High-density mapping of Koch's triangle during sinus rhythm and typical atrioventricular nodal re-entrant tachycardia, integrated with direct recording of atrio-ventricular node structure potential.

BACKGROUND: The mechanism of typical slow-fast atrioventricular nodal re-entrant tachycardia (AVNRT) and its anatomical and electrophysiological circuit inside the right atrium (RA) and Koch's Triangle (KT) are not well known. OBJECTIVE: To identify the potentials of the compact AV node and inferior extensions and to perform accurate mapping of the RA and KT in sinus rhythm (SR) and during AVNRT, to define the tachycardia circuit. METHODS: Consecutive patients with typical AVNRT were enrolled in 12 Italian centers and underwent mapping and ablation by means of a basket catheter with small electrode spacing for ultrahigh-density mapping and a modified signal-filtering toolset to record the potentials of the AV nodal structures. RESULTS: Forty-five consecutive cases of successful ablation of typical slow-fast AVNRT were included. The mean SR cycle length (CL) was 784.1 ± 6 ms and the mean tachycardia CL was 361.2 ± 54 ms. The AV node potential had a significantly shorter duration and higher amplitude in sinus rhythm than during tachycardia (60 ± 40 ms vs. 160 ± 40 ms, p < .001 and 0.3 ± 0.2 mV vs. 0.09 ± 0.12 mV, p < .001, respectively). The nodal potential duration extension was 169.4 ± 31 ms, resulting in a time-window coverage of 47.6 ± 9%. The recording of AV nodal structure potentials enabled us to obtain 100% coverage of the tachycardia CL during slow-fast AVNRT. CONCLUSION: Detailed recording of the potentials of nodal structures is possible by means of multipolar catheters for ultrahigh-density mapping, allowing 100% of the AVNRT CL to be covered. These results also have clinical implications for the ablation of right-septal and para-septal arrhythmias.

Timing of cryoballoon pulmonary vein isolation to prevent atrial fibrillation recurrence.

BACKGROUND: The aims of this analysis were: to evaluate the impact of timing of ablation on the rate of atrial arrhythmias recurrence, verify if the timing of ablation impact differently in patients with paroxysmal and persistent AF. METHODS: Three thousand two hundred and five patients (60.5 ± 10 years, female 28.4%%, 78.8%% paroxysmal AF) were included in the analysis. All patients underwent only cryoballoon (CB) pulmonary vein (PV) isolation during the index procedure. RESULTS: The mean procedure time was 102.8 ± 50 min, with a mean fluoroscopy time of 26.3 ± 49 min. Acute PV isolation was achieved in 11760/11793 (99.7%) PVs. A total of 91 (2.8%) patients experienced a procedure-related complication. During the observation period 913/3205 (28.5%) patients had at least one atrial arrhythmias episode: 28% of patients with paroxysmal AF vs 33% of patients with persistent AF. In multivariate analysis, persistent AF together with time from symptomatic AF diagnosis to ablation, female sex, and ablation time showed to be significant predictors for AF recurrence. In particular, months from first symptomatic AF episode > 18 months was a significant predictor of AF recurrence (HR = 1.23, 95% CI = 1.03-1.46, p = 0.020). In patients with paroxysmal AF, the multivariate analysis confirmed that months from first symptomatic AF episode > 18 month was an independent predictor of AF recurrence together with age > 62 years and female sex. In patients with persistent AF, the time from persistent AF showed to be significant predictor for AF recurrence. CONCLUSIONS: In this multicenter analysis, time from first symptomatic AF episode > 18 months was a significant predictor of AF recurrence after CB PV isolation.

Prognostic significance of remotely monitored nocturnal heart rate in heart failure patients with reduced ejection fraction.

BACKGROUND: Elevated resting heart rate is a risk factor for cardiovascular events. OBJECTIVE: The purpose of this study was to investigate the clinical significance of nocturnal heart rate (nHR) and 24-hour mean heart rate (24h-HR) obtained by continuous remote monitoring (RM) of implantable devices. METHODS: We analyzed daily-sampled trends of nHR, 24h-HR, and physical activity in patients on ß-blocker therapy for chronic heart failure and with implantable cardioverter-defibrillators or cardiac resynchronization therapy defibrillators (CRT-Ds). Patients were grouped by average nHR and 24h-HR quartile during follow-up to estimate the respective incidence of nonarrhythmic death and device-treated ventricular tachycardia/fibrillation (VT/VF). RESULTS: The study cohort included 1330 patients (median age 69 years [interquartile range 61-77 years]; 41% [n = 550] with CRT-D; median follow-up 25 months [interquartile range 13-42 months]). Compared with patients in the lowest nHR quartile (≤57 beats/min) group, patients in the highest quartile group (>65 beats/min) had an increased risk of nonarrhythmic death (adjusted hazard ratio [AHR] 2.25; 95% confidence interval [CI] 1.13-4.50; P = .021) and VT/VF (AHR 1.98; 95% CI 1.40-2.79; P < .001) and were characterized by the lowest level of physical activity (P ≤ .0004 vs every other nHR quartiles). The highest 24h-HR quartile group (>75 beats/min) showed an increased risk of VT/VF (AHR 2.13; 95% CI 1.52-2.99; P < .001) and a weaker though significant association with nonarrhythmic mortality (AHR 1.80; 95% CI 1.00-3.22; P = .05) as compared with the lowest 24h-HR quartile group (≤65 beats/min). CONCLUSION: In remotely monitored patients with implantable cardioverter-defibrillator/CRT-D on ß-blocker therapy for heart failure, elevated heart rates (nHR >65 beats/min and 24h-HR >75 beats/min) were associated with increased mortality and VT/VF risk. nHR showed a stronger association than 24h-HR with worst prognosis and lowest physical activity.

A DNA biosensors-based microfluidic platform for attomolar real-time detection of unamplified SARS-CoV-2 virus.

The emergence of the coronavirus 2019 (COVID-19) arose the need for rapid, accurate and massive virus detection methods to control the spread of infectious diseases. In this work, a device, deployable in non-medical environments, has been developed for the detection of non-amplified SARS-CoV-2 RNA. A SARS-CoV-2 specific probe was designed and covalently immobilized at the surface of glass slides to fabricate a DNA biosensor. The resulting system was integrated in a microfluidic platform, in which viral RNA was extracted from non-treated human saliva, before hybridizing at the surface of the sensor. The formed DNA/RNA duplex was detected in presence of SYBR Green I using an opto-electronic system, based on a high-power LED and a photo multiplier tube, which convert the emitted fluorescence into an electrical signal that can be processed in less than 10 min. The limit of detection of the resulting microfluidic platform reached six copies of viral RNA per microliter of sample (equal to 10 aM) and satisfied the safety margin. The absence of non-specific adsorption and the selectivity for SARS-CoV-2 RNA were established. In addition, the designed device could be applicable for the detection of a variety of viruses by simple modification of the immobilized probe.

"Shift and cover technique": conservative management of complications for the rescue of S-ICD subcutaneous implantable defibrillator systems.

BACKGROUND: The risk of complications has been shown to be lower with subcutaneous implantable defibrillator (S-ICD) than with conventional ICDs. Given the low frequency of complications, experience of how to manage them is limited. In this paper, we describe generator- and lead-related complications recorded in a series of S-ICD patients, and we propose our conservative approach to managing them. METHODS: The study cohort consisted of S-ICD patients who were referred to our institution owing to generator- or lead-related complications requiring surgical intervention. With our "shift and cover" approach, the system component involved is moved from its original position to an alternative, more protected location. In the case of the generator, this involves moving it to an intermuscular pocket. In the case of infections at the parasternal scar, the electrode sleeve is moved away from its original location, stitched, and then covered with the muscular fascia. RESULTS: Fourteen S-ICD patients were referred to our institution owing to system-related complications. Complications involved the generator in 7 cases (deep pocket infections with erosion, extrusion, or pain), the lead in 5 cases (parasternal infections at the xyphoid incision site), and both the generator and the lead in 2 cases. Complications were managed without completely removing the device and resolved in a single surgical session with no intraoperative complications. During defibrillation testing, the first shock at 65 J was effective in all patients. The shock impedance after revision was significantly lower than that measured during first implantation (59 ± 10 Ohm versus 86 ± 24 Ohm, P = 0.013). In all cases, the cosmetic result was satisfactory. No complications or recurrent infections were reported at the 12-month follow-up visit. CONCLUSIONS: The proposed conservative approach was successful in managing S-ICD complications. The revision procedure allowed to optimize the system configuration in terms of the defibrillation vector, resulting in lower shock impedance values and better device positioning.

Active fixation of bipolar left ventricular lead through a persistent left superior vena cava.

A left superior vena cava persistence was found in a 61 year-old patient affected by dilated and hypokinetic cardiopathy with severe dysfunction of the left ventricle (left ventricular ejection fraction of 32%) and valvular disease. After a negative coronary angiography, he was implanted with a cardiac resynchronization therapy with defibrillation function device (CRT-D). The present case describes the successful implantation of a biventricular defibrillator in this challenging congenital abnormality of cardiac venous system.

Performance of transcatheter pacing system use in relation to patients' age.

PURPOSE: Real-world safety data on the use of transcatheter pacing systems particularly in very elderly patients is still limited. The aim of this analysis was to investigate the effect of age on the safety and efficacy of leadless pacemaker implant. METHODS: From May 2016 through July 2019, 577 patients were implanted with a leadless single-chamber pacemaker according to current pacing indication in 15 Italian cardiologic centers. The population was divided into age quartiles for evaluation, including (1) < 70 years, (2) 70-77 years, (3) 78-83 years, and (4) ≥ 83 years. Procedural data, complications, and electrical parameters were collected at baseline and during the follow-up. RESULTS: Procedural-related complication occurrence was very low (< 1.0%) and similar in the four subgroups according to age even if the older patients were more frail. No cardiac tamponade was reported. Among the groups, no difference was observed in procedural time, fluoroscopy time duration, and electrical parameters (mean pacing impedance: 750 ± 192 and 599 ± 156, mean pacing threshold: 0.7 ± 0.5 and 0.7 ± 0.6, and mean right ventricular sensing 10.7 ± 6.1 and 11.5 ± 4.8 at implant and last follow-up, respectively). CONCLUSIONS: The reported data demonstrated a high degree of safety during leadless implant across all patient ages. Procedural complications and device electrical measurements were similar among the different ages.

Optimized radiofrequency lesions through local impedance guidance for effective CTI ablation in right atrial flutter.

BACKGROUND: Although radiofrequency (RF) catheter ablation of cavo-tricuspid isthmus (CTI) is an established treatment for typical right atrial flutter (RAFL), it remains to be established whether local tissue impedance (LI) is able to predict effective CTI ablation and what LI drop values during ablation should be used to judge a lesion as effective. We aimed to investigate the ability of LI to predict ablation efficacy in patients with RAFL. METHODS: RF delivery was guided by the DirectSense™ algorithm. Successful single RF application was defined according to a defragmentation of atrial potentials (DAP), reduction of voltage (RedV) by at least 80% or changes on unipolar electrogram (UPC). The ablation endpoint was the creation of bidirectional conduction block (BDB) across the isthmus. RESULTS: 392 point-by-point RF applications were analyzed in 48 consecutive RAFL patients. The mean baseline LI was 105.4 ± 12Ω prior to ablation and 92.0 ± 11Ω after ablation (p < 0.0001). According to validation criteria, absolute drops in impedance were larger at successful ablation sites than at ineffective ablation sites (DAP: 17.8 ± 6Ω vs. 8.7 ± 4Ω; RedV: 17.2 ± 6Ω vs. 7.8 ± 5Ω; UPC: 19.6 ± 6Ω vs. 10.1 ± 5Ω, all p < 0.0001). LI drop values significantly increased according to the number of criteria satisfied (ranging from 7.5Ω to 19.9). BDB was obtained in all cases. No procedure-related adverse events were reported. CONCLUSIONS: A LI-guided approach to CTI ablation was safe and effective in treating RAFL. The magnitude of LI drop was associated with effective lesion formation and BDB and could be used as a marker of ablation efficacy. CLINICAL TRIAL REGISTRATION: Catheter Ablation of Arrhythmias with a High-Density Mapping System in Real-World Practice (CHARISMA). URL: http://clinicaltrials.gov/ Identifier: NCT03793998.

Determinants of worse prognosis in patients with cardiac resynchronization therapy defibrillators. Are ventricular arrhythmias an adjunctive risk factor?

AIMS: Cardiac resynchronization therapy (CRT) is indicated in patients with systolic heart failure (HF), severe left ventricle (LV) dysfunction and interventricular dyssynchrony.In prospective observational research, we aimed to evaluate whether CRT-induced LV reverse remodelling and occurrence of ventricular arrhythmias (VT/VF) independently contribute to prognosis in patients with CRT defibrillators (CRT-D). METHODS: In 95 Italian cardiological centres, after a screening period of 6 months, patients were categorized according to VT/VF occurrence and CRT response, defined as LV end-systolic volume relative reduction >15% or LV ejection fraction absolute increase >5%. The main endpoint was death or HF hospitalizations. RESULTS: Among 1308 CRT-D patients (80% male, mean age 66 years), at 6 months, follow-up 71% were identified as CRT responders and 12% experienced appropriate VT/VF detections. The main endpoint was significantly and independently associated with previous myocardial infarction, New York Heart Association Class, VT/VF occurrence and with CRT response. CRT nonresponder patients who suffered VT/VF in the screening period had a risk of death or HF hospitalizations [HR = 7.82, 95% confidence interval (CI) = 3.95-15.48] significantly (P < 0.001) higher than CRT responders without VT/VF occurrence. This risk is mitigated without VT/VF occurrence (HR = 3.47, 95% CI = 2.03-5.91, P < 0.001) or in case of CRT response (HR = 3.11, 95% CI = 1.44-6.72, P = 0.004). CONCLUSION: Our data show that both CRT response and occurrence of VT/VF independently contribute to the risk of death or HF-related hospitalizations in CRT-D patients. Early VT/VF occurrence may be identified as a marker of disease severity than can be mitigated by CRT response both in terms of all-cause mortality and long-term VT/VF onset. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00147290 and NCT00617175.

Cardiac resynchronization therapy defibrillators in patients with permanent atrial fibrillation.

AIMS: There are conflicting data on the benefit of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with permanent atrial fibrillation (AF). We aimed to compare patient outcomes according to the presence or absence of permanent AF at device implantation. METHODS AND RESULTS: We retrospectively analysed remote monitoring data from 1141 CRT defibrillators. Propensity score with inverse-probability weighting method was used to balance AF and sinus rhythm (SR) groups. Analysis endpoints included total mortality, appropriate defibrillation shocks, and CRT percentage. There were 229 patients (20.1%) in the AF group and 912 patients (79.9%) in the SR group. Compared with SR patients, AF patients were older (median age, 77 vs. 72 years, P < 0.001), more frequently male (82.5% vs. 75.5%, P = 0.02), and had higher heart rate (75.7 vs. 71.0 b.p.m., P < 0.001). Of the 229 AF patients, 162 (70.7%) received suboptimal CRT (<98%) and 67 (29.3%) had adequate CRT (≥98%). During a median follow-up of 24 months, total mortality did not differ between AF and SR groups (propensity-score-weighted hazard ratio, HR 1.32 [95% confidence interval, 0.82-2.15], P = 0.25). The risk of appropriate shocks was significantly higher in the AF group with <98% CRT than in the SR group (weighted-HR, 1.99 [1.21-3.26], P = 0.006) and was similar in the AF group with ≥98% CRT versus the SR group (1.29 [0.66-2.53], P = 0.45). During follow-up, sinus rhythm was recovered in 23 patients in the AF group (10%) after a median time of 106 (42-256) days. The rate of sinus rhythm recovery in the AF group was 4.5 (95% CI, 2.8-6.7) per 100 patient-years; the rate of permanent AF occurrence in the SR group was 2.5 (95% CI, 1.9-3.3) per 100 patient-years. CONCLUSIONS: Although mortality was similar across patient groups, patients with permanent AF and suboptimal CRT had twofold higher risk of appropriate shocks than SR patients or AF patients with CRT ≥ 98%.

First-line therapy: insights from a real-world analysis of cryoablation in patients with atrial fibrillation.

AIMS: Pulmonary vein isolation (PVI) using cryoballoon ablation (CBA) is mainly reserved for patients with drug-refractory or drug-intolerant symptomatic atrial fibrillation. We evaluated a large cohort of patients treated in a real-world setting and examined the safety and efficacy profile of CBA when applied as a first-line treatment for atrial fibrillation. METHODS: In total, 249 patients (23% women; 56 ±â€Š13 years; mean left atrial diameter 41 ±â€Š7 mm; 73.5% paroxysmal atrial fibrillation; and 26.5% persistent atrial fibrillation) underwent an index PVI by CBA. Data were collected prospectively in the framework of the 1STOP ClinicalService project, involving 26 Italian cardiology centers. RESULTS: Median procedure and fluoroscopy times were 90.0 and 21.0 min, respectively. Acute procedural success was 99.8%. Acute/periprocedural complications were observed in seven patients (2.8%), including: four transient diaphragmatic paralyses, one pericardial effusion (not requiring any intervention), one transient ischemic attack, and one minor vascular complication. The Kaplan--Meier freedom from atrial fibrillation recurrence was 86.3% at 12 months and 76% at 24 months. Seventeen patients (6.8%) had a repeat catheter ablation procedure during the follow-up period. At last follow-up, 10% of patients were on an anticoagulation therapy, whereas 6.8% were on an antiarrhythmic drug. CONCLUSION: In our multicenter real-world experience, PVI by CBA in a first-line atrial fibrillation patient population was well tolerated, effective, and promising. CBA with a PVI strategy can be used to treat patients with paroxysmal and persistent atrial fibrillation with good acute procedural success, short procedure times, and acceptable safety. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov (NCT01007474).

Sex effect on efficacy of pulmonary vein cryoablation in patients with atrial fibrillation: data from the multicenter real-world 1STOP project.

PURPOSE: Pulmonary vein isolation (PVI) using cryoablation (PVI-C) is a widespread therapy for treating symptomatic, recurrent atrial fibrillation (AF). The impacts of sex on efficacy and safety of PVI-C in a real-world clinical practice is lacking. In a multicenter prospective project, we evaluated whether clinical characteristics, procedure parameters, procedural complications, long-term AF recurrence rates, and/or AF-related symptoms differed according to sex in patients treated with PVI-C. METHODS: Data from the study population were collected in the framework of the 1STOP ClinicalService® project, involving 47 Italian cardiology centers. Multivariable statistical analyses were conducted to determine if any baseline clinical characteristics impacted the efficacy of PVI-C. RESULTS: From April 2012, 2125 patients (27% female, 59 ± 11 years, 73% paroxysmal AF, and mean left atrial diameter = 42 ± 8 mm) underwent PVI-C. According to baseline characteristics, women were more likely to be older, with higher clinical risk scores (e.g., CHA2DS2-VASc), and a higher number of tested antiarrhythmic drugs before the index PVI-C procedure. Male and female cohorts showed comparable procedure time (mean = 107.7 ± 46.8 min) and a similar incidence of periprocedural complications (4.5% overall), even after adjustment for baseline characteristics (P = 0.880). The multivariable analyses demonstrated that the strongest predictor of AF recurrences was sex (0.74; 95% CI 0.58-0.93; P = 0.011). After propensity score adjustment, the hazard ratio from a multivariable model, which included age and AF type (persistent) as covariates, was 0.76 (0.60-0.97) (P = 0.025). CONCLUSIONS: According to the 1STOP project, in a real-world setting, PVI-C was relatively safe regardless of the patient's sex; however, when considering efficacy of the procedure, female patients had a lower long-term efficacy in comparison to males. CLINICAL TRIAL REGISTRATION: NCT01007474.

Cryoablation for paroxysmal and persistent AF in patients with structural heart disease and preserved ejection fraction: Clinical outcomes from 1STOP, a multicenter observational project.

BACKGROUND: Pulmonary vein isolation (PVI) is an accepted strategy for paroxysmal atrial fibrillation (PAF) and persistent AF (PerAF) ablation. Limited data are available on outcomes of cryoballoon (CB) PVI in patients with structural heart disease (SHD). The purpose is to assess the clinical efficacy of a single CB-PVI procedure in patients with PAF or PerAF who also have SHD. METHODS: From April 2012, 460 AF patients with concomitant SHD underwent CB-PVI and were followed prospectively in the framework of the 1STOP ClinicalService® project. Data on procedural outcomes and long-term freedom from AF recurrence were evaluated. Out of 460 subjects, 282 patients (61%) had PAF and 178 (39%) PerAF. RESULTS: SHD patients were predominantly male (80.9%), old (62.8±8.9 years), with preserved functional capacity (New York Heart Association class >1: 39.4%), high cardioembolic risk (CHA2DS2VASc score ≥2: 69.3%), and conserved left ventricular ejection fraction (56.5±8% LVEF). Both subjects with PAF and PerAF had similar baseline clinical characteristics except for left atrial diameter (43.8±7 vs. 45.7±7mm) and area (22.9±5.2 vs. 25.1±4.4cm2), respectively. Procedure time and fluoroscopic time as well as the rate of procedural complications were not different between subjects with PAF and PerAF. After a mean follow-up of 12 months, antiarrhythmic drug therapy had dropped from 71.7% before ablation to 33.6% post-ablation (p<0.001) and the freedom from symptomatic AF recurrence was 78% for PAF and 77% for PerAF (p=0.793). Furthermore, atrial arrhythmia recurrence rate was not related to SHD. CONCLUSIONS: In a large multicenter, real-world cohort, CB-PVI was used to treat patients with PAF and PerAF who also had SHD. The arrhythmia recurrence after a single procedure was not related to either the degree of cardiac structural remodeling or the type of AF, and the rate of AF recurrence was lower than previously reported in patients with SHD in other cohort series using focal radiofrequency catheter ablation. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov (NCT01007474).

A model of multi-disciplinary approach to the diagnosis and treatment of young patients with cryptogenic stroke and patent foramen ovale.

BACKGROUND: Treatment of patent foramen ovale in young patients with stroke is not supported by robust scientific evidence. In clinical practice, a pragmatic approach is needed to guide such therapeutic decisions. This study aims at standardising the diagnostic pathway for stroke patients younger than 55 years of age with a patent foramen ovale; elaborating a therapeutic algorithm; discussing every case in regular interdisciplinary counselling meeting; and setting up a follow-up schedule to assess clinical outcomes. METHODS: This is a cohort study on the effect of a standardised treatment of stroke patients with a patent foramen ovale. The primary endpoints include occurrence of recurrent ischaemic events, major bleeding, and device-related complications. The secondary endpoints include drug- or procedure-related side effects, persistence of right-to-left shunt, and persistent cardiac arrhythmia of new onset. RESULTS: A total of 103 patients have been enrolled. In all, 51 patients underwent percutaneous atrial septal repair; of these, one had minor post-procedural bleeding. At 12 months, 25% of this group of patients showed a latent I grade shunt, one patient a latent II degree shunt, and none had a persistent shunt. The remaining 52 patients were addressed to medical therapy; one of them experienced stroke recurrences while on medical therapy. CONCLUSIONS: This model of implementation of available evidence to clinical practice via a group-based, multi-disciplinary counselling provides a shared and coherent decision pathway and yielded a very low rate of recurrent events and therapy-related complications. This approach could be replicated in specific protocols for other complex or neglected clinical problems.