Functional substrate analysis in patients with persistent atrial fibrillation.

OBJECTIVES: The aim of this study was to describe the correlation between atrial electrogram duration map (AEDUM), spatiotemporal electrogram dispersion (STED) and low voltage areas (LVA) in patients with persistent atrial fibrillation (PsAF). BACKGROUND: The degree of left atrial (LA) tissue remodelling and augmented anisotropic conduction is one of the major issues related to PsAF ablation outcome. METHODS: This study enrolled consecutive patients with PsAF undergoing pulmonary vein isolation. In all patients, voltage, AEDUM and STED maps were created, and the correlation was reported between these three mapping methods. RESULTS: A total of 40 patients with PsAF were enrolled. The mean age was 62.2 ± 7.4 years, and males were 72.5% (n = 29). The overall bipolar voltage of the LA was 3.06 ± 1.87 mV. All patients had at least one AEDUM area (overall AEDUM area: 21.8 ± 8.2 cm2); the mean longest electrogram (EGMs) duration was 90 ± 19 ms. STED areas with < 120 ms was 46.3 ± 20.2 cm2 which covered 45 ± 22% of the LA surface. AEDUM and STED areas were most frequently reported on the roof, the anterior wall and the septum. The extension of the AEDUM areas was significantly smaller than STED areas with CL < 120 ms (21.8 ± 8.2 vs 46.3 ± 20.2; p-value < 0.0001). In 24 patients (60%), AEDUM areas was entirely included in the STED areas with CL < 120 ms. In the three (7.5%) patients with LVA, no correspondence with STED and AEDUM was noted. CONCLUSION: AEDUM and STED maps allow to identify areas of conductive dysfunction as a possible atrial substrate even if a normal voltage is detected.

National workflow experience with pulsed field ablation for atrial fibrillation: learning curve, efficiency, and safety.

BACKGROUND: Recent data on pulsed field ablation (PFA) for atrial fibrillation (AF) ablation suggest a progressive reduction in procedural times. Real-world data regarding the relationship between the learning curve of PFA and clinical outcomes are scarce. The objective was to evaluate the PFA learning curve and its impact on acute outcomes. METHODS: Consecutive patients undergoing AF ablation with the FARAPULSE™ PFA system were included in a prospective, non-randomized multicenter study. Procedural times were stratified on the operators' learning curve. Comparative analysis of skin-to-skin time was conducted with radiofrequency (RF) and cryoablation (CB) pulmonary vein isolation (PVI) procedures performed by the same operators in the previous year. RESULTS: Among 752 patients, 35.1% were females, and 66.9% had paroxysmal AF; mean age was 62.2 ± 10 years. A total of 62.5% of procedures were performed by operators with > 20 PFA procedures. Both time to PVI (25.6 ± 10 min vs 16.5 ± 8, p < 0.0001) and fluoroscopy time (19.8 ± 8 min vs 15.9 ± 8 min, p = 0.0045) significantly improved after 10 associated with consistent linear trend towards procedural time reduction (R2 0.92-0.68 across various procedural metrics). Current PFA skin-to-skin time was lower than the historical skin-to-skin one in 217 (62.4%) procedures; it was similar in 112 (32.2%) cases and higher than the historical skin-to-skin one in 19 (5.5%). No major complications were reported. CONCLUSIONS: In this nationwide multicentric experience, the novel PFA system proved to be fast, safe, and acutely effective in both paroxysmal and persistent AF patients. The learning curve appears to be rapid, as improvements in procedural parameters were observed after only a few procedures. CLINICAL TRIAL REGISTRATION: Advanced TecHnologies For SuccEssful AblatioN of AF in Clinical Practice (ATHENA). URL: http://clinicaltrials.gov/ Identifier: NCT05617456.

Long-Term Clinical-Pathologic Results of Enzyme Replacement Therapy in Prehypertrophic Fabry Disease Cardiomyopathy.

BACKGROUND: The limited ability of enzyme replacement therapy (ERT) in removing globotriaosylceramide from cardiomyocytes is recognized for advanced Fabry disease cardiomyopathy (FDCM). Prehypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here on the long-term clinical-pathologic impact of ERT on prehypertrophic FDCM. METHODS AND RESULTS: Fifteen patients with Fabry disease with left ventricular maximal wall thickness ≤10.5 mm at cardiac magnetic resonance required endomyocardial biopsy because of angina and ventricular arrhythmias. Endomyocardial biopsy showed coronary small-vessel disease in the angina cohort, and vacuoles in smooth muscle cells and cardiomyocytes ≈20% of the cell surface containing myelin bodies at electron microscopy. Patients received α-agalsidase in 8 cases, and ß-agalsidase in 7 cases. Both groups experienced symptom improvement except 1 patients treated with α-agalsidase and 1 treated with ß-agalsidase. After ERT administration ranging from 4 to 20 years, all patients had control cardiac magnetic resonance and left ventricular endomyocardial biopsy because of persistence of symptoms or patient inquiry on disease resolution. In 13 asymptomatic patients with FDCM, left ventricular maximal wall thickness and left ventricular mass, cardiomyocyte diameter, vacuole surface/cell surface ratio, and vessels remained unchanged or minimally increased (left ventricular mass increased by <2%) even after 20 years of observation, and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed, with larger and more engulfed by globotriaosylceramide myocytes being associated with myocardial virus-negative lymphocytic inflammation. CONCLUSIONS: ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with prehypertrophic FDCM. Globotriaosylceramide is never completely removed even after long-term treatment. Immune-mediated myocardial inflammation can overlap, limiting ERT activity.

Implantable loop recorders in patients with Brugada syndrome: the BruLoop study.

BACKGROUND AND AIMS: Available data on continuous rhythm monitoring by implantable loop recorders (ILRs) in patients with Brugada syndrome (BrS) are scarce. The aim of this multi-centre study was to evaluate the diagnostic yield and clinical implication of a continuous rhythm monitoring strategy by ILRs in a large cohort of BrS patients and to assess the precise arrhythmic cause of syncopal episodes. METHODS: A total of 370 patients with BrS and ILRs (mean age 43.5 ± 15.9, 33.8% female, 74.1% symptomatic) from 18 international centers were included. Patients were followed with continuous rhythm monitoring for a median follow-up of 3 years. RESULTS: During follow-up, an arrhythmic event was recorded in 30.7% of symptomatic patients [18.6% atrial arrhythmias (AAs), 10.2% bradyarrhythmias (BAs), and 7.3% ventricular arrhythmias (VAs)]. In patients with recurrent syncope, the aetiology was arrhythmic in 22.4% (59.3% BAs, 25.0% VAs, and 15.6% AAs). The ILR led to drug therapy initiation in 11.4%, ablation procedure in 10.9%, implantation of a pacemaker in 2.5%, and a cardioverter-defibrillator in 8%. At multivariate analysis, the presence of symptoms [hazard ratio (HR) 2.5, P = .001] and age >50 years (HR 1.7, P = .016) were independent predictors of arrhythmic events, while inducibility of ventricular fibrillation at the electrophysiological study (HR 9.0, P < .001) was a predictor of VAs. CONCLUSIONS: ILR detects arrhythmic events in nearly 30% of symptomatic BrS patients, leading to appropriate therapy in 70% of them. The most commonly detected arrhythmias are AAs and BAs, while VAs are detected only in 7% of cases. Symptom status can be used to guide ILR implantation.

Lower rate of major bleeding in very high risk patients undergoing left atrial appendage occlusion: A propensity score-matched comparison with direct oral anticoagulation.

BACKGROUND: Long-term oral anticoagulation is the mainstay therapy for thromboembolic (TE) prevention in patients with atrial fibrillation. However, left atrial appendage occlusion (LAAO) could be a safe alternative to direct oral anticoagulants (DOACs) in patients with a very high TE risk profile. OBJECTIVE: The purpose of this study was to compare the safety and efficacy of LAAO vs DOACs in patients with atrial fibrillation at very high stroke risk (CHA2DS2-VASc [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category] score ≥ 5). METHODS: Data from patients with CHA2DS2-VASc score ≥ 5 were extracted from a prospective multicenter database. To attenuate the imbalance in covariates between groups, propensity score matching was used (covariates: CHA2DS2-VASc and HAS-BLED [hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol] scores), which resulted in a matched population of 277 patients per group. The primary end point was a composite of cardiovascular death, TE events, and clinically relevant bleeding during follow-up. RESULTS: Of 2381 patients, 554 very high risk patients were included in the study (mean age 79 ± 7 years; CHA2DS2-VASc score 5.8 ± 0.9; HAS-BLED score 3.0 ± 0.9). The mean follow-up duration was 25 ± 11 months. A higher incidence of the composite end point was documented with DOACs compared with LAAO (14.9 events per 100 patient-years in the DOAC group vs 9.4 events per 100 patient-years in the LAAO group; P = .03). The annualized clinically relevant bleeding risk was higher with DOACs (6.3% vs 3.2%; P = .04), while the risk of TE events was not different between groups (4.1% vs 3.2%; P = .63). CONCLUSION: In high-risk patients, LAAO had a similar stroke prevention efficacy but a significantly lower risk of clinically relevant bleeding when compared with DOACs. The clinical benefit of LAAO became significant after 18 months of follow-up.

Ablation of persistent atrial fibrillation based on atrial electrogram duration map: methodology and clinical outcomes from the AEDUM pilot study.

BACKGROUND: Catheter ablation of persistent atrial fibrillation (PsAF) represents a challenge for the electrophysiologist and there are still divergences regarding the best ablative approach to adopt. Create a new map of the duration of atrial bipolar electrograms (Atrial Electrogram DUration Map, AEDUM) to recognize a functional substrate during sinus rhythm and guide a patient-tailored ablative strategy for PsAF. METHODS: Forty PsAF subjects were assigned in a 1:1 ratio to either for PVI alone (Group B1) or PVI+AEDUM areas ablation (Group B2). A cohort of 15 patients without AF history undergoing left-sided accessory pathway ablation was used as a control group (Group A). In all patients, voltage and AEDUM maps were created during sinus rhythm. The minimum follow-up was 12 months, with rhythm monitoring via 48-h ECG Holter or by implantable cardiac device. RESULTS: Electrogram (EGM) duration was higher in Group B than in Group A (49±16.2ms vs 34.2±3.8ms; p-value<0.001). In Group B the mean cumulative AEDUM area was 21.8±8.2cm2; no difference between the two subgroups was observed (22.3±9.1cm2 vs 21.2±7.2cm2; p-value=0.45). The overall bipolar voltage recorded inside the AEDUM areas was lower than in the remaining atrial areas [median: 1.30mV (IQR: 0.71-2.38mV) vs 1.54mV (IQR: 0.79-2.97mV); p-value: <0.001)]. Low voltage areas (<0.5mV) were recorded in three (7.5%) patients in Group B. During the follow-up [median 511 days (376-845days)] patients who underwent PVI-only experienced more AF recurrence than those receiving a tailored approach (65% vs 35%; p-value= 0.04). CONCLUSIONS: All PsAF patients exhibited AEDUM areas. An ablation approach targeting these areas resulted in a more effective strategy compared with PVI only.

Arrhythmic risk profile in mitral valve prolapse: A systematic review and metanalysis of 1715 patients.

INTRODUCTION: Mitral valve prolapse (MVP) is a common clinical condition in the general population. A subgroup of patients with MVP may experience ventricular arrhythmias and sudden cardiac death ("arrhythmic mitral valve prolapse" [AMVP]) but how to stratify arrhythmic risk is still unclear. Our meta-analysis aims to identify predictive factors for arrhythmic risk in patients with MVP. METHODS: We systematically searched Medline, Cochrane, Journals@Ovid, Scopus electronic databases for studies published up to December 28, 2022 and comparing AMVP and nonarrhythmic mitral valve prolapse (NAMVP) for what concerns history, electrocardiographic, echocardiographic and cardiac magnetic resonance features. The effect size was estimated using a random-effect model as odds ratio (OR) and mean difference (MD). RESULTS: A total of 10 studies enrolling 1715 patients were included. Late gadolinium enhancement (LGE) (OR: 16.67; p = .005), T-wave inversion (TWI) (OR: 2.63; p < .0001), bileaflet MVP (OR: 1.92; p < .0001) and mitral anulus disjunction (MAD) (OR: 2.60; p < .0001) were more represented among patients with AMVP than in NAMVP. Patients with AMVP were shown to have longer anterior mitral leaflet (AML) (MD: 2.63 mm; p < .0001), posterior mitral leaflet (MD: 2.96 mm; p < .0001), thicker AML (MD: 0.49 mm; p < .0001), longer MAD length (MD: 1.24 mm; p < .0001) and higher amount of LGE (MD: 1.41%; p < .0001) than NAMVP. AMVP showed increased mechanical dispersion (MD: 8.04 ms; 95% confidence interval: 5.13-10.96; p < .0001) compared with NAMVP. CONCLUSIONS: Our meta-analysis proved that LGE, TWI, bileaflet MVP, and MAD are predictive factors for arrhythmic risk in MVP patients.

Modified sympathicotomy in patients with refractory ventricular tachycardia and structural heart disease: a single-center experience.

BACKGROUND: Modified cardiac sympathetic denervation (CSD) with stellate ganglion (SG) sparing is a novel technique for cardiac neuromodulation in patients with refractory ventricular tachycardia (VT). OBJECTIVES: Our aim is to describe the mid- to long-term clinical outcome of the modified CSD with SG sparing in a series of patients with structural heart disease (SHD) and refractory VT. METHODS: All consecutive patients with SHD and refractory VT undergoing modified CSD were enrolled. Baseline clinical characteristics and periprocedural data were collected for all patients. The primary outcome was any recurrence of sustained VT. RESULTS: We enrolled 15 patients (age: 69.2 ± 7.9 years; male 100%) undergoing modified CSD. Left ventricular ejection fraction was 37 ± 11% and all patients had an implantable cardiac defibrillator (ICD); the underlying cardiomyopathy was non-ischemic in 73.3% of them. At least one previous ablation had been attempted in 66.6% of cases. The 73.3% of patients underwent bilateral CSD and the mean effective surgical time was 10.8 ± 2.4 min per side; no major periprocedural complication occurred. After a median follow-up time of 15 months (IQR: 8.5-24.5 months), the primary outcome occurred in 47.6% of cases. All patients experienced a reduction of ICD shocks after CSD (3.1 ICD shocks/patient before vs. 0.3 ICD shocks/patient after CSD; p-value: 0.001). Bilateral CSD and a VT cycle length < 340 ms were associated with better outcomes. CONCLUSIONS: A modified CSD approach with stellate ganglion sparing appears to be safe, fast, and effective in the treatment of patients with SHD and refractory VTs.

Catheter ablation in patients with paroxysmal atrial fibrillation and absence of structural heart disease: A meta-analysis of randomized trials.

Introduction: Rhythm control strategy in paroxysmal atrial fibrillation (AF) can be performed with antiarrhythmic drugs (AAD) or catheter ablation (CA). Nevertheless, a clear overview of the percentage of freedom from AF over time and complications is lacking. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) comparing CA versus AAD. Methods: We searched databases up to 5 May 2023 for RCTs focusing on CA versus AAD. The study endpoints were atrial tachyarrhythmia (AT) recurrence, progression to persistent AF, overall complications, stroke/TIA, bleedings, heart failure (HF) hospitalization and all-cause mortality. Results: Twelve RCTs enrolling 2393 patients were included. CA showed a significantly lower AT recurrence rate at one year [27.4 % vs 56.3 %; RR: 0.45; p < 0.00001], at two years [39.9 % vs 62.7 %; RR: 0.56; p = 0.0004] and at three years [45.7 % vs 80.9 %; RR: 0.54; p < 0.0001] compared to AAD. Furthermore, CA significantly reduced the progression to persistent AF [1.6 % vs 12.9 %; RR: 0.14; p < 0.00001] with no differences in overall complications [5.9 % vs 4.5 %; RR: 1.27; p = 0.22], stroke/TIA [0.6 % vs 0.6 %; RR: 1.10; p = 0.86], bleedings [0.4 % vs 0.6 %; RR: 0.90; p = 0.84], HF hospitalization [0,3% vs 0,7%; RR: 0.56; p = 0.37] and all-cause mortality [0,4% vs 0.5 %; RR: 0.78; p = 0.67]. Subgroup analysis between radiofrequency and cryo-ablation or considering RCTs with CA as first-line treatment showed no significant differences. Conclusion: CA demonstrated lower rates of AT recurrence over the time, as well as a significant reduction in the progression from paroxysmal to persistent AF, with no difference in terms of energy source, complications, and clinical outcomes.

Prognostic value of chronic kidney disease in patients undergoing left atrial appendage occlusion.

AIMS: Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist and share an increased risk of thrombo-embolism (TE). CKD concomitantly predisposes towards a pro-haemorrhagic state. Our aim was to evaluate the prognostic value of CKD in patients undergoing percutaneous left atrial appendage occlusion (LAAO). METHODS AND RESULTS: A total of 2124 consecutive AF patients undergoing LAAO were categorized into CKD stage 1+2 (n = 1089), CKD stage 3 (n = 796), CKD stage 4 (n = 170), and CKD stage 5 (n = 69) based on the estimated glomerular filtration rate at baseline. The primary endpoint included cardiovascular (CV) mortality, TE, and major bleeding. The expected annual TE and major bleeding risks were estimated based on the CHA2DS2-VASc and HAS-BLED scores. A non-significant higher incidence of major peri-procedural adverse events (1.7 vs. 2.3 vs. 4.1 vs. 4.3) was observed with worsening CKD (P = 0.14). The mean follow-up period was 13 ± 7 months (2226 patient-years). In comparison to CKD stage 1+2 as a reference, the incidence of the primary endpoint was significantly higher in CKD stage 3 (log-rank P-value = 0.04), CKD stage 4 (log-rank P-value = 0.01), and CKD stage 5 (log-rank P-value = 0.001). Left atrial appendage occlusion led to a TE risk reduction (RR) of 72, 66, 62, and 41% in each group. The relative RR of major bleeding was 58, 44, 51, and 52%, respectively. CONCLUSION: Patients with moderate-to-severe CKD had a higher incidence of the primary composite endpoint. The relative RR in the incidence of TE and major bleeding was consistent across CKD groups.

High power short duration versus low power long duration ablation in patients with atrial fibrillation: A meta-analysis of randomized trials.

BACKGROUND: High-power-short-duration (HPSD) radiofrequency (RF) ablation is a viable alternative to low-power-long-duration (LPLD) RF for pulmonary vein isolation (PVI). Nevertheless, trials showed conflicting results regarding atrial fibrillation (AF) recurrences and few data concerning complications. Therefore, we conducted a meta-analysis of randomized trials comparing HPSD versus LPLD. METHODS: We systematically searched the electronic databases for studies published from inception to March 31, 2023 focusing on HPSD versus LPLD. The study endpoints were AF recurrence, procedural times and overall complications. RESULTS: Five studies enrolling 424 patients met the inclusion criteria (mean age 61.1 years; 54.3% paroxysmal AF; mean LVEF 58.2%). Compared to LPLD, HPSD showed a significantly lower AF recurrence rate [16.3% vs. 30,1%; RR: 0.54 (95% CI: 0.38-0.79); p = 0.001] at a mean 10.9 months follow-up. Moreover, HPSD led to a significant reduction in total procedural time [MD: -26.25 min (95%CI: -42.89 to -9.61); p = 0.002], PVI time [MD: -26.44 min (95%CI: -38.32 to -14.55); p < 0.0001], RF application time [MD: -8.69 min (95%CI: -11.37 to -6.01); p < 0.00001] and RF lesion number [MD: -7.60 (95%CI: -10.15 to -5.05); p < 0.00001]. No difference was found in either right [80.4% vs. 78.2%; RR: 1.04 (95% CI: 0.81-1.32); p = 0.77] or left [92.3% vs. 90.2%; RR: 1.02 (95% CI: 0.94-1.11); p = 0.58] first-pass isolation and overall complications [6% vs. 3.7%; RR: 1.45 (95%CI: 0.53-3.99); p = 0.47] between groups. CONCLUSION: In our metanalysis of randomized trials, HPSD ablation appeared to be associated to a significantly improved freedom from AF and shorter procedures, without increasing the risk of complications.

Success and complication rates of conduction system pacing: a meta-analytical observational comparison of left bundle branch area pacing and His bundle pacing.

BACKGROUND: Left bundle branch area pacing (LBBAP) and His bundle pacing (HBP) are the main strategies to achieve conduction system pacing (CSP), but only observational studies with few patients have compared the two pacing strategies, sometimes with unclear results given the different definitions of the feasibility and safety outcomes. Therefore, we conducted a meta-analysis aiming to compare the success and complications of LBBAP versus HBP. METHODS: We systematically searched the electronic databases for studies published from inception to March 22, 2023, and focusing on LBBAP versus HBP. The study endpoints were CSP success rate, device-related complications, CSP lead-related complications and non-CSP lead-related complications. RESULTS: Fifteen observational studies enrolling 2491 patients met the inclusion criteria. LBBAP led to a significant increase in procedural success [91.1% vs 80.9%; RR: 1.15 (95% CI: 1.08-1.22); p < 0.00001] with a significantly lower complication rate [1.8% vs 5.2%; RR: 0.48 (95% CI: 0.29-0.78); p = 0.003], lead-related complications [1.1% vs 4.3%; RR: 0.38 (95% CI: 0.21-0.72); p = 0.003] and lead failure/deactivation [0.2% vs 3.9%; RR: 0.16 (95% CI: 0.07-0.35); p < 0.00001] than HBP. No significant differences were found between CSP lead dislodgement and non-CSP lead-related complications. CONCLUSION: This meta-analysis of observational studies showed a higher success rate of LBBAP compared to HBP with a lower incidence of complications.

A Systematic Review and Meta-Analysis Including 354 Patients from 13 Studies of Intravascular Lithotripsy for the Treatment of Underexpanded Coronary Stents.

Calcified coronary plaque (CCP) represents a challenging scenario for interventional cardiologists. Stent underexpansion (SU), often associated with CCP, can predispose to stent thrombosis and in-stent restenosis. To date, SU with heavily CCP can be addressed using very high-/high-pressure noncompliant balloons, off-label rotational atherectomy/orbital atherectomy, excimer laser atherectomy, and intravascular lithotripsy (IVL). In this meta-analysis, we investigated the success rate of IVL for the treatment of SU because of CCP. Studies and case-based experiences reporting on the use of IVL strategy for treatment of SU were included. The primary end point was IVL strategy success, defined as the adequate expansion of the underexpanded stent. A metanalysis was performed for the main focuses to calculate the proportions of procedural success rates with corresponding 95% confidence intervals (CIs). Random-effects models weighted by inverse variance were used because of clinical heterogeneity. This meta-analysis included 13 studies with 354 patients. The mean age was 71.3 years (95% CI 64.9 to 73.1), and 77% (95% CI 71.2% to 82.4%) were male. The mean follow-up time was 2.6 months (95% CI 1 to 15.3). Strategy success was seen in 88.7% (95% CI 82.3 to 95.1) of patients. The mean minimal stent area was reported in 6 studies, the pre-IVL value was 3.4 mm2 (95% CI 3 to 3.8), and the post-IVL value was 6.9 mm2 (95% CI 6.5 to 7.4). The mean diameter stenosis (percentage) was reported in 7 studies, the pre-IVL value was 69.4% (95% CI 60.7 to 78.2), and the post-IVL value was 14.6% (95% CI 11.1 to 18). The rate of intraprocedural complications was 1.6% (95% CI 0.3 to 2.9). In conclusion, the "stent-through" IVL plaque modification technique is a safe tool to treat SU caused by CCP, with a high success rate and a very low incidence of complications.

"Function follows form": Role of cardiac magnetic resonance for ventricular arrhythmia risk stratification in patients with cardiac sarcoidosis.

INTRODUCTION: Cardiac involvement is common and may become clinically relevant in approximately 5%-10% of patients with systemic sarcoidosis. Although reduced left ventricular ejection fraction is a recognized predictor of mortality, recent studies have suggested an increased risk of ventricular arrhythmia (VAs) and sudden cardiac death (SCD) in patients with cardiac sarcoidosis (CS) and evidence of late gadolinium enhancement-cardiac magnetic resonance (LGE-CMR), irrespective of the underlying left ventricular systolic function. We performed a meta-analysis to assess the correlation between VAs/SCD and presence of LGE-CMR in CS patients. METHODS: We systematically searched Medline, Embase, and Cochrane electronic databases up to January 2, 2023, for studies enrolling patients with suspected or confirmed CS undergoing LGE-CMR. Clinical outcomes of interest included clinically relevant VAs, defined as sustained ventricular tachycardia, ventricular fibrillation, SCD, or aborted SCD during follow-up. The effect size was estimated using a random-effect model as risk ratio (RR) and relative 95% confidence interval (CI). RESULTS: A total of 14 studies fulfilled the selection criteria and were included in the final analysis. Among 1273 patients, LGE was detected in 465 (36.5%; Group LGE+). Males accounted for 45.2% (95% CI: 40.5%-55.7%) of the total population and the average age was 56.8 (95% CI: 52.7%-60.9) years. A total of 104 (22.3%) of 465 LGE+ patients experienced a clinically relevant VA, compared to 6 (0.7%) of 808 LGE- ones. LGE+ was associated with a ninefold increased risk in life-threatening VAs (22.3% vs. 0.7%; RR = 9.52; 95% CI [5.18-17.49]; p < .0001) compared to patients without LGE (heterogeneity I2 = 0%). CONCLUSION: In our meta-analysis, LGE+ in patients with CS was associated with a ninefold increased risk in life-threatening VAs compared to patients without LGE.

Ventricular Electrograms Duration Map to Detect Ventricular Arrhythmia Substrate: the VEDUM Project Study.

BACKGROUND: The analysis of the wave-front activation patterns is crucial for the comprehension and treatment of ventricular tachycardia (VT). The ventricular electrograms duration map (VEDUM) is a potential method to identify areas (VEDUM area) with slow and inhomogeneous activation. There is no available data on the characteristics and the arrhythmogenic role of VEDUM areas identified during sinus/paced rhythm. METHODS: Patients referred for VT ablation were enrolled at 3 different centers. VEDUM maps during sinus/paced rhythm as well as substrate and functional maps were created; activation mapping was performed for all hemodynamically tolerated VT. RESULTS: Thirty-two patients (mean age:70.1±9.4 years; males 93.8%) were enrolled. The VEDUM approach was achieved in all patients and the mean size of the VEDUM area was 12.1±6.9 cm2 (interquartile range, 7.8-14.9 cm2). A significative difference was observed between the electrogram duration in the VEDUM area and the normal tissue (163.7 ms [interquartile range, 142.3-199.2 ms]; versus 65.5 ms [interquartile range, 59.5-76.2 ms]; P<0.001). The VEDUM area was visualized in a dense scar (<0.5 mV) in 19 (59.4%) patients. A deceleration zone and late potentials were recorded inside the VEDUM area in 56.3% and 81.3%, respectively. When a complete VT activation mapping was available, the isthmus projected in the VEDUM area in 93.5% of patients; 8 of them had multiple VTs mapped and in the 87.5% all VT isthmuses were included in the VEDUM area. CONCLUSIONS: VEDUM maps allow the identification of discrete areas of inhomogeneous and slow conduction. They represent a potential target for VT ablation, including patients with multiple morphologies.

Axillary vein puncture versus cephalic vein cutdown for cardiac implantable electronic device implantation: A meta-analysis.

INTRODUCTION: Cephalic vein cutdown (CVC) and axillary vein puncture (AVP) are both recommended for transvenous implantation of leads for cardiac implantable electronic devices (CIEDs). Nonetheless, it is still debated which of the two techniques has a better safety and efficacy profile. METHODS: We systematically searched Medline, Embase, and Cochrane electronic databases up to September 5, 2022, for studies that evaluated the efficacy and safety of AVP and CVC reporting at least one clinical outcome of interest. The primary endpoints were acute procedural success and overall complications. The effect size was estimated using a random-effect model as risk ratio (RR) and relative 95% confidence interval (CI). RESULTS: Overall, seven studies were included, which enrolled 1771 and 3067 transvenous leads (65.6% [n = 1162] males, average age 73.4 ± 14.3 years). Compared to CVC, AVP showed a significant increase in the primary endpoint (95.7 % vs. 76.1 %; RR: 1.24; 95% CI: 1.09-1.40; p = .001) (Figure 1). Total procedural time (mean difference [MD]: -8.25 min; 95% CI: -10.23 to -6.27; p < .0001; I2  = 0%) and venous access time (MD: -6.24 min; 95% CI: -7.01 to -5.47; p < .0001; I2  = 0%) were significantly shorter with AVP compared to CVC. No differences were found between AVP and CVC for incidence overall complications (RR: 0.56; 95% CI: 0.28-1.10; p = .09), pneumothorax (RR: 0.72; 95% CI: 0.13-4.0; p = .71), lead failure (RR: 0.58; 95% CI: 0.23-1.48; p = .26), pocket hematoma/bleeding (RR: 0.58; 95% CI: 0.15-2.23; p = .43), device infection (RR: 0.95; 95% CI: 0.14-6.60; p = .96) and fluoroscopy time (MD: -0.24 min; 95% CI: -0.75 to 0.28; p = .36). CONCLUSION: Our meta-analysis suggests that AVP may improve procedural success and reduce total procedural time and venous access time compared to CVC.

Endocardial versus epicardial pacing in pacemaker-dependent patients after device extraction: a meta-analysis.

INTRODUCTION: Pacemaker-dependent (PM) patients with cardiac implantable electronic device (CIED) infection require implantation of a temporary-pacemaker (TP) and delayed endocardial reimplantation or implantation of an epicardial-pacing-system (EPI) before device extraction. Our aim was to compare the TP and EPI-strategy after CIED extraction through a meta-analysis. METHODS: We searched electronic databases up to 25 March 2022, for observational studies that reported clinical outcomes of PM-dependent patients implanted with TP or EPI-strategy after device extraction. RESULTS: 3 studies were included enrolling 339 patients (TP: 156 patients; EPI: 183 patients). TP compared to EPI showed reduction in the composite outcome of relevant complications (all-cause death, infections, need for revision or upgrading of the reimplanted CIED) (12.1% vs 28.9%; RR: 0.45; 95%CI: 0.25-0.81; p = 0.008) and a trend in reduction of all-cause death (8.9% vs 14.2%; RR: 0.58; 95%CI: 0.33-1.05; p = 0.07). Furthermore, TP-strategy proved to reduce need of upgrading (0% vs 12%; RR: 0.07; 95%CI: 0.01-0.52; p = 0.009), reintervention on reimplanted CIED (1.9% vs 14.7%; RR: 0.15; 95%CI: 0.05-0.48; p = 0.001) and significant increase in pacing threshold (0% vs 5.4%; RR: 0.17; 95%CI: 0.03-0.92; p = 0.04), with a longer discharge time (MD: 9.60 days; 95%CI: 1.98-17.22; p = 0.01). CONCLUSION: TP-strategy led to a reduction of the composite outcome of all-cause death and complications, upgrading, reintervention on reimplanted CIED, and risk of increase in pacing threshold compared to EPI-strategy, with longer discharge time.

Circulating Anti-GB3 Antibody as a Biomarker of Myocardial Inflammation in Patients with Fabry Disease Cardiomyopathy.

BACKGROUND: Fabry disease cardiomyopathy (FDCM) has manifested some resistance to enzyme replacement therapy (ERT), particularly in its advanced phase. Recently, myocardial inflammation of autoimmune origin has been demonstrated in FDCM. AIMS: The objective of this study was the assessment of circulating anti-globotriaosylceramide (GB3) antibodies as potential biomarkers of myocardial inflammation in FDCM, defined by the additional presence of ≥CD3+ 7 T lymphocytes/low-power field associated with focal necrosis of adjacent myocytes. Its sensitivity was based on the evidence of overlapping myocarditis at left ventricular endomyocardial biopsy. METHODS AND RESULTS: From January 1996 to December 2021, 85 patients received a histological diagnosis of FDCM in our department and 48 (56.5%) of them had an overlapping myocardial inflammation with negative PCR for common cardiotropic viruses, positive antiheart, and antimyosin abs. The presence of anti-GB3 antibodies was evaluated with an in-house ELISA assay (BioGeM scarl Medical Investigational Research, MIR-Ariano Irpino, Italy), along with antiheart and antimyosin abs, in the FDCM patients and compared with control healthy individuals. The correlation between levels of circulating anti-GB3 autoantibody myocardial inflammation and FDCM severity was assessed. Anti-Gb3 antibodies were above the positivity cut-off in 87.5% of FDCM subjects with myocarditis (42 out of 48), while 81.1% of FDCM patients without myocarditis were identified as negative for Gb3 antibodies. Positive anti-Gb3 abs correlated with positive antiheart and antimyosin abs. CONCLUSIONS: The present study suggests a potential positive role of anti-GB3 antibodies as a marker of overlapping cardiac inflammation in patients with FDCM.

The Role of MicroRNA in the Myocarditis: a Small Actor for a Great Role.

PURPOSE OF REVIEW: Myocarditis is an inflammation of the myocardium secondary to a variety of agents such as infectious pathogens, toxins, drugs, and autoimmune disorders. In our review, we provide an overview of miRNA biogenesis and their role in the etiology and pathogenesis of myocarditis, evaluating future directions for myocarditis management. RECENT FINDINGS: Advances in genetic manipulation techniques allowed to demonstrate the important role of RNA fragments, especially microRNAs (miRNAs), in cardiovascular pathogenesis. miRNAs are small non-coding RNA molecules that regulate the post-transcriptional gene expression. Advances in molecular techniques allowed to identify miRNA's role in pathogenesis of myocarditis. miRNAs are related to viral infection, inflammation, fibrosis, and apoptosis of cardiomyocytes, making them not only promising diagnostic markers but also prognostics and therapeutic targets in myocarditis. Of course, further real-world studies will be needed to assess the diagnostic accuracy and applicability of miRNA in the myocarditis diagnosis.