[New frontiers in pacing: from myocardial pacing to conduction system pacing]. / Nuove frontiere dell'elettrostimolazione: dal pacing del miocardio comune al pacing del sistema di conduzione.

For many years, cardiac pacing has been based on the stimulation of right ventricular common myocardium to correct diseases of the conduction system. The birth and the development of cardiac resynchronization have led to growing interest in the correction and prevention of pacing-induced dyssynchrony. Many observational studies and some randomized clinical trials have shown that conduction system pacing (CSP) can not only prevent pacing-induced dyssynchrony but can also correct proximal conduction system blocks, with reduction of QRS duration and with equal or greater effectiveness than biventricular pacing. Based on these results, many Italian electrophysiologists have changed the stimulation target from the right ventricular common myocardium to CSP. The two techniques with greater clinical impact are the His bundle stimulation and the left bundle branch pacing. The latter, in particular, because of its easier implantation technique and better electric parameters, is spreading like wildfire and is representing a real revolution in the cardiac pacing field. However, despite the growing amount of data, until now, the European Society of Cardiology guidelines give a very limited role to CSP.

[Temporary cardiac pacing: 50 years old and still young]. / La stimolazione cardiaca temporanea: dopo 50 anni una metodica ancora giovane.

Temporary cardiac pacing (TCP) is a 50-year-old technique but it is still young. It is used in all cardiology departments for saving lives of patients with bradycardia and hemodynamic instability. The know-how of TCP cannot miss in clinical competence of cardiologists that work in the cardiac intensive care unit. However, despite its wide diffusion, the scientific evidence supporting TCP is not so strong and in Italian hospitals the management of some aspects of TCP is highly variable, including indications as well as antibiotic and anticoagulant prophylaxis. Due to the high risk of TCP-related complications, the 2021 European guidelines on cardiac pacing recommend whenever possible to avoid TCP before cardiac implantable electronic device implantation and, in all cases, TCP duration should be as short as possible. In the last years, if on the one hand, TCP indications have gradually decreased, on the other hand high-frequency TCP during aortic valvuloplasty or transcatheter aortic valve implantation procedures have progressively increased.

Recurrence of atrial fibrillation postablation: which is the most effective approach for detection?

Over the last 20 years, catheter ablation of atrial fibrillation (AF) has evolved from a research tool into a fundamental therapeutic measure, with the potential to improve symptoms, quality of life, and even risk of major adverse cardiac events (among patients with heart failure and a reduced ejection fraction). Notwithstanding the tremendous evolution in techniques and tools, risk of AF recurrences postablation is not negligible, and a comprehensive structured follow-up is highly needed to deliver optimal patient care. In this follow-up process, monitoring of heart rhythm is quintessential to detect recurrences, and may be accomplished by means of symptoms-triggered, intermittent, or continuous monitors. In recent years, the development and widespread adoption of implantable cardiac monitors, by allowing continuous long-term rhythm assessment, has surged to become the gold-standard strategy, both in research settings and in clinical practice. In this review, we both summarize the present state-of-the art on the detection of postablation AF recurrences and provide future perspectives on this emerging yet often neglected topic, aiming to give practical hints for evidence-based, personalized patient care.

Myocardial Inflammation, Sports Practice, and Sudden Cardiac Death: 2021 Update.

Myocardial inflammation is an important cause of cardiovascular morbidity and sudden cardiac death in athletes. The relationship between sports practice and myocardial inflammation is complex, and recent data from studies concerning cardiac magnetic resonance imaging and endomyocardial biopsy have substantially added to our understanding of the challenges encountered in the comprehensive care of athletes with myocarditis or inflammatory cardiomyopathy (ICM). In this review, we provide an overview of the current knowledge on the epidemiology, pathophysiology, diagnosis, and treatment of myocarditis, ICM, and myopericarditis/perimyocarditis in athletes, with a special emphasis on arrhythmias, patient-tailored therapies, and sports eligibility issues.

Sports Activity and Arrhythmic Risk in Cardiomyopathies and Channelopathies: A Critical Review of European Guidelines on Sports Cardiology in Patients with Cardiovascular Diseases.

The prediction and prevention of sudden cardiac death is the philosopher's stone of clinical cardiac electrophysiology. Sports can act as triggers of fatal arrhythmias and therefore it is essential to promptly frame the athlete at risk and to carefully evaluate the suitability for both competitive and recreational sports activity. A history of syncope or palpitations, the presence of premature ventricular complexes or more complex arrhythmias, a reduced left ventricular systolic function, or the presence of known or familiar heart disease should prompt a thorough evaluation with second level examinations. In this regard, cardiac magnetic resonance and electrophysiological study play important roles in the diagnostic work-up. The role of genetics is increasing both in cardiomyopathies and in channelopathies, and a careful evaluation must be focused on genotype positive/phenotype negative subjects. In addition to being a trigger for fatal arrhythmias in certain cardiomyopathies, sports also play a role in the progression of the disease itself, especially in the case arrhythmogenic right ventricular cardiomyopathy. In this paper, we review the latest European guidelines on sport cardiology in patients with cardiovascular diseases, focusing on arrhythmic risk stratification and the management of cardiomyopathies and channelopathies.

Recent advances in three-dimensional electroanatomical mapping guidance for the ablation of complex atrial and ventricular arrhythmias.

PURPOSE: To provide a brief overview of some relevant technological advances in the field of three-dimensional electroanatomical mapping (3D-EAM) that have recently entered the clinical arena and their role in guiding catheter ablation (CA) of complex atrial and ventricular arrhythmias. METHODS: In this technical report, we describe the general features of three novel algorithms featured in the updated CARTO PRIME™ mapping module for CARTO®3 version 7 3D-EAM system (Biosense Webster Inc., Diamond Bar, CA, USA): local activation time (LAT) hybrid, coherent mapping and map replay modules. We also report three challenging arrhythmia cases in which CA was successfully guided by these softwares. RESULTS: The LAT hybrid module was used in a case of premature ventricular complex originating from the right coronary cusp. This algorithm facilitated safe positioning of the ablation catheter away from the right coronary ostium, avoiding potential harm to this vital structure. The coherent mapping module helped to identify the critical as well as a bystander isthmus of an atrial macro-re-entrant tachycardia in a grown-up patient with congenital heart disease. The map replay module allowed rapid retrospective activation mapping of two unstable ventricular tachycardias in a case of nonischemic cocaine-associated cardiomyopathy. CONCLUSION: 3D-EAM systems offer significant advantages in the management of challenging arrhythmias, and the introduction of novel algorithms underpins improvements in patients' outcomes. Given the increasing sophistication of these systems, however, a close collaboration among cardiac electrophysiologists, engineers and technicians is highly needed in order to get the best from the available technology.

Out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation in patients with normal electrocardiograms: results from a multicentre long-term registry.

AIMS: To define the clinical characteristics and long-term clinical outcomes of a large cohort of patients with idiopathic ventricular fibrillation (IVF) and normal 12-lead electrocardiograms (ECGs). METHODS AND RESULTS: Patients with ventricular fibrillation as the presenting rhythm, normal baseline, and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular conduction abnormalities, and without structural heart disease were included in a registry. A total of 245 patients (median age: 38 years; males 59%) were recruited from 25 centres. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25-110 months), 12 patients died (5%); in four of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, P = 0.001). Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.18-0.92; P = 0.03]. CONCLUSION: Patients with IVF and persistently normal ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences.

Novel SCN5A Frameshift Mutation in Brugada Syndrome Associated With Complex Arrhythmic Phenotype.

In this case report, we characterize a novel inherited frameshift mutation c.4700_4701del (p.Phe1567Cysfs*221) in a single copy of the SCN5A gene and its association with Brugada syndrome (BrS). The proband experienced a life-threatening ventricular arrhythmia successfully treated with DC-shock and he also suffered from supraventricular tachycardia. Ajmaline test confirmed the BrS diagnosis. No other mutation nor low frequency variants in the other 23 analyzed genes were detected. The same mutation was found in the father and sister, who were both diagnosed with BrS. We hypothesize that this mutation could be responsible for BrS and potentially linked to supraventricular tachycardias. Further studies are needed to confirm this observation and to assess the clinical relevance of this mutation, in terms of risk-stratification.

Non-paroxysmal atrial fibrillation mapping: characterization of the electrophysiological substrate using a novel integrated mapping technique.

AIMS: Clinical outcomes after radiofrequency catheter ablation (RFCA) remain suboptimal in the treatment of non-paroxysmal atrial fibrillation (AF). Electrophysiological mapping may improve understanding of the underlying mechanisms. To describe the arrhythmia substrate in patients with persistent (Pers) and long-standing persistent (LSPers) AF, undergoing RFCA, using an integrated mechanism mapping technique. METHODS AND RESULTS: Patients underwent high-density electroanatomical mapping before and after catheter ablation. Integrated maps characterized electrogram (EGM) cycle length (CL) in regions with repetitive-regular (RR) activations, stable wavefront propagation, fragmentation, and peak-to-peak bipolar voltage. Among 83 patients (72% male, 60 ± 11 years old), RR activations were identified in 376 regions (mean CL 180 ± 31 ms). PersAF patients (n = 43) showed more RR sites per patient (5.3 ± 2.4 vs. 3.7 ± 2.1, P = 0.002) with faster CL (166 ± 29 vs. 190 ± 29 ms; P < 0.001) and smaller surface area of fragmented EGMs (15 ± 14% vs. 27 ± 17%, P < 0.001) compared with LSPersAF. The post-ablation map in 50 patients remaining in AF, documented reduction of the RR activities per patient (1.5 ± 0.7 vs. 3.7 ± 1.4, P < 0.001) and area of fragmentation (22 ± 17% vs. 8 ± 9%, P < 0.001). Atrial fibrillation termination during ablation occurred at RR sites (0.48 ± 0.24 mV; 170.5 ± 20.2 ms CL) in 31/33 patients (94%). At the latest follow-up, arrhythmia freedom was higher among patients receiving ablation >75% of RR sites (Q4 82.6%, Q3 63.1%, Q2 35.1%, and Q1 0%; P < 0.001). CONCLUSION: The integrated mapping technique allowed characterization of multiple arrhythmic substrates in non-paroxysmal AF patients. This technique might serve as tool for a substrate-targeted ablation approach.

SCN5A Nonsense Mutation and NF1 Frameshift Mutation in a Family With Brugada Syndrome and Neurofibromatosis.

In this case series, we report for the first time a family in which the inherited nonsense mutation [c. 3946C > T (p.Arg1316*)] in the SCN5A gene segregates in association with Brugada syndrome (BrS). Moreover, we also report, for the first time, the frameshift mutation [c.7686delG (p.Ile2563fsX40)] in the NF1 gene, as well as its association with type 1 neurofibromatosis (NF1), characterized by pigmentary lesions (café au lait spots, Lisch nodules, freckling) and cutaneous neurofibromas. Both of these mutations and associated phenotypes were discovered in the same family. This genetic association may identify a subset of patients at higher risk of sudden cardiac death who require the appropriate electrophysiological evaluation. This case series highlights the importance of genetic testing not only to molecularly confirm the pathology but also to identify asymptomatic family members who need clinical examinations and preventive interventions, as well as to advise about the possibility of avoiding recurrence risk with medically assisted reproduction.

Multipoint left ventricular pacing improves response to cardiac resynchronization therapy with and without pressure-volume loop optimization: comparison of the long-term efficacy of two different programming strategies.

PURPOSE: Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP]) improves long-term LV reverse remodeling, though questions persist about how to program LV pacing vectors and delays. We evaluated if an empirical method of programming MPP vectors and delays between pacing pulses improved CRT response similar to pressure-volume loop (PVL) optimized MPP programming. METHODS: Patients undergoing CRT implant (Quadra Assura MP™ CRT-D and Quartet™ LV lead) received MPP with programmed settings optimized either by PVL measurements at implant (PVL-OPT group) or empirically determined by maximizing the spatial separation between the two cathodes and minimal delays between the three ventricular pacing pulses (MAX-SEP group). CRT response was prospectively defined as a reduction in end-systolic volume (ESV) of ≥ 15% relative to baseline at 6 months as determined by a blinded observer. RESULTS: Patient characteristics at baseline (NYHA II-III, ejection fraction [EF] 27 ± 6%, QRS 151 ± 17 ms) were not significantly different between the PVL-OPT (n = 27) and MAX-SEP (n = 26) groups. During the follow-up period, there were no differences in the number of patients requiring reprogramming due to phrenic nerve stimulation or a high threshold for PVL-OPT vs. MAX-SEP (5/27 [19%] vs. 7/26 [27%], p = 0.53). After 6 months, ESV reduction, EF increase, and CRT response rate (RR) were similar for PVL-OPT vs. MAX-SEP (ESV - 20 ± 11 vs. - 22 ± 11%, p = 0.59; EF + 10 ± 4 vs. + 9 ± 7%, p = 0.53; RR 20/27 [74%] vs. 21/26 [81%], p = 0.74), while fewer patients in the PVL-OPT group experienced NYHA class reduction ≥ 2 (4/27 [15%] vs.15/26 [58%], p = 0.002). CONCLUSIONS: Both evaluated methods of MPP programming resulted in similar CRT outcomes. Empirical MPP programming by maximum spatial separation of LV cathodes may be an effective, simple, and non-invasive alternative to pressure-volume optimization.

General Anesthesia Attenuates Brugada Syndrome Phenotype Expression: Clinical Implications From a Prospective Clinical Trial.

OBJECTIVES: This study investigates the electrocardiographic-electrophysiological effects of administration of anesthetic drugs for general anesthesia (GA) in patients with BrS at high risk of sudden cardiac death (SCD). BACKGROUND: The safety of anesthetic agents in Brugada syndrome (BrS) is under debate. METHODS: All consecutive patients with spontaneous type 1 BrS electrocardiographic (ECG) patterns undergoing epicardial ablation of the arrhythmogenic substrate (AS) under GA were enrolled. Anesthesia was induced with single bolus of propofol and maintained with sevofluorane. ECG measurements were collected before, immediately after, and 20 min after induction of GA. Three-dimensional maps during GA and after ajmaline indicated the epicardial AS before ablation. RESULTS: Thirty-six patients with BrS (32 male, 88.9%; mean age 38.8 ± 12.0 years) with a spontaneous type 1 ECG pattern underwent GA. Induction was performed using propofol at mean dose of 1.6 to 2.6 mg/kg (2.1 ± 0.3 mg/kg). Twenty-eight (28 of 36, 77.8%) patients showed a reversion to a nondiagnostic pattern. ST-segment elevation (0.32 ± 0.01 mV vs. 0.19 ± 0.02 mV; p < 0.001) and J-wave amplitude (0.47 ± 0.02 mV vs. 0.31 ± 0.03 mV; p < 0.001) decreased after propofol. The AS area during GA, in the absence of BrS pattern, significantly enlarged after administration of ajmaline (3.6 ± 0.5 cm2 vs. 20.3 ± 0.8 cm2). No patient developed malignant arrhythmias during GA induction and maintenance. CONCLUSIONS: This study shows that GA using single-bolus propofol and volatile anesthetics is safe in high-risk patients with BrS, and it may exert a modulating effect by reducing the manifestation of type 1 BrS pattern and AS in the form of epicardial abnormal ECGs. (Epicardial Ablation in Brugada Syndrome: An Extension Study of 200 BrS Patients; NCT03106701).

Atrial Fibrillation in Autoimmune Rheumatic Diseases: from Pathogenesis to Treatment.

Atrial Fibrillation (AF) is the most commonly described cardiac arrhythmia found in the general population and can lead to adverse outcomes. Its onset and maintenance requires the presence of an arrhythmogenic substrate that predisposes the patient for risk of these types of arrhythmias and the occurrence of a trigger event. A major characteristic of AF-related structural remodelling is atrial fibrosis, a process closely related to inflammation. Autoimmune rheumatic diseases constitute systemic inflammatory disorders that can also present with cardiovascular manifestations, including a high incidence of AF, thus supporting the idea of a link between AF and inflammation. A vicious cycle exists in which inflammation leads to a higher prevalence of structural cardiovascular disease, which in turn leads to more inflammation and AF; in fact, inflammation is known to affect signalling pathways that lead to the development of AF. Therapy must first target systemic inflammation, since decreasing the inflammatory burden has consistently shown to positively ameliorate the prognosis. When this approach is not sufficient, rhythm or, when not feasible, rate control is indicated in addition to anticoagulant therapy. As far as the rhythm control strategy is concerned, antiarrhythmic drugs and/or catheter ablation should be considered. New mapping techniques allowing the characterization of the arrhythmic substrate have opened new perspectives and may help in the treatment of AF in these patients, since atrial tissue is the target of inflammation-induced arrhythmic alterations. In cases where the natural history of the arrhythmia itself is more advanced, in order to minimize the impact of AF on cardiac function as well as quality of life, a device-based therapy, including an "ablate and pace" approach could be adopted.

Assessing the Malignant Ventricular Arrhythmic Substrate in Patients With Brugada Syndrome.

BACKGROUND: Guidelines recommend the use of implanted cardioverter-defibrillators in patients with Brugada syndrome and induced ventricular tachyarrhythmias, but there is no evidence supporting it. OBJECTIVES: This prospective registry study was designed to explore clinical and electrophysiological predictors of malignant ventricular tachyarrhythmia inducibility in Brugada syndrome. METHODS: A total of 191 consecutive selected patients with (group 1; n = 88) and without (group 2; n = 103) Brugada syndrome-related symptoms were prospectively enrolled in the registry. Patients underwent electrophysiological study and substrate mapping or ablation before and after ajmaline testing (1 mg/kg/5 min). RESULTS: Overall, before ajmaline testing, 53.4% of patients had ventricular tachyarrhythmia inducibility, which was more frequent in group 1 (65.9%) than in group 2 (42.7%; p < 0.001). Regardless of clinical presentation, larger substrates with more fragmented long-duration ventricular potentials were found in patients with inducible arrhythmias than in patients without inducible arrhythmias (p < 0.001). One extrastimulus was used in more extensive substrates (median 13 cm2; p < 0.001), and ventricular fibrillation was the more frequently induced rhythm (p < 0.001). After ajmaline, patients without arrhythmia inducibility had arrhythmia inducibility without a difference in substrate characteristics between the 2 groups. The substrate size was the only independent predictor of inducibility (odds ratio: 4.51; 95% confidence interval: 2.51 to 8.09; p < 0.001). A substrate size of 4 cm2 best identified patients with inducible arrhythmias (area under the curve: 0.98; p < 0.001). Substrate ablation prevented ventricular tachyarrhythmia reinducibility. CONCLUSIONS: In Brugada syndrome dynamic substrate variability represents the pathophysiological basis of lethal ventricular tachyarrhythmias. Substrate size is independently associated with arrhythmia inducibility, and its determination after ajmaline identifies high-risk patients missed by clinical criteria. Substrate ablation is associated with electrocardiogram normalization and not arrhythmia reinducibility. (Epicardial Ablation in Brugada Syndrome [BRUGADA_I]; NCT02641431; Epicardial Ablation in Brugada Syndrome: An Extension Study of 200 BrS Patients; NCT03106701).

Clinical Outcome of Electrophysiologically Guided Ablation for Nonparoxysmal Atrial Fibrillation Using a Novel Real-Time 3-Dimensional Mapping Technique: Results From a Prospective Randomized Trial.

BACKGROUND: Clinical outcomes after ablation of persistent atrial fibrillation remain suboptimal. Identification of AF drivers using a novel integrated mapping technique may be crucial to ameliorate the clinical outcome. METHODS AND RESULTS: Persistent AF patients were prospectively enrolled to undergo high-density electrophysiological mapping to identify repetitive-regular activities (RRas) before modified circumferential pulmonary vein (PV) ablation. They have been randomly assigned (1:1 ratio) to ablation of RRa followed by modified circumferential PV ablation (mapping group; n=41) or modified circumferential PV ablation alone (control group; n=40). The primary end point was freedom from arrhythmic recurrences at 1 year. In total, 81 persistent AF patients (74% male; mean age, 61.7±10.6 years) underwent mapping/ablation procedure. The regions exhibiting RRa were 479 in 81 patients (5.9±2.4 RRa per patient): 232 regions in the mapping group (n=41) and 247 in the control group (n=40). Overall, 185 of 479 (39%) RRas were identified within the PVs, whereas 294 of 479 (61%) in non-PV regions. Mapping-guided ablation resulted in higher arrhythmia termination rate when compared with conventional strategy (25/41, 61% versus 12/40, 30%; P<0.007). Total radiofrequency duration (P=0.38), mapping (P=0.46), and fluoroscopy times (P=0.69) were not significantly different between the groups. No major procedure-related adverse events occurred. After 1 year, 73.2% of mapping group patients were free from recurrences versus 50% of control group (P=0.03). CONCLUSIONS: Targeted ablation of regions showing RRa provided an adjunctive benefit in terms of arrhythmia freedom at 1-year follow-up in the treatment of persistent AF. These findings might support a patient-tailored strategy in subjects with nonparoxysmal AF and should be confirmed by additional larger, randomized, multicenter studies. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier NCT02571218.

Multipoint pacing improves peripheral hemodynamic response: Noninvasive assessment using radial artery tonometry.

BACKGROUND: Multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP], Abbott, Sylmar, CA, USA) improves the response rate to cardiac resynchronization therapy (CRT). We evaluated the feasibility of noninvasive radial artery tonometry (RAT) to characterize arterial pressure morphology changes (pre-ejection period [PEP] and ejection duration [ED]) between conventional CRT and MPP pacing interventions. METHODS: Patients with a MPP-enabled CRT device (Quadra Assura MP™, Abbott) underwent noninvasive RAT assessment (SphygmoCor CVMS, AtCor Medical Inc., Itasca, IL, USA) at 3-6 months after implantation. A pacing protocol was performed in a randomized order including one optimized conventional biventricular CRT (CONV) configuration using the distal electrode and five MPP configurations. The PEP, ED, and PEP/ED ratio were determined for each intervention from the RAT pressure waveform and electrocardiogram. RESULTS: Pressure waveforms were successfully recorded in 19 patients (89% male, QRS 147 ± 16 ms, 63% ischemic). In 17/19 (89%) patients, at least one MPP intervention resulted in improved PEP, ED, and PEP/ED compared to CONV. The MPP intervention with greatest separation of LV cathodes and minimum intra-LV delay significantly improved PEP (mean PEP -15 ± 33% vs -8 ± 32% [CONV], P = 0.04) and ED (mean ED +8 ± 8% [MPP] vs +4 ± 7% [CONV], P = 0.02), and PEP/ED (-0.07 ± 0.14 [MPP] vs -0.04 ± 0.13 [CONV], P = 0.02) compared with CONV. CONCLUSIONS: Noninvasive RAT efficiently characterizes changes in PEP and ED between CONV and MPP interventions. MPP configurations using the widest separation among LV cathodes and minimum intra-LV delay may significantly improve RAT-derived parameters as compared to conventional CRT.

Thrombosis on a left atrial appendage occluder device: the double-edged sword of stroke prevention strategies in atrial fibrillation.

: A huge thrombus, developing after percutaneous left atrial appendage occlusion, has been successfully treated with dabigatran and aspirin as combination therapy.Although novel oral anticoagulants alone may be effective in thrombus dissolution, the association of an antiplatelet drug may safely enhance this process.