Arrhythmic Risk Stratification in Cardiac Amyloidosis: A Review of the Current Literature.

Cardiac amyloidosis is the most frequent infiltrative disease caused by the deposition of misfolded proteins in the cardiac tissue, leading to heart failure, brady- and tachyarrhythmia and death. Conduction disorders, atrial fibrillation (AF) and ventricular arrhythmia (VA) significantly impact patient outcomes and demand recognition. However, several issues remain unresolved regarding early diagnosis and optimal management. Extreme bradycardia is the most common cause of arrhythmic death, while fast and sustained VAs can be found even in the early phases of the disease. Risk stratification and the prevention of sudden cardiac death are therefore to be considered in these patients, although the time for defibrillator implantation is still a subject of debate. Moreover, atrial impairment due to amyloid fibrils is associated with an increased risk of AF resistant to antiarrhythmic therapy, as well as recurrent thromboembolic events despite adequate anticoagulation. In the last few years, the aging of the population and progressive improvements in imaging methods have led to increases in the diagnosis of cardiac amyloidosis. Novel therapies have been developed to improve patients' functional status, quality of life and mortality, without data regarding their effect on arrhythmia prevention. In this review, we consider the latest evidence regarding the arrhythmic risk stratification of cardiac amyloidosis, as well as the available therapeutic strategies.

Exploring suitability to electrical storm ablation in patients in waiting list for heart transplantation: A single center experience.

Electrical storm (ES) is among the most fearsome events in patients in waiting list for heart transplantation (HT) and catheter ablation (CA) demonstrated to be effective in reduce the arrhythmic burden. However, selection criteria for CA suitability in this specific population have never been addressed before. We retrospectively enrolled 36 patients (mean age 51 ± 8 years; 83% men) waiting HT referred to our department for ES resistant to antiarrhythmic drugs and percutaneous stellate ganglion blockade. Twenty patients were judged suitable for VT ablation according to specific criteria including absence of increased arrhythmic burden secondary to volume overload and hemodynamic decompensation; expected CA outcome favorable due to etiology of the cardiomyopathy, no need for coronary revascularization and technical feasibility of the procedure. The pre-emptive use of mechanical circulatory supports (MCS) were discussed integrating the PAINESD score with additional clinical and hemodynamic parameters. Acute procedural success was accounted in 85% of cases with only two major complications. The CA group reported lower length of in-hospital stay after CA suitability evaluation (56 ± 17 vs. 131 ± 64 days, p = .004). Furthermore, at a mean follow-up of 703 ± 145 days, this group showed reduction of ventricular arrhythmia (VA) recurrence leading to implantable cardioverter defibrillator shock (4 vs. 8, p = .051) and underwent HT with a lower level of urgency (0 vs. 6 patients needed for UNOS1 status upgrade). Respectively, one patient of the CA group and two patients of the conservative group died (p = .839). At the end of follow-up, eight patients underwent heart transplantation (p = .964) while four patients underwent Left Ventricular Assist device (LVAD) implantation (p = .440). This pilot study should be a proof for further studies exploring CA of VAs as a possible bridge therapy to HT.

Impact on Outcome of Different Mechanisms, Baseline Degree and Changes of Mitral Regurgitation in Patients With Aortic Stenosis Who Underwent Transcatheter Aortic Valve Replacement.

BACKGROUND: Mitral regurgitation (MR) is frequent in patients with aortic stenosis (AS). Although primary MR is an established negative prognostic factor, whether different mechanisms of MR have different effects on outcome is currently unknown. The aim of this study was to evaluate the impact of the MR mechanism in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: This is a retrospective observational study of patients who underwent TAVR for severe aortic stenosis in a high-volume tertiary care center. Echocardiographic comprehensive MR assessment was performed at baseline and within 3 months post TAVR. The study population was divided into 4 groups according to MR mechanism: Group I: fibro-calcific leaflet degeneration; Group II: prolapse/flail; Group III: ventricular secondary MR (functional MR); and Group IV: atrial functional MR. The study end point was a combination of death from cardiovascular cause and heart failure-related hospitalization. The study population included 427 patients (mean age 81.7±6.5 years; 71% primary MR; 62% ≥moderate MR). At 3-year follow-up, survival free from the composite end point significantly differs according to MR mechanism: it was higher in group IV (atrial functional MR, 96.6%) compared with group I (80.4%, P=0.002) and group II patients (60.7%, P=0.001), and group III (84.8%, P=0.037); patients with MR due to leaflet prolapse showed poorer prognosis compared with patients with functional MR (group III, P=0.023 and group IV, P=0.001) and with group I (P=0.040). Overall, severe MR after TAVR identified patients with poorer prognosis and was significantly more frequent in group II (46.4%, P=0.001). CONCLUSIONS: In patients undergoing TAVR, preprocedural identification of MR mechanism and mechanism provides prognostic insights.

Preprocedural imaging with cardiac computed tomography for endo-epicardial ventricular tachycardia ablation.

BACKGROUND: Studies evaluating the systematic use of cardiac computed tomography (CCT) for the preprocedural assessment of myocardial fibrosis are limited. Their implementation in the electrophysiology workflow has not been extensively described. OBJECTIVE: This study aimed to explore the degree of concordance between CCT and electroanatomic mapping (EAM) for the evaluation of cardiac fibrosis in patients undergoing endo-epicardial ventricular tachycardia (VT) ablation. METHODS: From November 2017 to December 2021, patients undergoing endo-epicardial VT catheter ablation with CCT as the only source of preprocedural scar assessment were prospectively enrolled. After image integration, myocardial fibrosis detected with CCT was compared with low-voltage areas identified by endo-epicardial EAM. Postprocedural VT recurrences of this approach were evaluated after at least 1 year of follow-up. RESULTS: The study enrolled 35 patients (mean age, 60.7 ± 13.2 years; 94.2% male). The most common underlying arrhythmic substrate was dilated cardiomyopathy (48.6%). CCT was employed for contraindications to cardiac magnetic resonance, such as unstable VTs (31.4%) or nonconditional implantable cardioverter-defibrillators (28.6%), but also for patients' and operators' preferences (14.3%-25.7%). Myocardial fibrosis was correctly identified by CCT and EAM, with strong agreement between these techniques both overall (Cohen κ for agreement, 0.933) and in per-segment analysis (κ ranging from 0.796 to 1.0). Ischemic patients showed the best correlation (κ = 1.000), whereas myocarditis showed the worst (κ = 0.750). After a median follow-up of 14 (12-24) months, 1-year freedom from recurrences was achieved in 74.3% patients; overall freedom from recurrences was 60.0%. CONCLUSION: A CCT-based preprocedural assessment before VT ablation is feasible, showing high diagnostic concordance with EAM in detecting myocardial fibrosis.

Contemporary Advances in Cardiac Remote Monitoring: A Comprehensive, Updated Mini-Review.

Over the past decade, remote monitoring (RM) has become an increasingly popular way to improve healthcare and health outcomes. Modern cardiac implantable electronic devices (CIEDs) are capable of recording an increasing amount of data related to CIED function, arrhythmias, physiological status and hemodynamic parameters, providing in-depth and updated information on patient cardiovascular function. The extensive use of RM for patients with CIED allows for early diagnosis and rapid assessment of relevant issues, both clinical and technical, as well as replacing outpatient follow-up improving overall management without compromise safety. This approach is recommended by current guidelines for all eligible patients affected by different chronic cardiac conditions including either brady- and tachy-arrhythmias and heart failure. Beyond to clinical advantages, RM has demonstrated cost-effectiveness and is associated with elevated levels of patient satisfaction. Future perspectives include improving security, interoperability and diagnostic power as well as to engage patients with digital health technology. This review aims to update existing data concerning clinical outcomes in patients managed with RM in the wide spectrum of cardiac arrhythmias and Hear Failure (HF), disclosing also about safety, effectiveness, patient satisfaction and cost-saving.

Atrial tachycardia ablation through the sub-pulmonary ventricle in a patient with multiple malformations associated with congenitally corrected transposition of the great arteries and double-sided slow-pathway.

A 46-year-old woman with congenitally corrected transposition of the great arteries (ccTGA) associated with dextrocardia, situs viscerus inversus, and left superior vena cava persistence presented with an incessant supraventricular tachycardia. Electrophysiological study was not conclusive in differential diagnosis of atrial tachycardia versus atypical atrioventricular (AV) nodal reentrant tachycardia, also due to the unconventional anatomy of the coronary sinus. By a comprehensive mapping of cardiac chambers, a double side slow-pathway was localized in both atrial chambers and subsequently ablated by radiofrequency delivery without tachycardia changes. Aortic root and cusps were devoid of electrical activity. The muscular part of the sub-pulmonary ventricle at the level of interatrial septum showed an earliest activation signal of -90 ms and ablation of this site was effective in abolish the tachycardia. This is the first case to report technical concerns of septal atrial tachycardia ablation in ccTGA associated with multiple anatomical malformations. Moreover, some peculiarities have been reported for the first time including the presence of double-side AV nodal slow-pathway and atypical localization of the tachycardia origin into the muscular part of the sub-pulmonary ventricle instead of posterior pulmonary cusp.

SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits.

An increasing number of individuals are at high risk of type 2 diabetes (T2D) and its cardiovascular complications, including heart failure (HF), chronic kidney disease (CKD), and eventually premature death. The sodium-glucose co-transporter-2 (SGLT2) protein sits in the proximal tubule of human nephrons to regulate glucose reabsorption and its inhibition by gliflozins represents the cornerstone of contemporary T2D and HF management. Herein, we aim to provide an updated overview of the pleiotropy of gliflozins, provide mechanistic insights and delineate related cardiovascular (CV) benefits. By discussing contemporary evidence obtained in preclinical models and landmark randomized controlled trials, we move from bench to bedside across the broad spectrum of cardio- and cerebrovascular diseases. With landmark randomized controlled trials confirming a reduction in major adverse CV events (MACE; composite endpoint of CV death, non-fatal myocardial infarction, and non-fatal stroke), SGLT2 inhibitors strongly mitigate the risk for heart failure hospitalization in diabetics and non-diabetics alike while conferring renoprotection in specific patient populations. Along four major pathophysiological axes (i.e. at systemic, vascular, cardiac, and renal levels), we provide insights into the key mechanisms that may underlie their beneficial effects, including gliflozins' role in the modulation of inflammation, oxidative stress, cellular energy metabolism, and housekeeping mechanisms. We also discuss how this drug class controls hyperglycaemia, ketogenesis, natriuresis, and hyperuricaemia, collectively contributing to their pleiotropic effects. Finally, evolving data in the setting of cerebrovascular diseases and arrhythmias are presented and potential implications for future research and clinical practice are comprehensively reviewed.

Left Atrial Appendage Closure in Patients With a Mechanical Mitral Valve Prosthesis: A Multicentre Italian Pilot Study.

BACKGROUND: In patients with atrial fibrillation (AF) on vitamin K antagonist (VKA) therapy and therapeutic international normalized ratio (INR) range, the incidence of cardiac thromboembolism is not negligible, and the subgroup of patients who have a mechanical prosthetic mitral valve (PMV) has the highest risk. We aimed to assess the long-term effects of left atrial appendage closure (LAAC) in AF patients with a mechanical PMV who experienced a failure of VKA therapy. METHODS: In this retrospective, multicentre study, patients underwent LAAC because of thrombotic events including transient ischemic attack and/or stroke, systemic embolism, and evidence of left atrial appendage thrombosis and/or sludge, despite VKA therapy, were enrolled. Patients with a mechanical PMV were included and compared with those affected by nonvalvular AF. The primary endpoint was the composite of all-cause death, major cardiovascular events, and major bleedings at follow-up. The feasibility and safety of LAAC also were assessed. RESULTS: A total of 55 patients (42% female; mean age, 70 ± 9 years), including 12 with a mechanical PMV, were enrolled. The most-frequent indication to LAAC (71%) was LAA thrombosis or sludge. Procedural success was achieved in 96% of overall cases, and in 100% of patients with a PMV. In 35 patients, a cerebral protection device was used. During a median follow-up of 6.1 ± 4.3 years, 4 patients with a PMV, and 20 patients without a PMV, reported adverse events (hazard ratio 0.73 [95% confidence interval 0.25-2.16, P = 0.564]). CONCLUSIONS: LAAC seems to be a valuable alternative in patients with AF who have a mechanical PMV, with failure of VKA therapy. This off-label, real-world clinical practice indication deserves validation in further studies.

The Fluoroless Future in Electrophysiology: A State-of-the-Art Review.

Fluoroscopy has always been the cornerstone imaging method of interventional cardiology procedures. However, radiation exposure is linked to an increased risk of malignancies and multiorgan diseases. The medical team is even more exposed to X-rays, and a higher incidence of malignancies was reported in this professional group. In the last years, X-ray exposure has increased rapidly, involving, above all, the medical team and young patients and forcing alternative fluoroless imaging methods. In cardiac electrophysiology (EP) and pacing, the advent of 3D electroanatomic mapping systems with dedicated catheters has allowed real-time, high-density reconstruction of both heart anatomy and electrical activity, significantly reducing the use of fluoroscopy. In addition, the diffusion of intracardiac echocardiography has provided high anatomical resolution of moving cardiac structures, providing intraprocedural guidance for more complex catheter ablation procedures. These methods have largely demonstrated safety and effectiveness, allowing for a dramatic reduction in X-ray delivery in most arrhythmias' ablations. However, some technical concerns, as well as higher costs, currently do not allow their spread out in EP labs and limit their use to only procedures that are considered highly complex and time-consuming and in young patients. In this review, we aim to update the current employment of fluoroless imaging in different EP procedures, focusing on its strengths and weaknesses.

Arrhythmogenic Cardiomyopathy: Definition, Classification and Arrhythmic Risk Stratification.

Arrhythmogenic cardiomyopathy (ACM) is a heart disease characterized by a fibrotic replacement of myocardial tissue and a consequent predisposition to ventricular arrhythmic events, especially in the young. Post-mortem studies and the subsequent diffusion of cardiac MRI have shown that left ventricular involvement in arrhythmogenic cardiomyopathy is common and often develops early. Regarding the arrhythmic risk stratification, the current scores underestimate the arrhythmic risk of patients with arrhythmogenic cardiomyopathy with left involvement. Indeed, the data on arrhythmic risk stratification in this group of patients are contradictory and not exhaustive, with the consequence of not correctly identifying patients at a high arrhythmic risk who deserve protection from arrhythmic death. We propose a literature review on arrhythmic risk stratification in patients with ACM and left involvement to identify the main features associated with an increased arrhythmic risk in this group of patients.

Fighting Cardiac Thromboembolism during Transcatheter Procedures: An Update on the Use of Cerebral Protection Devices in Cath Labs and EP Labs.

Intraprocedural stroke is a well-documented and feared potential risk of cardiovascular transcatheter procedures (TPs). Moreover, subclinical neurological events or covert central nervous system infarctions are concerns related to the development of dementia, future stroke, cognitive decline, and increased risk of mortality. Cerebral protection devices (CPDs) were developed to mitigate the risk of cardioembolic embolism during TPs. They are mechanical barriers designed to cover the ostium of the supra-aortic branches in the aortic arch, but newer devices are able to protect the descending aorta. CPDs have been mainly designed and tested to provide cerebral protection during transcatheter aortic valve replacement (TAVR), but their use in both Catheterization and Electrophysiology laboratories is rapidly increasing. CPDs have allowed us to perform procedures that were previously contraindicated due to high thromboembolic risk, such as in cases of intracardiac thrombosis identified at preprocedural assessment. However, several concerns related to their employment have to be defined. The selection of patients at high risk of thromboembolism is still a subjective choice of each center. The aim of this review is to update the evidence on the use of CPDs in either Cath labs or EP labs, providing an overview of their structural characteristics. Future perspectives focusing on their possible future employment are also discussed.

Subcutaneous Implantable Cardioverter Defibrillator: A Contemporary Overview.

The difference between subcutaneous implantable cardioverter defibrillators (S-ICDs) and transvenous ICDs (TV-ICDs) concerns a whole extra thoracic implantation, including a defibrillator coil and pulse generator, without endovascular components. The improved safety profile has allowed the S-ICD to be rapidly taken up, especially among younger patients. Reports of its role in different cardiac diseases at high risk of SCD such as hypertrophic and arrhythmic cardiomyopathies, as well as channelopathies, is increasing. S-ICDs show comparable efficacy, reliability, and safety outcomes compared to TV-ICD. However, some technical issues (i.e., the inability to perform anti-bradycardia pacing) strongly limit the employment of S-ICDs. Therefore, it still remains only an alternative to the traditional ICD thus far. This review aims to provide a contemporary overview of the role of S-ICDs compared to TV-ICDs in clinical practice, including technical aspects regarding device manufacture and implantation techniques. Newer outlooks and future perspectives of S-ICDs are also brought up to date.

Network Meta-Analysis of Initial Antithrombotic Regimens After Left Atrial Appendage Occlusion.

BACKGROUND: The optimal antithrombotic therapy following left atrial appendage occlusion (LAAO) in patients with nonvalvular atrial fibrillation (AF) remains uncertain. OBJECTIVES: In this study, the authors sought to compare the efficacy and safety of various antithrombotic strategies after LAAO. METHODS: We searched the Medline, Cochrane, EMBASE, LILACS, and ClinicalTrials.gov databases for studies reporting outcomes after LAAO, stratified by antithrombotic therapy prescribed at postprocedural discharge. Direct oral anticoagulants (DOACs), vitamin K antagonists (VKAs), single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), DOAC plus SAPT, VKA plus SAPT, and no antithrombotic therapy were analyzed. We performed a frequentist random effects model network meta-analysis to estimate the OR and 95% CI for each comparison. P-scores provided a ranking of treatments. RESULTS: Forty-one studies comprising 12,451 patients with nonvalvular AF were included. DAPT, DOAC, DOAC plus SAPT, and VKA were significantly superior to no therapy to prevent device-related thrombosis. DOAC was associated with lower all-cause mortality than VKA (OR: 0.39; 95% CI: 0.17-0.89; P = 0.03). Compared with SAPT, DAPT was associated with fewer thromboembolic events (OR: 0.50; 95% CI: 0.29-0.88; P = 0.02), without a difference in major bleeding. In the analysis of P-scores, DOAC monotherapy was the strategy most likely to have lower thromboembolic events and major bleeding. CONCLUSIONS: In this network meta-analysis comparing initial antithrombotic therapies after LAAO, monotherapy with DOAC had the highest likelihood of lower thromboembolic events and major bleeding. DAPT was associated with a lower incidence of thromboembolic events compared with SAPT and may be a preferred option in patients unable to tolerate anticoagulation.

Intravascular coronary lithotripsy for the treatment of iatrogenic calcium embolization: The "block and crack" technique.

Intracoronary calcium embolization during percutaneous procedure is a very rare and unpredictable event, that  can lead to serious complications and even expert operators could face some technical issues to solve it. This case report presents a technique called "block and crack" used to manage iatrogenic intracoronary calcium embolization of left anterior descending coronary artery. The technique involves implanting a drug eluting stent (DES) to block the embolus against the vessel wall, followed by the use of lithotripsy balloon inflated inside the DES to crack the calcium and achieve a better stent expansion. This technique allowed to avoid further distal calcium embolization as well as to minimize residual stenosis degree after stent implantation.

Left atrial appendage occlusion in the absence of intraprocedural product specialist monitoring: is it time to proceed alone? Results from a multicenter real-world experience.

Background: Percutaneous left atrial appendage occlusion (LAAO) presents many technical complex features, and it is often performed under the intraprocedural surveillance of a product specialist (PS). Our aim is to assess whether LAAO is equally safe and effective when performed in high-volume centers without PS support. Methods: Intraprocedural results and long-term outcome were retrospectively assessed in 247 patients who underwent LAAO without intraprocedural PS monitoring between January 2013 and January 2022 at three different hospitals. This cohort was then matched to a population who underwent LAAO with PS surveillance. The primary end point was all-cause mortality at 1 year. The secondary end point was a composite of cardiovascular mortality plus nonfatal ischemic stroke occurrence at 1 year. Results: Of the 247 study patients, procedural success was achieved in 243 patients (98.4%), with only 1 (0.4%) intraprocedural death. After matching, we did not identify any significant difference between the two groups in terms of procedural time (70 ± 19 min vs. 81 ± 30 min, p = 0.106), procedural success (98.4% vs. 96.7%, p = 0.242), and procedure-related ischemic stroke (0.8% vs. 1.2%, p = 0.653). Compared to the matched cohort, a significant higher dosage of contrast was used during procedures without specialist supervision (98 ± 19 vs. 43 ± 21, p < 0.001), but this was not associated with a higher postprocedural acute kidney injury occurrence (0.8% vs. 0.4%, p = 0.56). At 1 year, the primary and the secondary endpoints occurred in 21 (9%) and 11 (4%) of our cohort, respectively. Kaplan-Meier curves showed no significant difference in both primary (p = 0.85) and secondary (p = 0.74) endpoint occurrence according to intraprocedural PS monitoring. Conclusions: Our results show that LAAO, despite the absence of intraprocedural PS monitoring, remains a long-term safe and effective procedure, when performed in high-volume centers.

Left atrial appendage occlusion after thromboembolic events or left atrial appendage sludge during anticoagulation therapy: Is two better than one? Real-world experience from a tertiary care hospital.

Background: The role of left atrial appendage occlusion (LAAO) for atrial fibrillation patients that during oral anticoagulant therapy (OAC) suffer from ischemic events or present LAA sludge, and the best postinterventional anticoagulant regimen, need to be defined. We present our experience with a hybrid approach of LAAO+ lifelong OAC therapy in this cohort of patients. Methods: Out of 425 patients treated with LAAO, 102 underwent LAAO because, despite OAC, suffered from ischemic events or presented with LAA sludge. Patients without high bleeding risk were discharged with the aim of maintaining lifelong OAC. This cohort was then matched to a population who underwent LAAO in primary ischemic events prevention. The primary endpoint was the composite of all-cause death and major adverse cardiovascular events consisting of ischemic stroke, systemic embolism (SE), and major bleeding. Results: Procedural success was 98%, and 70% of patients were discharged with anticoagulant therapy. After a median follow-up of 47.2 months, the primary endpoint occurred in 27 patients (26%). At multivariate analyses, coronary artery disease (OR 5.1, CI 1.89-14.27, p = .003) and OAC at discharge (OR 0.29, CI 0.11-0.80, p = .017) were associated with the primary endpoint. After propensity score matching, no significant difference was found in the survival free from the primary endpoint according to the indication for LAAO (p = .19). Conclusions: In this high-ischemic risk cohort, LAAO + OAC seem a long-term safe and effective therapeutical approach, with no difference in the survival free from the primary endpoint according to the indication for LAAO in a matched cohort.