Bifascicular block in unexplained syncope is underrecognized and under-evaluated: A single-center audit of ESC guidelines adherence.

BACKGROUND: The presence of bifascicular block on electrocardiography suggests that otherwise-unexplained syncope may be due to complete heart block. European Society of Cardiology (ESC) recommends investigating it with electrophysiology study (EPS). PPM is indicated if high-degree atrioventricular block is inducible. Long term rhythm monitoring with implantable loop recorder (ILR) is recommended if EPS is negative. We evaluated adherence to these guidelines. METHODS: This is a single-center retrospective audit of adult patients with bifascicular block hospitalized for unexplained syncope between January 2018 and August 2019 under general medicine service. Patients with an alternative explanation for syncope were excluded. Guideline adherence was assessed by formal cardiology consult and whether EPS followed by ILR and/or PPM were offered. RESULTS: 65 out of 580 adult patients (11.2%) admitted to general medicine service for syncope had a bifascicular block; 29 (5%) were identified to have bifascicular block and unexplained syncope. Median age was 77 ±10 years; 9 (31%) were female, and 6 (20.7%) patients had at least one prior hospital visit for syncope at our academic medical center. Cardiology was consulted on 17 (58.6%) patients. Two patients were evaluated by EPS (1 refused) followed by ILR. Overall, 3 out of 29 patients (10.3%) received guideline-directed evaluation during the hospitalization based on ESC guidelines. None of the patients received empiric PPM during the index hospitalization. CONCLUSION: Among patients admitted to the general medicine service with unexplained syncope and bifascicular block, a minority (10.3%) underwent guideline-directed evaluation per ESC recommendations. Cardiology was consulted in 58.6% of cases.

Conduction abnormalities and role of cardiac pacing in cardiac amyloidosis: A systematic review.

Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure, characterized by extracellular deposition of insoluble protein fibrils leading to progressive myocardial dysfunction. The most common types of cardiac amyloidosis are immunoglobin light-chain (AL) and transthyretin (ATTR). Conduction abnormalities are commonly encountered among patients with cardiac amyloidosis and are an important cause of morbidity and mortality. Abnormalities range from infra-Hisian intraventricular conduction delay and bundle branch block to complete atrioventricular block. Pacemaker placement in CA patients follows established guidelines, similar to those for patients without CA, with generally good efficacy. The role and appropriate timing of pacemakers for primary prevention of brady-arrhythmias in CA remains uncertain. While biventricular (BiV) pacing has been shown to improve clinical outcomes in patients with systolic heart failure without CA, there are few data examining the utility of BiV pacing in patients with CA. With the advent of effective treatments for AL and ATTR, appropriate application of pacing is important to support patients with CA and conduction disease through therapeutic trials. This systematic review summarizes the current literature examining the utility of pacing in CA.

Initiation and termination of reentry-like activity in rat cardiomyocytes cultured in a microelectrode array.

Cardiac reentry is a lethal arrhythmia associated with cardiac diseases. Although arrhythmias are reported to be due to localized propagation abnormalities, little is known about the mechanisms underlying the initiation and termination of reentry. This is primarily because of a lack of an appropriate experimental system in which activity pattern switches between reentry and normal beating can be investigated. In this study, we aimed to develop a culture system for measuring the spatial dynamics of reentry-like activity during its onset and termination. Rat cardiomyocytes were seeded in microelectrode arrays and purified with a glucose-free culture medium to generate a culture with a heterogeneous cell density. Reentry-like activity was recorded in purified cardiomyocytes, but not in the controls. Reentry-like activity occurred by a unidirectional conduction block after shortening of the inter-beat interval. Furthermore, reentry-like activity was terminated after propagation with a conduction delay of less than 300 ms, irrespective of whether the propagation pattern changed or not. These results indicate that a simple purification process is sufficient to induce reentry-like activity. In the future, a more detailed evaluation of spatial dynamics will contribute to the development of effective treatment methods.

Segment Length in Cine Strain Analysis Predicts Cardiac Resynchronization Therapy Outcome Beyond Current Guidelines.

BACKGROUND: Patients with a class I recommendation for cardiac resynchronization therapy (CRT) are likely to benefit, but the effect of CRT in class II patients is more heterogeneous and additional selection parameters are needed in this group. The recently validated segment length in cine strain analysis of the septum (SLICE-ESSsep) measurement on cardiac magnetic resonance cine imaging predicts left ventricular functional recovery after CRT but its prognostic value is unknown. This study sought to evaluate the prognostic value of SLICE-ESSsep for clinical outcome after CRT. METHODS: Two hundred eighteen patients with a left bundle branch block or intraventricular conduction delay and a class I or class II indication for CRT who underwent preimplantation cardiovascular magnetic resonance examination were enrolled. SLICE-ESSsep was manually measured on standard cardiovascular magnetic resonance cine imaging. The primary combined end point was all-cause mortality, left ventricular assist device, or heart transplantation. Secondary end points were (1) appropriate implantable cardioverter defibrillator therapy and (2) heart failure hospitalization. RESULTS: Two-thirds (65%) of patients had a positive SLICE-ESSsep ≥0.9% (ie, systolic septal stretching). During a median follow-up of 3.8 years, 66 (30%) patients reached the primary end point. Patients with positive SLICE-ESSsep were at lower risk to reach the primary end point (hazard ratio 0.36; P<0.001) and heart failure hospitalization (hazard ratio 0.41; P=0.019), but not for implantable cardioverter defibrillator therapy (hazard ratio, 0.66; P=0.272). Clinical outcome of class II patients with a positive ESSsep was similar to those of class I patients (hazard ratio, 1.38 [95% CI, 0.66-2.88]; P=0.396). CONCLUSIONS: Strain assessment of the septum (SLICE-ESSsep) provides a prognostic measure for clinical outcome after CRT. Detection of a positive SLICE-ESSsep in patients with a class II indication predicts improved CRT outcome similar to those with a class I indication whereas SLICE-ESSsep negative patients have poor prognosis after CRT implantation.

Propagation Vectors Facilitate Differentiation Between Conduction Block, Slow Conduction, and Wavefront Collision.

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Anodal stimulation in pediatric patients with permanent epicardial ventricular pacemakers.

OBJECTIVES: We aimed to measure the frequency and factors associated with anodal stimulation in a pediatric population with epicardial pacing leads. BACKGROUND: In bipolar pacemakers, capture of the myocardium typically occurs at the cathode. However, AS with capture at the anode has been described. This has not been described in epicardial pacemakers. METHODS: Retrospective data were collected from patients ≤ 21 years of age with permanent bipolar epicardial ventricular pacemakers from 1/2017 to 1/2018. AS was defined as a clear change on surface ECG in at least one of the 12 leads assessed by two blinded pediatric electrophysiologists. RESULTS: Twenty-four bipolar leads in 23 patients were included in the study. One patient had both biventricular leads tested. Median age was 7.1 years (IQR 5.0-10.9), weight was 20.9 kg (IQR 16.5-33.5), and 65% were male. Testing was performed at a median of 2.8 years (IQR 1.6-6.1) after implant. Congenital heart disease was present in 57%. Complete heart block was the pacemaker indication in 78%. AS was identified in 16/24 (67%) of leads tested. Identification of AS was associated with presence of congenital heart disease (p = 0.004) and 3DD between electrodes (p = 0.04). CONCLUSIONS: AS is common in pediatric patients and was associated with a history of congenital heart disease and greater estimated 3DD between electrodes. The prevalent nature of AS may allow clinicians to utilize existing pacemakers as multisite pacing systems.

Clinical symptoms of limited exercise capacity linked to AAI-DDD functionality: An in silico and in vivo approach.

BACKGROUND: Exercise capacity is an important aspect of quality of life in patients undergoing pacemaker implantation. Device algorithms for ventricular pacing avoidance have been developed to avoid unnecessary and potentially harmful effects of right ventricular pacing. However, little data exists on the immediate response of these algorithms to sudden AV block during exercise. METHODS: The ventricular pacing avoidance algorithms of four pacemaker manufacturers were tested in an ex-vivo model. The RSIM-1500-USB Device-Interactive Heart Simulator (Rivertek Medical Systems, Inc.) was used to simulate three different scenarios: the first one starting with an initially conducted atrial pacing rate of 60 min-1 , the second one starting with an atrial rate of 120 min-1 and finally a scenario starting with an atrial rate of 150 min-1 . In all three scenarios, the initially conducted atrial rate was followed by a sudden, long lasting episode of third-degree AV-block. The response to those scenarios was recorded for each of the (brand-specific) ventricular pacing avoidance algorithms. RESULTS: In the first scenario, the simulation resulted in a ventricular pause of 1333 ms (Boston Scientific), 2000 ms (Medtronic and Microport), and 2340 ms (Biotronik). In the second and third scenario, different results were observed across devices. All simulations of the second and third scenario resulted in repetitive 2:1 block response (during eight cycles) in Boston Scientific and Biotronik devices. These scenarios were confirmed in patient cases. CONCLUSION: Simulator based observations of unanticipated pacemaker-induced 2:1 block response during exercise may explain clinical symptoms experienced by some patients having a two-chamber pacemaker.

Insights into sinus arrhythmia of the dog: Acetylcholine perfusion of canine right atrium results in beat-to-beat patterns that mimic sinus arrhythmia supporting exit block in the sinoatrial conduction pathways.

Sinus arrhythmia of the dog is unique because of the pronounced alternating beat-to-beat intervals. The clustering of these short (faster rates) and long (slower rates) intervals is not just influenced by autonomic input from breathing; sinus arrhythmia can persist in the panting or apneic dog. The multiplicity of central and peripheral influences on the sinus node complicates the unraveling of the mechanisms of sinus arrhythmia. Studies of the sinus node suggest that acetylcholine can slow cellular depolarization and block sinoatrial conduction. Electrocardiographic monitoring of the dog supports this notion in that abrupt bifurcation into short and long intervals develop at lower heart rates. We sought to determine whether this phenomenon could be recapitulated in canine atrial preparations perfused with acetylcholine and whether selective pharmacologic blockade of the voltage and calcium clocks could provide insight into its mechanism. Spontaneous beat to beat (A-A) intervals were obtained from monophasic action potential recordings of perfused canine right atrial preparations before and during perfusion with acetylcholine (2-5 µM). The calcium clock was blocked with ryanodine (2-3 µM). The membrane clock was blocked with diltiazem hydrochloride (ICa,L blocker; 0.25 µM) and ZD7288 (If blocker; 3 µM). Hyperpolarization was hindered by blockade of IK,Ado/IK,Ach with tertiapin Q (100 nM) before and during acetylcholine perfusion. Acetylcholine resulted in beat clusters similar to those seen in sinus arrhythmia of the dog. Beat clusters were consistent with intermittent 2:1 and 3:1 sinoatrial conduction block. Tertiapin Q abolished this patterning suggesting a role of IK,Ado/IK,ACh in the mechanism of these acetylcholine-induced beat-to-beat patterns.

Cardiogenic shock with first-degree heart block in a patient with glyphosate-surfactant poisoning.

Glyphosate is a commonly used non-selective herbicide in agriculture and aquafarms. Gastrointestinal, respiratory and cardiovascular symptoms are predominant manifestations of glyphosate poisoning. Cardiac dysfunction should be kept as a possibility in patients presenting with shock, and the treatment is mainly supportive. We present such a case.

Factors associated with implantable cardioverter defibrillators appropriate therapy in cardiac sarcoidosis: a meta-analysis.

BACKGROUND: Patients with cardiac sarcoidosis (CS) are at increased risk of atrioventricular blocks, ventricular arrhythmias, and sudden cardiac death. Objectives We aimed to investigate the characteristics associated with appropriate therapy in implantable cardiac defibrillator (ICD) -implanted CS patients. METHODS: We performed a PubMed and Web of Science search for studies reporting patients with CS who underwent an ICD implantation. The primary criterion was an appropriate therapy. RESULTS: We screened 705 studies, of which 5 were included in the final analysis. We conducted a meta-analysis including 464 patients (mean age 55 years, 282 males (60%)). The mean follow-up was 3.5 years. Among the 464 patients, 180 received an appropriate therapy (39%). Patients who received an appropriate therapy were younger (-3.33, 95% confidence interval (CI) -6.42 to -0.23, p=0.004), were more likely to be male (OR 2.06, 95% CI 1.37-3.09, p=0.0005), had a lower left ventricular ejection fraction (LVEF) (-10.5, 95% CI -18.23 to -2.78, p=0.008), had a higher rate of complete heart block (OR 2.19, 95% CI 1.20 to 3.99, p=0.01), and more frequently had ventricular pacing (OR 6.44 95% CI 2.57 to 16.16, p<0.0001). CONCLUSIONS: Appropriate ICD therapy during CS is associated with young age, male sex, low LVEF, history of complete heart block, and ventricular pacing. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 17-23).

Electrocardiographic QT Intervals in Infants Exposed to Hydroxychloroquine Throughout Gestation.

BACKGROUND: Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine is being considered as prophylaxis and treatment of coronavirus disease-19 (COVID-19). Although hydroxychloroquine is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematosus and other rheumatic conditions, there may still be reluctance to institute this antimalarial during pregnancy for the sole purpose of antiviral therapy. METHODS: To provide data regarding any potential fetal/neonatal cardiotoxicity, we leveraged a unique opportunity in which neonatal ECGs and hydroxychloroquine blood levels were available in a recently completed study evaluating the efficacy of hydroxychloroquine 400 mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro (anti-Sjögren's Syndrome A/Ro) antibodies. RESULTS: Forty-five ECGs were available for corrected QT interval (QTc) measurement, and levels of hydroxychloroquine were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of hydroxychloroquine and the neonatal QTc (R=0.02, P=0.86) or the mean of hydroxychloroquine values obtained throughout each individual pregnancy and the QTc (R=0.04, P=0.80). In total 5 (11% [95% CI, 4%-24%]) neonates had prolongation of the QTc >2 SD above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal. CONCLUSIONS: In aggregate, these data provide reassurances that the maternal use of hydroxychloroquine is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01379573.

Right ventricular septal pacing via transmural approach for resynchronization in a child with postoperative heart block.

An infant with transposition of the great arteries was paced for postoperative heart block (single-site, right ventricular [RV] epicardial). She developed severe left ventricular (LV) dysfunction and septal dyskinesis. Resynchronization was performed at the age of 4 with an LV epicardial lead and an RV septal endocardial lead. The endocardial lead was affixed to the interventricular septum, then tunneled through the RV free wall and attached to an abdominal pulse generator. QRS duration decreased (176 to 122 ms) and LV ejection fraction improved (26 to 61%) and remained stable for 8 years. We present a case of successful resynchronization in congenital heart disease using a transmural RV septal lead.

Congenital complete heart block in the setting of severe pre-eclampsia requiring urgent cesarean section.

Congenital complete heart block is a rare phenomenon that may be discovered during pregnancy in patients who were previously asymptomatic. Peripartum management of these patients mandates a multidisciplinary approach with careful planning regarding indications for pacing, appropriate anesthetic technique, and contingency planning. Approaches to anesthetic management for congenital complete heart block have been described, but management in association with severe pre-eclampsia has not been reported. We describe the anesthetic management of a parturient with complete heart block who presented with severe pre-eclampsia requiring urgent cesarean section.

Simultaneous Endo-Epicardial Mapping of the Human Right Atrium: Unraveling Atrial Excitation.

Background The significance of endo-epicardial asynchrony (EEA) and atrial conduction block (CB), which play an important role in the pathophysiology of atrial fibrillation (AF) during sinus rhythm is poorly understood. The aim of our study was therefore to examine 3-dimensional activation of the human right atrium (RA). Methods and Results Eighty patients (79% men, 39% history of AF) underwent simultaneous endo-epicardial sinus rhythm mapping of the inferior, middle and superior RA. Areas of CB were defined as conduction delays of ≥12 ms, EEA as activation time differences of opposite electrodes of ≥15 ms and transmural CB as CB at similar endo-epicardial sites. CB was more pronounced at the endocardium (all locations P<0.025). Amount, extensiveness and severity of CB was higher at the superior RA. Transmural CB at the inferior RA was associated with a higher incidence of post-operative AF (P=0.03). EEA occurred up to 84 ms and was more pronounced at the superior RA (superior: 27 ms [interquartile range, 18.3-39.3], versus mid-RA: 20.3 ms [interquartile range, 0-29.9], and inferior RA: 0 ms [interquartile range, 0-21], P<0.001). Hypertension (P=0.009), diabetes mellitus (P=0.018), and hypercholesterolemia (P=0.015) were associated with a higher degree of EEA. CB (P=0.007) and EEA (P=0.037) were more pronounced in patients with a history of persistent AF compared with patients without AF history. Conclusions This study provides important insights into complex atrial endo-epicardial excitation. Significant differences in conduction disorders between the endo- and epicardium and a significant degree of EEA are already present during sinus rhythm and are more pronounced in patients with cardiovascular risk factors or a history of persistent AF.