treatment is associated with longer time to recurrence. METHODS AND RESULTS: This is a subanalysis over an extended follow-up period of a prospective randomized study (ClinicalTrials.gov Identifier NCT01791699). Among 291 patients, 2 propensity score-matched subgroups of patients who received or did not receive statins after pulmonary vein isolation were created. In the unmatched cohort, there was no difference in the rate of recurrence between statin-treated and not treated patients, with a 1-year recurrence estimate of 19% and 23%, respectively (Gehan statistic 0.59, P = 0.443). In the propensity-matched cohort (N = 166, 83 per group), recurrence-free survival did not differ significantly between groups (839 days, 95% confidence interval 755-922 days, in the no statin group vs. 904 days, 95% confidence interval 826-983 in the statin group; P = 0.301). The 1-year recurrence rate estimate was 30% in the no statin group versus 27% in the statin group (Gehan statistic 0.56, P = 0.455). CONCLUSION: Statin treatment does not seem to affect AF recurrence in following radiofrequency ablation for paroxysmal AF, over a follow-up time of about 2.5 years.

Effect of pulmonary vein isolation on left atrial appendage flow in paroxysmal atrial fibrillation.

BACKGROUND: Left atrial appendage (LAA) functional modification in the context of pulmonary vein isolation has been a focus point of research and LAA emptying flow velocity (LAAEFV) is considered to reflect LAA contractility, stunning, and fibrosis. OBJECTIVE: In the present study, we sought to prospectively evaluate short-term LAAEFV changes after radiofrequency (RF) or cryoballoon ablation in paroxysmal AF. METHODS: This was a prospective substudy of the Effect of Cryoballoon and RF Ablation on Left Atrial Function (CryoLAEF) study (ClinicalTrials.gov Identifier: NCT02611869). Thirty patients, randomly assigned to RF or cryoablation, were prospectively followed. Transesophageal echocardiograms were performed at baseline and at 3 months postablation to measure LAAEFV. RESULTS: All measurements were performed in sinus rhythm. Overall, LAAEFV was 44.2 [38.5-62.8] cm/s at baseline and was increased to 70.8 [64.8-77.6] cm/s at 3 months' postablation (P < 0.001). Baseline LAAEFV was 52.5 [37.7-68.0] cm/s in the RF group and 42.8 [38.7-52.9] cm/s in the CryoBalloon group (P  =  0.653). At 3 months, the corresponding values were 68.5 [61.9-76.6] cm/s and 73.9 [69.2-79.9] cm/s, respectively (P  =  0.081 for the difference between the two groups at 3 months). The median change in LAAEFV was 11.0 [4.7-26.2] cm/s in the RF group versus 29.6 [15.8-37.0] cm/s in the CryoBalloon group (P  =  0.033). CONCLUSION: LAA function is improved after catheter ablation with RF or balloon cryoablation in patients with paroxysmal AF, evaluated while in sinus rhythm both at baseline and on follow-up.

Left atrial voltage mapping using a new impedance-based algorithm in patients with paroxysmal atrial fibrillation.

AIMS: Atrial fibrosis is associated with the pathogenesis and progression of atrial fibrillation (AF). We sought to evaluate the extent of left atrial (LA) scarring in patients with paroxysmal AF (PAF) undergoing catheter ablation using a new impedance-based algorithm. METHODS: We prospectively enrolled 73 consecutive patients (43 males, 58 years) with PAF who underwent pulmonary vein antral isolation. We first performed high-density bipolar voltage mapping during sinus rhythm using Tissue Proximity Indicator (TPI), one of the features of the ConfiDense mapping module integrated in the electroanatomic mapping system. A dense LA shell was created initially without TPI (mean points 2,411) and subsequently activating TPI (mean points 1,167). Each point was classified according to the peak-to-peak bipolar voltage electrogram based on two criteria (criterion A: healthy >0.8 mV, border zone: 0.4-0.8 mV, scarred: <0.4 mV; criterion B: healthy: >0.5 mV, border zone: 0.25-0.5 mV, scarred: <0.25 mV). RESULTS: LA voltage analysis represented significantly smaller scarred areas when mapping was performed with TPI-ON compared with TPI-OFF in both voltage criteria (average LA voltage area: 3.02 ± 5.28 cm2 vs 9.15 ± 13.11 cm2 vs in criterion A and 1.19 ± 2.54 cm2 vs 5.61 ± 9.56 cm2 in criterion B). A statistically significant voltage difference was observed in all segments of the left atrium between the two mapping protocols, particularly on the inferior wall. CONCLUSION: A more specific delineation of LA fibrosis may be produced using the TPI feature of the ConfiDense mapping module, through elimination of false-positive annotated mapping points due to low contact.

Coincidental ganglionated plexus modification during radiofrequency pulmonary vein isolation and post-ablation arrhythmia recurrence.

AIMS: Vagal responses (VR) during left atrial ablation for atrial fibrillation (AF) treatment have been reported to be associated with less recurrences, presumably because they are a sign of ganglionated plexi modification. Our objective was to evaluate whether coincidentally elicited VR during left atrial ablation are associated with lower AF recurrence rates. METHODS AND RESULTS: This is a post hoc analysis of a prospective study of 291 patients with paroxysmal AF undergoing radiofrequency pulmonary vein isolation (PVI). Vagal responses were defined as episodes of heart rate <40 bpm or asystole lasting >5 s elicited during energy application. Sixty-eight patients (23.4%) had a VR during ablation. In Kaplan-Meier analysis, mean recurrence-free survival was 449 days (95% confidence interval 411-488) in patients with VR when compared with 435 days (95% confidence interval 415-455) in those without (P = 0.310). The 12-month recurrence rate estimates were 25 and 27%, respectively. In an unadjusted Cox model, VR was associated with an odds ratio for recurrence of 0.77 (95% confidence interval 0.46-1.28). CONCLUSION: Coincidentally elicited VR during radiofrequency PVI in patients with paroxysmal AF do not appear to be related to lower risk of arrhythmia recurrence. This may mean that, even if a VR is truly a sign of coincidental ablation of a ganglionated plexus, this does not necessarily mean that a therapeutic modification has been effected, at least to a degree associated with clinical benefit.

Central sympathetic inhibition to reduce postablation atrial fibrillation recurrences in hypertensive patients: a randomized, controlled study.

BACKGROUND: The autonomic system is an important determinant of atrial arrhythmogenesis. Current evidence indicates that a combined sympathovagal drive is most commonly responsible for eliciting atrial fibrillation (AF) episodes. The purpose of this study was to test whether moxonidine, a centrally acting sympathoinhibitory agent, can lead to a reduction in postablation AF recurrence. METHODS AND RESULTS: This was a prospective, double-blinded, randomized study of 291 hypertensive patients with symptomatic paroxysmal AF who were scheduled to undergo pulmonary vein isolation. Patients were randomly assigned to receive either moxonidine (0.2-0.4 mg daily) or placebo, along with standard antihypertensive treatment. No significant differences in blood pressure levels were observed between the 2 groups. In the primary outcome analysis, mean recurrence-free survival was 467 days (95% CI, 445-489 days) in the moxonidine group as compared with 409 days (95% CI, 381-437 days) in control subjects (log rank test, P=0.006). The calculated 12-month recurrence rate estimates were 36.9% in the control group and 20.0% in the moxonidine group (P=0.007). Moxonidine treatment was associated with lower recurrence risk after adjustment for age, body mass index, number of AF episodes in the previous year, and left atrial diameter (adjusted hazard ratio, 0.35 [95% CI, 0.22-0.55]; P<0.001). CONCLUSIONS: Treatment with moxonidine is associated with less AF recurrences after ablation treatment for drug-refractory AF in patients with hypertension. The observed effect does not appear to depend on the antihypertensive action of this agent. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01791699.

CHADS2 and CHA2DS2-VASc scores as predictors of left atrial ablation outcomes for paroxysmal atrial fibrillation.

AIMS: The selection of patients with atrial fibrillation (AF) that will benefit most by left atrial ablation remains suboptimal. CHADS2 score has been shown to be associated with post-ablation AF recurrences. However, data regarding the CHA2DS2-VASc score are lacking. In addition, there is paucity of data regarding the exact predictive value, in terms of sensitivity and specificity, of each of these scores as to AF recurrence. This study aimed to evaluate the merit of the CHADS2 and CHA2DS2-VASc scores in predicting arrhythmia recurrence after a single ablation procedure for paroxysmal AF. METHODS AND RESULTS: One hundred and twenty-six patients (78 males, median age 61 years) with symptomatic paroxysmal AF underwent left atrial ablation. Over 16 months (interquartile range: 10.8-26.0), 89 patients were recurrence-free (70.6%). Larger left atrial volume (P: 0.039), diabetes (P: 0.001), dyslipidemia (P: 0.003), coronary artery disease (P: 0.003), class III antiarrhythmic drugs (P: 0.017), CHADS2 (P: 0.006), and CHA2DS2-VASc (P: 0.016) scores were univariately associated with recurrence. In the multivariate analysis, both CHADS2 (hazard ratio: 1.91, 95% confidence interval 1.09-3.36, P: 0.023) and CHA2DS2-VASc (hazard ratio: 1.97, 95% confidence interval 1.16-3.33, P: 0.012) were independently associated with AF recurrence. Cut-off analysis showed that a score ≥2 for both the CHADS2 (sensitivity = 46% and specificity = 79%, area under the Receiver's operating characteristic curve, AUC = 0.644) and CHA2DS2-VASc score (sensitivity = 57% and specificity = 65%, AUC = 0.627) showed the highest predictive value for AF recurrence. CONCLUSIONS: CHA2DS2-VASc score is an independent predictor of left atrial ablation outcomes for paroxysmal AF, with a similar predictive value to CHADS2. However, the predictive accuracy of both is mediocre.

Epicardial Adipose Tissue and Atrial Fibrillation Recurrence following Catheter Ablation: A Systematic Review and Meta-Analysis.

(1)Introduction: Catheter ablation has become a cornerstone for the management of patients with atrial fibrillation (AF). Nevertheless, recurrence rates remain high. Epicardial adipose tissue (EAT) has been associated with AF pathogenesis and maintenance. However, the literature has provided equivocal results regarding the relationship between EAT and post-ablation recurrence.(2) Purpose: to investigate the relationship between total and peri-left atrium (peri-LA) EAT with post-ablation AF recurrence. (3) Methods: major electronic databases were searched for articles assessing the relationship between EAT, quantified using computed tomography, and the recurrence of AF following catheter ablation procedures. (4) Results: Twelve studies (2179 patients) assessed total EAT and another twelve (2879 patients) peri-LA EAT. Almost 60% of the included patients had paroxysmal AF and recurrence was documented in 34%. Those who maintained sinus rhythm had a significantly lower volume of peri-LA EAT (SMD: -0.37, 95%; CI: -0.58-0.16, I2: 68%). On the contrary, no significant difference was documented for total EAT (SMD: -0.32, 95%; CI: -0.65-0.01; I2: 92%). No differences were revealed between radiofrequency and cryoenergy pulmonary venous isolation. No publication bias was identified. (5) Conclusions: Only peri-LA EAT seems to be predictive of post-ablation AF recurrence. These findings may reflect different pathophysiological roles of EAT depending on its location. Whether peri-LA EAT can be used as a predictor and target to prevent recurrence is a matter of further research.

Weekly physical activity and incident atrial fibrillation in females - A dose-response meta-analysis.

BACKGROUND: For years, physical activity (PA) has been considered a mixed blessing in terms of the risk of incident atrial fibrillation (AF). Previous analyses have had equivocal results regarding the cut-off of PA level beyond which AF risk increases, if such a limit really does exist. Data regarding females in particular have been scarce. METHODS: We performed a dose-response meta-analysis to investigate the relationship between weekly PA and the risk for AF in females. Major electronic databases were searched for studies assessing the association between leisure time PA and the risk for incident AF in females from the general population. The linearity of the dose-response curve was assessed using the restricted cubic spline model. RESULTS: A total of 15 studies, which involved 1,821,422 females, were included in the final analysis. AF incidence was 3.7%. Dose-response analysis revealed an inverse nonlinear relationship between weekly PA and the risk for incident AF (p for linearity <0.0001). No significant heterogeneity was documented (I2 = 37%). Cautious interpretation is needed for PA exceeding 50 metabolic equivalents of task- hours per week (METs- h/w), due to limited available data for these high levels of PA. CONCLUSION: According to this analysis, physicians can safely advise females to perform up to 50METs- h/w of moderate or vigorous PA, to reduce the risk for future AF. Interestingly, significant benefit can be attained even at low levels of regular weekly PA.

Atrial strain and occult atrial fibrillation in cryptogenic stroke patients: a systematic review and meta-analysis.

BACKGROUND: Cryptogenic stroke (CS) remains a significant cause of morbidity. Failure to identify the underlying pathology increases the rate of recurrence. Atrial fibrillation (AF) seems to be responsible for a substantial proportion of CS. Thus, there is an unmet need to identify and properly treat those with silent AF. PURPOSE: To investigate the association between left atrial strain and newly diagnosed AF in CS patients. OBJECTIVES: We searched major electronic databases for articles assessing the relationship between either peak left atrial longitudinal (PALS) or peak contractile (PACS) strain-quantified using speckle tracking echocardiography-and the incidence of occult AF during the diagnostic work-up of CS patients. RESULTS: Eleven studies (two thousand and eighty-one patients) were analyzed. Incidence of occult AF was 19%. Both PALS and PACS were significantly lower in patients with newly diagnosed AF (MD - 8.6%, 95%CI - 10.7 to - 6.4, I2 86.4% and MD - 5.5, 95%CI - 6.8 to - 4.2, I2 80.8%). According to the diagnostic accuracy meta-analysis, PALS < 20% present 71% (95%CI 47-87%) sensitivity and 71% (95%CI 60-81%) specificity for the diagnosis of occult AF, assuming a prevalence of 20%. The corresponding values for PACS < 11% are 83% (95%CI 57-94%) and 78% (95%CI 56-91%). CONCLUSION: Both PALS and PACS are significantly lower in patients with CS and silent AF. It seems that the cut-off values mentioned above could help physicians in identifying patients who may benefit more from prolonged rhythm monitoring. More studies are needed to confirm these findings.

Efficacy, Safety and Feasibility of Superior Vena Cava Isolation in Patients Undergoing Atrial Fibrillation Catheter Ablation: An Up-to-Date Review.

Pulmonary vein isolation (PVI) is the cornerstone in atrial fibrillation (AF) ablation; yet, the role of arrhythmogenic superior vena cava (SVC) is increasingly recognized and different ablation strategies have been employed in this context. SVC can act as a trigger or perpetuator of AF, and its significance might be more pronounced in patients undergoing repeated ablation. Several cohorts have examined efficacy, safety and feasibility of SVC isolation (SVCI) among AF patients. The majority of these studies explored as-needed SVCI during index PVI, and only a minority of them included repeated ablation subjects and non-radiofrequency energy sources. Studies of heterogeneous design and intent have explored both empiric and as-needed SVCI on top of PVI and reported inconclusive results. These studies have largely failed to demonstrate any clinical benefit in terms of arrhythmia recurrence, although safety and feasibility are undisputable. Mixed population demographics, small number of enrollees and short follow-up are the main limitations. Procedural and safety data are comparable between empiric SVCI and as-needed SVCI, and some studies suggested that empiric SVCI might be associated with reduced AF recurrences in paroxysmal AF patients. Currently, no study has compared different ablation energy sources in the setting of SVCI, and no randomized study has addressed as-needed SVCI on top of PVI. Furthermore, data regarding cryoablation are still in their infancy, and regarding SVCI in patients with cardiac devices more safety and feasibility data are needed. PVI non-responders, patients undergoing repeated ablation and patients with long SVC sleeves could be potential candidates for SVCI, especially via an empiric approach. Although many technical aspects remain unsettled, the major question to answer is which clinical phenotype of AF patients might benefit from SVCI?

Advances in the Management of Heart Failure with Reduced Ejection Fraction; The Role of SGLT2is, ARNI, Myotropes, Vericiguat, and Anti-inflammatory Agents: A Mini-review.

Heart failure with reduced ejection fraction (HFrEF) has been associated with poor prognosis, reduced quality of life, and increased healthcare expenditure. Despite tremendous advances in HFrEF management, reduced survival and a high rate of hospitalization remain unsolved issues. Furthermore, HFrEF morbidity and economic burden are estimated to increase in the following years; hence, new therapies are constantly emerging. In the last few years, a series of landmark clinical trials have expanded our therapeutic armamentarium with a ground-breaking change in HFrEF-related outcomes. Sodium-glucose co-transporter 2 inhibitors (mainly dapagliflozin and empagliflozin) have already revolutionized the management of HFrEF patients via a significant reduction in cardiovascular mortality and heart failure hospitalizations. Furthermore, vericiguat and omecamtiv mecarbil have emerged as promising and novel disease-modifying therapies. The former restores the impaired cyclic guanosine monophosphate pathway, and the latter stimulates cardiac myosin without marked arrhythmogenesis. Both vericiguat and omecamtiv mecarbil have been shown to reduce heart failure admissions. Sacubitril/valsartan is an established and effective therapy in HFrEF patients and should be considered as a replacement for angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs). Lastly, inflammasome activity is implicated in HFrEF pathophysiology, and the role of anti-inflammatory agents in HFrEF trajectories is readily scrutinized, yet available therapies are ineffective. This mini-review summarizes the major and most recent studies in this field, thus covering the current advances in HFrEF therapeutics.

Left atrial appendage morphofunctional indices could be predictive of arrhythmia recurrence post-atrial fibrillation ablation: a meta-analysis.

BACKGROUND: Left atrium changes are implicated in atrial fibrillation (AF) substrate and are predictive of AF outcomes. Left atrial appendage (LAA) is an integral component of left atrial structure and could be affected by atrial cardiomyopathy. We aimed to elucidate the association between LAA indices and late arrhythmia recurrence after atrial fibrillation catheter ablation (AFCA). METHODS: The MEDLINE database, ClinicalTrials.gov, medRxiv and Cochrane Library were searched for studies evaluating LAA and late arrhythmia recurrence in patients undergoing AFCA. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was pre-ablation difference in LAA anatomic or functional indices. RESULTS: A total of 34 studies were found eligible and five LAA indices were analyzed. LAA ejection fraction and LAA emptying velocity were significantly lower in patients with AF recurrence post-ablation [SMD = - 0.66; 95% CI (- 1.01, - 0.32) and SMD = - 0.56; 95% CI (- 0.73, - 0.40) respectively] as compared to arrhythmia free controls. LAA volume and LAA orifice area were significantly higher in patients with AF recurrence post-ablation (SMD = 0.51; 95% CI 0.35-0.67, and SMD = 0.35; 95% CI 0.20-0.49, respectively) as compared to arrhythmia free controls. LAA morphology was not predictive of AF recurrence post-ablation (chicken wing morphology; OR 1.27; 95% CI 0.79-2.02). Moderate statistical heterogeneity and small case-control studies are the main limitations of our meta-analysis. CONCLUSIONS: Our findings suggest that LAA ejection fraction, LAA emptying velocity, LAA orifice area and LAA volume differ between patients suffering from arrhythmia recurrence post-ablation and arrhythmia free counterparts, while LAA morphology is not predictive of AF recurrence.

The role of left atrial peak systolic strain in atrial fibrillation recurrence after catheter ablation. A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis was performed to assess the prognostic role of left atrial peak systolic longitudinal strain (LA-PLSsys) as a predictor of atrial fibrillation (AF) recurrence after catheter ablation. METHODS: We systematically searched major electronic databases and grey literature for studies assessing the role of pre-ablation LA-PLSsys, measured in at least two segments, in post-ablation AF recurrence, after a follow-up period of at least 6 months. RESULTS: Seventeen eligible studies were included, resulting in 1704 patients (68.6% men) with a pooled mean age of 59.9 ± 10.6 years, 65.9% with paroxysmal AF. Recurrence occurred in 32.7% of patients. Those without recurrence had significantly higher LA-PLSsys (pooled mean ± SD: 22.22 ± 10.64%, weighted mean difference: 5.43%, 95%CI: 4.03-6.84%, I2: 82.7%). Subgroup analysis revealed that the methodology used (echocardiographic view and segments assessed), was a significant source of heterogeneity (p = 0.02). Meta-regression analysis demonstrated that the effect size was inversely related to the baseline LA volume index (p = 0.004), while concerns are also raised about patients with extremely high/low pre-ablation LA strain. CONCLUSIONS: Pre-ablation LA-PLSsys seems to be a useful predictor of post-ablation AF recurrence, that could optimise patients selection. Nevertheless, the substantial heterogeneity that was noted may limit its clinical use. Further investigation using a uniform methodological assessment technique is required to derive a reference range, with adequate positive and negative predictive value for recurrence.

The prognostic role of late gadolinium enhancement on cardiac magnetic resonance in patients with nonischemic cardiomyopathy and reduced ejection fraction, implanted with cardioverter defibrillators for primary prevention. A systematic review and meta-analysis.

BACKGROUND: Previous studies suggest that late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is associated with arrhythmic events in patients with nonischemic cardiomyopathy (NICM), while others have questioned the role of left ventricular ejection fraction (LVEF) as a sole predictor of future events. OBJECTIVES: To evaluate the role of LGE on CMR in identifying patients with NICM and reduced LVEF for whom a benefit from defibrillator implantation for primary prevention is not anticipated, thus they are mainly exposed to potential risks. METHODS: Major electronic databases were searched for studies reporting the incidence of appropriate device therapy (ADT), sudden cardiac death (SCD), and cardiac death based on the presence of LGE on CMR, among patients with NICM and reduced LVEF, implanted with a cardioverter defibrillator for primary prevention. RESULTS: Eleven studies (1652 patients, 947 with LGE) were included in the final analysis. LGE presence was strongly associated with ADT (logOR: 1.95, 95%CI: 1.21-2.69) and cardiac death (logOR: 0.91, 95%CI: 0.14-1.68), but not with SCD (logOR: 0.26, 95%CI: -1.09-1.6). Diagnostic accuracy analysis demonstrated that contrast enhancement is a sensitive marker of future ADT and cardiac death (93%, 95%CI: 85.8-96.7%; 82.9%, 95%CI: 70.6-90.7%; respectively), with moderate specificity ( 44%, 95%CI: 27.2-62.6%; 37.7%, 95%CI: 23.4-54.6%; respectively). CONCLUSION: LGE is a highly sensitive predictor of ADT and cardiac death in NICM patients implanted with a defibrillator for primary prevention. However, due to moderate specificity, derivation of a cutoff with adequate predictive values and probably a multifactorial approach are needed to improve discrimination of patients who will not benefit from ICDs.

Inflammatory Biomarkers in Coronary Artery Ectasia: A Systematic Review and Meta-Analysis.

Isolated coronary artery ectasia (CAE) is a relatively rare clinical entity, the pathogenesis of which is poorly understood. More and more evidence is accumulating to suggest a critical inflammatory component. We aimed to elucidate any association between neutrophil to lymphocyte ratio and coronary artery ectasia. A systematic MEDLINE database, ClinicalTrials.gov, medRxiv, Scopus and Cochrane Library search was conducted: 50 studies were deemed relevant, reporting on difference in NLR levels between CAE patients and controls (primary endpoint) and/or on high-sensitive CRP, IL-6, TNF-a and RDW levels (secondary endpoint), and were included in our final analysis. (PROSPERO registration number: CRD42021224195). All inflammatory biomarkers under investigation were found higher in coronary artery ectasia patients as compared to healthy controls (NLR; SMD = 0.73; 95% CI: 0.27-1.20, hs-CRP; SMD = 0.96; 95% CI: 0.64-1.28, IL-6; SMD = 2.68; 95% CI: 0.95-4.41, TNF-a; SMD = 0.50; 95% CI: 0.24-0.75, RDW; SMD = 0.56; 95% CI: 0.26-0.87). The main limitations inherent in this analysis are small case-control studies of moderate quality and high statistical heterogeneity. Our findings underscore that inflammatory dysregulation is implicated in coronary artery ectasia and merits further investigation.