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Aims: Left atrial appendage (LAA) imaging is critical during percutaneous occlusion procedures. 3D-intracardiac echocardiography (ICE) features direct visualization of LAA from multiple cross-sectional planes at a time. We aimed at reporting procedural success of 3D-ICE-guided LAA occlusion and the correlation between pre-procedural transoesophageal echocardiography (TEE) and intraprocedural 3D-ICE for LAA sizing., Methods and Results: Among 274 patients undergoing left atrial appendage occlusion (LAAO) with a Watchman FLX, periprocedural ICE guidance was achieved via a commercially available 2D-ICE catheter (220 patients) or a novel (NUVISION™) 3D-ICE one (54 patients). Primary endpoint was a composite of procedural success and LAA sealing at follow-up TEE. Secondary endpoint was a composite of periprocedural device recapture/resizing plus presence of leaks ≥ 3 mm at follow-up TEE. 3D-ICE measurements of maximum landing zone correlated highly with pre-procedural TEE reference values [Pearson's: 0.94; P < 0.001; bias: -0.06 (-2.39, 2.27)]. The agreement between 3D-ICE-based device selection and final device size was 96.3% vs. 79.1% with 2D-ICE (P = 0.005). The incidence of the primary endpoint was 98.1% with 3D-ICE and 97.3% with 2D-ICE (P = 0.99). 2D-ICE patients had a trend towards a higher incidence of periprocedural device recapture/redeployment (31.5% vs. 44.5%; P = 0.09). The secondary endpoint occurred in 31.5% of 3D-ICE patients vs. 45.9% of 2D-ICE ones (P = 0.065)., Conclusion: Intracardiac echocardiography-guided LAAO showed a very high success, with no major adverse events. A very high level of agreement for LAA sizing was found between pre-procedural TEE and periprocedural 3D-ICE. 3D-ICE performed significantly better than 2D-ICE for FLX size selection and may provide better guidance during device deployment., Competing Interests: Conflict of interest: G.-B.C. received compensation from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. C.d.A. received research grants on behalf of the centre from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus. D.J.B. is a consultant for Biosense Webster and Stereotaxis. L.D.B. is a consultant for Biosense Webster, Boston Scientific, Stereotaxis, and St. Jude Medical. A.N. received speaker honoraria from Boston Scientfic, Biosense Webster, St. Jude Medical, Biotronik, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Ablate and pace (A&P) with conduction system pacing (CSP) improves outcomes in patients with symptomatic permanent atrial fibrillation (AF). Data on spontaneous sinus rhythm restoration (SSRR) in this setting are lacking. This study aimed to assess the incidence and the predictors of SSRR in a population of patients with permanent AF who underwent A&P with CSP. Prospective, observational study, enrolling consecutive patients with symptomatic permanent AF (of documented duration >6 months) and uncontrolled, drug-refractory high ventricular rate, who underwent A&P with CSP. The incidence and predictors of SSRR were prospectively assessed. A total of 107 patients (79.0 ± 9.1 years, 33.6% male, 74.8% with New York Heart Association class ≥III, 56.1% with ejection fraction <40%) were enrolled: 40 received His' bundle pacing, 67 left bundle branch area pacing. During a median follow-up of 12 months SSRR was observed in 14 patients (13.1%), occurring a median of 3 months after A&P (interquartile range 1 to 6; range 0 to 17). Multivariable analysis identified a duration of permanent AF <12 months (hazard ratio 7.7, p = 0.040) and a left atrial volume index <49 ml/m 2 (hazard ratio 14.8, p = 0.008) as independent predictors of SSRR. In patients with coexistence of both predictors the incidence of SSRR was of 41.4%. In a population of patients with symptomatic, permanent AF, treated with A&P with CSP, SSRR was observed in 13% of patients during follow-up. A duration of permanent AF <12 months and a left atrial volume index <49 ml/m 2 were independent predictors of this phenomenon., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Catheter ablation (CA) is an established treatment for atrial fibrillation (AF). A computed tomography (CT) may be performed before ablation to evaluate the anatomy of pulmonary veins. The aim of this study is to investigate the prevalence of patients with coronary artery disease (CAD) detected by cardiac CT scan pre-ablation and to evaluate the impact of CAD and revascularization on outcomes after AF ablation., Methods and Results: All consecutive patients with AF diagnosis, hospitalized at Universitair Ziekenhuis Brussel, Belgium, between 2015 and 2019, were prospectively screened for enrolment in the study. Inclusion criteria were (i) AF diagnosis, (ii) first procedure of AF ablation with cryoballoon CA, and (iii) contrast CT scan performed pre-ablation. A total of 576 consecutive patients were prospectively included and analysed in this study. At CT scan, 122 patients (21.2%) were diagnosed with CAD, of whom 41 patients (7.1%) with critical CAD. At survival analysis, critical CAD at CT scan was a predictor of atrial tachyarrhythmia (AT) recurrence during the follow-up, only in Cox univariate analysis [hazard ratio (HR) = 1.79] but was not an independent predictor in Cox multivariate analysis. At Cox multivariate analysis, independent predictors of AT recurrence were as follows: persistent AF (HR = 2.93) and left atrium volume index (HR = 1.04)., Conclusion: In patients undergoing CT scan before AF ablation, critical CAD was diagnosed in 7.1% of patients. Coronary artery disease and revascularization were not independent predictors of recurrence; thus, in this patient population, AF ablation should not be denied and can be performed together with CAD treatment., Competing Interests: Conflict of interest: Ant.S. received research grants from Daiichi-Sankyo and Bayer; he has received speaker fees from Menarini and Bayer. M.L.M. is consultant for AtriCure. P.B. received compensation for teaching purposes from Biotronik. G.B.C. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. C.d.A. receives research grants on behalf of the centre from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus; C.d.A. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, LivaNova, Boston Scientific, AtriCure, Acutus Medical, and Daiichi-Sankyo. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Chierchia received compensation for teaching purposes and proctoringfrom Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. Dr. de Asmundis receives research grants on behalf of the center from Biotronik, Medtronic, Abbott, LivaNova, BostonScientific, AtriCure, Philips, and Acutus, and compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Livanova, Boston Scientific, Atricure, Acutus Medical, and Daiichi Sankyo., (© 2023 The Author(s).)

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., Competing Interests: Conflict of interest: G.B.C. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. C.dA. received research grants on behalf of the centre from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus and compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Livanova, Boston Scientific, Atricure, Acutus Medical, and Daiichi Sankyo. J.C.G. is a consultant and has received speaker fees from Boston Scientific, Abbott, Medtronic, Biotronik, Pfizer, Bayer, Novartis, Daiichi Sankyo, and Boehringer Ingelheim. M.M. serves as a consultant for Boston Scientific and Abbott. L.D.B. is a consultant for Stereotaxis, Biosense Webster, Boston Scientific, Rhythm Management, and Abbott Medical. J.S. is a consultant for Boston Scientific, Abbott, Baylis, Gore, and FEops, and a proctor for Boston Scientific and Abbott. D.G. is a consultant for Boston Scientific, Abbot, Acutus, and Biosense Webster. A.N. is as a consultant for Abbott, Biosense Webster, Inc., Biotronik, Boston Scientific, Baylis, and Medtronic. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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., (© 2023 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Introduction: Pulmonary vein isolation (PVI) with thermal energy is characterized by concomitant ablation of the surrounding ganglionated plexi (GP). Pulsed-field ablation (PFA) selectively targets the myocardium and seems associated with only negligible effects on the autonomic nervous system (ANS). However, little is known about the dynamic effects of PFA on the GP immediately after PVI. This study sought to investigate the degree and acute vagal modulation induced by the Farapulse TM PFA system during PVI compared with single-shot thermal ablation., Methods: A total of 76 patients underwent first-time PVI with either Farapulse TM PFA (PFA group, n = 40) or cryoballoon ablation (thermal ablation group, n = 36) for paroxysmal atrial fibrillation (AF). The effect on the ANS in the two groups was assessed before and after PVI with extracardiac vagal stimulation (ECVS). To capture any transient effects of PFA on the ANS, in a subgroup of PFA patients ECVS was repeated at three predefined timepoints: (1) before PVI (T0); (2) immediately after PVI (T1); and (3) 10 min after the last energy application (T2)., Results: Despite similar baseline values, the vagal response induced by ECVS after PVI almost disappeared in the thermal ablation group but persisted in the PFA group (thermal group: 840 [706-1090] ms, p < .001 compared to baseline; PFA group: 11 466 [8720-12 293] ms, p = .70 compared to baseline). Intraprocedural vagal reactions (defined as RR increase >50%, transitory asystole, or atrioventricular block) occurred more frequently with PFA than thermal ablation (70% vs. 28%, p = .001). Moreover, heart rate 24 h post-PVI increased more with thermal ablation than with PFA (16.5 ± 9.0 vs. 2.6 ± 6.1 beats/min, p < .001). In the subgroup of PFA patients undergoing repeated ANS modulation assessment (n = 11), ECVS demonstrated that PFA determined a significant acute suppression of the vagal response immediately after PVI (p < .001 compared to baseline), which recovered almost completely within 10 min., Conclusion: PVI with the Farapulse TM PFA system is associated with only transitory and short-lasting vagal effects on the ANS which recover almost completely within a few minutes after ablation. The impact of this phenomenon on AF outcome needs to be further investigated., (© 2023 Wiley Periodicals LLC.)

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 mm 2 (95% CI 3 to 3.8), and the post-IVL value was 6.9 mm 2 (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., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

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; I 2  = 0%) and venous access time (MD: -6.24 min; 95% CI: -7.01 to -5.47; p < .0001; I 2  = 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., (© 2023 Wiley Periodicals LLC.)

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 I 2  = 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., (© 2023 Wiley Periodicals LLC.)

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.

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., (© 2023. The Author(s).)

Introduction: Cardiac resynchronization therapy (CRT) reduces heart failure (HF) hospitalization and all-cause mortality in HF patients with left bundle branch block (LBBB). Biventricular pacing (BVP) is the gold standard for achieving CRT, but about 30%-40% of patients do not respond to BVP-CRT. Recent studies showed that left bundle branch pacing (LBBP) provided remarkable results in CRT. Therefore, we conducted a meta-analysis aiming to compare LBBP-CRT versus BVP-CRT in HF patients., Methods: We systematically searched the electronic databases for studies published from inception to December 29, 2022 and focusing on LBBP-CRT versus BVP-CRT in HF patients. The primary endpoint was HF hospitalization. The effect size was estimated using a random-effect model as Risk Ratio (RR) and mean difference (MD)., Results: Ten studies enrolling 1063 patients met the inclusion criteria. Compared to BVP-CRT, LBBP-CRT led to significant reduction in HF hospitalization [7.9% vs.14.5%; RR: 0.60 (95%CI: 0.39-0.93); p = .02], QRSd [MD: 30.26 ms (95%CI: 26.68-33.84); p < .00001] and pacing threshold [MD: -0.60 (95%CI: -0.71 to -0.48); p < .00001] at follow up. Furthermore, LBBP-CRT improved LVEF [MD: 5.78% (95%CI: 4.78-6.77); p < .00001], the rate of responder [88.5% vs.72.5%; RR: 1.19 (95%CI: 1.07-1.32); p = .002] and super-responder [60.8% vs. 36.5%; RR: 1.56 (95%CI: 1.27-1.91); p < .0001] patients and the NYHA class [MD: -0.42 (95%CI: -0.71 to -0.14); p < .00001] compared to BVP-CRT., Conclusion: In HF patients, LBBP-CRT was superior to BVP-CRT in reducing HF hospitalization. Further significant benefits occurred within the LBBP-CRT group in terms of QRSd, LVEF, pacing thresholds, NYHA class and the rate of responder and super-responder patients., (© 2023 Wiley Periodicals LLC.)

A diagnosis of Brugada syndrome (BrS) is based on the presence of a type 1 electrocardiogram (ECG) pattern, either spontaneously or after a Sodium Channel Blocker Provocation Test (SCBPT). Several ECG criteria have been evaluated as predictors of a positive SCBPT, such as the β-angle, the α-angle, the duration of the base of the triangle at 5 mm from the r'-wave (DBT- 5 mm), the duration of the base of the triangle at the isoelectric line (DBT- iso), and the triangle base/height ratio. The aim of our study was to test all previously proposed ECG criteria in a large cohort study and to evaluate an r'-wave algorithm for predicting a BrS diagnosis after an SCBPT. We enrolled all patients who consecutively underwent SCBPT using flecainide from January 2010 to December 2015 in the test cohort and from January 2016 to December 2021 in the validation cohort. We included the ECG criteria with the best diagnostic accuracy in relation to the test cohort in the development of the r'-wave algorithm (β-angle, α-angle, DBT- 5 mm, and DBT- iso.) Of the total of 395 patients enrolled, 72.4% were male and the average age was 44.7 ± 13.5 years. Following the SCBPTs, 24.1% of patients (n = 95) were positive and 75.9% (n = 300) were negative. ROC analysis of the validation cohort showed that the AUC of the r'-wave algorithm (AUC: 0.92; CI 0.85-0.99) was significantly better than the AUC of the β-angle (AUC: 0.82; 95% CI 0.71-0.92), the α-angle (AUC: 0.77; 95% CI 0.66-0.90), the DBT- 5 mm (AUC: 0.75; 95% CI 0.64-0.87), the DBT- iso (AUC: 0.79; 95% CI 0.67-0.91), and the triangle base/height (AUC: 0.61; 95% CI 0.48-0.75) ( p < 0.001), making it the best predictor of a BrS diagnosis after an SCBPT. The r'-wave algorithm with a cut-off value of ≥2 showed a sensitivity of 90% and a specificity of 83%. In our study, the r'-wave algorithm was proved to have the best diagnostic accuracy, compared with single electrocardiographic criteria, in predicting the diagnosis of BrS after provocative testing with flecainide.

Background: Early diagnosis of Coronary Artery Disease (CAD) plays a key role to prevent adverse cardiac events such as myocardial infarction and Left Ventricular (LV) dysfunction. Myocardial Work (MW) indices derived from echocardiographic speckle tracking data in combination with non-invasive blood pressure recordings seems promising to predict CAD even in the absence of impairments of standard echocardiographic parameters. Our aim was to compare the diagnostic accuracy of MW indices to predict CAD and to assess intra- and inter-observer variability of MW through a meta-analysis., Methods: Electronic databases were searched for observational studies evaluating the MW indices diagnostic accuracy for predicting CAD and intra- and inter-observer variability of MW indices. Pooled sensitivity, specificity, and Summary Receiver Operating Characteristic (SROC) curves were assessed., Results: Five studies enrolling 501 patients met inclusion criteria. Global Constructive Work (GCW) had the best pooled sensitivity (89%) followed by GLS (84%), Global Work Index (GWI) (82%), Global Work Efficiency (GWE) (80%), and Global Wasted Work (GWW) (75%). GWE had the best pooled specificity (78%) followed by GWI (75%), GCW (70%), GLS (68%), and GWW (61%). GCW had the best accuracy according to SROC curves, with an area under the curve of 0.86 compared to 0.84 for GWI, 0.83 for GWE, 0.79 for GLS, and 0.74 for GWW. All MW indices had an excellent intra- and inter-observer variability., Conclusions: GCW is the best MW index proving best diagnostic accuracy in the prediction of CAD with an excellent reproducibility., (© 2023 Wiley Periodicals LLC.)

Background: Catheter ablation (CA) of atrial fibrillation (AF) is used routinely to establish rhythm control. There is mounting evidence that CA procedures should be performed during continuous oral anticoagulation and direct oral anticoagulants (DOACs) are considered the first anticoagulation strategy. Few real-life data are now available and even less in the Italian panorama., Methods: IRIS is an Italian multicenter, non-interventional, prospective study which will be enrolled consecutive AF patients eligible for CA and treated with Rivaroxaban; patients in treatment with Rivaroxaban proceeded directly to CA while Rivaroxaban-naive patients were scheduled for CA after 4 weeks of uninterrupted anticoagulation unless the exclusion of atrial thrombi. Rivaroxaban was uninterrupted or shortly uninterrupted (<24 hours) prior CA, in line with routinely practice of each operator. Patients will be followed on continuous anticoagulation for 1 month after the ablation. The primary efficacy outcome is the cumulative incidence of all-cause death and systemic embolism while the primary safety outcome is the incidence of major bleeding events. The secondary outcomes are represented by non-major bleeding events. All events must be occurred within the first 30 days after the procedure., Results: Two hundred fifty patients are expected to be enrolled and the study is estimated to be completed by the end of 2022. Up to now 56 patients have been enrolled., Conclusions: This study is the first large Italian prospective study on the management of Rivaroxaban in patients undergoing CA of AF. It aims to depict a comprehensive view of anticoagulation strategy prior CA in several Italian electrophysiology labs.

Introduction: The implantable cardioverter defibrillator (ICD) has been demonstrated to successfully prevent sudden cardiac death (SCD) in children and young adults. A wide range of device-related complications/malfunctions have been described, which depend on the intrinsic design of the defibrillation system (transvenous-implantable cardioverter defibrillator [TV-ICD] vs. subcutaneous-implantable cardioverter defibrillator [S-ICD])., Objective: To compare the device-related complications and inappropriate shocks with TV-ICD versus S-ICD., Methods and Results: Electronic databases were queried for studies focusing on the prevention of SCD in children and young adults with TV-ICD or S-ICD. The effect size was estimated using a random-effect model as odds ratio (OR) and relative 95% confidence interval (CI). The primary endpoint was a composite of any device-related complications and inappropriate shocks. We identified a total of five studies including 236 patients (Group S-ICD: 76 patients; Group TV-ICD: 160 patients) with a mean follow-up time of 54.2 ± 24.9 months. S-ICD implantation contributed to a significant reduction in the risk of the primary endpoint of any device-related complications and inappropriate shocks (OR: 0.18; 95% CI: 0.05-0.73; p = .02). S-ICD was also associated with a significantly lower incidence of inappropriate shocks (OR: 0.28; 95% CI: 0.11-0.74; p = .01) and lead-related complications (OR: 0.18; 95% CI: 0.05-0.66; p = .01). A trend toward a higher risk of pocket complications (OR: 5.91; 95% CI: 0.98-35.63; p = .05) was recorded in patients with S-ICD., Conclusion: Children and young adults undergoing S-ICD implantation may have a lower risk of a composite of device-related complications and inappropriate shocks, compared to TV-ICD patients., (© 2022 Wiley Periodicals LLC.)

Background: Atrial fibrillation (AF) and heart failure (HF) often coexist and synergistically contribute to an increased risk of hospitalization, stroke, and mortality. Objective: To compare the efficacy of catheter ablation (CA) versus medical therapy (MT) in HF patients with AF. Methods: Electronic databases were queried for randomized controlled trials (RCTs) of CA versus MT of AF in patients with HF. Risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs) were measured using the Mantel−Haenszel method. Results: A total of nine RCTs enrolling 2155 patients met the inclusion criteria. Compared to MT, CA led to a significant reduction in the composite of all-cause mortality and HF hospitalization (24.6% vs. 37.1%; RR: 0.65 (95% CI: 0.53−0.80); p < 0.0001), all-cause mortality (8.8% vs. 13.6%; RR: 0.65 (95% CI: 0.51−0.82); p = 0.0005), HF hospitalization (15.4% vs. 22.4%; (RR: 0.67 (95% CI: 0.54−0.82); p = 0.0001), AF recurrence (31.8% vs. 77.0%; RR: 0.36 (95% CI: 0.24−0.54); p < 0.0001), and cardiovascular (CV) death (4.9% vs. 8.4%; RR: 0.58 (95% CI: 0.39−0.86); p = 0.007). CA improved the left ventricular ejection fraction (MD:4.76% (95% CI: 2.35−7.18); p = 0.0001), 6 min walk test (MD: 20.48 m (95% CI: 10.83−30.14); p < 0.0001), peak oxygen consumption (MD: 3.1 2mL/kg/min (95% CI: 1.01−5.22); p = 0.004), Minnesota Living with Heart Failure Questionnaire score (MD: −6.98 (95% CI: −12−03, −1.93); p = 0.007), and brain natriuretic peptide levels (MD:−133.94 pg/mL (95% CI: −197.33, −70.55); p < 0.0001). Conclusions: In HF patients, AF catheter ablation was superior to MT in reducing CV and all-cause mortality. Further significant benefits occurred within the ablation group in terms of HF hospitalizations, AF recurrences, the systolic function, exercise capacity, and quality of life.

Introduction: Atrial fibrillation (AF) is the main cardiac cause of stroke, but it frequently remains undetected. In patients with cryptogenic stroke an Holter electrocardiogram (ECG) monitoring for AF is recommended., Objective: To evaluate the prognostic role of Non-Conducted Premature Atrial Complexes (ncPACs) recorded on Holter ECG., Methods: We prospectively enrolled consecutive patients admitted to the Stroke Unit of our hospital with a diagnosis of cryptogenic stroke between December 2018 and January 2020; all patients underwent 24-h Holter ECG monitoring during hospitalization. Two follow-up visits were scheduled, including a 24-h Holter ECG at 3 and 6 months to detect AF., Results: Among 112 patients, 58% were male with an average age of 72.2 ± 12.2 years. At follow-up, AF was diagnosed in 21.4% of the population. The baseline 24-h Holter ECG burden of ncPACs and Premature Atrial Complexes (PACs) was higher in patients with AF detected on follow-up (13.5 vs 2, p = 0.001; 221.5 vs 52; p = 0.01). ROC analysis showed that ncPACs had the best diagnostic accuracy in predicting AF (AUC:0.80; 95% CI 0.68-0.92). Cut-off value of ≥7 for ncPACs burden showed the highest accuracy with sensitivity of 62.5% and specificity 97.7% to predict AF onset at follow-up. Moreover, at multivariate Cox-proportional hazard analysis ncPACs burden ≥7 was a powerful independent predictor of AF onset (HR 12.4; 95% CI 4.8-32.8; p < 0.0001)., Conclusions: NcPACs burden ≥7 represents a new predictor of AF that could guide the screening of this arrhythmia in cryptogenic stroke patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is the most common cardiac arrhythmia in adults with substantial morbidity and mortality. The diagnosis of AF is established by electrocardiogram showing heart rhythm without clear P waves with irregular RR intervals. The electrocardiographic diagnosis of AF is not always easy and can still hide pitfalls even for the most experienced cardiologist. We present the case of an 86 years old patient admitted to our hospital for Covid-19 infection affected by dilated cardiomyopathy with an electrocardiogram showing a non-specific intraventricular conduction delay mimicking sinus rhythm in the presence of AF., Competing Interests: Declaration of Competing Interest The Authors declares that there is no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Direct oral anticoagulants (DOACs) are the preferred anticoagulant drugs for the prevention of atrial fibrillation (AF)-related thromboembolic complications and for the treatment and the prevention of recurrences of venous thromboembolism (VTE). The evaluation of self-reported adverse drug reactions (ADRs) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision making., Objective: To assess the safety profile of DOACs by analyzing ADR rates in the real-world Italian scenario., Methods: Post-marketing surveillance data recorded by the National Pharmacovigilance Network were retrieved for the time period 2017-2021 from the AIFA online site. The following data were collected for each DOAC: total ADR number, serious ADR number, gastrointestinal (GI) ADR, intracranial hemorrhage events (ICH ADR), and more frequently reported ADR for the study year. The safety profile was expressed by the risk index (RI)., Results: Rivaroxaban use was associated with consistent and stable low rates of serious ADR, GI ADR, and ICH ADR across the 5-year study period. Rivaroxaban and apixaban showed the lowest RI for serious ADR and GI ADR, while rivaroxaban use was associated with significantly lower ICH events as compared to apixaban. Dabigatran was related to the highest RIs for every ADR class, in particular GI ADRs., Conclusions: DOACs presented an acceptable safety profile in the current post-market analysis. However, rivaroxaban and apixaban were associated with more favorable safety profiles as compared to dabigatran, while rivaroxaban provoked statistically significantly fewer ICH events as compared to apixaban.

The burden of cardiovascular comorbid conditions was significantly higher in patients with atrial fibrillation (AF); most of them are affected by hypertension, chronic kidney disease (CKD) and/or diabetes mellitus (DM). DM represents a well-known risk factor for the development and maintenance of AF; the coexistence of DM and AF is also associated with an increased risk of mortality and stroke. Moreover, DM is currently the main cause of renal impairment and the leading cause of dialysis in the world. The hyperglycemia is responsible for inducing redox imbalance and both systemic and intrarenal inflammation, playing a critical role in the pathogenesis of diabetic kidney disease. Long-term thromboembolic preventive therapy in AF patients with DM and CKD may be more challenging because both DM and CKD have been independently associated with an increased thromboembolic and bleeding risk, which results from the prothrombotic and proinflammatory status. Vitamin K antagonists (VKAs) are characterized by numerous critical issues such as a narrow therapeutic window, increased tissue calcification and an unfavorable risk/benefit ratio with low stroke prevention effect and augmented risk of major bleeding. On the other hand, Direct Oral Anticoagulants (DOACs) are currently contraindicated in dialysis patients even if mounting evidence suggests that they may have a nephroprotective role in AF patients with DM and CKD. Consequently, the choice of anticoagulant therapy in this setting of patient seems to be very challenging. The aim of this review is to investigate the role of DOACs in diabetic patients and its nephroprotective role by reviewing the current literature.

Background: The remote device management (RM) is recommended for patients with cardiac implantable electronic devices (CIEDs). RM underutilization is frequently driven by the lack of correct system activation. The MyLATITUDE Patient App (Boston Scientific) has been developed to encourage patient compliance with RM by providing information on communicator setup, troubleshooting, and connection status of the communicator., Methods: At 14 centers, patients with CIEDs were invited to download and install the App on a mobile device. After 3 months, patients were asked to complete an ad hoc questionnaire to evaluate their experience., Results: The App was proposed to 242 consecutive patients: 81 before RM activation, and 161 during follow-up. The App was successfully installed by 177 (73%) patients. The time required for activation of the communicator and the need for additional support were similar between patients who followed the indications provided by the App and those who underwent standard in-clinic training. During follow-up, notifications of lack of connection were received by 20 (11%) patients and missed transmission by 22 (12%). The median time from notification to resolution was 2 days. After 3 months, 175 (99%) communicators of the 177 patients who installed the App were in "Monitored" status versus 113 (94%) of 120 patients without the App installed (p=0.033). The use of the app made 84% of patients feel reassured., Conclusions: The App was well accepted by CIED patients and offered support for communicator management and installation. Its use enabled patients to remain connected with greater continuity during follow-up., (© 2022. The Author(s).)

Atrial fibrillation (AF) and chronic kidney disease (CKD) are strictly related and share several risk factors (i.e. hypertension, diabetes mellitus, congestive heart failure). As consequence, AF is very common among CKD patients, especially in those with end stage renal disease (ESRD). Moreover, patients with AF and advanced kidney disease have a higher mortality rate than patients with preserved renal function due to an increased incidence of stroke and an unpredicted elevated hemorrhagic risk. The adequate long-term oral anticoagulation in this subgroup of patients represents a major challenging issue faced by physicians in clinical practice. Direct oral anticoagulants (DOACs) are currently contraindicated in patients with ESRD while vitamin K antagonists (VKAs) are characterized by a narrow therapeutic window, increased tissue calcification and an unfavorable risk/benefit ratio with low stroke prevention effect and augmented risk of major bleeding. The purpose of this review is to shed light on the applications of DOAC therapy in CKD patients, especially in ESRD patients., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

During the coronavirus disease 2019 (COVID-19) worldwide pandemic, patients with cardiac implantable electronic device (CIED) refused scheduled follow-up visits because of the risk of infection. In this scenario, different telemedicine strategies have been implemented to ensure continuity of care to CIED patients. Patients can be monitored through dedicated applications, telephone calls, or virtual visits providing easy access to valuable information, such as arrhythmic events, acute decompensation manifestations, and device-related issues, without the need for in-person visits. This review provides a comprehensive description of the many possible applications of telemedicine for CIED patients during the COVID-19 period., Competing Interests: Disclosures The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

COVID-19 mainly affects the respiratory system but has been correlated with cardiovascular manifestations such as myocarditis, heart failure, acute coronary syndromes, and arrhythmias. Cardiac arrhythmias are the second most frequent complication affecting about 30% of patients. Several mechanisms may lead to an increased risk of cardiac arrhythmias during COVID-19 infection, ranging from direct myocardial damage to extracardiac involvement. The aim of this review is to describe the role of COVID-19 in the pathogenesis of cardiac arrhythmias and provide a comprehensive guidance for their monitoring and management., Competing Interests: Disclosure Dr J.D. Burkhardt is a consultant for Biosense Webster and Stereotaxis. Dr L. Di Biase is a consultant for Biosense Webster, Boston Scientific, Stereotaxis, and St. Jude Medical; and has received speaker honoraria from Medtronic, Atricure, EPiEP, and Biotronik. Dr A. Natale has received speaker honoraria from Boston Scientific, Biosense Webster, St. Jude Medical, Biotronik, and Medtronic; and is a consultant for Biosense Webster, St. Jude Medical, and Janssen. All other authors have reported that they have no relationships relevant to the contents of this article to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Flecainide is an IC antiarrhythmic drug (AAD) that received in 1984 Food and Drug Administration approval for the treatment of sustained ventricular tachycardia (VT) and subsequently for rhythm control of atrial fibrillation (AF). Currently, flecainide is mainly employed for sinus rhythm maintenance in AF and the treatment of idiopathic ventricular arrhythmias (IVA) in absence of ischaemic and structural heart disease on the basis of CAST data. Recent studies enrolling patients with different structural heart diseases demonstrated good effectiveness and safety profile of flecainide. The purpose of this review is to assess current evidence for appropriate and safe use of flecainide, 30 years after CAST data, in the light of new diagnostic and therapeutic tools in the field of ischaemic and non-ischaemic heart disease.

In elderly patients with heart failure and an indication for implantable cardioverter defibrillator (ICD) implantation, the incidence of sudden cardiac death (SCD) increases progressively with age, up to 80-85 years. ICD implantation is a recognized therapy, included in the guidelines for the prevention of SCD in the general population, which is also applied to elderly patients, albeit in an uneven manner, given the lack of robust data in the literature. In fact, the average age of patients included in the main randomized trials on ICDs is about 60 years. All this brings to a series of doubts in this regard, compounded by recent studies that have raised the suspicion of therapeutic futility in the implantation of ICDs in primary prevention in subjects aged ≥70 years, especially in the absence of ischemic heart disease. In the elderly, although the risk of SCD does not vary, the mortality rate for other causes tends progressively to increase with age, as the main consequence of the simultaneous presence of situations such as frailty syndrome and comorbidity. In order to avoid an ageistic attitude, it is therefore necessary to promote randomized controlled trials aimed at a multidimensional evaluation of the elderly patients with an indication for ICD implantation, from which more robust data can be obtained to allow the heart team a selectively targeted evaluation of elderly patients.

Since its introduction right ventricular apical (RVA) pacing has been the mainstay in cardiac pacing. However, in recent years there has been an upsurge of interest in permanent His bundle pacing (HBP), given the scientific evidence of the harmful role of dyssynchronous ventricular activation, induced by RVA pacing, in promoting the onset of heart failure and atrial fibrillation. After an intermediate period in which attention was focused on algorithms aimed at minimizing ventricular pacing, with partially inadequate and harmful results, scientific attention shifted to HBP, which proved to ensure a physiological electro-mechanical activation of the ventricles. The encouraging results obtained have allowed the introduction of HBP in recent guidelines for cardiac pacing in patients with bradicardia and cardiac conduction delay. Recent studies have also demonstrated the potential of HBP in patients with left bundle branch block and heart failure. HBP is promising as an attractive way to achieve physiological stimulation in patients with an indication for cardiac resynchronization therapy (CRT). Comparative studies of HB-CRT and biventricular pacing have shown similar results in numerically modest cohorts, although HB-CRT has been shown to promote better ventricular electrical resynchronization as demonstrated by a greater QRS narrowing. A widespread use of this pacing tecnique also depends on improvements in technology, as well as further validation of effectiveness in large randomised clinical trials.

Background: Twelve-lead ECG represents the most common diagnostic tool in clinical cardiology and allows an immediate screening of left ventricular hypertrophy (LVH), but current criteria might have poor clinical usefulness in everyday clinical practice due to lack of sensitivity., Methods: The current study aims to review and compare the clinical performance of known ECG criteria of LVH in a real-life setting; 2134 patients had ECG and echocardiographic exams performed during the same hospitalization. All traces were retrospectively analysed, and the amplitudes of the waves were manually measured. Transthoracic echocardiography was considered as the gold standard to assess LVH., Results: LVH had a prevalence of 58%. Considering the diagnostic performance of ECG criteria for LVH, the Cornell voltage carried the best area under the receiver operating characteristic curve (0.678), while RaVF (R wave in aVF lead) had the poorer result (0.440). The R5/R6 criterion had the best sensitivity (60%), but with the worst specificity (37.4%). The 'Q or S aVR' had the best specificity (99.9%) but lacks sensitivity (0.80%). The Peguero Lo Presti criterion had a sensitivity of 42.3% and a specificity of 75.8%. The Cornell voltage and the Cornell product had similar area under the receiver operating characteristic curve values which were found to be significantly greater compared with other criteria., Conclusion: Current ECG criteria of LVH have low sensitivity despite an acceptable specificity. Among these, Cornell voltage and Cornell product criteria were equally found to have a more accurate diagnostic performance compared with other criteria. To overcome the intrinsic limitations of the current ECG LVH criteria, a new paradigm in the analysis of electrocardiographic data might be necessary.

Heart failure is a widespread disease in the western world whose incidence and prevalence are constantly increasing, mainly involving the more advanced age groups. Cardiac resynchronization therapy (CRT) has been shown able to reduce sudden cardiac death and all-cause mortality in patients with heart failure and reduced ejection fraction. Elderly patients are generally under-represented in the clinical trials aimed to evaluate the efficacy of CRT and, chiefly, of implantable cardiac defibrillator (ICD). The simultaneous presence of confounding factors such as co-morbidities, polypharmacy, changes in cognitive status, frailty, are the most important causes for the exclusion of subjects of advanced age from RCTs on the ICD or CRT implant. Current guidelines do not suggest any upper age limit for ICD and CRT but recommend avoiding their use in frail older patients with a life expectancy of less than 1 year. Data from the literature show that CRT has equal dignity in both the elderly and the young, in fostering effective functional and morphological improvements, also suggesting that, in older patients, CRT-D may have little practical value compared to CRT-P given the low incidence of arrhythmic death. Nevertheless, it is necessary to develop RCTs that consider aspects of the elderly patient in relation to CRT such as functional, cognitive and nutritional status.

Over the past few decades, the progressive aging of the population combined with the resulting increase in cardiovascular disease and the marked improvement of technologies applied to surgery justify the marked increase of the elderly patients requiring cardiovascular surgery. This claims a highly skilled perioperative management, which should be aimed at treating cardiac disease without increasing risk of hospitalization-related harmful events. Current preoperative assessment for cardiac surgery, such as the European System for Cardiac Operative Risk Evaluation II (EUROSCORE II) and the Society of Thoracic Surgeons (STS) risk score, are limited in their ability to predict perioperative outcomes in older patients.  This is because patients' chronological age should not be considered as the only tool to identify the surgical risk. In recent years, indeed, several studies have highlighted the role of frailty syndrome in determining the prognosis of elderly patients undergoing cardiac surgery. Particularly, some functional aspects, such as gait speed seem to have a high sensitivity and specificity in this regard. Therefore, further research is needed in order not only to identify a unique, fast and easy to use tool aimed to recognize frailty syndrome, but chiefly resulting able to give us information about the effectiveness of focused preoperative interventions. Finally, we need to have scientific data on the role that surgical, percutaneous and transcatheter procedures have on outcome in elderly patients in terms of perioperative mortality, postoperative quality of life and regarding the possible reversibility of frailty. Cardiovascular surgery is to date a "moving target", due to changing face of patients and changing face of technical requirements and perioperative management should reflect such changes.