A Left Atrial Appendage Closure Combined Procedure Review: past, present and future perspectives

Atrial fibrillation (AF) represents the most common cardiac arrhythmia worldwide; it poses a great burden in terms of quality of life reduction and yearly stroke risk. Left atrial appendage closure (LAAC) is a stroke prevention strategy that has been proven a viable alternative to anti-thrombotic regimens in non-valvular AF patients. LAAC can be performed as a stand-alone procedure or alongside a concomitant AF trans catheter ablation, in a procedure known as "Combined Procedure". Aim of this study is to summarize the scientific evidence backing this combined strategy

Changes in Exercise Capacity and Ventricular Function in Arrhythmogenic Right Ventricular Cardiomyopathy: The Impact of Sports Restriction during Follow-Up

(1) Background: Physical exercise has been suggested to promote disease progression in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed to investigate the exercise performance and ventricular function of ARVC patients during follow-up, while taking into account their adherence to exercise restriction recommendations. (2) Methods: This retrospective study included 49 patients (33 male, 67%) who had an exercise test at baseline and after 4.2 ± 1.6 years. Of the 49 ARVC patients, 27 (55%) were athletes, while 22 (45%) were non-athletes. Of the athletes, 12 (44%) continued intensive sports activity (non-adherent), while 15 (56%) stopped intensive physical activity upon recommendation (adherent). The maximum workload in Watts (W), percentage of the target workload (W%), and double product (DP) factor were measured for all patients. (3) Results: The non-adherent cohort had a significant decrease in physical performance (W at baseline vs. follow-up, p = 0.012; W% at baseline vs. follow-up, p = 0.025; DP-factor at baseline vs. follow-up, p = 0.012) over time. Left ventricular (LV) function (LV ejection fraction at baseline vs. follow-up, p = 0.082) showed a decreasing trend in the non-adherent cohort, while the performance of the adherent cohort remained at a similar level. (4) Conclusions: If intensive sports activities are not discontinued, exercise capacity and left ventricular function of athletes with ARVC deteriorates during follow-up. All patients with ARVC need to strictly adhere to the recommendation to cease intense sports activity in order to halt disease progression

Electroanatomical voltage mapping with contact force sensing for diagnosis of arrhythmogenic right ventricular cardiomyopathy

Background Three-dimensional electroanatomical mapping (EAM) can be helpful to diagnose arrhythmogenic right ventricular cardiomyopathy (ARVC). Yet, previous studies utilizing EAM have not systematically used contact-force sensing catheters (CFSC) to characterize the substrate in ARVC, which is the current gold standard to assure adequate tissue contact. Objective To investigate reference values for endocardial right ventricular (RV) EAM as well as substrate characterization in patients with ARVC by using CFSC. Methods Endocardial RV EAM during sinus rhythm was performed with CFSC in 12 patients with definite ARVC and 5 matched controls without structural heart disease. A subanalysis for the RV outflow tract (RVOT), septum, free-wall, subtricuspid region, and apex was performed. Endocardial bipolar and unipolar voltage amplitudes (BVA, UVA), signal characteristics and duration as well as the impact of catheter orientation on endocardial signals were also investigated. Results ARVC patients showed lower BVA vs. controls (p = 0.018), particularly in the subtricuspid region (1.4, IQR:0.5–3.1 vs. 3.8, IQR:2.5-5 mV, p = 0.037) and RV apex (2.5, IQR:1.5–4 vs. 4.3,IQR:2.9–6.1 mV, p = 0.019). BVA in all RV regions yielded a high sensitivity and specificity for ARVC diagnosis (AUC 59–78%, p < 0.05 for all), with the highest performance for the subtricuspid region (AUC 78%, 95% CI:0.75–0.81, p < 0.001, negative predictive value 100%). A positive correlation between BVA and an orthogonal catheter orientation (46°-90°:r = 0.106, p < 0.001), and a negative correlation between BVA and EGM duration (r = −0.370, p < 0.001) was found. Conclusions EAM using CFSC validates previous bipolar cut-off values for normal endocardial RV voltage amplitudes. RV voltages are generally lower in ARVC as compared to controls, with the subtricuspid area being commonly affected and having the highest discriminatory power to differentiate between ARVC and healthy controls. Therefore, EAM using CFSC constitutes a promising tool for diagnosis of ARVC

Is Less Always More? A Prospective Two-Centre Study Addressing Clinical Outcomes in Leadless versus Transvenous Single-Chamber Pacemaker Recipients

(1) Background: Leadless (LL) stimulation is perceived to lower surgical, vascular, and lead-related complications compared to transvenous (TV) pacemakers, yet controlled studies are lacking and real-life experience is non-conclusive. (2) Aim: To prospectively analyse survival and complication rates in leadless versus transvenous VVIR pacemakers. (3) Methods: Prospective analysis of mortality and complications in 344 consecutive VVIR TV and LL pacemaker recipients between June 2015 and May 2021. Indications for VVIR pacing were “slow” AF, atrio-ventricular block in AF or in sinus rhythm in bedridden cognitively impaired patients. LL indication was based on individualised clinical judgement. (4) Results: 72 patients received LL and 272 TV VVIR pacemakers. LL pacemaker indications included ongoing/expected chronic haemodialysis, superior venous access issues, active lifestyle with low pacing percentage expected, frailty causing high bleeding/infectious risk, previous valvular endocarditis, or device infection requiring extraction. No significant difference in the overall acute and long-term complication rate was observed between LL and TV cohorts, with greater mortality occurring in TV due to selection of older patients. (5) Conclusions: Given the low complication rate and life expectancy in this contemporary VVIR cohort, extending LL indications to all VVIR candidates is unlikely to provide clear-cut benefits. Considering the higher costs of LL technology, careful patient selection is mandatory for LL PMs to become advantageous, i.e., in the presence of vascular access issues, high bleeding/infectious risk, and long life expectancy, rendering lead-related issues and repeated surgery relevant in the long-term perspective

Novel risk calculator performance in athletes with arrhythmogenic right ventricular cardiomyopathy

Background: Disease progression and ventricular arrhythmias (VAs) in arrhythmogenic right ventricular cardiomyopathy (ARVC) are correlated with physical exercise, and clinical detraining and avoidance of competitive sport practice are suggested for ARVC patients. An algorithm assessing primary arrhythmic risk in ARVC patients was recently developed by Cadrin-Tourigny et al. Data regarding its transferability to athletes are lacking. Objective: The purpose of this study was to assess the reliability of the Cadrin-Tourigny risk prediction algorithm in a cohort of athletes with ARVC and to describe the impact of clinical detraining on disease progression. Methods: All athletes undergoing clinical detraining after ARVC diagnosis at our institution were enrolled. Baseline and follow-up clinical characteristics and data on VA events occurring during follow-up were collected. The Cadrin-Tourigny algorithm was used to calculate the a priori predicted VA risk, which was compared with the observed outcomes. Results: Twenty-five athletes (age 36.1 \ub1 14.0 years; 80% male) with definite ARVC who were undergoing clinical detraining were enrolled. Over median (interquartile range) follow-up of 5.3 (3.2\u20136.6) years, a reduction in premature ventricular complex (PVC) burden (P = .001) was assessed, and 10 VA events (40%) were recorded. The a priori algorithm-predicted risk seemed to fit with the observed cohort arrhythmic risk [mean observed\u2013predicted risk difference over 5 years \u20130.85% (interquartile range \u20134.8% to +3.1%); P = .85]. At 1-year follow-up, 11 patients (44%) had an improved stress ECG response, and no significant changes in right ventricular ejection fraction were observed. Conclusion: Clinical detraining is associated with PVC burden reduction in athletes with ARVC. The novel risk prediction algorithm does not seem to require any correction for its application to ARVC athletes

Proliferative activity in human breast cancer: Ki-67 automated evaluation and the influence of different Ki-67 equivalent antibodies

<p>Abstract</p> <p>Background</p> <p>Ki67 labeling index (Ki67 LI), the percentage Ki67 immunoreactive cells, is a measure of tumor proliferation, with important clinical relevance in breast cancer, and it is extremely important to standardize its evaluation.</p> <p>Aim</p> <p>To test the efficacy of computer assisted image analysis (CAIA) applied to completely digitized slides and to assess its feasibility in routine practice and compare the results obtained using two different Ki67 monoclonal antibodies.</p> <p>Materials and methods</p> <p>315 consecutive breast cancer routinely immunostained for Ki-67 (223 with SP6 and 92 with MM1 antibodies previously examined by an experienced pathologist, have been re-evaluated using Aperio Scanscope Xs.</p> <p>Results</p> <p>Mean human Ki67 LI values were 36%± 14.% and 28% ± 18% respectively for SP6 and MM1 antibodies; mean CAM Ki67 LI values were 31%± 19% and 22% ± 18% respectively for SP6 and MM1. Human and CAIA evaluation are statistically highly correlated (Pearson: 0.859, p<0.0001), although human LI are systematically higher. An interobserver variation study on CAIA performed on 84 cases showed that the correlation between the two evaluations was linear to an excellent degree.</p> <p>Discussion</p> <p>Our study shows that a) CAIA can be easily adopted in routine practice, b) human and CAIA Ki67 LI are highly correlated, although human LI are systematically higher, c) Ki67 LI using different evaluation methods and different antibodies shows important differences in cut-off values.</p

Cryoballoon pulmonary vein ablation and left atrialappendage closure combined procedure: A long-termfollow-up analysis

BACKGROUND: The combined left atrial appendage closure (LAAC) and cryoenergy pulmonary vein isolation (PVI) procedure has been proven safe and effective in managing stroke in patients with nonvalvular atrial fibrillation (AF), although most data refer to procedures performed using radiofrequency as the main energy source. OBJECTIVE: The purpose of this study was to evaluate long-term follow-up of patients with AF undergoing concomitant LAAC and cryoenergy PVI. METHODS: Patients undergoing LAAC and cryoballoon PVI at our institution were enrolled. At 3, 6, and 24 months from the index procedure, we determined the atrial arrhythmia recurrence rate, the extent of LAAC, and the rate of cerebrovascular/bleeding events. RESULTS: Forty-nine patients (mean age 69 \ub1 8 years; 67% men; CHA2DS2-VASc score 2.8 \ub1 1.2; HAS-BLED score 3 \ub1 1) with a guideline LAAC indication were included. Acute PVI and complete LAAC were achieved in 100% of patients. All patients completed at least 24 months of follow-up. At 8 weeks and 6 months, complete or satisfactory (&lt;5 mm leak) LAAC rates were achieved in 82% and 18% and in 86% and 14% of patients, respectively. The overall freedom from atrial arrhythmia rate at 24 months was 60%, and 92% of patients were off antithrombotic drugs. The observed annualized stroke and bleeding rates were 1% and 2%, respectively, a 71% and 60% risk reduction in comparison to event rates predicted from CHA2DS2-VASc and HAS-BLED scores. CONCLUSION: Concomitant cryoballoon ablation and LAAC procedures appear safe and effective at long-term follow-up, with high antithrombotic drug withdrawal rates at 24 months

Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy : external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator

Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus. Methods and results: In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%. Conclusion: Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC

Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy: external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator

Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus.Methods and results In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%.Conclusion Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC