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.

H2FPEF and HFA-PEFF scores performance and the additional value of cardiac structure and function in patients with atrial fibrillation.

BACKGROUND: The H2FPEF and the HFA-PEFF scores have become useful tools to diagnose heart failure with preserved ejection fraction (HFpEF). Their accuracy in patients with a history of atrial fibrillation (AF) is less known. This study evaluates the association of these scores with invasive left atrial pressure (LAP) and the additional value of cardiac measures. METHODS: This is a multicenter observational prospective study involving patients undergoing ablation of AF. Patients with left ventricular ejection fraction (LVEF) < 40%, congenital cardiopathy, any severe cardiac valve disease and prosthetic valves were excluded. Elevated filling pressure was defined as a mean LAP ≥15 mmHg. RESULTS: A total of 135 patients were enrolled in the study (mean age 65.2 ± 9.1 years, 32% female, mean LVEF 56.9 ± 7.9%). Patients with H2FPEF ≥ 6 or HFA-PEFF ≥5 had higher values of NTproBNP and more impaired cardiac function. However, neither H2FPEF nor HFA-PEFF score showed a meaningful association with elevated mean LAP (respectively, OR 1.05 [95%CI 0.83-1.34] p = 0.64, and OR 1.09 [95%CI: 0.86-1.39] p = 0.45). The addition of LA indexed minimal volume (LAVi min) improved the ability of the scores (baseline C-statistic 0.51 [95%CI 0.41-0.61] for the H2FPEF score and 0.53 [95%CI 0.43-0.64] for the HFA-PEFF score) to diagnose elevated filling pressure (H2FPEF + LAVi min: C-statistic 0.70 [95%CI 0.60-0.80], p-value = 0.005; HFA-PEFF + LAVi min: C-statistic 0.70 [95%CI 0.60-0.80], p-value = 0.02). CONCLUSION: In a cohort of patients with a history of AF, the use of the available diagnostic scores did not predict elevated mean LAP. The integration of LAVi min improved the ability to correctly identify elevated filling pressure.

Determinants of invasive left atrial pressure in patients with atrial fibrillation.

AIMS: Estimation of left ventricular (LV) filling pressures in patients with atrial fibrillation (AF) is challenging due to lack of reliable parameters. This study investigates the association between cardiac structure and function and invasive mean left atrial pressure (LAP). METHODS AND RESULTS: This is a multi-center prospective study enrolling patients undergoing transcatheter ablation for AF. The invasive measurement of LAP was performed at the time of the procedure while the echocardiography within the previous 24 hours. A mean LAP ≥ 15 mmHg was considered as increased. Overall, 101 patients were included (mean age 65.8 ± 8.5 years, 68% male, mean LV ejection fraction 56.6 ± 8.0%). No significant differences regarding clinical characteristics were detected between the group of patients with normal (n=47) or increased LAP (n=54). The latter showed lower values of LV global longitudinal strain, larger left atrial volumes (LAV) and worse right ventricular (RV) function. After multivariable adjustment, higher E/e' ratio (p=0.041) and minimal LAV index (LAVI min) (p=0.031), lower peak atrial longitudinal strain (PALS) (p=0.030) and RV free wall strain (p=0.037), but not maximal LAV index (LAVI max) (p=0.137), were significantly associated with mean LAP. The associations were not modified by cardiac rhythm. Overall, LAVI min showed the best diagnostic accuracy to predict elevated LAP (AUC 0.703). CONCLUSION: LA structure and function assessment well correlates with mean LAP in patients with AF. These measures may be used in the assessment of filling pressure in these patients.

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.

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.

Mechanism of Charge Transport in Lithium Thiophosphate.

Lithium ortho-thiophosphate (Li3PS4) has emerged as a promising candidate for solid-state electrolyte batteries, thanks to its highly conductive phases, cheap components, and large electrochemical stability range. Nonetheless, the microscopic mechanisms of Li-ion transport in Li3PS4 are far from being fully understood, the role of PS4 dynamics in charge transport still being controversial. In this work, we build machine learning potentials targeting state-of-the-art DFT references (PBEsol, r2SCAN, and PBE0) to tackle this problem in all known phases of Li3PS4 (α, ß, and γ), for large system sizes and time scales. We discuss the physical origin of the observed superionic behavior of Li3PS4: the activation of PS4 flipping drives a structural transition to a highly conductive phase, characterized by an increase in Li-site availability and by a drastic reduction in the activation energy of Li-ion diffusion. We also rule out any paddle-wheel effects of PS4 tetrahedra in the superionic phases-previously claimed to enhance Li-ion diffusion-due to the orders-of-magnitude difference between the rate of PS4 flips and Li-ion hops at all temperatures below melting. We finally elucidate the role of interionic dynamical correlations in charge transport, by highlighting the failure of the Nernst-Einstein approximation to estimate the electrical conductivity. Our results show a strong dependence on the target DFT reference, with PBE0 yielding the best quantitative agreement with experimental measurements not only for the electronic band gap but also for the electrical conductivity of ß- and α-Li3PS4.

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.

Electrocardiogram Changes in the Postictal Phase of Epileptic Seizure: Results from a Prospective Study.

BACKGROUND: The brain and heart are strictly linked and the electrical physiologies of these organs share common pathways and genes. Epilepsy patients have a higher prevalence of electrocardiogram (ECG) abnormalities compared to healthy people. Furthermore, the relationship between epilepsy, genetic arrhythmic diseases and sudden death is well known. The association between epilepsy and myocardial channelopathies, although already proposed, has not yet been fully demonstrated. The aim of this prospective observational study is to assess the role of the ECG after a seizure. MATERIALS AND METHODS: From September 2018 to August 2019, all patients admitted to the emergency department of San Raffaele Hospital with a seizure were enrolled in the study; for each patient, neurological, cardiological and ECG data were collected. The ECG was performed at the time of the admission (post-ictal ECG) and 48 h later (basal ECG) and analyzed by two blinded expert cardiologists looking for abnormalities known to indicate channelopathies or arrhythmic cardiomyopathies. In all patients with abnormal post-ictal ECG, next generation sequencing (NGS) analysis was performed. RESULTS: One hundred and seventeen patients were enrolled (females: 45, median age: 48 ± 12 years). There were 52 abnormal post-ictal ECGs and 28 abnormal basal ECGs. All patients with an abnormal basal ECG also had an abnormal post-ictal ECG. In abnormal post-ictal ECG, a Brugada ECG pattern (BEP) was found in eight patients (of which two had BEP type I) and confirmed in two basal ECGs (of which zero had BEP type I). An abnormal QTc interval was identified in 20 patients (17%), an early repolarization pattern was found in 4 patients (3%) and right precordial abnormalities were found in 5 patients (4%). Any kind modification of post-ictal ECG was significantly more pronounced in comparison with an ECG recorded far from the seizure (p = 0.003). A 10:1 higher prevalence of a BEP of any type (particularly in post-ictal ECG, p = 0.04) was found in our population compared to general population. In three patients with post-ictal ECG alterations diagnostic for myocardial channelopathy (BrS and ERP), not confirmed at basal ECG, a pathogenic gene variant was identified (KCNJ8, PKP2 and TRMP4). CONCLUSION: The 12-lead ECG after an epileptic seizure may show disease-related alterations otherwise concealed in a population at a higher incidence of sudden death and channelopathies. Post-ictal BEP incidence was higher in cases of nocturnal seizure.

Left Atrial Appendage Occlusion in Patients with Failure of Antithrombotic Therapy: Good Vibes from Early Studies.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and predisposes patients to an increased risk of cardioembolic events (CE), such as ischemic stroke, TIA, or systemic embolism [...].

Left Bundle Branch Area Pacing over His Bundle Pacing: How Far Have We Come?

Implantable cardiac pacemakers have greatly evolved during the few past years, focusing on newer modalities of physiologic cardiac pacing [...].

Uric acid significantly correlates with the presence of low-voltage areas at the endocardial mapping in patients with non-valvular atrial fibrillation.

BACKGROUND AND AIMS: Interest in the role of atrial substrate in maintaining Atrial Fibrillation (AF) is growing. Fibrosis is the culprit in the electrical derangement of the myocytes. Many cardiovascular risk factors are known to be linked to atrial scarring; among them Uric Acid (UA) is emerging. The purpose of our study is to find whether UA is associated with Left Atrium (LA) with pathological substrate. METHODS AND RESULTS: 81 patients who underwent radiofrequency transcatheter ablation for nonvalvular AF at the cardiological department of the Niguarda Hospital were enrolled in an observational, cross-sectional, single-center study. UA levels were analysed before the procedure. High density electroanatomic mapping of the LA was performed and patients were divided according to the presence or not of areas of pathological substrate (bipolar voltage <0.5 mV in sinus rhythm). 19 patients showed a LA with pathological substrate. These subjects showed a significant higher prevalence of persistent phenotype of AF (84.2 vs. 25.8%, p < 0.001). UA levels were significantly higher in the group of patients with LA with pathological substrate (6.8 ± 1.9 vs 5.3 ± 1.4 mg/dL, p < 0.001) as well as the prevalence of hyperuricemia (26.5 vs. 6.5%, p = 0.021). The association between uric acid LA with pathological substrate remains significant even after correction for confounding factors (age, left ventricular dysfunction, valvular disease, arrythmia phenotype and furosemide use) and also when the ratio UA/creatinine was evaluated. CONCLUSIONS: In a population of patients who underwent AF ablation, higher UA levels were significantly associated with pathological LA substrate at electro-anatomical mapping.

Direct anchoring technique for pacing and defibrillation leads inserted through cephalic vein: insight for a single high-volume center.

BACKGROUND: Direct anchoring of PM and ICD leads over cephalic vein body is officially discouraged by manufactures due to a supposed risk of conductor fracture or insulation failure, however careful tightening of anchoring knots can probably prevent lead damage. Direct anchoring (DA) technique is routinely used in our center for all leads inserted by cephalic vein while standard anchoring sleeves are used to secure subclavian leads only. Aim of the study is to assess short- and long-term safety of cephalic direct anchoring technique. METHODS: All patients undergoing PM and ICD implantation in our center from November 2014 to March 2016 were consecutively enrolled. Primary endpoints were acute lead fracture, lead dislodgement and chronic lead failure. Secondary endpoint was a composite of short-term surgical complications (pocket hematoma, pneumothorax, and pericardial effusion) plus device infections. Subclavian leads secured with sleeve anchoring (SA) were used as control. RESULTS: A total of 550 leads were implanted in 310 consecutive patients. DA involved 323 leads (59%) while SA was used for 227 (41%). Median follow-up was 50 months (IQR 24-62 months). 17 lead malfunctions (3.1%) were observed during follow-up. No difference was observed between groups (10 DA vs. 7 SP, P=ns). Survival analysis found no difference between groups. Secondary endpoints were not statistically different between groups (5 vs. 1, P=0.08). CONCLUSIONS: Direct anchoring technique of PM and ICD leads is a safe technique and does not increase lead malfunction risk.

[Leadless pacemakers: results of a survey from implanter centers in the Lombardy region]. / Pacemaker leadless: risultati di una survey condotta nei centri impiantatori della Regione Lombardia.

BACKGROUND: Transvenous pacing is nowadays the cornerstone of interventional management of bradyarrhythmias. It is still associated, however, with significant complications, mostly related to indwelling transvenous leads or device pocket. In order to reduce these complications, leadless pacemakers have been recently introduced into clinical practice, but no guidelines are yet available to indicate who are those patients that might benefit the most and whether leadless pacing should be preferred in the old or young population. This survey aims to describe the use of leadless pacemaker devices in a real-world setting. METHODS: Eleven arrhythmia centers in the Lombardy region (out of a total of 17 participating centers) responded to the proposed questionnaire regarding patient characteristics and indications to leadless pacing. RESULTS: Out of a total of 411 patients undergoing leadless pacing during 4.2 ± 0.98 years, the median age was 77 years, with 0.18% of patients having less than 18 years, 29.9% 18-65 years, 34.3% 65-80 years and 35.6% >80 years. The most common indication was slow atrial fibrillation (49% of patients), followed by atrioventricular block and sinoatrial dysfunction. Two centers reported in-hospital complications. CONCLUSIONS: Leadless pacemakers proved to be a safe pacing strategy actually destined mostly to elderly patients.

Clinical characteristics and outcomes of patients with ventricular arrhythmias after continuous-flow left ventricular assist device implant.

BACKGROUND: Ventricular arrhythmias (VAs) are observed in 25%-50% of continuous-flow left ventricular assist device (CF-LVAD) recipients, but their role on mortality is debated. METHODS: Sixty-nine consecutive patients with a CF-LVAD were retrospectively analyzed. Study endpoints were death and occurrence of first episode of VAs post CF-LVAD implantation. Early VAs were defined as VAs in the first month after CF-LVAD implantation. RESULTS: During a median follow-up of 29.0 months, 19 patients (27.5%) died and 18 patients (26.1%) experienced VAs. Three patients experienced early VAs, and one of them died. Patients with cardiac resynchronization therapy (CRT-D) showed a trend toward more VAs (p = 0.076), compared to patients without CRT-D; no significant difference in mortality was found between patients with and without CRT-D (p = 0.63). Patients with biventricular (BiV) pacing ≥98% experienced more frequently VAs (p = 0.046), with no difference in mortality (p = 0.56), compared to patients experiencing BiV pacing <98%. There was no difference in mortality among patients with or without VAs after CF-LVAD [5 patients (27.8%) vs. 14 patients (27.5%), p = 0.18)], and patients with or without previous history of VAs (p = 0.95). Also, there was no difference in mortality among patients with a different timing of implant of implantable cardioverter-defibrillator (ICD), before and after CF-LVAD (p = 0.11). CONCLUSIONS: VAs in CF-LVAD are a common clinical problem, but they do not impact mortality. Timing of ICD implantation does not have a significant impact on patients' survival. Patients with BiV pacing ≥98% experienced more frequently VAs.