Noninvasive Mapping System for the Stereotactic Radioablation Treatment of Ventricular Tachycardia: A Case Description.

OBJECTIVES: Sustained monomorphic ventricular tachycardia (SMVT) is a life-threatening condition that is often observed in patients with structural heart disease. Catheter ablation (CA) ablation is an effective and well-established treatment for the scar-related ventricular tachycardias (VTs). Sometimes, due to patient fragility or contraindications to CA, a noninvasive procedure is required. In these cases, VT ablation with stereotactic arrhythmia radioablation (STAR) for SMVTs supported by the CardioInsight mapping system seems to be a promising and effective noninvasive approach. METHODS AND RESULTS: We report a case of a 55-year-old male smoker and heavy alcohol consumer who developed ischemic heart disease and frequent refractory SMVT relative to antiarrhythmic drugs. Catheter ablation was not practicable due to the presence of an apical thrombosis in the left ventricle. The CardioInsightTM system (Cardioinsight Technologies Inc., Cleveland, OH, USA) was useful for noninvasively mapping the VTs, identifying two target areas on the septum and anterior wall of the left ventricle. A personalized STAR treatment plan was carefully designed, and it was delivered in a few minutes. During follow-up, a significant reduction in the arrhythmia burden was documented. CONCLUSIONS: Stereotactic arrhythmia radioablation supported by the CardioInsight system could be an alternative treatment for VTs when catheter ablation is not possible. Larger studies are needed to investigate this technique.

Left atrial strain after paroxysmal atrial fibrillation linac-based cardiac radioablation in elderly population.

Catheter ablation of atrial fibrillation (AF) may increase the risk of complication in aged patients. Stereotactic arrhythmia radioablation (STAR) is a non-invasive therapeutic alternative for cardiac arrhythmia. This sub-study evaluated left atrial strain (LAS) in elderly AF patients underwent STAR. Symptomatic paroxysmal AF patients aged > 70 years, with antiarrhythmic drugs failure or intolerance, enrolled in a phase II trial that have demonstrated the feasibility of LINAC-based STAR (total dose of 25 Gy single fraction delivered in 3 min), performed a 15-day electrocardiogram Holter monitoring to detect AF episodes (≥ 30 s) and an echocardiographic LAS evaluation before and after STAR (at 1-, 3-, 6- and 12-month). Out 18 patients underwent STAR in the trial, 16 (7 males, 78 ± 5 years) completed the follow-up for LAS study. No baseline difference in echocardiographic and LAS parameters was observed between the 9 patients with AF recurrence during follow-up and those who maintained sinus rhythm. At 6- and 12-month after STAR, LAS reservoir was lower in patients with AF episodes than those without (respectively, p = 0.039 and p = 0.001). Values of left atrial area and volume as well as LAS conduit and contractile phase were not statistically significant different by patient's outcome across evaluations. Although no baseline LAS parameter before STAR seems predict AF recurrence after treatment in elderly patients, lower values of reservoir phase were observed during follow-up in those experiencing AF episodes. More research is needed to better assess the value of LAS monitoring in paroxysmal AF patients underwent Stereotactic cardiac radioablation.

Zero-Fluoroscopy Catheter Ablation of Right Appendage Focal Atrial Tachycardia in a Pregnant Woman.

BACKGROUND: Arrhythmias in pregnancy are complex to manage due to the teratogenic effects of many antiarrhythmic drugs and the common use of ionizing radiation during catheter ablation procedures. Furthermore, pregnant women are extremely vulnerable and difficult to treat because of the progressive physical and hormonal changes that occur during the nine months of pregnancy. CASE PRESENTATION: In this case report, we describe a complex clinical case of a 34-year-old pregnant woman who was affected by an incessant right atrial tachycardia, with signs and symptoms of initial hemodynamic instability. This tachycardia was refractory to antiarrhythmic drugs, so a zero-fluoroscopy ablation was performed. The first procedure was complicated by cardiac tamponade, quickly resolved without further complications for the mother or the fetus. In the following days, a deep venous thrombosis occurred at the femoral venous access. After a few days, the patient underwent a second procedure that was successful and resulted in the restoration of a sinus rhythm. CONCLUSIONS: The management of this clinical case was complex both from a procedural and a clinical (cardiological and gynecological) point of view. Finally, the integration of the various skills led to an excellent result.

A case report of cardiac neuromodulation in a young patient with a third-degree atrioventricular block.

Background: There are some functional bradyarrhythmias that are caused by a dysregulation of the autonomic nervous system, for which a therapeutic strategy of cardioneuroablation (CNA) is conceivable. Case summary: In this study, we report the case of a 19-year-old woman with a non-congenital third-degree atrioventricular block (AVB), symptomatic for lipothymia and dyspnea caused by mild exertion. She had a structurally normal heart and no other comorbidities. The atropine test and the exercise stress test documented a sinus tachycardia at 190 bpm with a 2:1 AVB, a narrow QRS, and an atrioventricular conduction of 1:1 until reaching a sinus rhythm rate of 90 bpm. She underwent the CNA procedure, which targeted the inferior paraseptal ganglion plexus, with a gradual change in the ECG levels recorded during the radiofrequency delivery from a third-degree AVB to a first-degree AVB. After the procedure, we observed a complete regression of the third-degree AVB, with evidence of only a first-degree AVB and a complete regression of symptoms until the 6-month follow-up. Conclusions: Although not yet included in current guidelines, the CNA procedure could be used to treat AV node dysfunction in young subjects, as it could represent an alternative to pacemaker implantation. However, more randomized studies are needed to assess the long-term efficacy of this promising technique.

Linear accelerator-based stereotactic arrhythmia radioablation for paroxysmal atrial fibrillation in elderly: a prospective phase II trial.

AIMS: Stereotactic arrhythmia radioablation (STAR) is a novel therapeutic approach for cardiac arrhythmias. The aim of this trial is to investigate the feasibility of STAR for the treatment of paroxysmal atrial fibrillation (AF) in elderly patients. METHODS AND RESULTS: Inclusion criteria were age >70 years, symptomatic AF, antiarrhythmic drugs failure, or intolerance. All patients underwent to 4D cardiac computed tomography simulation. The clinical target volume was identified in the area around pulmonary veins (PV). Stereotactic arrhythmia radioablation was performed with a total dose of 25 Gy (single fraction) delivered in 3 min. Twenty patients were enrolled and 18 underwent STAR. One patient withdrew informed consent before treatment and one patient was excluded due to unfavourable oesophagus position. With a median follow-up (FU) of 16 months (range 12-23), no acute toxicity more than Grade 3 was reported. Five patients had a Grade 1 oesophagitis 24 h after STAR; eight patients had an asymptomatic Grade 1 pericardial effusion, and one patient had a torsade de pointes treated effectively by electrical cardioversion and subsequent cardiac implantable cardioverter-defibrillator implantation. Most patients had a significant reduction in AF episodes. Five patients, due to arrhythmias recurrences after STAR, performed electrophysiological study documenting successful PV isolation. Finally, a significant improvement of quality of life was documented (48 ± 15 at enrolment vs. 75 ± 15 at 12 months FU; P < 0.001). CONCLUSION: The present phase II trial demonstrated the feasibility of STAR in paroxysmal AF elderly patients and its potential role in increasing the quality of life. Surely, more robust data are needed about safety and efficacy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04575662.

Phase II Trial of LINAC-Based STereotactic Arrhythmia Radioablation (STAR) for Paroxysmal Atrial Fibrillation in Elderly: Planning and Dosimetric Point of View.

Purpose: Approaching treatment for elderly patients with atrial fibrillation is difficult. A prospective phase II trial evaluating LINAC-based stereotactic arrhythmia radioablation (STAR) safety in this population started in 2021. Dosimetric and planning data were reported. Materials and Methods: A vac-lock bag was used for immobilization in the supine position and a computed tomography (CT, 1 mm) was performed. The clinical target volume (CTV) was defined as the area around the pulmonary veins. An internal target volume (ITV) was added to the CTV to compensate heart and respiratory movement. The planning target volume (PTV) was defined by adding 0-3 mm to the ITV. STAR was performed during free-breathing with a PTV prescription total dose (Dp) of 25 Gy/1 fraction. Flattening filter-free volumetric-modulated arc therapy plans were generated, optimized, and delivered by TrueBeamTM. Image-guided radiotherapy with cone-beam CT and surface-guided radiotherapy with Align-RT (Vision RT) were employed. Results: From May 2021 to March 2022, 10 elderly patients were treated. Mean CTVs, ITVs, and PTVs were 23.6 cc, 44.32 cc, and 62.9 cc, respectively; the mean prescription isodose level and D2% were 76.5% and 31.2 Gy, respectively. The average heart and left anterior descending artery (LAD) Dmean were 3.9 and 6.3 Gy, respectively; the mean Dmax for LAD, spinal cord, left and right bronchus, and esophagus were 11.2, 7.5, 14.3, 12.4, and 13.6 Gy, respectively. The overall treatment time (OTT) was 3 min. Conclusions: The data showed an optimal target coverage, sparing surrounding tissue, in 3 min of OTT. LINAC-based STAR for AF could represent a valid non-invasive alternative for elderly patients who were excluded from catheter ablation.

Pulsed Field Ablation to Treat Atrial Fibrillation: A Review of the Literature.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and catheter ablation, which can be used in symptomatic patients refractory to antiarrhythmic therapy. Pulmonary vein isolation (PVI) remains the cornerstone of any ablation procedure. A major limitation of current catheter ablation procedures is important to recognize because even when the PVI is performed in highly experienced centers, PVI reconnection was documented in about 20% of patients. Therefore, better technology is needed to improve ablation lesions. One of the novelties in recent years is pulsed filed ablation (PFA), a non-thermal energy that uses trains of high-voltage, very-short-duration pulses to kill the cells. The mechanism of action of this energy consists of creating pores in the myocardiocyte cell membrane in a highly selective and tissue-specific way; this leads to death of the target cells reducing the risk of damage to surrounding non-cardiac tissues. In particular during the animal studies, PVI and atrial lines were performed effectively without PV stenosis. Using PFA directly on coronary arteries, there was no luminal narrowing, there has been no evidence of incidental phrenic nerve injury, and finally, PFA has been shown not to injure esophageal tissue when directly applied to the esophagus or indirectly through ablation in the left atrium. The aim of this review is to report all published animal and clinical studies regarding this new technology to treat paroxysmal and persistent AF.

Remote monitoring for heart failure management during COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic impacted on heart failure patients' lifestyle and quality of life, affecting both physical activity levels and state of health. METHODS: Demographic data and device records were extracted for patients with heart failure in the 16 weeks at the turn of lockdown during pandemic. To explore the variability across the lockdown period, a week-to-week analysis was performed. Patients were interviewed to investigate physical activity and psychological insights. The primary endpoint was the variation in physical activity at the turn of lockdown. RESULTS: At our facility, 2225 patients implanted with a cardiac device were screened and data were collected for 211 patients fulfilling the inclusion criteria. Patients' physical activity significantly decreased in the lockdown period compared with the control period (active time per day 8.0% vs. 10.8%; relative reduction [RRR] 25.9%; p < 0.0001). A small decrease was noted for mean heart rate (70.1 vs. 71.7 beats per minute [bpm]; RRR 2.2%; p < 0.0001), while thoracic impedance slightly increased (82.2 vs. 82.7 ohm; RRR 0.6%; p = 0.001). Patients' physical activity decreased from week 7 to week 11 (10.9% vs. 6.9%; RRR 36.7%; P < 0.0001) with an increase between week 11 and week 16 (6.9% vs. 8.5%; RRR 18.8%; P < 0.0001). Patients' perceptions about physical activity showed a very low correlation with remote monitoring-assessed physical activity levels (r2 = 0.035, p = 0.039). CONCLUSIONS: Telemedicine and remote monitoring can explore the impact of COVID-19 pandemic on vital signs and physical activity levels of heart failure patients, playing a crucial role in the prediction of heart failure worsening during circumstances discouraging outpatient visits.

Sex differences in stroke and major adverse clinical events in patients with atrial fibrillation: A systematic review and meta-analysis of 993,600 patients.

BACKGROUND: Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia, which is associated with an increased risk of stroke. Several studies have suggested that female AF patients could have a greater risk for stroke and thromboembolic events (TE). METHODS: A systematic literature review update and meta-analysis was conducted using Pubmed. The search used the terms "atrial fibrillation", "gender", "sex", "female", "women", "stroke", "thromboembolism". Main aim of the study was to compare and male AF patients for occurrence of stroke and TE. Secondary outcomes were: major bleeding, cardiovascular (CV) death and all-cause death. RESULTS: Forty-four studies were included in the analysis including 993,603 patients (48.9% women). After pooling the data, there was a higher risk of stroke for women vs. male AF patients (hazard ratio [HR]: 1.24; 95% confidence intervals [CIs]: 1.14-1.36). Overall, TE risk was not different between female and male patients, despite sensitivity analysis left some uncertainties. No sex differences were found for major bleeding, CV death and all-cause death. A significant relationship between increasing age and the difference in stroke risk between female and male AF patients was found (Delta HR: 1.01; 95% CI: 1.00-1.03 for each year of age increase). CONCLUSIONS: Female patients with AF are at increased risk of stroke compared to men. A significant relationship between increasing age and stroke risk in women compared to men was found, most evident at age > 65 years. Female sex may act as a stroke risk modifier, particularly in elderly and very elderly AF subjects, conferring a significant increase in stroke risk.

Estimated Effectiveness and Safety of Nonvitamin K Antagonist Oral Anticoagulants Compared With Optimally Acenocoumarol Anticoagulated "Real-World" in Patients With Atrial Fibrillation.

Nonvitamin K antagonist oral anticoagulants (NOACs) have been proposed as an alternative to vitamin K antagonists in atrial fibrillation (AF) patients but the comparative benefits between NOACs and optimally anticoagulated patients is unknown. We estimated the absolute benefit in clinical outcomes rates of real-world effect of NOACs in optimally anticoagulated AF patients with acenocoumarol. We included 1,361 patients stable on acenocoumarol with time in therapeutic range of 100% and 6.5 years of follow-up. Estimation of clinical events avoided was calculated applying hazard ratio, absolute and relative risk reduction from the real-world meta-analysis. Compared with an optimally anticoagulated population, dabigatran 110 mg had the highest estimated stroke reduction (0.97%/year vs 1.47%/year; p = 0.002), and the benefit was higher than in RE-LY trial. For major bleeding, apixaban showed the highest estimated reduction (1.81%/year vs 2.83%/year; p <0.001). For mortality, the largest estimated reduction was with apixaban (2.68%/year). For gastrointestinal bleeding, only apixaban had a significant reduction compared with acenocoumarol (0.69%/year vs 1.10%/year; p = 0.004), and the reduction was significantly higher than in ARISTOTLE trial. All NOACs showed significantly lower rates for intracranial hemorrhage and had a positive Net Clinical Benefit compared with acenocoumarol. Apixaban showed the highest extended estimated Net Clinical Benefit 2.64 (95%CI 2.34 to 2.96). In conclusion, in optimally acenocoumarol anticoagulated AF patients, estimated reductions in all clinical outcomes with various NOACs are evident, with the best effectiveness and safety profile with apixaban. Indeed, the estimated effect with "real world" NOACs would probably be higher than that seen in phase-III clinical trials.

Restarting oral anticoagulant therapy after major bleeding in atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Use of oral anticoagulant (OAC) therapy in atrial fibrillation (AF) is associated with an inherited risk of bleeding. Benefits and risks of OAC restarting after a major bleeding are still uncertain. We aimed to assess effectiveness and safety of restarting OAC in AF patients after a major bleeding event. METHODS: We performed a systematic review and meta-analysis of all studies reporting data about AF patients that sustained a major bleeding, reporting data on restarting or not restarting OAC therapy. RESULTS: A total of seven studies were included, involving 5685 patients. No significant difference was found in "any stroke" occurrence between OAC restarters and non-restarters (odds ratio [OR]: 0.75, 95% confidence interval [CI]: 0.37-1.51), with a significant 46% relative risk reduction (RRR) (p < 0.00001) for "any thromboembolism" in OAC restarters, with consistent results when the index bleeding event was an intracranial or gastrointestinal bleeding. A significantly higher risk of recurrent major bleeding was seen (OR: 1.85, 95% CI: 1.48-2.30), but no difference in risk for recurrence of index event. OAC restarters had a 10.8% absolute risk reduction for all-cause death (OR: 0.38, 95% CI: 0.24-0.60); p < 0.00001). Net clinical benefit (NCB) analysis demonstrated that restarting OAC therapy after a major bleeding was significantly associated with a clinical advantage (NCB: 0.11, 95% CI: 0.09-0.14; p < 0.001). CONCLUSIONS: Restarting OAC therapy after a major bleeding event in AF was associated with a positive clinical benefit when compared to non-restarting OAC, with a significant reduction in any thromboembolism and all-cause mortality.

Real-World Use of Apixaban for Stroke Prevention in Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: The use of oral anticoagulant therapy for stroke prevention in atrial fibrillation has been transformed by the availability of the nonvitamin K antagonist oral anticoagulants. Real-world studies on the use of nonvitamin K antagonist oral anticoagulants would help elucidate their effectiveness and safety in daily clinical practice. Apixaban was the third nonvitamin K antagonist oral anticoagulants introduced to clinical practice, and increasing real-world studies have been published. Our aim was to summarize current evidence about real-world studies on apixaban for stroke prevention in atrial fibrillation. METHODS: We performed a systematic review and meta-analysis of all observational real-world studies comparing apixaban with other available oral anticoagulant drugs. RESULTS: From the original 9680 results retrieved, 16 studies have been included in the final meta-analysis. Compared with warfarin, apixaban regular dose was more effective in reducing any thromboembolic event (odds ratio: 0.77; 95% confidence interval: 0.64-0.93), but no significant difference was found for stroke risk. Apixaban was as effective as dabigatran and rivaroxaban in reducing thromboembolic events and stroke. The risk of major bleeding was significantly lower for apixaban compared with warfarin, dabigatran, and rivaroxaban (relative risk reduction, 38%, 35%, and 46%, respectively). Similarly, the risk for intracranial hemorrhage was significantly lower for apixaban than warfarin and rivaroxaban (46% and 54%, respectively) but not dabigatran. The risk of gastrointestinal bleeding was lower with apixaban when compared with all oral anticoagulant agents (P<0.00001 for all comparisons). CONCLUSIONS: Use of apixaban in real-life is associated with an overall similar effectiveness in reducing stroke and any thromboembolic events when compared with warfarin. A better safety profile was found with apixaban compared with warfarin, dabigatran, and rivaroxaban.

Estimated absolute effects on efficacy and safety outcomes of using non-vitamin K antagonist oral anticoagulants in 'real-world' atrial fibrillation patients: A comparison with optimally acenocoumarol anticoagulated patients.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) have been proposed as an alternative to vitamin K antagonists (VKA) for atrial fibrillation (AF) patients. Some studies have proposed that well-managed warfarin therapy is still a valid alternative as efficacious as NOACs but the potential impact and absolute effect of NOACs in "real world" optimally management of VKA AF patients is unknown. PURPOSE: To estimate the potential absolute benefit in clinical outcome rates if the optimally anticoagulated "real-world" AF patients with acenocoumarol had been treated with NOACs. METHODS: We included 1361 patients stable on acenocoumarol with a time in therapeutic range of 100% for the previous 6months and 6.5years of follow-up. The estimation of clinical events avoided was calculated applying absolute risk reductions, relative risk reductions and hazard ratios from the pivotal clinical trials, relative to acenocoumarol. RESULTS: Compared to acenocoumarol, the highest estimated event reduction for stroke was seen with dabigatran 150mg, with an estimated reduction of 0.53%/year. For major bleeding, the highest estimated reduction was seen with apixaban (0.88%/year). For mortality, the largest estimated reduction was with dabigatran 150mg (0.75%/year). In net clinical outcome, apixaban had the estimated highest reduction (1.23%/year). All NOACs showed significantly lower rates for intracranial haemorrhage. CONCLUSION: In optimally acenocoumarol anticoagulated AF patients, estimated reductions in stroke, bleeding and net clinical outcomes with various NOACs are evident. NOACs would potentially show an improvement even among optimally VKA AF patients.