Left Atrial Appendage Occlusion in Patients With Anticoagulation Failure vs Anticoagulation Contraindication.

BACKGROUND: Left atrial appendage occlusion (LAAO) provides mechanical cardioembolic protection for atrial fibrillation (AF) patients who cannot use oral anticoagulation therapy (OAT). Patients with a thrombotic event despite OAT are at high risk for recurrence and may also benefit from LAAO. OBJECTIVES: This study sought to investigate the efficacy of LAAO in AF patients with a thrombotic event on OAT compared to: 1) LAAO in AF patients with a contraindication for OAT; and 2) historical data. METHODS: The international LAAO after stroke despite oral anticoagulation (STR-OAC LAAO) collaboration included patients who underwent LAAO because of thrombotic events on OAT. This cohort underwent propensity score matching and was compared to the EWOLUTION (Evaluating Real-Life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology) registry, which represents patients who underwent LAAO because of OAT contraindications. The primary outcome was ischemic stroke. Event rates were compared between cohorts and with historical data without OAT, yielding relative risk reductions based on risk scores. RESULTS: Analysis of 438 matched pairs revealed no significant difference in the ischemic stroke rate between the STR-OAC LAAO and EWOLUTION cohorts (2.5% vs 1.9%; HR: 1.37; 95% CI: 0.72-2.61). STR-OAC LAAO patients exhibited a higher thromboembolic risk (HR: 1.71; 95% CI: 1.04-2.83) but lower bleeding risk (HR: 0.39; 95% CI: 0.18-0.88) compared to EWOLUTION patients. The mortality rate was slightly higher in EWOLUTION (4.3% vs 6.9%; log-rank P = 0.028). Relative risk reductions for ischemic stroke were 70% and 78% in STR-OAC LAAO and EWOLUTION, respectively, compared to historical data without OAT. CONCLUSIONS: LAAO in patients with a thrombotic event on OAT demonstrated comparable stroke rates to the OAT contraindicated population in EWOLUTION. The thromboembolic event rate was higher and the bleeding rate lower, reflecting the intrinsically different risk profile of both populations. Until randomized trials are available, LAAO may be considered in patients with an ischemic event on OAT.

Left atrial appendage occlusion after thromboembolic events or left atrial appendage sludge during anticoagulation therapy: Is two better than one? Real-world experience from a tertiary care hospital.

Background: The role of left atrial appendage occlusion (LAAO) for atrial fibrillation patients that during oral anticoagulant therapy (OAC) suffer from ischemic events or present LAA sludge, and the best postinterventional anticoagulant regimen, need to be defined. We present our experience with a hybrid approach of LAAO+ lifelong OAC therapy in this cohort of patients. Methods: Out of 425 patients treated with LAAO, 102 underwent LAAO because, despite OAC, suffered from ischemic events or presented with LAA sludge. Patients without high bleeding risk were discharged with the aim of maintaining lifelong OAC. This cohort was then matched to a population who underwent LAAO in primary ischemic events prevention. The primary endpoint was the composite of all-cause death and major adverse cardiovascular events consisting of ischemic stroke, systemic embolism (SE), and major bleeding. Results: Procedural success was 98%, and 70% of patients were discharged with anticoagulant therapy. After a median follow-up of 47.2 months, the primary endpoint occurred in 27 patients (26%). At multivariate analyses, coronary artery disease (OR 5.1, CI 1.89-14.27, p = .003) and OAC at discharge (OR 0.29, CI 0.11-0.80, p = .017) were associated with the primary endpoint. After propensity score matching, no significant difference was found in the survival free from the primary endpoint according to the indication for LAAO (p = .19). Conclusions: In this high-ischemic risk cohort, LAAO + OAC seem a long-term safe and effective therapeutical approach, with no difference in the survival free from the primary endpoint according to the indication for LAAO in a matched cohort.

A Referral Center Experience with Cerebral Protection Devices: Challenging Cardiac Thrombus in the EP Lab.

BACKGROUND: Cerebral protection devices (CPD) are designed to prevent cardioembolic stroke and most evidence that exists relates to TAVR procedures. There are missing data on the benefits of CPD in patients that are considered high risk for stroke undergoing cardiac procedures like left atrial appendage (LAA) closure or catheter ablation of ventricular tachycardia (VT) when cardiac thrombus is present. PURPOSE: This work aimed to examine the feasibility and safety of the routine use of CPD in patients with cardiac thrombus undergoing interventions in the electrophysiology (EP) lab of a large referral center. METHODS: The CPD was placed under fluoroscopic guidance in all procedures in the beginning of the intervention. Two different CPDs were used according to the physician's discretion: (1) a capture device consisting of two filters for the brachiocephalic and left common carotid arteries placed over a 6F sheath from a radial artery; or (2) a deflection device covering all three supra-aortic vessels placed over an 8F femoral sheath. Retrospective periprocedural and safety data were obtained from procedural reports and discharge letters. Long-term safety data were obtained by clinical follow-up in our institution and telephone consultations. RESULTS: We identified 30 consecutive patients in our EP lab who underwent interventions (21 LAA closure, 9 VT ablation) with placement of a CPD due to cardiac thrombus. Mean age was 70 ± 10 years and 73% were male, while mean LVEF was 40 ± 14%. The location of the cardiac thrombus was the LAA in all 21 patients (100%) undergoing LAA-closure, whereas, in the 9 patients undergoing VT ablation, thrombus was present in the LAA in 5 cases (56%), left ventricle (n = 3, 33%) and aortic arch (n = 1, 11%). The capture device was used in 19 out of 30 (63%) and the deflection device in 11 out of 30 cases (37%). There were no periprocedural strokes or transitory ischemic attacks (TIA). CPD-related complications comprised the vascular access and were as follows: two cases of pseudoaneurysm of the femoral artery not requiring surgery (7%), 1 hematoma at the arterial puncture site (3%) and 1 venous thrombosis (3%) resolved by warfarin. At long-term follow-up, 1 TIA and 2 non-cardiovascular deaths occurred, with a mean follow-up time of 660 days. CONCLUSIONS: Placement of a cerebral protection device prior to LAA closure or VT ablation in patients with cardiac thrombus proved feasible, but possible vascular complications needed to be taken into account. A benefit in periprocedural stroke prevention for these interventions seemed plausible but has yet to be proven in larger and randomized trials.

Peri-procedural and mid-term follow-up age-related differences in leadless pacemaker implantation: Insights from a multicenter European registry.

BACKGROUND: Age-related differences on leadless pacemaker (LP) are poorly described. Aim of this study was to compare clinical indications, periprocedural and mid-term device-associated outcomes in a large real-world cohort of LP patients, stratified by age at implantation. METHODS: Two cohorts of younger and older patients (≤50 and > 50 years old) were retrieved from the iLEAPER registry. The primary outcome was to compare the underlying indication why a LP was preferred over a transvenous PM across the two cohorts. Rates of peri-procedural and mid-term follow-up major complications as well as LP electrical performance were deemed secondary outcomes. RESULTS: 1154 patients were enrolled, with younger patients representing 6.2% of the entire cohort. Infective and vascular concerns were the most frequent characteristics that led to a LP implantation in the older cohort (45.8% vs 67.7%, p < 0.001; 4.2% vs 16.4%, p = 0.006), while patient preference was the leading cause to choose a LP in the younger (47.2% vs 5.6%, p < 0.001). Median overall procedural (52 [40-70] vs 50 [40-65] mins) and fluoroscopy time were similar in both groups. 4.3% of patients experienced periprocedural complications, without differences among groups. Threshold values were higher in the younger, both at discharge and at last follow-up (0.63 [0.5-0.9] vs 0.5 [0.38-0-7] V, p = 0.004). CONCLUSION: When considering LP indications, patient preference was more common in younger, while infective and vascular concerns were more frequent in the older cohort. Rates of device-related complications did not differ significantly. Younger patients tended to have a slightly higher pacing threshold at mid-term follow-up.

Long-Term Follow-Up of Catheter Ablation for Premature Ventricular Complexes in the Modern Era: The Importance of Localization and Substrate.

Background: Large-scale studies evaluating long-term recurrence rates in both idiopathic and non-idiopathic PVC catheter ablation (CA) patients have not been reported. Objective: To evaluate the efficacy and safety of idiopathic and non-idiopathic PVC CA, investigating the predictors of acute and long-term efficacy. Methods: This retrospective multicentric study included 439 patients who underwent PVC CA at three institutions from April-2015 to December-2021. Clinical success at 6 months' follow-up, defined as a reduction of at least 80% of the pre-procedural PVC burden, was deemed the primary outcome. The secondary aims of the study were: clinical success at the last available follow-up, predictors of arrhythmic recurrences at long-term follow-up, and safety outcomes. Results: The median age was 51 years, with 24.9% patients being affected suffering from structural heart disease. The median pre-procedural PVC burden was 20.1%. PVCs originating from the RVOT were the most common index PVC observed (29.1%), followed by coronary cusp (CC) and non-outflow tract (OT) LV PVCs (23.1% and 19.0%). The primary outcome at 6 months was reached in 85.1% cases, with a significant reduction in the 24 h% PVC burden (−91.4% [−83.4; −96.7], p < 0.001); long-term efficacy was observed in 82.1% of cases at almost 3-year follow-up. The presence of underlying structural heart disease and non-OT LV region origin (aHR 1.77 [1.07−2.93], p = 0.027 and aHR = 1.96 [1.22−3.14], p = 0.005) was independently associated with recurrences. Conclusion: CA of both idiopathic and non-idiopathic PVCs showed a very good acute and long-term procedural success rate, with an overall low complication. Predictors of arrhythmic recurrence at follow-up were underlying structural heart disease and non-OT LV origin.

Patients with Cardiac Implantable Electronic Device Undergoing Radiation Therapy: Insights from a Ten-Year Tertiary Center Experience.

BACKGROUND: The number of patients with cardiac implantable electronic devices (CIEDs) receiving radiotherapy (RT) is increasing. The management of CIED-carriers undergoing RT is challenging and requires a collaborative multidisciplinary approach. AIM: The aim of the study is to report the real-world, ten-year experience of a tertiary multidisciplinary teaching hospital. METHODS: We conducted an observational, real-world, retrospective, single-center study, enrolling all CIED-carriers who underwent RT at the San Raffaele University Hospital, between June 2010 and December 2021. All devices were MRI-conditional. The devices were programmed to an asynchronous pacing mode for patients who had an intrinsic heart rate of less than 40 beats per minute. An inhibited pacing mode was used for all other patients. All tachyarrhythmia device functions were temporarily disabled. After each RT session, the CIED were reprogrammed to the original settings. Outcomes included adverse events and changes in the variables that indicate lead and device functions. RESULTS: Between June 2010 and December 2021, 107 patients were enrolled, among which 63 (58.9%) were pacemaker carriers and 44 (41.1%) were ICD carriers. Patients were subjected to a mean of 16.4 (±10.7) RT sessions. The most represented tumors in our cohort were prostate cancer (12; 11%), breast cancer (10; 9%) and lung cancer (28; 26%). No statistically significant changes in device parameters were recorded before and after radiotherapy. Generator failures, power-on resets, changes in pacing threshold or sensing requiring system revision or programming changes, battery depletions, pacing inhibitions and inappropriate therapies did not occur in our cohort of patients during a ten-year time span period. Atrial arrhythmias were recorded during RT session in 14 patients (13.1%) and ventricular arrhythmias were observed at device interrogation in 10 patients (9.9%). CONCLUSIONS: Changes in device parameters and arrhythmia occurrence were infrequent, and none resulted in a clinically significant adverse event.

Prognostic value of right atrial pressure-corrected cardiac power index in cardiogenic shock.

AIM: The pulmonary artery catheter (PAC)-derived cardiac power index (CPI) has been found of prognostic value in cardiogenic shock (CS) patients. The original CPI equation included the right atrial pressure (RAP), accounting for heart filling pressure as a determinant of systolic myocardial work, but this term was subsequently omitted. We hypothesized that the original CPI formula (CPIRAP ) is superior to current CPI for risk stratification in CS. METHODS AND RESULTS: A single-centre cohort of 80 consecutive Society for Cardiovascular Angiography and Interventions (SCAI) B-D CS patients with available PAC records was included. Overall in-hospital mortality was 21.3%. Results showed CPIRAP to be the strongest haemodynamic predictor of in-hospital death (padj  = 0.038), outperforming CPI [area under the receiver operating characteristic (ROC) curves: 0.726 and 0.673, P-for-difference = 0.025]. When the population was stratified according to the identified CPIRAP (0.28 W/m2 ) and accepted CPI (0.32 W/m2 ) thresholds, the cohort with discordant indexes (low CPIRAP and high CPI) comprised a group of 13 patients featuring a congested phenotype with frequent right ventricle or biventricular involvement. In this group, in-hospital mortality was high (30.8%) similar to those with concordant low CPI and CPIRAP . CONCLUSION: Incorporating RAP in CPI calculation (CPIRAP ) improves the prognostic yield in patients with CS SCAI B-D. A cut-off of 0.28 W/m2 identifies patients at higher risk of in-hospital mortality. The improved prognostic value of CPIRAP may derive from identification of patients with more intravascular congestion who may experience substantial in-hospital mortality, uncaptured by the commonly used CPI equation.

Age-related differences and associated mid-term outcomes of subcutaneous implantable cardioverter-defibrillators: A propensity-matched analysis from a multicenter European registry.

BACKGROUND: A few limited case series have shown that the subcutaneous implantable cardioverter-defibrillator (S-ICD) system is safe for teenagers and young adults, but a large-scale analysis currently is lacking. OBJECTIVES: The purpose of this study was to compare mid-term device-associated outcomes in a large real-world cohort of S-ICD patients, stratified by age at implantation. METHODS: Two propensity-matched cohorts of teenagers + young adults (≤30 years old) and adults (>30 years old) were retrieved from the ELISIR Registry. The primary outcome was the comparison of inappropriate shock rate. Complications, freedom from sustained ventricular arrhythmias, and overall and cardiovascular mortality were deemed secondary outcomes. RESULTS: Teenagers + young adults represented 11.0% of the entire cohort. Two propensity-matched groups of 161 patients each were used for the analysis. Median follow-up was 23.1 (13.2-40.5) months. In total, 15.2% patients experienced inappropriate shocks, and 9.3% device-related complications were observed, with no age-related differences in inappropriate shocks (16.1% vs 14.3%; P = .642) and complication rates (9.9% vs 8.7%; P = .701). At univariate analysis, young age was not associated with increased rates of inappropriate shocks (hazard ratio [HR] 1.204 [0.675-2.148]: P = .529). At multivariate analysis, use of the SMART Pass algorithm was associated with a strong reduction in inappropriate shocks (adjusted HR 0.292 [0.161-0.525]; P <.001), whereas arrhythmogenic right ventricular cardiomyopathy (ARVC) was associated with higher rates of inappropriate shocks (adjusted HR 2.380 [1.205-4.697]; P = .012). CONCLUSION: In a large multicenter registry of propensity-matched patients, use of the S-ICD in teenagers/young adults was safe and effective. The rates of inappropriate shocks and complications between cohorts were not significantly different. The only predictor of increased inappropriate shocks was a diagnosis of ARVC.

Leadless Pacemaker Implantation in the Emergency Bradyarrhythmia Setting: Results from a Multicenter European Registry.

Background. Data on leadless pacemaker (LPM) implantation in an emergency setting are currently lacking. Objective. We aimed to investigate the feasibility of LPM implantation for emergency bradyarrhythmia, in patients referred for urgent PM implantation, in a large, multicenter, real-world cohort of LPM recipients. Methods. Two cohorts of LPM patients, stratified according to the LPM implantation scenario (patients admitted from the emergency department (ED+) vs. elective patients (ED−)) were retrieved from the iLEAPER registry. The primary outcome of the study was a comparison of the peri-procedural complications between the groups. The rates of peri-procedural characteristics (overall procedural and fluoroscopic duration) were deemed secondary outcomes. Results. A total of 1154 patients were enrolled in this project, with patients implanted due to an urgent bradyarrhythmia (ED+) representing 6.2% of the entire cohort. Slow atrial fibrillation and complete + advanced atrioventricular blocks were more frequent in the ED+ cohort (76.3% for ED+ vs. 49.7% for ED−, p = 0.025; 37.5% vs. 27.3%, p = 0.027, respectively). The overall procedural times were longer in the ED+ cohort (60 (45−80) mins vs. 50 (40−65) mins, p < 0.001), showing higher rates of temporary pacing (94.4% for ED+ vs. 28.9% for ED−, p < 0.001). Emergency LPM implantation was not correlated with an increase in the rate of major complications compared to the control group (6.9% ED+ vs. 4.2% ED−, p = 0.244). Conclusion. LPM implantation is a feasible procedure for the treatment of severe bradyarrhythmia in an urgent setting. Urgent LPM implantation was not correlated with an increase in the rate of major complications compared to the control group, but it was associated with longer procedural times.

Long-term outcome of left atrial appendage occlusion with multiple devices.

BACKGROUND: To evaluate long-term efficacy of left atrial appendage occlusion with multiple devices. METHODS: All consecutive patients who underwent left atrial appendage occlusion (LAAO) with a follow-up of at least 4 years, were included in this single center, retrospective registry. No specific exclusion criteria were applied. LAA occlusion was performed with the Watchman, Watchman FLX, Amplatzer Cardiac plug or Amplatzer Amulet occluder devices. RESULTS: A total of 224 consecutive patients underwent LAAO occlusion. Mean age was 72.5 ± 9.0 years. A history of stroke was present in 29%, TIA in 8.5% and a previous episode of bleeding in 64.7% of patients. In 63% there was a contraindication to oral anticoagulants. The average CHADS-VASc was 4.0 ± 1.6 and the average HAS-BLED was 3.4 ± 1.3. There was a reduction of strokes of 72.9%, thromboembolic events of 59.7% and major bleeding events of 70.9% compared to historic data. During follow-up, 48.3% of the ischemic and major bleeding events occurred within the first year. The annual mortality rate of 7.5 deaths/ 100 patients years. There were no significant differences in terms of outcome between the devices used and there were no late events associated with any device. The main antithrombotic regimen in the long term was with single antiplatelet therapy and the second one was no therapy. CONCLUSION: LAAO is a safe and effective procedure, that reduces ischemic and bleeding events in the long-term, regardless of the type of device used, in AF patients at high risk of ischemic stroke and major bleeding, without the need of anticoagulation.

Check the Need-Prevalence and Outcome after Transvenous Cardiac Implantable Electric Device Extraction without Reimplantation.

BACKGROUND: after transvenous lead extraction (TLE) of cardiac implantable electric devices (CIEDs), some patients may not benefit from device reimplantation. This study sought to analyse predictors and long-term outcome of patients after TLE with vs. without reimplantation in a high-volume centre. METHODS: all patients undergoing TLE at our centre between January 2010 and November 2015 were included into this analysis. RESULTS: a total of 223 patients (median age 70 years, 22.0% female) were included into the study. Cardiac resynchronization therapy-defibrillator (CRT-D) was the most common device (40.4%) followed by pacemaker (PM) (31.4%), implantable cardioverter-defibrillator (ICD) (26.9%), and cardiac resynchronization therapy-PM (CRT-P) (1.4%). TLE was performed due to infection (55.6%), malfunction (35.9%), system upgrade (6.7%) or other causes (1.8%). In 14.8%, no reimplantation was performed after TLE. At a median follow-up of 41 months, no preventable arrhythmia-related events were documented in the no-reimplantation group, but 11.8% received a new CIED after 17-84 months. While there was no difference in short-term survival, five-year survival was significantly lower in the no-reimplantation group (78.3% vs. 94.7%, p = 0.014). CONCLUSIONS: in patients undergoing TLE, a re-evaluation of the indication for reimplantation is safe and effective. Reimplantation was not related to preventable arrhythmia events, but all-cause survival was lower.

Impact of the rs73598374 polymorphism of the adenosine deaminase gene on platelet reactivity and long-term outcomes among patients with acute coronary syndrome treated with ticagrelor.

BACKGROUND: The positive interaction of ticagrelor with the metabolism of adenosine has been claimed for the large antithrombotic and antiischemic benefits of this antiplatelet agent in acute coronary syndromes (ACS). Adenosine catabolism is regulated by the activity of the adenosine deaminase enzyme (ADA), for which several polymorphisms have been identified. Therefore, the aim of our study was to explore the impact of the rs73598374 polymorphism of ADA gene on platelet reactivity in ACS patients treated with ticagrelor. METHODS: We included consecutive patients receiving ASA and ticagrelor after an ACS and coronary intervention. Platelet reactivity was evaluated by impedance aggregometry at 30-90 days post-discharge. The genetic analysis was carried out by PCR and RFLP. Clinical endpoints were mortality, cardiovascular death, recurrent myocardial infarction or coronary revascularization at the maximum available follow-up. RESULTS: Our population is represented by 464 patients, of whom 33.4% were A-heterozygotes and 6 homozygotes. A-allele carriers showed a greater prevalence of renal failure (p = 0.02) and a lower rate of previous coronary artery bypass graft (p = 0.03) and statin treatment (p = 0.02). No differences in the mean values of platelet reactivity or HRPR on ticagrelor were found according to the ADA genotype (11.3%vs13.9%, p = 0.45; adjusted OR[95% CI] = 1.17[0.64-2.14], p = 0.61). At follow up, patients carrying the A-allele showed a non-significantly lower incidence of ACS and repeated unplanned revascularization, although with no effect on mortality. CONCLUSIONS: In the present study the rs73598374 polymorphism of the ADA gene did not affect platelet reactivity or the long-term prognosis in patients with ACS receiving dual antiplatelet therapy with ASA and ticagrelor.

Gender Differences in Platelet Reactivity in Diabetic Patients Receiving Dual Antiplatelet Therapy.

BACKGROUND: Increased comorbidities and a perceived high-bleeding risk often prevent the use of dual antiplatelet therapy (DAPT) in female patients. However, more aggressive antiplatelet treatment would certainly offer additional outcome benefits in coronary artery disease, especially among diabetic patients. The aim of the present study was to evaluate the gender differences in high-residual on treatment platelet reactivity (HRPR) among diabetic patients treated with DAPT. METHODS: Our population is represented by a consecutive cohort of diabetic patients treated with DAPT (ASA + clopidogrel, ticagrelor or dose-adjusted prasugrel) for an acute coronary syndrome or elective PCI, undergoing platelet reactivity assessment at 30-90 days post-discharge. Aggregation was assessed by multiple-electrode aggregometry and in diabetic patients naïve to antiplatelet therapy, by light transmission aggregometry, surface expression of P-selectin and plasma concentration of Thromboxane B2. RESULTS: We included 472 patients, 113 (23.9%) women. Female gender was associated with more advanced age, and increased comorbidities. Mean platelet reactivity did not differ according to gender. The rate of HRPR was similar in women as compared to men (for ASA: adjusted OR[95%CI] = 0.59[0.27-1.33], p = 0.21, for ADP-antagonists: adjusted OR[95%CI] = 1.24[0.25-1.80], p = 0.27), however, the benefits of the new ADP-antagonists on platelet reactivity were lower in women than in men (p interaction = 0.01). No impact of gender on platelet reactivity was confirmed among 50 diabetic patients naïve to antiplatelet therapy. CONCLUSIONS: Among diabetic patients receiving dual antiplatelet therapy gender does not affect platelet reactivity or high-on treatment platelet reactivity. However, the enhanced platelet inhibition provided by the new-ADP antagonists of new-ADP antagonists could be mitigated in women.