Cardiac resynchronization therapy: present and future.

Cardiac resynchronization therapy (CRT) via biventricular pacing (BVP) is a well-established therapy for patients with heart failure with reduced ejection fraction and left bundle branch block, who remain symptomatic despite optimal medical therapy. Despite the long-standing clinical evidence, as well as the familiarity of cardiac electrophysiologists with the implantation technique, CRT via BVP cannot be achieved or may result ineffective in up to one-third of the patients. Therefore, new alternative techniques, such as conduction system pacing and left ventricular pacing, are emerging as potential alternatives to this technique, not only in case of BVP failure, but also as a stand-alone first choice due to several potential advantages over traditional CRT. Specifically, due to its procedural characteristics, left bundle branch area pacing appears to be the most convincing technique, showing comparable efficacy outcomes when compared with traditional CRT, not increasing short-term device-related complications, as well as improving procedural times. However, transvenous leads remain a major limitation of all these pacing modalities. To overcome this limit, a leadless left ventricular endocardial pacing has been developed as an additional tool to achieve a left endocardial activation, although being still associated with non-negligible pitfalls, limiting its current use in clinical practice. This article focuses on the current state and latest progresses in cardiac resynchronization therapy.

Etiologic reclassification of cryptogenic stroke after implantable cardiac monitoring and computed tomography angiography re-assessment.

INTRODUCTION: Different mechanisms may underlie cryptogenic stroke, including subclinical atrial fibrillation (AF), nonstenotic carotid plaques (NCP), and aortic arch atherosclerosis (AAA). In a cohort of cryptogenic stroke patients, we aimed to: (1) evaluate the prevalence of subclinical AF, NCP, and AAA, and reclassify the etiology accordingly; (2) compare the clinical features of patients with reclassified etiology with those with confirmed cryptogenic stroke. METHODS: Data of patients hospitalized for cryptogenic stroke between January 2018 and February 2021 were retrospectively analyzed. Patients were included if they received implantable cardiac monitoring (ICM) to detect subclinical AF. Baseline computed tomography angiography (CTA) was re-evaluated to assess NCP and AAA. Since aortic plaques with ulceration/intraluminal thrombus were considered pathogenetic during the initial workup, only patients with milder AAA were included. Stroke etiology was reclassified as "cardioembolic", "atherosclerotic", or "mixed" based on the detection of AF and NCP/AAA. Patients with "true cryptogenic" stroke (no AF, ipsilateral NCP, or AAA detected) were compared with those with reclassified etiology. RESULTS: Among 63 patients included, 21 (33%) were diagnosed with AF (median follow-up time of 15 months), 12 (19%) had ipsilateral NCP, and 6 (10%) had AAA. Stroke etiology was reclassified in 30 patients (48%): cardioembolic in 14 (22%), atherosclerotic in 9 (14%), and mixed in 7 (11%). Patients with true cryptogenic stroke were younger compared to those with reclassified etiology (p = 0.001). DISCUSSION: One or more potential covert stroke sources can be recognized in half of the patients with a cryptogenic stroke through long-term cardiac monitoring and focused CTA re-assessment.

Clinical Management of New-Onset Atrial Fibrillation in COVID-19 Patients Referred to a Tertiary Cardiac Arrhythmia Center after Hospital Discharge.

BACKGROUND: Available reports on the post-discharge management of atrial fibrillation (AF) in COVID-19 patients are scarce. The aim of this case series was to describe the clinical outcomes of new-onset AF in COVID-19 patients referred to a tertiary cardiac arrhythmia center after hospital discharge. METHODS: All consecutive patients referred to our center for an ambulatory evaluation from 18 May 2020 to 15 March 2022 were retrospectively screened. Patients were included in the current analysis if new-onset AF was diagnosed during hospitalization for COVID-19 and then referred to our clinic. RESULTS: Among 946 patients, 23 (2.4%) were evaluated for new-onset AF during COVID-19. The mean age of the study cohort was 71.5 ± 8.1 years; 87.0% were male. Median time from COVID-19 discharge and the first ambulatory evaluation was 53 (41.5-127) days; median follow-up time was 175 (83-336) days. At the in-office evaluation, 14 (60.9%) patients were in sinus rhythm, and nine patients were in AF. In 13.0% of cases, oral anticoagulation was stopped according to CHADS-VASc. Eight patients in AF were scheduled for electrical cardioversion; one patient was rate-controlled. Four patients were treated with catheter ablation (CA) during follow-up. Two post-cardioversion AF recurrences were detected during follow-up, while no recurrences were diagnosed among patients who underwent CA. CONCLUSION: Our data suggest that AF may not be considered as a simple bystander of the in-hospital COVID-19 course. Management of new-onset AF in post-COVID-19 patients referred to our clinic did not significantly differ from our usual practice, both in terms of long-term oral anticoagulation and in terms of rhythm control strategy.

Comparing Left Internal Mammary Angiography via Right Radial or Femoral Access With a Single-Catheter Technique.

BACKGROUND: We compared the safety and effectiveness of left internal mammary artery (LIMA) angiography through right radial (Rad) or femoral (Fem) artery access with a single-catheter technique. METHODS: LIMA selective imaging was attempted through Rad access with a Bartorelli-Cozzi 5.2Fr catheter in 190 consecutive patients. They were compared with 190 consecutive patients in whom LIMA was imaged with a mammary catheter via Fem access. Successful LIMA imaging within 15 min and time needed for imaging were efficacy end-point. Safety metrics were cerebral ischemic events and access site complications. RESULTS: Overall success rate of Rad LIMA imaging was 62 %. The success rate of Fem LIMA imaging was 97 %. In Rad group, patient age emerged as the single independent correlate of success at multivariate analysis (OR 9.938, CI 0.902-0.977 p = 0.002), with 77 % success rate in the lowest age quartile (<67 years). Median time needed to obtain selective LIMA imaging was significantly longer in Rad than in Fem (5.5 min vs. 4.0 min, p < 0.001), but right radial access was not a significant predictor of time needed to image LIMA at multivariate analysis (K 0.726, CI [-0.130-1.581], p = 0.09). Access site complications (6 vs. 0 cases, p = 0.030), and clinically significant bleeding (4 vs. 0 cases, p = 0.1) occurred in Fem group only. No peri-procedural cerebrovascular events were seen in either Group. CONCLUSIONS: Right radial artery is a suboptimal, yet reasonable access for LIMA-graft selective imaging in younger patients. The technique is free from vascular complications and peri-procedural cerebrovascular events.

Combined Use of S-ICD and Absorbable Antibacterial Envelopes: A Proof-of-concept Study.

BACKGROUND: Absorbable antibacterial envelopes (AAEs) are currently recommended in patients undergoing a transvenous ICD implantation in cases at high risk of infection, who are now preferably implanted with a subcutaneous ICD (S-ICD). Nevertheless, experiences using a combined approach with S-ICD and AAE have not been reported. The aim of our study was to evaluate this strategy in patients at very high risk of infection. METHODS: Twenty-five patients were implanted with the S-ICD+AAE using our combined approach, restricted to patients who would fit our decisional flow algorithm identifying very high-risk patients. Patients were followed up 1 month after discharge and every 6 months thereafter. Complications were defined as device-related events requiring medical or surgical intervention for resolution and/or device reprogramming. RESULTS: Twenty-five patients (92% males, mean age 58.5±14.1 years) were implanted with the S-ICD device and the AAE using our combined approach. The most common high-infective risk factors were diabetes requiring insulin treatment (80%) and CKD requiring hemodialysis (48%), with 7 (28%) patients presenting with more than 2 risk factors. A single mild early post-operative hematoma was observed that was managed conservatively with a spontaneous resolution. Despite a very high-risk cohort, only a single late pocket infection was detected and solved conservatively with antibiotic therapy. CONCLUSIONS: The preliminary data of this proof-of-concept study show how a combined deployment of AAE and S-ICD in selected patients at very high risk of infection is a safe and feasible technique and may offer a reliable treatment option in specific and selected clinical settings.

Long-term comparisons of atrial fibrillation ablation outcomes with a cryoballoon or laser-balloon: A propensity-matched analysis based on continuous rhythm monitoring.

OBJECTIVE: Cryoballoon (CB) and laser-balloon (LB) catheter ablation (CA) has been demonstrated to achieve durable and effective pulmonary vein isolation (PVI). Only one head-to-head comparison with an intermittent rhythm monitor strategy is currently available. The aim of this study was to compare acute and long-term outcomes of CB and LB atrial fibrillation ablation procedures, by using a continuous rhythm monitoring strategy. METHODS: This was a prospective two-arm nonrandomized propensity-matched observational trial that compared the outcomes of atrial fibrillation (AF) ablation using LB and CB techniques. To evaluate AF recurrences, an implantable cardiac monitor (ICM) was implanted before hospital discharge to detect atrial tachyarrhythmia (ATA) recurrences. RESULTS: A total of 110 propensity-matched patients undergoing AF ablation with an LB (n = 55) or with a CB system (n = 55) were enrolled (paroxysmal AF 57.3%). Procedural time (LB: 87 [73-104] vs. CB 90 [70-130] min; p = 0.264) and fluoroscopy time did not differ. No differences in ATA recurrences were observed at 12 months (LB-30.9% vs. CB-29.1% and LB-45.5% vs. CB-38.2%; log-rank 0.539). As for AF burden, the 12-month median was 0 [0-1] vs. 0 [0-3]% (p = 0.127) in the LB and CB groups, respectively. When considering only PeAF patients, the median 12-month ATA burden was 26 [18.5-40.5] vs. 29 [26-35]% (p = 0.919) for the LB and CB patients, respectively. CONCLUSION: In a propensity-matched cohort undergoing AF ablation, arrhythmia outcomes assessed by continuous rhythm monitoring did not differ between LB and CB, with an overall low ATA burden. The only predictor of recurrences was persistent AF. There was no difference in procedure or fluoroscopy time.

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.

Arrhythmogenic Risk and Mechanisms of QT-Prolonging Drugs to Treat COVID-19.

While looking for a solution to treat COVID-19, the massive off-label use of several drugs in COVID-19 has generated concerns in the early phase of the pandemic because of possible arrhythmogenic effects in relation to QTc interval prolongation. Indeed, some of these drugs have been historically associated with QT prolongation and Torsade de Point, a potentially lethal ventricular arrhythmia, and their first-time use on a very large scale has raised several concerns in the scientific community. This work aims to summarize the underlying arrhythmogenic mechanisms related to the use of potentially QT-prolonging drugs used during the pandemic to treat COVID-19.

Intraoperative sensing increase predicts long-term pacing threshold in leadless pacemakers.

PURPOSE: High pacing threshold (HPT) and very high pacing threshold (VHPT) are known to have a negative impact on leadless pacemaker battery longevity, representing the most common reason for device repositioning. In this study, we evaluated if intraoperative electrical parameters recorded during Micra™ VR implant would be able to predict device performance during follow-up (FU). METHODS: A total of 93 patients undergoing Micra™ VR implant were retrospectively considered. Patients were enrolled in the study if electrical assessment was performed at least twice at implant, at Micra™ final positioning and after removal of the delivery system. All patients received a FU visit at 1 and 12 month after discharge. R-wave sensing amplitude, pacing threshold (PT), and impedance were recorded at each visit. RESULTS: When compared to the first assessment, R-wave sensing amplitude increased by 19.1% after 13 ± 4 min (+ 1.71 ± 0.2 mV, 95% CI 1.4 to 2.02; p < .001). Conversely, there was a significant PT decrease of 22.1% at 12-month FU (- 0.22 ± 0.03 V, 95% CI - 0.13 to - 0.31; p < .001). Among patients with HPT, acute increase of R-wave sensing of 1.5 mV after 14 ± 4 min predicted a significant reduction of PT below 1 V/0.24, at 12-month post-implant (R = 0.72, 95% CI 0.13 to 0.33, p < .001), with a sensitivity of 87.5% (95% CI 0.61-0.98) and a specificity of 88.8% (95% CI 0.51-0.99). CONCLUSION: A 1.5-mV increase in R-wave amplitude at implant is predictive of PT normalization (< 1.0 V/0.24 ms) at 12-month FU. This finding may have practical implications for device repositioning in case of HPT recording at implant.

Factors affecting signal quality in implantable cardiac monitors with long sensing vector.

PURPOSE: Electrical artefacts are frequent in implantable cardiac monitors (ICMs). We analyzed the subcutaneous electrogram (sECG) provided by an ICM with a long sensing vector and factors potentially affecting its quality. METHODS: Consecutive ICM recipients underwent a follow-up where demographics, body mass index (BMI), implant location, and surface ECG were collected. The sECG was then analyzed in terms of R-wave amplitude and P-wave visibility. RESULTS: A total of 84 patients (43% female, median age 68 [58-76] years) were enrolled at 3 sites. ICMs were positioned with intermediate inclination (n = 44, 52%), parallel (n = 35, 43%), or perpendicular (n = 5, 6%) to the sternum. The median R-wave amplitude was 1.10 (0.72-1.48) mV with P waves readily visible in 69.2% (95% confidence interval, CI: 57.8%-79.2%), partially visible in 23.1% [95% CI: 14.3%-34.0%], and never visible in 7.7% [95% CI: 2.9%-16.0%] of patients. Men had higher R-wave amplitudes compared to women (1.40 [0.96-1.80] mV vs 1.00 [0.60-1.20] mV, P = .001), while obese people tended to have lower values (0.80 [0.62-1.28] mV vs 1.10 [0.90-1.50] mV, P = .074). The P-wave visibility reached 86.2% [95% CI: 68.3%-96.1%] in patients with high-voltage P waves (≥0.2 mV) at surface ECG. The sECG quality was not affected by implant site. CONCLUSION: In ordinary clinical practice, ICMs with long sensing vector provided median R-wave amplitude above 1 mV and reliable P-wave visibility of nearly 70%, regardless of the position of the device. Women and obese patients showed lower but still very good signal quality.

Micra-AV leadless pacemaker and atrioventricular (dys)synchrony: A stepwise process.

Leadless pacemakers have become a major breakthrough in the management of bradyarrhythmia as an attractive alternative to the standard transvenous pacemakers, but safety and long-term outcomes of the new Micra-AV, which is capable guarantee atrioventricular (AV) synchrony, have been poorly described. Hence, we describe how we managed a 57-year-old patient who developed pacemaker syndrome due to significant Micra-AV dyssynchrony. This case emphasizes how leadless pacemaker AV synchrony could be overestimated, thereby requiring a stepwise process leading to adequate device reprogramming. Holter-ECG monitoring and exercise test resulted to be valuable tools for an early detection of inadequate AV synchrony, integrating and completing device reports.

Subcutaneous implantable cardioverter-defibrillator and defibrillation testing: A propensity-matched pilot study.

BACKGROUND: To date, only a few comparisons between subcutaneous implantable cardioverter-defibrillator (S-ICD) patients undergoing and those not undergoing defibrillation testing (DT) at implantation (DT+ vs DT-) have been reported. OBJECTIVE: The purpose of this study was to compare long-term clinical outcomes of 2 propensity-matched cohorts of DT+ and DT- patients. METHODS: Among consecutive S-ICD patients implanted across 17 centers from January 2015 to October 2020, DT- patients were 1:1 propensity-matched for baseline characteristics with DT+ patients. The primary outcome was a composite of ineffective shocks and cardiovascular mortality. Appropriate and inappropriate shock rates were deemed secondary outcomes. RESULTS: Among 1290 patients, a total of 566 propensity-matched patients (283 DT+; 283 DT-) served as study population. Over median follow-up of 25.3 months, no significant differences in primary outcome event rates were found (10 DT+ vs 14 DT-; P = .404) as well as for ineffective shocks (5 DT- vs 3 DT+; P = .725). At multivariable Cox regression analysis, DT performance was associated with a reduction of neither the primary combined outcome nor ineffective shocks at follow-up. A high PRAETORIAN score was positively associated with both the primary outcome (hazard ratio 3.976; confidence interval 1.339-11.802; P = .013) and ineffective shocks alone at follow-up (hazard ratio 19.030; confidence interval 4.752-76.203; P = .003). CONCLUSION: In 2 cohorts of strictly propensity-matched patients, DT performance was not associated with significant differences in cardiovascular mortality and ineffective shocks. The PRAETORIAN score is capable of correctly identifying a large percentage of patients at risk for ineffective shock conversion in both cohorts.

Atrioventricular synchronous leadless pacemaker: state of art and broadened indications.

Leadless pacemakers (LLPMs) have become a major breakthrough in the management of bradyarrhythmia as an attractive alternative to the standard transvenous pacemakers (TV-PMs). Recently, the introduction of a second-generation LLPMs (Micra AV-MC1AVR1) has expanded pacing modes to obtain atrioventricular (AV) synchronous pacing, providing an interesting alternative in the actual scenario of leadless pacing. Nevertheless, actual reports have highlighted some concerns regarding those devices. In this review, we sought to provide an overview of this technology based on its approval studies and major reports.

[A case of concomitant aortic stenosis and aortic arch aneurysm: a combined endovascular approach]. / Aneurisma dell'arco aortico e stenosi valvolare aortica: un approccio endovascolare combinato.

Aortic valve stenosis and aortic aneurysmal disease are increasingly prevalent with advancing age. When associated, their treatment is very challenging. A female patient with previous Tirone-David procedure presented to our hospital with acute heart failure. She was diagnosed with severe aortic stenosis, aneurysm of the aortic arch and the descending thoracic aorta. She underwent successful concomitant aortic arch TEVAR and transcatheter aortic valve repair, with optimal acute and mid-term result. Our case demonstrates that a careful pre-procedural planning, along with a good cooperation between interventional cardiologists, cardiac surgeons, radiologists and clinical cardiologists, are essential in order to guarantee an excellent outcome for the patient.

Second-generation laser balloon ablation for the treatment of atrial fibrillation assessed by continuous rhythm monitoring: the LIGHT-AF study.

AIMS: Balloon-based technologies have been developed to simplify catheter ablation of atrial fibrillation (AF), to improve the clinical outcome of the procedure and to achieve durable pulmonary vein isolation (PVI). The objective of this study is to evaluate the safety and efficacy of second-generation laser balloon (LB2) ablation in the treatment of AF using a continuous cardiac rhythm monitoring strategy. Atrial tachyarrhythmias (ATas) recurrences were assessed with implantable cardiac monitors (ICMs) or devices. METHODS AND RESULTS: All patients underwent LB2 ablation procedure. The primary endpoint was the first recurrence of any, >5.5 and >24 h duration ATas after the blanking period (90 days). In-hospital visits were performed at 3, 6, and 12 months. Seventy-three patients (68% male, mean age 59.8 ± 11.3) were included in the study. The average procedure, fluoroscopy, and laser ablation times were 81.5 ± 30.1, 21.5 ± 12.4, and 33.8 ± 9.7, respectively. All PVs were isolated using the LB2 with no need of touch-up using focal catheters. No major complications occurred during or after the procedures. The one-year freedom from recurrences was 66.9% (95% CI: 57.0-76.7%), 81.0% (69.5-88.5%), and 86.8% (76.1-92.9%) considering any, 5.5-h and 24-h cut-off duration, respectively. At 3, 6, and 12 months, any ATas was recorded in 22%, 32%, and 25% of patients, with a ≥5% arrhythmic burden documented in 4%, 5%, and 3%, respectively. Few patients reported AF-related symptoms (7%, 8%, and 5%). CONCLUSION: LB2 ablation is a safe and effective procedure, showing a high freedom from recurrences and low arrhythmic burden as documented by a continuous rhythm monitoring strategy.

Impact of prior statin use on clinical outcomes in COVID-19 patients: data from tertiary referral hospitals during COVID-19 pandemic in Italy.

BACKGROUND: Epidemiological evidence suggests that anti-inflammatory and immunomodulatory properties of statins may reduce the risk of infections and infection-related complications. OBJECTIVE: We aimed to assess the impact of prior statin use on coronavirus disease (COVID-19) severity and mortality. METHODS: In this observational multicenter study, consecutive patients hospitalized for COVID-19 were enrolled. In-hospital mortality and severity of COVID-19 assessed with National Early Warning Score (NEWS) were deemed primary and secondary outcomes, respectively. Propensity score (PS) matching was used to obtain balanced cohorts. RESULTS: Among 842 patients enrolled, 179 (21%) were treated with statins before admission. Statin patients showed more comorbidities and more severe COVID-19 (NEWS 4 [IQR 2-6] vs 3 [IQR 2-5], p < 0.001). Despite having similar rates of intensive care unit admission, noninvasive ventilation, and mechanical ventilation, statin users appeared to show higher mortality rates. After balancing pre-existing relevant clinical conditions that could affect COVID-19 prognosis with PS matching, statin therapy confirmed its association with a more severe disease (NEWS ≥5 61% vs. 48%, p = 0.025) but not with in-hospital mortality (26% vs. 28%, p = 0.185). At univariate logistic regression analysis, statin use was confirmed not to be associated with mortality (OR 0.901; 95% CI: 0.537 to 1.51; p = 0.692) and to be associated with a more severe disease (NEWS≥5 OR 1.7; 95% CI 1.067-2.71; p = 0.026). CONCLUSIONS: Our results did not confirm the supposed favorable effects of statin therapy on COVID-19 outcomes. Conversely, they suggest that statin use should be considered as a proxy of underlying comorbidities, which indeed expose to increased risks of more severe COVID-19.

QT Interval Monitoring and Drugs Management During COVID-19 Pandemic.

While facing potentially high morbidity from COVID-19 without known effective therapies, the off-label use of several non-specific drugs has been advocated, including re-purposed anti- viral (e.g., remdesivir or the lopinavir/ritonavir combination), biologic agents (e.g., tocilizumab), and antimalarial drugs such as chloroquine and hydroxychloroquine, in association with or without azithromycin. Data regarding the effectiveness of these drugs in treating COVID-19 has been shown in some trials and clinical settings, but further randomised controlled trials are still being carried out. One of the main concerns regarding their widespread use, however, is their possible effects on the QT interval and arrhythmogenic potential. Some of these drugs have been associated with QT prolongation and Torsades de Point, a potentially lethal ventricular arrhythmia. The review aims to highlight the magnitude of this problem, to quickly refresh clinically impacting cornerstones of QT interval and TdP pathophysiology, to summarize the available evidence regarding the QT and arrhythmia impact of drugs used in different clinical settings in COVID-19 patients, and to help the physicians dealing with the knowledge needed in the everyday clinical duties in case of doubts regarding QT-induced arrhythmias in this time of emergency.