Transient 2:1 Atrioventricular Block with Peri-Conduction System Pacing After Leadless Pacemaker Implantation.

This report discusses a case of transient 2:1 atrioventricular block with conduction system pacing 4 hours after leadless right ventricular pacemaker implantation in a 19-year-old patient with a history of cardioinhibitory syncope and asystole cardiac arrest but without preexisting atrioventricular block. The atrioventricular block was resolved spontaneously. Pacing morphology was suggestive of right bundle branch pacing. Neither 2:1 atrioventricular block nor conduction system pacing has previously been a reported outcome of right ventricular leadless pacemaker implantation. The report demonstrates that conduction system pacing with leadless devices is achievable. Further study of techniques, limitations, and complications related to intentional right ventricular leadless conduction system pacing is warranted.

Understanding yellow fever-associated myocardial injury: an autopsy study.

BACKGROUND: Yellow fever (YF) is a viral hemorrhagic fever, endemic in parts of South America and Africa. There is scarce evidence about the pathogenesis of the myocardial injury. The objective of this study is to evaluate the cardiac pathology in fatal cases of YF. METHODS: This retrospective autopsy study included cases from the São Paulo (Brazil) epidemic of 2017-2019. We reviewed medical records and performed cardiac tissue histopathological evaluation, electron microscopy, immunohistochemical assays, RT-qPCR for YF virus (YFV)-RNA, and proteomics analysis on inflammatory and endothelial biomarkers. FINDINGS: Seventy-three confirmed YF cases with a median age of 48 (34-60) years were included. We observed myocardial fibrosis in 68 (93.2%) patients; cardiomyocyte hypertrophy in 68 (93.2%); endothelial alterations in 67 (91.8%); fiber necrosis in 50 (68.5%); viral myocarditis in 9 (12.3%); and secondary myocarditis in 5 (6.8%). Four out of five patients with 17DD vaccine-associated viscerotropic disease presented with myocarditis. The cardiac conduction system showed edema, hemorrhages and endothelial fibrinoid necrosis. Immunohistochemistry detected CD68-positive inflammatory interstitial cells and YFV antigens in endothelial and inflammatory cells. YFV-RNA was detected positive in 95.7% of the cardiac samples. The proteomics analysis demonstrated that YF patients had higher levels of multiple inflammatory and endothelial biomarkers in comparison to cardiovascular controls, and higher levels of interferon gamma-induced protein 10 (IP-10) in comparison to sepsis (p = 0.01) and cardiovascular controls (p < 0.001) in Dunn test. INTERPRETATION: Myocardial injury is frequent in severe YF, due to multifactorial mechanisms, including direct YFV-mediated damage, endothelial cell injury, and inflammatory response, with a possible prominent role for IP-10. FUNDING: This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo, Bill and Melinda Gates Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

Extracellular Perinexal Separation Is a Principal Determinant of Cardiac Conduction.

BACKGROUND: Cardiac conduction is understood to occur through gap junctions. Recent evidence supports ephaptic coupling as another mechanism of electrical communication in the heart. Conduction via gap junctions predicts a direct relationship between conduction velocity (CV) and bulk extracellular resistance. By contrast, ephaptic theory is premised on the existence of a biphasic relationship between CV and the volume of specialized extracellular clefts within intercalated discs such as the perinexus. Our objective was to determine the relationship between ventricular CV and structural changes to micro- and nanoscale extracellular spaces. METHODS: Conduction and Cx43 (connexin43) protein expression were quantified from optically mapped guinea pig whole-heart preparations perfused with the osmotic agents albumin, mannitol, dextran 70 kDa, or dextran 2 MDa. Peak sodium current was quantified in isolated guinea pig ventricular myocytes. Extracellular resistance was quantified by impedance spectroscopy. Intercellular communication was assessed in a heterologous expression system with fluorescence recovery after photobleaching. Perinexal width was quantified from transmission electron micrographs. RESULTS: CV primarily in the transverse direction of propagation was significantly reduced by mannitol and increased by albumin and both dextrans. The combination of albumin and dextran 70 kDa decreased CV relative to albumin alone. Extracellular resistance was reduced by mannitol, unchanged by albumin, and increased by both dextrans. Cx43 expression and conductance and peak sodium currents were not significantly altered by the osmotic agents. In response to osmotic agents, perinexal width, in order of narrowest to widest, was albumin with dextran 70 kDa; albumin or dextran 2 MDa; dextran 70 kDa or no osmotic agent, and mannitol. When compared in the same order, CV was biphasically related to perinexal width. CONCLUSIONS: Cardiac conduction does not correlate with extracellular resistance but is biphasically related to perinexal separation, providing evidence that the relationship between CV and extracellular volume is determined by ephaptic mechanisms under conditions of normal gap junctional coupling.

Atrial fibrillation activation patterns predict freedom from arrhythmias after catheter ablation: utility of ExTRa mapping™.

Background: Mechanisms underlying atrial fibrillation (AF) are widely complex and vary tremendously among individuals. Objectives: This retrospective study aimed to investigate the association between AF activation patterns and clinical outcomes post-ablation. Methods: Fifty-five AF patients (64.0 ± 12.9 years; 41 men; 17 paroxysmal) underwent bi-atrial endocardial driver mapping during AF pre-ablation with a real-time phase mapping system (ExTRa Mapping). The nonpassively activated ratio (%NP) of meandering rotors and multiple wavelets relative to the recording time was evaluated in 26 atrial segments [15 in the left atrium (LA) and 11 in the right atrium]. Irrespective of the mapping results, all patients underwent standard AF ablation via cryoballoons and/or radiofrequency catheters. Results: In a median follow-up interval of 27(14-30) months, 69.1% of patients were free from recurrent arrhythmias and antiarrhythmic drugs at one year post-procedure. Patients with recurrent AF were more likely to have non-paroxysmal AF, a significantly larger LA size, and higher LA maximal %NP(LAmax%NP) and LA anterior wall %NP(LAAW%NP) than those without recurrent AF. A multivariate Cox regression analysis showed that both an LAmax%NP (hazard ratio [HR] = 1.075; 95% confidence interval [CI] = 1.02-1.14, p = 0.012) and LAAW%NP (HR = 1.061; 95% CI = 1.01-1.11, p = 0.013) were independent predictors of atrial arrhythmia recurrence. The optimal cutoff points for the LAmax%NP and LAAW%NP for predicting AF recurrence were 64.5% and 60.0%, respectively. A Kaplan-Meier analysis demonstrated that both an LAmax%NP > 64.5% (p = 0.0062) and LAAW%NP > 60.0% (p = 0.014) were associated with more frequent AF recurrences. Conclusion: Baseline AF activation pattern mapping may aid in predicting freedom from arrhythmias after standard AF ablation procedures.

Método rápido para determinar el eje cardíaco con D1 y D3 / Fast method to determine the cardiac axis with D1 and D3

El eje cardíaco representa el promedio de la dirección del proceso de activación eléctrica de las células cardíacas, es uno de los parámetros que debe determinarse en la correcta lectura e interpretación del electrocardiograma y es útil no solo como criterio diagnóstico de cardiopatías, sino también como marcador de pronóstico y mortalidad de otras enfermedades. Con el paso de los años han surgido nuevas fórmulas que permiten calcular con mayor exactitud su valor. El método que utiliza D1 y aVF es uno de los más populares, sin embargo, presenta dos puntos no medibles. El primero es entre 0 y -30 grados, y el segundo entre los valores de 90 y 110 grados. Aunque existen propuestas con algoritmos que utilizan otras derivaciones, se exploró un método alternativo con D1 y D3 basados en la fórmula algebraica de la tangente inversa y método matemático para el cálculo exacto del eje cardíaco. Se destaca este como una propuesta de método rápido que mantiene la confiabilidad de la fórmula algebraica para determinar si el eje cardíaco se encuentra dentro de los rangos normales (-30 a 110 grados)

The cardiac axis represents the average of the direction of the electrical activation process of the cardiac cells. It is one of the parameters determined in the correct reading and interpretation of the electrocardiogram. Also, not only is it useful as a diagnostic criterion for heart disease but also as a marker of prognosis and mortality in other diseases. Over the years, new formulas have emerged that allow its value to be calculated more accurately. The method using D1 and aVF is one of the most popular. However, it has two unmeasurable points. The first is between 0 and -30 degrees, and the second is between the values of 90 and 110 degrees. Although there are proposals with algorithms that use other leads, an alternative method was explored with D1 and D3 based on the algebraic formula of the inverse tangent and mathematical method for the exact calculation of the cardiac axis. A quick method is proposed that maintains the reliability of the algebraic formula to determine if the cardiac axis is within the normal ranges (-30 to 110 degrees)

Heinrich Ewald Hering's discovery of the heart pacemaker: Hering, Tawara and Aschoff's search for its morphological basis, the sinoatrial node, and why they failed.

Two groups of investigators investigated the heart pacemaker and its morphological basis in the early twentieth century. The first group was formed by Henrich Ewald Hering (physiologist), Sunao Tawara and Ludwig Aschoff (morphologists). The second group was composed of James Mackenzie (general practitioner and clinical investigator), Arthur Keith and Martin Flack (morphologists). These groups were formed almost at the same time in 1903. Their work resulted in the discovery of the atrioventricular node and Purkinje network (Sunao Tawara, in 1906), heart pacemaker (H E Hering, in 1907) and sinoatrial node (Keith and Flack, in 1907). Here, it is shown how the interconnections of the concurrent works of these groups resulted in the discovery not only of the function, but also of the structure of the sinoatrial node.

Lack of evidence for longitudinal dissociation of the atrioventricular conduction axis.

Longitudinal dissociation of the aggregated specialized cardiomyocytes within the non-branching portion of atrioventricular conduction axis has proved a controversial topic for both morphologists and electrophysiologists. We have now used morphological methods, including three-dimensional assessment, to revisit, in human, canine, and bovine hearts, the presence or absence of interconnections between the aggregated cardiomyocytes making up the non-branching bundle. We analyzed three datasets from human and canine hearts, and two from bovine hearts, using longitudinal and orthogonal serial histological sections. In addition, we assessed three hearts using translucent India ink injected specimens, permitting assessment of the three-dimensional arrangement of the cardiomyocytes. Using the longitudinal sections, we found numerous oblique interconnections between the groups of specialized cardiomyocytes. When assessing orthogonal sections, we noted marked variation in the grouping of the cardiomyocytes. We interpreted this finding as evidence of bifurcation and convergence of the groups seen in the longitudinal sections. The three-dimensional assessment of the bovine material confirmed the presence of the numerous interconnections. The presence of multiple connections between the cardiomyocytes in the non-branching bundle rules out the potential for longitudinal dissociation.

The effect of insulin resistance on the heart rate recovery in healthy individuals with a low-to-moderate cardiovascular disease risk profile.

The association between insulin resistance (IR) and heart rate recovery index (HRRI) has been reported previously, but the cardiovascular disease (CVD) risk profile of the subjects was unclear in these studies. Therefore, we evaluated the association between IR and HRRI in apparently healthy individuals without metabolic syndrome who had a low-to-moderate CVD risk profile. A total of 182 eligible subjects were retrospectively included in the study. The subjects were divided into two groups according to the homeostasis model assessment of IR (HOMA-IR) value. HOMA-IR ≥2.5 was defined as IR (+) group (92 subjects), and <2.5 as IR (-) group (88 subjects). HRRI-2 was found by subtracting the heart rate at the second minute in the post-exercise recovery period from the maximum heart rate. Abnormal HRRI was defined as HRRI-2 that is ≤42 beats. The mean age of the patients was 41.91 ± 8.64 and 49.4% of them were female. Abnormal HRRI rates were significantly higher in the IR (+) group (37.2% vs 18.2%; p = 0.004). A negative correlation was detected between HRRI-2 and HOMA-IR (r = -0.416; p < 0.001). HOMA-IR (Odds Ratio (OR) = 1.57; confidence interval (CI) = 1.10-2.23; p = 0.013) and maximum heart rate during exercise (OR = 0.95; CI = 0.91-0.99; p = 0.013) as independent variables of abnormal HRRI. The HOMA-IR value of 2.82 was identified as an effective cutoff point for the prediction of abnormal HRRI (area under the curve: 0.658; CI: 0.570-0.746; p = 0.001). In this study, it was shown that IR without metabolic syndrome reduces HRRI in healthy individuals with a low-to-moderate CVD risk profile.

Dynamical behavior analysis of the heart system by the bifurcation structures.

The functioning of the heart rhythm can exhibit a wide variety of dynamic behaviours under certain conditions. In the case of rhythm disorders or cardiac arrhythmias, the natural rhythm of the heart is usually involved in the sinoatrial node, the atrioventricular node, the atria of the carotid sinus, etc. The study of heart related disorders requires an important analysis of its rhythm because the regularity of cardiac activity is conditioned by a large number of factors. The cardiac system is made up of a combination of nodes ranging from the sinus node, the atrioventricular node to its Purkinje bundles, which interact with each other via communicative aspects. Due to the nature of their respective dynamics, the above are treated as self-oscillating elements and modelled by nonlinear oscillators. By modelling the cardiac conduction system as a model of three nonlinear oscillators coupled by delayed connections and subjected to external stimuli depicting the behavior of a pacemaker, its dynamic behavior is studied in this paper by nonlinear analysis tools. From an electrocardiogram (ECG) assessment, the heart rhythm reveals normal and pathological rhythms. Three forms of ventricular fibrillation, ventricular flutter, ventricular tachycardia and atrial fibrillation are observed. The results are confirmed by the respective maximum Lyapunov exponents. Considering the cardiac nodes as microchips, using microcontroller simulation technology, the cardiac conduction system was modelled as a network of four ATmega 328P microcontrollers. A similarity with the results obtained numerically can be observed.

Pseudo superior vena cava entrance block during sinus rhythm uncovered by continuous atrial pacing.

Usually, superior vena cava (SVC) entrance block is confirmed when SVC potentials disappear during sinus rhythm. We present a case of pseudo SVC entrance block during sinus rhythm, which was uncovered by continuous atrial pacing.

Incidence, predictors and prognostic value of permanent pacemaker implantation following sutureless valve implantation in low-risk aortic stenosis patients.

OBJECTIVES: Sutureless aortic valve replacement (SU-SAVR) has been associated with higher rates of permanent pacemaker (PPM) compared with conventionally implanted aortic bioprostheses. The purpose of this study was to determine the incidence, predictors and mid-term prognostic impact of PPM after Perceval (Livanova, London, UK) SU-SAVR in low-risk patients. METHODS: A total of 400 consecutive low-risk (EuroSCORE II < 4%) patients without prior pacemaker who underwent surgical aortic valve replacement with the Perceval prosthesis from 2013 to 2019 in 2 centres were included. Baseline, clinical and electrocardiographic parameters, procedural characteristics and follow-up data were collected. RESULTS: PPM was required in 36 (9%) patients after SU-SAVR, with a median time between the procedure and PPM implantation of 7.5 (4.5-10.5) days. Older age and prior right bundle branch block (RBBB) were associated with an increased risk of PPM (P < 0.05 for all), but only baseline RBBB was found to be an independent predictor of new PPM requirement (odds ratio: 2.60, 95% confidence interval: 1.15-5.81; P = 0.022). At a median follow-up of 3.4 (2.3-4.5) years, there were no differences between groups in mortality (PPM: 36%, no PPM: 22%, P = 0.105) or heart failure rehospitalization (PPM: 25%, no PPM: 21%, P = 0.839). CONCLUSIONS: About 1 out of 10 low-risk patients with aortic stenosis undergoing SU-SAVR with the Perceval prosthesis required PPM implantation. Prior RBBB determined an increased risk (close to 3-fold) of PPM following the procedure. PPM was not associated with a higher risk of clinical events at 3-year follow-up.

The atrioventricular conduction axis and the aortic root-Inferences for transcatheter replacement of the aortic valve.

Conduction problems still occur following transcatheter aortic valvar replacement. With this in mind, we have assessed the relationship of the conduction axis to the aortic root. We used serial histological sections, made perpendicular to the base of the triangle of Koch in nine hearts, and perpendicular to the aortic root in 11 hearts. We first defined the extent of the fibrous tissues forming the boundaries of an infero-septal recess of the subaortic outflow tract, found in all datasets but one. When the recess was present, the axis penetrated through its rightward wall, giving rise to the left bundle branch prior to entering the outflow tract. The axis itself was usually on the crest of the ventricular septum, but could be deviated leftward or rightward. Its proximity to the virtual basal plane reflected the angulation of the muscular septum. On average, the superior edge of the left bundle was within 3.3 mm of the hinge of the right coronary leaflet, with a range from 0.4 to 10.2 mm. The arrangement was markedly different in the case lacking an infero-septal recess. Our findings necessitated a redefinition of the right fibrous trigone and the central fibrous body. The atrioventricular conduction axis, having entered the aortic root, is usually closest at the hinge of the right coronary leaflet. Knowledge of the depth of the infero-septal recess, and the angulation of the muscular ventricular septal, may help to avoid conduction problems following transcatheter implantation of the aortic valve.

Flecainide-Induced Atrial Flutter With 1:1 Conduction Complicated by Ventricular Fibrillation After Electrical Cardioversion.

Flecainide, a widely prescribed class IC agent used to treat atrial arrhythmias, can in rare cases cause 1:1 atrial flutter with rapid conduction. We describe the case of a 59-year-old man who was on a maintenance regimen of flecainide for refractory atrial fibrillation. When 1:1 atrial flutter with rapid conduction developed, emergency medical technicians attempted synchronized cardioversion, which caused ventricular fibrillation necessitating defibrillation. The patient ultimately underwent radiofrequency ablation and cryoablation to resolve his symptomatic atrial flutter. We discuss the atrial proarrhythmic effects of flecainide and how to mitigate complications in high-risk patients.

Assessment of Structure, Function, and Rhythm of the Heart with Echocardiography and Electrocardiography in Adolescent Swimmers.

The aim of this study was to evaluate the cardiac parameters by using electrocardiography and echocardiography in adolescent swimmers. Twenty-two adolescent swimmers and 22 gender- and age-matched sedentary controls admitted to our center between November 2018 and May 2019 were included in this study. In addition to demographical characteristics, participants were assessed via a 12-lead electrocardiography and two-dimensional echocardiography for cardiac function. On the echocardiography, end-systolic and end-diastolic interventricular septum, end-systolic and end-diastolic left ventricular posterior wall thicknesses, left atrial width, Tricuspid E, left ventricular mass and left ventricular mass index were higher in the swimmers when compared to the sedentary controls (P < 0.05). On the electrocardiography, Tp-e duration which reflects ventricular transmural repolarization, and Tp-e/QT and Tp-e/corrected QT ratios were higher in the swimmers than the sedentary controls (P < 0.05). In conclusion, swimming exercise in children leads to concentric thickening of left ventricle and induces an increase in Tp-e duration, and Tp-e/QT and Tp-e/corrected QT ratios, which are the novel markers for risk of ventricular arrhythmias.

Conduction Disorders: The Value of Surface ECG.

PURPOSE OF REVIEW: The purpose of the current mini-review is to describe the importance of surface ECG for the diagnosis of conduction disorder. METHODS: The MEDLINE/PubMed database was used, with the keywords "ECG" and "conduction disorders"; over the past 10 years. Other documents were included because of their relevance. MAIN FINDINGS: Data on the anatomy and function of the cardiac electrical system have been described. Conduction disorders including sinus node dysfunction, atrioventricular blocks, intraventricular conduction disorders are exposed as to their epidemiology, etiology, presentation, anatomical site of impaired conduction of the electrical stimulus. The importance of ECG in patients with a cardiac implantable electronic device was also discussed, in addition to future perspectives. CONCLUSION: Surface ECG allows the diagnosis of atrioventricular and intraventricular conduction disorder and its anatomical block site most of the time, without the need for invasive tests such as electrophysiological study. Dysfunctions of cardiac implantable electronic devices can be diagnosed by ECG, as well as the prediction of response to cardiac resynchronization therapy.

Sunao Tawara : further musings on his tribulations in providing the basis for the modern-day understanding of cardiac electrophysiology.

Sunao Tawara, who was born in 1873 and died in 1952, is considered the father of modern cardiac electrophysiology. He published his monumental monograph describing the atrioventricular conduction axis in 1906. He achieved this task in the face of multiple tribulations as a doctoral student working in a cultural environment that was not his own. Although his letters underscoring the publication of the monograph have been published, little emphasis has been placed on the potential problems he encountered in bringing his task to fruition. For example, it was not until the final 6 months of his studies that he resolved the issue of the connection between the atrioventricular bundle and the so called "Purkinje cardiomyocytes". His exchanges with his mentor, Ludwig Aschoff, emphasized that the difficulties he encountered in making the connection caused him quite some turmoil. We believe that this issue, and others that he identified in his correspondence, are worthy of further attention.

Visualization of left ventricular Purkinje fiber distribution using widefield optical coherence microscopy.

BACKGROUND: The distribution and connection of ventricular Purkinje fibers are known to be associated with idiopathic left ventricular arrhythmias. Unusual anatomy is one of the important factors associated with catheter ablation success rate. With the widefield high-speed, swept-source optical coherence microscopy (OCM) and light microscope, we visualized the left ventricular Purkinje fiber distribution. METHODS: Left ventricular walls of five adult ovine hearts were incised from the mitral annulus to the apex. Using the widefield OCM technique and light microscopy, we observed the distribution, direction, depth, and dividing patterns of the Purkinje network with multiple tangential angles and without tissue destruction. RESULTS: Widefield OCM was used to characterize the ovine heart Purkinje network system in a 4 × 4 mm2 field. Left ventricular Purkinje fibers traveled in the sub-endocardial area near the left-sided peri-membranous septal area and ran like a wide hair bundle. The distal branching fibers penetrated to the endocardium and connected to the contractile muscle. In this distal area, Purkinje fibers were connected to each other, forming multiple layers. Some Purkinje fibers were directly connected within the false tendon between the papillary muscles or between the trabeculations. Some free-running Purkinje fibers were directly connected to the papillary muscle from the left bundle. CONCLUSION: Using widefield OCM, we were able to observe the left bundle and its branching patterns in ovine left ventricle without tissue destruction. This might be applied to future cardiac ablation procedures.