Arrhythmia detection using an implantable loop recorder after a negative electrophysiology study in Brugada syndrome: Observations from a multicenter international registry.

BACKGROUND: Risk stratification in Brugada syndrome (BrS) remains controversial. In this respect, the role of the electrophysiology study (EPS) has been a subject of debate. In some centers, it is common practice to use an implantable loop recorder (ILR) after a negative EPS to help in risk stratification. However, the diagnostic value of this approach has never been specifically addressed. OBJECTIVE: The aim of this study was to describe the baseline characteristics and the main findings of a diagnostic workup strategy with an ILR after a negative EPS in BrS. METHODS: We conducted a retrospective international registry including patients with BrS and negative EPS (ie, noninducible ventricular tachycardia or ventricular fibrillation) before ILR monitoring. RESULTS: The study included 65 patients from 8 referral hospitals in The Netherlands, Spain, and the United Kingdom (mean age, 39 ± 16 years; 72% male). The main indication for ILR monitoring was unexplained syncope/presyncope (66.2%). During a median follow-up of 39.0 months (Q1 25.0-Q3 47.6 months), 18 patients (27.7%) experienced 21 arrhythmic events (AEs). None of the patients died during follow-up. Bradyarrhythmias were the most common finding (47.6%), followed by atrial tachyarrhythmias (38.1%). Only 3 patients presented with ventricular arrhythmias. AEs were considered incidental in 12 patients (66.7%). In 11 patients (61.1%), AEs led to specific changes in treatment. CONCLUSION: The use of ILR after a negative EPS in BrS is a safe strategy that reflected the high negative predictive value of EPS for ventricular arrhythmia in this syndrome. In addition, it allowed the detection of AEs in a significant proportion of patients, with therapeutic implications in most of them.

Incidence of ventricular arrhythmias in patients with chronic total coronary occlusion: Results of the VACTOR study.

Background: A chronic total coronary occlusion (CTO) is associated with ventricular arrhythmias (VA) in patients with an implantable cardioverter-defibrillator (ICD). Limited data is available on the incidence of VA in CTO patients without an ICD. Objectives: To investigate the incidence of sustained VA in CTO patients after successful CTO revascularization and in patients with untreated CTO or failed CTO revascularization. Methods: Prospective, multicenter observational pilot study including CTO patients who were not eligible for an ICD and had a left ventricular ejection fraction >35 %. We enrolled patients with a successful CTO revascularization (group A) and patients with untreated CTO or failed CTO revascularization (group B). All patients received an implantable loop recorder with remote monitoring. The primary endpoint was sustained VA. Results: Ninety patients were enrolled (mean age 63 ± 10 years, 83.3 % man, mean LVEF 55 ± 8 %). Group A (n = 45) had a higher prevalence of CTO in the left anterior descending artery in comparison to group B (n = 45) (28.9 % versus 4.4 %, P = 0.002). Other baseline characteristics were similar. During a median follow-up time of 26 months (IQR, 19-35), five patients (5.6 %) had a sustained VA. There was no difference in the incidence of sustained VA between groups (3-year cumulative event rate: 8.8 % (group A) versus 4.5 % (Group B), log-rank P = 0.71). Conclusion: Patients with an CTO, who do not qualify for an ICD, have a substantial risk of sustained VA. In our study the incidence was not different between patients with revascularized and those with untreated CTO.

Effect of myocardial scar size on the risk of ventricular arrhythmias in patients with chronic total coronary occlusion.

BACKGROUND: The presence of an untreated chronic total coronary occlusion (CTO) is associated with a higher risk of ventricular arrhythmias (VAs). This increased risk may be modulated by the presence of an existing scar. OBJECTIVES: To evaluate whether scar size is associated with VA in patients with an implantable cardioverter-defibrillator (ICD) and a CTO. METHODS: In this retrospective study we included patients with a CTO that received an ICD between 2005 and 2015. Scar size was estimated using the Selvester QRS score on a baseline 12­lead ECG. The primary endpoint was any appropriate ICD therapy. RESULTS: Our study population comprised 148 CTO patients with a median scar size at baseline of 18% (IQR, 9-27%). Patients with a scar size ≥18% more often had a CTO located in the left anterior descending artery and a higher proportion of poor left ventricular function (<35%) and infarct-related CTO compared to patients with a smaller scar size (<18%). During a median follow-up of 35 months (interquartile range [IQR], 8-60 months), 42 patients (28%) received appropriate ICD therapy. The cumulative 5-year event rate was higher in the patients with a large scar in comparison to those with a smaller or no scar (36% versus 19%, P = 0.04). Multivariable Cox regression analysis demonstrated that large scar and diabetes mellitus were independent factors associated with appropriate ICD therapy. CONCLUSION: In ICD recipients with an untreated CTO, a larger scar is an independent factor associated with an increased risk of VA.

Usefulness of insertable cardiac monitors for risk stratification: current indications and clinical evidence.

INTRODUCTION: The 2018 ESC Syncope guidelines expanded the indications for an insertable cardiac monitor (ICM) to patients with unexplained syncope and primary cardiomyopathy or inheritable arrhythmogenic disorders. AREAS COVERED: This review article discusses the clinical evidence for using an ICM for risk stratification in different patient populations including Brugada syndrome, long QT syndrome, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, cardiac sarcoidosis, and congenital heart disease. EXPERT OPINION: Clinical data on the usefulness of ICMs in different patient populations is limited but most studies demonstrate early detection of clinically relevant arrhythmias, such as nonsustained ventricular tachycardia or atrial fibrillation. It is important to emphasize that the study populations usually comprise selected populations where conventional diagnostic methods fail to clarify the mechanism of symptoms. The effect of an ICM on prognosis by earlier detection of arrhythmias is difficult to demonstrate in populations with rare disease. Risk stratification in patients with cardiomyopathy or inheritable arrhythmogenic disorders remains a niche indication for ICMs. The most important indication for an ICM remains unexplained syncope in patients at low risk of SCD. Given the device costs and uncertain clinical value of device-detected arrhythmias, it is unclear whether it is also useful in non-syncopal patients.

Comparison of the acute outcome of two cryoballoon technologies for pulmonary vein isolation: An updated systematic review and meta-analysis.

Initial experience suggests that the POLARx cryoballoon system (Boston Scientific) has a similar procedural efficacy and safety as Arctic Front Advance Pro (AFA-Pro, Medtronic). We performed an updated systematic review and meta-analysis comparing POLARx and AFA-Pro. Embase, MEDLINE, Web of Science, Cochrane, and Google Scholar databases were searched until 12/01/2022 for studies comparing POLARx versus AFA-Pro in patients undergoing pulmonary vein (PV) isolation for AF. A total of 8 studies, involving 1146 patients from 11 European centers were included (POLARx n = 317; AFA-Pro n = 819). There were no differences in acute PV isolation, procedure time, fluoroscopy time, ablation time, minimal esophageal temperature, and risk of phrenic nerve palsy or thromboembolic events. Balloon nadir temperatures were lower for POLARx in all PVs. Compared with AFA-Pro, POLARx had a higher rate of first freeze isolation in the left inferior PV (LIPV) (odds ratio [OR]: 2.60; 95 % confidence interval [CI]: 1.06 to 6.43; P = 0.04), higher likelihood of time-to-isolation (TTI) recording in LIPV (OR: 2.91; 95 % CI: 1.54 to 5.49; P = 0.001) and right inferior PV (OR: 3.23; 95 % CI: 1.35 to 7.74; P = 0.008). In contrast, the TTI in LIPV was longer with POLARx in comparison to AFA-Pro (mean difference: 7.61 sec; 95 % CI 2.43 to 12.8 sec; P = 0.004). In conclusion, POLARx and AFA-Pro have a similar acute outcome. Interestingly, there was a higher rate of TTI recording in the inferior PVs with POLARx. This updated meta-analysis provides new safety data on esophageal temperature and thromboembolic events.

Accuracy of atrial fibrillation detection by an insertable cardiac monitor in patients undergoing catheter ablation: Results of the BioVAD study.

BACKGROUND: Insertable cardiac monitors (ICMs) are increasingly used to evaluate the atrial fibrillation (AF) burden after catheter ablation of AF. BioMonitor III (BM3) is an ICM with a long sensing vector, which enhances sensing capabilities. The AF detection algorithm of the BM3 is based on R-R interval variability. OBJECTIVE: To evaluate the performance of the AF detection algorithm of BM3 in patients before and after catheter ablation of AF using simultaneous Holter recordings. METHODS: In this prospective study, we enrolled patients scheduled for catheter ablation of paroxysmal or persistent AF. After BM3 implantation, patients had a 4 days Holter registration before and 3 months after ablation. All true AF episodes ≥2 min on the Holter were annotated and matched with BM3 detected AF detections. RESULTS: Thirty-one patients were enrolled (mean age 60 ± 8, 74% male, 68% paroxysmal AF). Fifty-six Holter registrations were performed in 30 patients. Twelve patients demonstrated at least one true AF episode with a total AF duration of 570 h. The AF burden accuracy of BM3 before catheter ablation was 99.6%, with a duration sensitivity of 98.6% and a duration specificity of 99.9%. The AF burden accuracy of BM3 after catheter ablation was 99.8%, with a duration sensitivity of 90.2% and a duration specificity of 99.9%. Overall, the AF burden detected on the Holter and BM3 demonstrated a high Pearson correlation coefficient of 0.996. CONCLUSION: BM3 accurately detects AF burden in patients before and after catheter ablation of AF.

Implantable loop recorders in patients with heart disease: comparison between patients with and without syncope.

OBJECTIVE: Patients with heart disease are at increased risk for sudden cardiac death. Guidelines recommend an implantable loop recorder (ILR) for symptomatic patients when symptoms are sporadic and possibly arrhythmia-related. In clinical practice, an ILR is mainly used in patients with unexplained syncope. We aimed to compare the clinical value of an ILR in patients with heart disease and a history of syncope versus those with non-syncopal symptoms. METHODS: In this observational single-centre study, we included symptomatic patients with heart disease who received an ILR. The primary endpoint was an actionable event which was defined as an arrhythmic event leading to a change in clinical management. The secondary endpoint was an event leading to device implantation. RESULTS: One hundred and twenty patients (mean age 47±17 years, 49% men) were included. The underlying disease substrate was inherited cardiomyopathy (31%), congenital heart disease (28%), channelopathy (23%) and other (18%). Group A consisted of 43 patients with prior syncope and group B consisted of 77 patients with palpitations and/or near-syncope. The median follow-up duration was 19 months (IQR 8-36). The 3-year cumulative event rate was similar between groups with regard to the primary endpoint (38% vs 39% for group A and B, respectively, logrank p=0.54). There was also no difference in the 3-year cumulative rate of device implantation (21% vs 13% for group A and B, respectively, logrank p=0.65). CONCLUSION: In symptomatic patients with heart disease, there is no difference in the yield of an ILR in patients presenting with or without syncope.

Comparison of procedural efficacy, balloon nadir temperature, and incidence of phrenic nerve palsy between two cryoballoon technologies for pulmonary vein isolation: A systematic review and meta-analysis.

INTRODUCTION: In May 2020, a novel cryoballoon system (POLARx; Boston Scientific) became available for catheter ablation of atrial fibrillation (AF). The design of the cryoballoon is comparable to the Arctic Front Advance Pro (AFA-Pro; Medtronic), but it is more compliant during freezing. We compared the procedural efficacy, biophysical parameters, and risk of phrenic nerve palsy (PNP) between the two cryoballoons. METHODS: Embase, MEDLINE, Web of Science, Cochrane, and Google Scholar databases were searched until June 1, 2021 for relevant studies comparing POLARx versus AFA-Pro in patients undergoing pulmonary vein isolation (PVI) for AF. RESULTS: A total of four studies, involving 310 patients were included. There was no difference between the two groups for outcomes regarding procedural efficacy: acute PVI (odds ratio [OR]: 0.43; 95% confidence interval [CI]: 0.06 to 3.03; p = .40), procedure time (mean difference [MD]: 8.15 min; 95% CI: -8.09 to 24.39; p = .33), fluoroscopy time (MD: 1.32 min; 95% CI: -1.61 to 4.25; p = .38) and ablation time (MD: 1.00 min; 95% CI: -0.20 to 2.20; p = .10). The balloon nadir temperature was lower for all individual pulmonary veins (PV) in POLARx compared with AFA-Pro (MD: -9.74°C, -9.98°C, -6.72°C, -7.76°C, for left superior PV, left inferior PV, right superior PV, and right inferior PV, respectively; all p < .001). The incidence of PNP was similar between groups (OR: 0.79; 95% CI: 0.22 to 2.85; p = .72). CONCLUSION: In AF patients undergoing PVI, POLARx and AFA-Pro had a similar procedural efficacy. Balloon nadir temperatures were lower with POLARx, however, the incidence of PNP was similar.

Incremental Value of an Insertable Cardiac Monitor in Patients with Hypertrophic Cardiomyopathy with Low or Intermediate Risk for Sudden Cardiac Death.

AIMS: The aim of the present study was to compare the rate of actionable arrhythmic events between patients with hypertrophic cardiomyopathy (HCM) who are monitored with an insertable cardiac monitor (ICM) or Holter monitoring. METHODS: We studied 50 patients (mean age 52 years, 72% men) with HCM at low or intermediate risk for sudden cardiac death (SCD), of whom 25 patients received an ICM between November 2014 and February 2019. We retrospectively identified a control group of 25 patients who were matched on age, sex, and HCM Risk-SCD score category. The mean HCM Risk-SCD score was 3.41 ± 1.31 and 3.31 ± 1.43 for the ICM and Holter groups, respectively. The primary endpoint was an actionable event which was defined as an arrhythmic event resulting in a change in patient management. The secondary endpoint was the occurrence of ventricular tachycardia (VT). RESULTS: The cumulative actionable event rate at 30 months was higher in the ICM group (51 vs. 27%, log-rank p value <0.01). De novo atrial fibrillation requiring oral anticoagulation occurred only in the ICM group (n = 3). Overall, 4 implantable cardioverter-defibrillators were implanted for primary prevention (n = 2 in each group). The cumulative rate of VT episodes at 30 months was similar between groups (23% [ICM group] vs. 42% [Holter group], log-rank p value = 0.71). Furthermore, the characteristics of VT were similar between groups with regard to the number of beats and rate. CONCLUSIONS: In adults with HCM, an ICM will detect more arrhythmic events requiring an intervention than a conventional Holter strategy. In contrast, the diagnostic yield of detecting VT seems similar for both groups.

Efficacy and safety of direct oral anticoagulants in patients undergoing elective electrical cardioversion: A real-world patient population.

BACKGROUND: Direct oral anticoagulants (DOACs) have emerged as the preferred choice of oral anticoagulation in patients with atrial fibrillation. Randomized trials have demonstrated the efficacy and safety of DOAC in patients undergoing electrical cardioversion (ECV); however, there is limited real-world data. OBJECTIVE: To evaluate the outcome of patients undergoing an elective ECV for atrial tachyarrhythmia in a tertiary referral center who were treated with DOAC or vitamin K antagonist (VKA) without routine trans esophageal echocardiography (TEE). METHODS: This was a retrospective single-center cohort study of consecutive patients undergoing an elective ECV for atrial tachyarrhythmia from January 2013 to February 2020. The primary endpoints were thromboembolism (composite of stroke, transient ischemic attack or systemic embolism) and major bleeding events within 60 days. RESULTS: A total of 1431 ECV procedures were performed in 920 patients. One-third of the procedures were performed under DOAC (N = 488, 34%) and the remainder of the procedures was performed under VKA (N = 943, 66%). There were no differences between groups with regard to demographic variables (mean age 62.4 ± 11.7, 72% men) and mean CHA2DS2-VASc score (2.3 ± 1.6); however, the VKA group had a higher proportion of patients with co-morbidity. Thromboembolism occurred in 0.41% in the DOAC group versus 0.64% in the VKA group (P = 0.72). Major bleeding events occurred in 0.41% in the DOAC group versus 0.11% in the VKA group (P = 0.27). CONCLUSION: In a real-world population, the rates of thromboembolism and major bleeding events were low after elective ECV in patients using DOAC or VKA, even without routine TEE.

Vulnerability for ventricular arrhythmias in patients with chronic coronary total occlusion.

INTRODUCTION: The presence of a chronic total occlusion (CTO) is associated with an increased risk of ventricular arrhythmias. AREAS COVERED: This review provides an overview of the relationship between CTO and ventricular arrhythmias, arrhythmogenic mechanisms, and the effect of revascularization. EXPERT OPINION: Studies in recipients of an implantable cardioverter-defibrillator (ICD) have shown that a CTO is an independent predictor of appropriate ICD therapy. The myocardial territory supplied by a CTO is a pro-arrhythmogenic milieu characterized by scar tissue, large scar border zone, hibernating myocardium, residual ischemia despite collaterals, areas of slow conduction, and heterogeneity in repolarization. Restoring coronary flow by revascularization might be associated with electrical homogenization as reflected by a decrease in QT(c) dispersion, decrease in T wave peak-to-end interval, reduction of late potentials, and decrease in scar border zone area. Future research should explore whether CTO revascularization results in a lower burden of ventricular arrhythmias. Furthermore, risk stratification of CTO patients without severe LV dysfunction is interesting to identify potential ICD candidates. Potential tools for risk stratification are the use of electrocardiographic parameters, body surface mapping, electrophysiological study, and close rhythm monitoring using an insertable cardiac monitor.

Outcome of Insertable Cardiac Monitors in Symptomatic Patients with Brugada Syndrome at Low Risk of Sudden Cardiac Death.

INTRODUCTION: There is limited data on the experience with insertable cardiac monitors (ICMs) in patients with Brugada syndrome. OBJECTIVE: To evaluate the outcome of ICM in symptomatic patients with Brugada syndrome who are at suspected low risk of sudden cardiac death (SCD). METHODS: We conducted a prospective single-center cohort study including all symptomatic patients with Brugada syndrome who received an ICM (Reveal LINQ) between July 2014 and October 2019. The main indication for monitoring was to exclude ventricular arrhythmias as the cause of symptoms and to establish a symptom-rhythm relationship. RESULTS: A total of 20 patients (mean age, 39 ± 12 years; 55% male) received an ICM during the study period. Nine patients (45%) had a history of syncope (presumed nonarrhythmogenic), and 5 patients had a recent syncope (<6 months). During a median follow-up of 32 months (interquartile range, 11-36 months), 3 patients (15%) experienced an episode of nonsustained ventricular arrhythmia. No patient died suddenly or experienced a sustained ventricular arrhythmia, and no patient had a recurrence of syncope. Overall, 17 patients (85%) experienced symptoms during follow-up, of whom 10 patients had an ICM-detected arrhythmia. In 4 patients (20%), the ICM-detected arrhythmia was an actionable event. ICM-guided management included antiarrhythmic drug therapy for symptomatic ectopic beats (n = 3), pulmonary vein isolation, and oral anticoagulation for atrial fibrillation (n = 1), electrophysiological study for risk stratification (n = 1), and pacemaker implantation for atrioventricular block (n = 1). CONCLUSIONS: An ICM can be used to exclude ventricular arrhythmias in symptomatic patients with Brugada syndrome at low risk of SCD. Furthermore, an ICM-detected arrhythmia changed clinical management in 20% of patients.

Design and rationale of the COMPARE-ACUTE trial: Fractional flow reserve-guided primary multivessel percutaneous coronary intervention to improve guideline indexed actual standard of care for treatment of ST-elevation myocardial infarction in patients with multivessel coronary disease.

What the best strategy is for nonculprit lesions in ST-elevation myocardial infarction (STEMI) patients presenting with multivessel disease remains a clinical dilemma. Based on recent clinical studies suggesting that complete revascularization in the acute phase is beneficial, the European Society of Cardiology and American College of Cardiology/American Heart Association guidelines have been recently changed from class 3 discouragement to a class 2B recommendation concerning the treatment of the nonculprit lesions in the acute index procedure. However, in these recent studies, nonculprit lesion treatment was guided by angiography, which is known for its poor accuracy in determining ischemia. Fractional flow reserve (FFR) guidance for treatment of nonculprit vessels seems to be a reasonable approach, and in the acute setting of STEMI, it is not yet investigated. The COMPARE-ACUTE trial aims to investigate FFR-guided complete revascularization in comparison to a culprit lesion treatment-only strategy in STEMI patients with multivessel disease presenting for primary percutaneous coronary intervention. METHODS AND RESULTS: COMPARE-ACUTE is an investigator-initiated, prospective multicenter randomized controlled trial. After successful primary percutaneous coronary intervention, patients will be randomized in a 1:2 fashion toward FFR-guided complete revascularization or culprit lesion treatment-only strategies. The chosen primary end point is a composite of all-cause mortality, nonfatal myocardial infarction, any revascularization, and cerebrovascular events (major adverse cardiac and cerebrovascular events) at 12 months, with 3-year follow-up. Based on estimated event rates, a sample size of 885 patients is needed to show superiority of the FFR-guided revascularization with 80% power. CONCLUSION: The aim of the COMPARE-ACUTE trial is to assess whether FFR-guided complete revascularization in the acute setting is superior to culprit lesion treatment-only therapy.

Discovery of Innovative Therapies for Rare Immune-Mediated Inflammatory Diseases via Off-Label Prescription of Biologics: The Case of IL-6 Receptor Blockade in Castleman's Disease.

Biologics have revolutionized the field of clinical immunology and proven to be both effective and safe in common immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, inflammatory bowel diseases, and various hematological disorders. However, in patients with rare, severe IMIDs failing on standard therapies, it is virtually impossible to conduct randomized controlled trials. Therefore, biologics are usually prescribed off-label in these often severely ill patients. Unfortunately, off-label prescription is sometimes hampered in these diseases due to a lack of reimbursement that is often based on a presumed lack of evidence for effectiveness. In the present article, we will discuss that off-label prescription of biologics can be a good way to discover new treatments for rare diseases. This will be illustrated using a case of multicentric Castleman's disease, an immune-mediated lymphoproliferative disorder, in which off-label tocilizumab (humanized anti-IL-6 receptor blocking antibody) treatment resulted in remarkable clinical improvement. Furthermore, we will give recommendations for monitoring efficacy and safety of biologic treatment in rare IMIDs, including the use of registries. In conclusion, we put forward that innovative treatments for rare IMIDs can be discovered via off-label prescription of biologicals, provided that this is based on rational arguments including knowledge of the pathophysiology of the disease.

[Off-label use of biologics for rare immunological disorders]. / Off-labelgebruik van biologicals voor zeldzame immunologische aandoeningen.

Patients with severe therapy-refractory immune-mediated inflammatory diseases (IMIDs) are increasingly treated with biologics. Since official practice guidelines for these rare diseases are lacking, these drugs are often prescribed off-label. However, treating physicians encounter difficulties and risks when prescribing drugs off-label. Access to these biologics for off-label indications is currently not well organized, which may result in suboptimal care. This also blocks innovation in patient care. In this article we introduce the recently initiated RUBRIC (Rational Use of Biologics in Refractory Immune-mediated inflammatory diseases Consortium) register. This national register documents the efficacy and safety of off-label biologic treatment in combination with the development of treatment protocols and practice guidelines. We believe that the results from this register will ultimately lead to a more evidence-based use of biologics in patients with rare IMIDs, which may also result in better access to these drugs. Ultimately, both the individual patient and the group as a whole will benefit.