Single versus dual antiplatelet therapy following percutaneous left atrial appendage closure-A systematic review and meta-analysis.

BACKGROUND: In the last few years, percutaneous LAA occlusion (LAAO) has become a plausible alternative in atrial fibrillation (AF) patients with contraindications to anticoagulation therapy. Nevertheless, the optimal antiplatelet strategy following percutaneous LAAO remains to be defined. METHODS: Studies comparing single antiplatelet therapy (SAPT) versus dual antiplatelet therapy (DAPT) following LAAO were systematically searched and screened. The outcomes of interest were ischemic stroke, device-related thrombus (DRT) and major bleeding. A random-effect meta-analysis was performed comparing outcomes in both groups. The moderator effect of baseline characteristics on outcomes was evaluated by univariate meta-regression analyses. RESULTS: Sixteen observational studies with 3255 patients treated with antiplatelet therapy (SAPT, n = 1033; DAPT, n = 2222) after LAAO were included. Mean age was 74.5 ± 8.3 years, mean CHA2DS2-VASc and HAS-BLED scores were 4.3 ± 1.5 and 3.2 ± 1.0, respectively. At a weighted mean follow-up of 12.7 months, the occurrence of stroke (RR 1.33; 95% CI 0.64-2.77; p =.44), DRT (RR 1.52; 95% CI 0.90-2.58; p =.12), and the composite of stroke and DRT (RR 1.26; 95% CI 0.67-2.37; p =.47) did not differ significantly between SAPT and DAPT groups. The rate of major bleedings was also not different between groups (RR 1.41; 95% CI 0.64-3.12; p =.39). CONCLUSIONS: Among AF patients at high bleeding risk undergoing percutaneous LAAO, a post-procedural minimalistic antiplatelet strategy with SAPT did not significantly differ from DAPT regimens regarding the rate of stroke, DRT and major bleeding.

Continuous stellate ganglion block for ventricular arrhythmias: case series, systematic review, and differences from thoracic epidural anaesthesia.

AIMS: Percutaneous stellate ganglion block (PSGB) through single-bolus injection and thoracic epidural anaesthesia (TEA) have been proposed for the acute management of refractory ventricular arrhythmias (VAs). However, data on continuous PSGB (C-PSGB) are scant. The aim of this study is to report our dual-centre experience with C-PSGB and to perform a systematic review on C-PSGB and TEA. METHODS AND RESULTS: Consecutive patients receiving C-PSGB at two centres were enrolled. The systematic literature review follows the latest Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Our case series (26 patients, 88% male, 60 ± 16 years, all with advanced structural heart disease, left ventricular ejection fraction 23 ± 11%, 32 C-PSGBs performed, with a median duration of 3 days) shows that C-PSGB is feasible and safe and leads to complete VAs suppression in 59% and to overall clinical benefit in 94% of cases. Overall, 61 patients received 68 C-PSGBs and 22 TEA, with complete VA suppression in 63% of C-PSGBs (61% of patients). Most TEA procedures (55%) were performed on intubated patients, as opposed to 28% of C-PSGBs (P = 0.02); 63% of cases were on full anticoagulation at C-PSGB, none at TEA (P < 0.001). Ropivacaine and lidocaine were the most used drugs for C-PSGB, and the available data support a starting dose of 12 and 100 mg/h, respectively. No major complications occurred, yet TEA discontinuation rate due to side effects was higher than C-PSGB (18 vs. 1%, P = 0.01). CONCLUSION: Continuous PSGB seems feasible, safe, and effective for the acute management of refractory VAs. The antiarrhythmic effect may be accomplished with less concerns for concomitant anticoagulation compared with TEA and with a lower side-effect related discontinuation rate.

Convolutional neural network (CNN)-enabled electrocardiogram (ECG) analysis: a comparison between standard twelve-lead and single-lead setups.

Background: Artificial intelligence (AI) has shown promise in the early detection of various cardiac conditions from a standard 12-lead electrocardiogram (ECG). However, the ability of AI to identify abnormalities from single-lead recordings across a range of pathological conditions remains to be systematically investigated. This study aims to assess the performance of a convolutional neural network (CNN) using a single-lead (D1) rather than a standard 12-lead setup for accurate identification of ECG abnormalities. Methods: We designed and trained a lightweight CNN to identify 20 different cardiac abnormalities on ECGs, using data from the PTB-XL dataset. With a relatively simple architecture, the network was designed to accommodate different combinations of leads as input (<100,000 learnable parameters). We compared various lead setups such as the standard 12-lead, D1 alone, and D1 paired with an additional lead. Results: This has been corrected to "The CNN based on single-lead ECG (D1) achieved satisfactory performance compared to the standard 12-lead framework (average percentage AUC difference: −8.7%). Notably, for certain diagnostic classes, there was no difference in the diagnostic AUC between the single-lead and the standard 12-lead setups. When a second lead was detected in the CNN in addition to D1, the AUC gap was further reduced to an average percentage difference of -2.8% compared with that of the standard 12-lead setup. Conclusions: A relatively lightweight CNN can predict different classes of cardiac abnormalities from D1 alone and the standard 12-lead ECG. Considering the growing availability of wearable devices capable of recording a D1-like single-lead ECG, we discuss how our findings contribute to the foundation of a large-scale screening of cardiac abnormalities.

The Intrinsic Cardiac Nervous System: From Pathophysiology to Therapeutic Implications.

The cardiac autonomic nervous system (CANS) plays a pivotal role in cardiac homeostasis as well as in cardiac pathology. The first level of cardiac autonomic control, the intrinsic cardiac nervous system (ICNS), is located within the epicardial fat pads and is physically organized in ganglionated plexi (GPs). The ICNS system does not only contain parasympathetic cardiac efferent neurons, as long believed, but also afferent neurons and local circuit neurons. Thanks to its high degree of connectivity, combined with neuronal plasticity and memory capacity, the ICNS allows for a beat-to-beat control of all cardiac functions and responses as well as integration with extracardiac and higher centers for longer-term cardiovascular reflexes. The present review provides a detailed overview of the current knowledge of the bidirectional connection between the ICNS and the most studied cardiac pathologies/conditions (myocardial infarction, heart failure, arrhythmias and heart transplant) and the potential therapeutic implications. Indeed, GP modulation with efferent activity inhibition, differently achieved, has been studied for atrial fibrillation and functional bradyarrhythmias, while GP modulation with efferent activity stimulation has been evaluated for myocardial infarction, heart failure and ventricular arrhythmias. Electrical therapy has the unique potential to allow for both kinds of ICNS modulation while preserving the anatomical integrity of the system.

Electrical storm treatment by percutaneous stellate ganglion block: the STAR study.

BACKGROUND AND AIMS: An electrical storm (ES) is a clinical emergency with a paucity of established treatment options. Despite initial encouraging reports about the safety and effectiveness of percutaneous stellate ganglion block (PSGB), many questions remained unsettled and evidence from a prospective multicentre study was still lacking. For these purposes, the STAR study was designed. METHODS: This is a multicentre observational study enrolling patients suffering from an ES refractory to standard treatment from 1 July 2017 to 30 June 2023. The primary outcome was the reduction of treated arrhythmic events by at least 50% comparing the 12 h following PSGB with the 12 h before the procedure. STAR operators were specifically trained to both the anterior anatomical and the lateral ultrasound-guided approach. RESULTS: A total of 131 patients from 19 centres were enrolled and underwent 184 PSGBs. Patients were mainly male (83.2%) with a median age of 68 (63.8-69.2) years and a depressed left ventricular ejection fraction (25.0 ± 12.3%). The primary outcome was reached in 92% of patients, and the median reduction of arrhythmic episodes between 12 h before and after PSGB was 100% (interquartile range -100% to -92.3%). Arrhythmic episodes requiring treatment were significantly reduced comparing 12 h before the first PSGB with 12 h after the last procedure [six (3-15.8) vs. 0 (0-1), P < .0001] and comparing 1 h before with 1 h after each procedure [2 (0-6) vs. 0 (0-0), P < .001]. One major complication occurred (0.5%). CONCLUSIONS: The findings of this large, prospective, multicentre study provide evidence in favour of the effectiveness and safety of PSGB for the treatment of refractory ES.

[Electrical storm management in the cardiac care unit]. / Gestione della tempesta aritmica in terapia intensiva cardiologica.

Electrical storm (ES) is characterized by at least three separate episodes of ventricular arrhythmia (VA) over 24 h that require treatment or an incessant VA lasting >12 h. The incidence is higher in patients with implantable cardioverter-defibrillators (ICDs) in secondary prevention and the main manifestation is monomorphic VA. ES onset represents a major event in the history of patients with cardiomyopathies that significantly worsens prognosis. The management of ES is complex and requires a multidisciplinary approach including a comprehensive clinical assessment, resuscitation and sedation management skills, ICD reprogramming, ablation, and neuromodulation procedures. ES early recognition and prompt treatment initiation increase the chances of therapeutic success. Each one of these aspects will be properly discussed in the present decalogue. Notably, ES management remains a challenge, with only limited available evidence from small retrospective series and a substantial lack/limited number of randomized or prospective trials. The spectrum of available antiarrhythmic drugs is limited, as well as their efficacy. The future hope is that larger prospective studies will be able to answer important questions, concerning the most effective pharmacologic strategies, the timing for the invasive treatment, the indications for acute neuromodulation strategies and for the circulatory support tools.

Machine learning-based prediction of in-hospital death for patients with takotsubo syndrome: The InterTAK-ML model.

AIMS: Takotsubo syndrome (TTS) is associated with a substantial rate of adverse events. We sought to design a machine learning (ML)-based model to predict the risk of in-hospital death and to perform a clustering of TTS patients to identify different risk profiles. METHODS AND RESULTS: A ridge logistic regression-based ML model for predicting in-hospital death was developed on 3482 TTS patients from the International Takotsubo (InterTAK) Registry, randomly split in a train and an internal validation cohort (75% and 25% of the sample size, respectively) and evaluated in an external validation cohort (1037 patients). Thirty-one clinically relevant variables were included in the prediction model. Model performance represented the primary endpoint and was assessed according to area under the curve (AUC), sensitivity and specificity. As secondary endpoint, a K-medoids clustering algorithm was designed to stratify patients into phenotypic groups based on the 10 most relevant features emerging from the main model. The overall incidence of in-hospital death was 5.2%. The InterTAK-ML model showed an AUC of 0.89 (0.85-0.92), a sensitivity of 0.85 (0.78-0.95) and a specificity of 0.76 (0.74-0.79) in the internal validation cohort and an AUC of 0.82 (0.73-0.91), a sensitivity of 0.74 (0.61-0.87) and a specificity of 0.79 (0.77-0.81) in the external cohort for in-hospital death prediction. By exploiting the 10 variables showing the highest feature importance, TTS patients were clustered into six groups associated with different risks of in-hospital death (28.8% vs. 15.5% vs. 5.4% vs. 1.0.8% vs. 0.5%) which were consistent also in the external cohort. CONCLUSION: A ML-based approach for the identification of TTS patients at risk of adverse short-term prognosis is feasible and effective. The InterTAK-ML model showed unprecedented discriminative capability for the prediction of in-hospital death.

Impact of Right Ventricular Pacing in Patients With TAVR Undergoing Permanent Pacemaker Implantation.

BACKGROUND: Long-term right ventricular pacing (VP) has been related to negative left ventricular remodeling and heart failure (HF), but there is a lack of evidence regarding the prognostic impact on transcatheter aortic valve replacement (TAVR) patients. OBJECTIVES: The aim of the PACE-TAVI registry is to evaluate the association of high percentage of VP with adverse outcomes in patients with pacemaker implantation after TAVR. METHODS: PACE-TAVI is an international multicenter registry of all consecutive TAVR patients who underwent permanent pacemaker implantation for conduction disturbances in the first 30 days after the procedure. Patients were divided into 2 subgroups according to the percentage of VP (<40% vs ≥40%) at pacemaker interrogation. The primary endpoint was the composite of cardiovascular mortality or hospitalization for HF. RESULTS: A total of 377 patients were enrolled, 158 with VP <40% and 219 with VP ≥40%. After multivariable adjustment, VP ≥40% was associated with a higher incidence of the primary endpoint (HR: 2.76; 95% CI: 1.39-5.51; P = 0.004), first HF hospitalization (HR: 3.37; 95% CI: 1.50-7.54; P = 0.003), and cardiovascular death (HR: 3.77; 95% CI: 1.02-13.88; P = 0.04), while the incidence of all-cause death was not significantly different (HR: 2.17; 95% CI: 0.80-5.90; P = 0.13). Patients with VP ≥ 40% showed a higher New York Heart Association functional class both at 1 year (P = 0.009) and at last available follow-up (P = 0.04) and a nonsignificant reduction of left ventricular ejection fraction (P = 0.18) on 1-year echocardiography, while patients with VP <40% showed significant improvement (P = 0.009). CONCLUSIONS: In TAVR patients undergoing permanent pacemaker implantation, a high percentage of right VP at follow-up is associated with an increased risk for cardiovascular death and HF hospitalization. These findings suggest the opportunity to minimize right VP through dedicated algorithms in post-TAVR patients without complete atrioventricular block and to evaluate a more physiological VP modality in patients with persistent complete atrioventricular block.

Electrical storm management in structural heart disease.

Electrical storm (ES) is a life-threatening condition characterized by at least three separate episodes of ventricular arrhythmias (VAs) over 24 h, each requiring therapeutic intervention, including implantable cardioverter defibrillator (ICD) therapies. Patients with ICDs in secondary prevention are at higher risk of ES and the most common presentation is that of scar-related monomorphic VAs. Electrical storm represents a major unfavourable prognostic marker in the history of patients with structural heart disease, with an associated two- to five-fold increase in mortality, heart transplant, and heart failure hospitalization. Early recognition and prompt treatment are crucial to improve the outcome. Yet, ES management is complex and requires a multidisciplinary approach and well-defined protocols and networks to guarantee a proper patient care. Acute phase stabilization should include a comprehensive clinical assessment, resuscitation and sedation management skills, ICD reprogramming, and acute sympathetic modulation, while the sub-acute/chronic phase requires a comprehensive heart team evaluation to define the better treatment option according to the haemodynamic and overall patient's condition and the type of VAs. Advanced anti-arrhythmic strategies, not mutually exclusive, include invasive ablation, cardiac sympathetic denervation, and, for very selected cases, stereotactic ablation. Each of these aspects, as well as the new European Society of Cardiology guidelines recommendations, will be discussed in the present review.

The Brugada syndrome: pharmacological therapy.

Brugada syndrome is an inherited channelopathy with an increased risk of sudden cardiac death (SCD) due to ventricular arrhythmias (VA) and an increased incidence of supraventricular arrhythmias, as compared with the general population. For the prevention of SCD, the guidelines recommend the implantable cardioverter-defibrillator (ICD); however, ICD does not prevent VA. In this article, we provide a brief review of the literature on the Brugada syndrome pharmacological therapy, mainly focusing on quinidine treatment. The efficacy of quinidine therapy in the prevention of VA in Brugada syndrome has been demonstrated by several small studies in patients with ICD and recurrent shocks or in asymptomatic patients with inducible ventricular fibrillation (VF) at electrophysiological study. Quinidine has also been tested for the prophylaxis of supraventricular arrhythmias, especially atrial fibrillation/flutter, and in paediatric patients. In these studies, quinidine proved highly effective in preventing re-induction of VF and spontaneous recurrences of both ventricular and supraventricular arrhythmias. Unfortunately, this therapy is burdened by a high incidence of side effects, which may lead to drug discontinuation.

Echocardiographic Parameters to Predict Malignant Events in Arrhythmic Mitral Valve Prolapse Population.

Bileaflet Mitral Valve Prolapse (bMVP) has been linked to major arrhythmic events and sudden cardiac death (SCD). Consistent predictors in this field are still lacking. Echocardiography is the best tool for the analysis of the prolapse and its impact on the ventricular mechanics. The aim of this study was to find new echocardiographic predictors of malignant events within an arrhythmic MVP population. We evaluated 22 patients with arrhythmic bMVP with a transthoracic echocardiogram focused on mitral valve anatomy and ventricular contraction. Six of them had major arrhythmic events that required ICD implantation (ICD-MVP group), while sixteen presented with a high arrhythmic burden without major events (A-MVP group). The best predictors of malignant events were the Anterior Mitral Leaflet (AML) greater length and greater Mechanical Dispersion (MD) of basal and mid-ventricular segments, while other significant predictors were the larger mitral valve annulus (MVA) indexed area, lower MVA anteroposterior diameter/AML length ratio, higher inferolateral basal segment S3 velocity.

In-hospital outcomes in nonagenarian patients undergoing primary percutaneous coronary intervention.

BACKGROUND: The aim of the present analysis was to evaluate the incidence and predictors of in-hospital adverse outcomes in nonagenarian patients undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI). METHODS: Consecutive nonagenarian patients undergoing pPCI for STEMI from 2009 to 2019 were retrospectively included in an international multicenter registry. In-hospital all-cause death was the primary outcome. RESULTS: A total of 308 patients were included (mean age 92.5±2.5 years, 65.6% female). Mean systolic blood pressure (SBP) at hospital admission was 130.7±33.5 mmHg, 46 (17%) patients presented with a Killip class III-IV, mean left ventricle ejection fraction (LVEF) was 40.0±11.5% and 147 (58%) patients were independent in everyday activities. In-hospital death occurred in 99 patients (32%). After multivariate adjustment, lower LVEF (OR per unit reduction 1.08, 95% CI: 1.03-1.11, P value <0.001), lower SBP (OR 1.02 per mmHg reduction, 95% CI: 1.01-1.03, P value 0.001) and being not independent at home (OR 2.56, 95% CI: 1.25-5.26, P value 0.01) resulted independent predictors of in-hospital mortality. A sensitivity analysis performed in final TIMI 3 flow population confirmed the prognostic role of LVEF and independency on in-hospital mortality. CONCLUSIONS: Nonagenarian patients presenting with STEMI and undergoing pPCI have high in-hospital mortality. Independency in everyday life is a strong independent predictor of survival to hospital discharge.

A case report of long-term successful stereotactic arrhythmia radioablation in a cardiac contractility modulation device carrier with giant left atrium, including a detailed dosimetric analysis.

Introduction: Catheter ablation (CA) is the current standard of care for patients suffering drug-refractory monomorphic ventricular tachycardias (MMVTs). Yet, despite significant technological improvements, recurrences remain common, leading to increased morbidity and mortality. Stereotactic arrhythmia radioablation (STAR) is increasingly being adopted to overcome the limitations of conventional CA, but its safety and efficacy are still under evaluation. Case presentation: We hereby present the case of a 73-year-old patient implanted with a mitral valve prosthesis, a cardiac resynchronization therapy-defibrillator, and a cardiac contractility modulation device, who was successfully treated with STAR for recurrent drug and CA-resistant MMVT in the setting of advanced heart failure and a giant left atrium. We report a 2-year follow-up and a detailed dosimetric analysis. Conclusion: Our case report supports the early as well as the long-term efficacy of 25 Gy single-session STAR. Despite the concomitant severe heart failure, with an overall heart minus planned target volume mean dosage below 5 Gy, no major detrimental cardiac side effects were detected. To the best of our knowledge, our dosimetric analysis is the most accurate reported so far in the setting of STAR, particularly for what concerns cardiac substructures and coronary arteries. A shared dosimetric planning among centers performing STAR will be crucial in the next future to fully disclose its safety profile.

Neuromodulation devices for heart failure.

Autonomic imbalance with a sympathetic dominance is acknowledged to be a critical determinant of the pathophysiology of chronic heart failure with reduced ejection fraction (HFrEF), regardless of the etiology. Consequently, therapeutic interventions directly targeting the cardiac autonomic nervous system, generally referred to as neuromodulation strategies, have gained increasing interest and have been intensively studied at both the pre-clinical level and the clinical level. This review will focus on device-based neuromodulation in the setting of HFrEF. It will first provide some general principles about electrical neuromodulation and discuss specifically the complex issue of dose-response with this therapeutic approach. The paper will thereafter summarize the rationale, the pre-clinical and the clinical data, as well as the future prospectives of the three most studied form of device-based neuromodulation in HFrEF. These include cervical vagal nerve stimulation (cVNS), baroreflex activation therapy (BAT), and spinal cord stimulation (SCS). BAT has been approved by the Food and Drug Administration for use in patients with HfrEF, while the other two approaches are still considered investigational; VNS is currently being investigated in a large phase III Study.

The impact of particle radiotherapy on the functioning of cardiac implantable electronic devices: a systematic review of in vitro and in vivo studies according to PICO criteria.

The number of oncological patients who may benefit from proton beam radiotherapy (PBT) or carbon ion radiotherapy (CIRT), overall referred to as particle radiotherapy (RT), is expected to strongly increase in the next future, as well as the number of cardiological patients requiring cardiac implantable electronic devices (CIEDs). The management of patients with a CIED requiring particle RT deserves peculiar attention compared to those undergoing conventional photon beam RT, mostly due to the potential generation of secondary neutrons by particle beams interactions. Current consensus documents recommend managing these patients as being at intermediate/high risk of RT-induced device malfunctioning regardless of the dose on the CIED and the beam delivery method used, despite the last one significantly affects secondary neutrons generation (very limited neutrons production with active scanning as opposed to the passive scattering technique). The key issues for the current review were expressed in four questions according to the Population, Intervention, Control, Outcome criteria. Three in vitro and five in vivo studies were included. Based on the available data, PBT and CIRT with active scanning have a limited potential to interfere with CIED that has only emerged from in vitro study so far, while a significant potential for neutron-related, not severe, CIED malfunctions (resets) was consistently reported in both clinical and in vitro studies with passive scattering.

Feasibility of an Automatic Ultrasonographic Image Acquisition System Associated With an Artificial Intelligence Algorithm for Real-Time Monitoring of Cardiac Motion During Cardiac Radio-Ablation.

Background: The management of the cardio-respiratory motion of the target and the reduction of the uncertainties related to patient's positioning are two of the main challenges that stereotactic arrhythmia radio-ablation (STAR) has to overcome. A prototype of a system was developed that can automatically acquire and interpret echocardiographic images using an artificial intelligence (AI) algorithm to calculate cardiac displacement in real-time. Methods: We conducted a single center study enrolling consecutive patients with a history of ventricular arrhythmias (VA) in order to evaluate the feasibility of this automatic acquisition system. Echocardiographic images were automatically acquired from the parasternal and apical views with a dedicated probe. The system was designed to hold the probe fixed to the chest in the supine position during both free-breathing and short expiratory breath-hold sequences, to simulate STAR treatment. The primary endpoint was the percentage of patients reaching a score ≥2 in a multi-parametric assessment evaluating the quality of automatically acquired images. Moreover, we investigated the potential impact of clinical and demographic characteristics on achieving the primary endpoint. Results: We enrolled 24 patients (63 ± 14 years, 21% females). All of them had a history of VA and 21 (88%) had an ICD. Eight patients (33%) had coronary artery disease, 12 (50%) had non-ischemic cardiomyopathy, and 3 had idiopathic VA. Parasternal, as well as apical images were obtained from all patients except from one, in whom parasternal view could not be collected due to the patient's inability to maintain the supine position. The primary endpoint was achieved in 23 patients (96%) for the apical view, in 20 patients (87%) for the parasternal view, and in all patients in at least one of the two views. The images' quality was maximal (i.e., score = 4) in at least one of the two windows in 19 patients (79%). Atrial fibrillation arrhythmia was the only clinical characteristics associated with a poor score outcome in both imaging windows (apical p = 0.022, parasternal p = 0.014). Conclusions: These results provide the proof-of-concept for the feasibility of an automatic ultrasonographic image acquisition system associated with an AI algorithm for real-time monitoring of cardiac motion in patients with a history of VA.