Alternating Early Afterdepolarizations Underlying Bradycardia-Dependent Macroscopic T Wave and Discordant Mechanical Alternans.

BACKGROUND: Macroscopic T wave alternans (macro-TWA) often heralds the onset of Torsades de Pointes in patients with QT prolongation. However, the mechanisms underlying macro-TWA remain unclear. We examined the cellular and ionic basis for macro-TWA in rabbits with left ventricular hypertrophy (LVH). METHODS: The renovascular hypertension model was used to induce LVH in rabbits. Action potentials were simultaneously recorded from epicardium and endocardium together with a transmural ECG and isometric contractility in arterially perfused left ventricular wedges. Late sodium current (INa-L) was recorded in single-isolated left ventricular myocytes with the whole cell patch-clamp technique. RESULTS: Macro-TWA and accompanied mechanical alternans occurred spontaneously in 8 of 33 LVH rabbits (P<0.05, versus 0/15 in controls) and were induced by an INa-L enhancer ATX-II at 1 to 3 nM in additional 7. Macro-TWA and mechanical alternans occurred discordantly, that is, that longer QT interval and larger T wave were associated with weaker isometric contvractility. Alternating early afterdepolarizations in the endocardium caused macro-TWA in 12 of 15 LVH rabbits and, therefore, early afterdepolarization-dependent R-from-T extrasystoles and Torsades de Pointes always originated from the beats with longer QT and larger T wave during macro-TWA. INa-L density was significantly larger in LVH myocytes than that of control myocytes. Macro-TWA, mechanical alternans, R-from-T extrasystoles, and Torsades de Pointes were all abolished by INa-L blocker ranolazine or mexiletine. CONCLUSIONS: LVH enhances INa-L density and promotes alternating early afterdepolarizations in the left ventricular endocardium that manifest as macro-TWA with discordant mechanical alternans. INa-L blockade abolishes macro-TWA, mechanical alternans, early afterdepolarization-dependent R-from-T extrasystoles, and Torsades de Pointes.

The incidence of cardiac arrhythmias during exercise stress testing: a focus on patients with severe obesity undergoing sleeve gastrectomy.

INTRODUCTION: Obesity is associated with a higher risk of cardiac arrhythmias. Sleeve gastrectomy (SG) is a common bariatric surgery with beneficial effects on weight loss and comorbidities. The study aimed to investigate the prevalence of arrhythmias during maximal exercise testing in patients with moderate-severe obesity and to evaluate the impact of SG on these arrhythmic events. METHODS: All patients with moderate or severe obesity who were considered suitable candidates for SG between June 2015 and September 2020 were recruited. Each patient underwent three incremental, maximal, ECG-monitored cardiopulmonary exercise test 1 month before and 6 and 12 months after SG; the frequency and complexity of ventricular premature beats (VPBs) and atrial premature beats (APBs) have been evaluated during rest, exercise and recovery phases. RESULTS: Fifty patients with severe obesity (BMI 46.39 ± 7.89 kg/m2) were included in the study. After SG, patients presented a decreased BMI (34.15 ± 6.25 kg/m2 at 6 months post-SG and 31.87 ± 5.99 kg/m2 at 12 months post-SG). At 6 months post-SG, an increase in VPBs, mainly during the recovery phase, was observed. At 12 months post-SG, a reduction in VPBs compared with the 6 months evaluation was showed. CONCLUSION: Although in the early post-surgical phase the risk of exercise-induced arrhythmias may be higher, SG does not seem to increase the occurrence of arrhythmias in the long-term. No life-threating arrhythmias were found during post-SG evaluations.

Cryptogenic Stroke In The Context of Pandemic-Related Stress: The Role of Arterial Hemodynamics.

BACKGROUND: Up to 45% of ischemic strokes are cryptogenic, which is an impediment to proposing preventative measures. In this investigation we aimed to study underlying heart arrhythmias in patients with cryptogenic stroke, taking into consideration the context of the COVID-19 pandemic and stressful lockdown conditions. SUBJECTS AND METHODS: In this cross-sectional study we observed 52 patients with cryptogenic stroke >1 month after acute presentation, and a control group consisting of 88 patients without stroke. All patients undewent the laboratory and instrumental investigation consisting of the following: lipid spectrum; hemostasiograms; hemoglobin A1c; transthoracic or/and transesophageal echocardiography; 24-hours monitoring of ECG; computer tomography or magnetic resonance imaging of the brain. We studied the hemodynamics of the common carotid arteries using Doppler ultrasound imaging and digital sphygmography (SG). RESULTS: The groups were indentical with respect to the preponderance of study parameters (sex, age, comorbidities, instrumental and laboratory data). The ischemic stroke group had a statistically significant difference in the prevalence of the first type of extrasystolic arrhythmia according to our gradation of extrasystoles, which are ventricular systoles of extrasystolic contraction appearing before the transmitral blood flow peak (peak E in echocardiography). We observed that earlier ventricular systoles of extrasystole in the cardiac cycle predicted for greater growth of hemodynamic and kinetic parameters. Calculating the indices of a four-field table established the significant relationship between the moment of appearance of extrasystolic ventricular contraction in the cardiac cycle and the risk for cryptogenic stroke (normalized value of the Pearson coefficient (C`) of the two paramaters was 0.318). CONCLUSIONS: Extrasystolic arrhythmia appeared as an additional risk factor of earlier stroke. The most dangerous type of arrhythmia was when the ventricular contraction of the extrasystole appeared before the transmitral blood flow peak in the cardiac cycle. This observation could present a risk-marker for brain-related cardiovascular complications such as stroke, which might be patients suffering from different internal diseases, especially in the context of environmental stress conditions of the current pandemic and its related lockdown measures.

Inferior Vena Cava as a Trigger for Paroxysmal Atrial Fibrillation: Incidence, Characteristics, and Implications.

BACKGROUND: Identifying nonpulmonary vein triggers during atrial fibrillation (AF) ablation is of great importance. Currently, there are limited data on AF triggered by the inferior vena cava (IVC). OBJECTIVES: This study was performed to investigate the incidence, characteristics, and implications of IVC triggers for AF. METHODS: A total of 661 patients who underwent initial paroxysmal AF ablation were included. After pulmonary vein isolation, ectopic beats that triggered AF were further studied. Activation mapping and angiography were performed to confirm the location of ectopic origin. Electrocardiographic analysis of the ectopic P-wave (P'-wave) was performed. RESULTS: Six patients (0.91%) with AF triggered by the IVC were confirmed. The mean distance from the earliest activation site to the IVC ostium was 6.8 ± 2.5 mm (5.2 to 11.2 mm). Furthermore, the arrhythmogenic foci within the IVC were all located at the apical hemisphere of the IVC (3 at the septal side and 3 at the anterior side). A total of 2.3 ± 0.5 applications of radiofrequency energy were delivered to eliminate IVC triggers. The mean duration of the P' wave was 91.2 ± 11.2 milliseconds (81 to 108 milliseconds), which was narrower than that of the sinus P-wave (115.2 ± 19.3 milliseconds [87 to 139 milliseconds]; P = 0.002). Moreover, the configuration of all P' waves in the inferior leads was negative. During a mean follow-up period of 25.5 ± 7.3 months, all 6 patients remained arrhythmia free without antiarrhythmic drugs. CONCLUSIONS: IVC trigger, a rare but latent source of paroxysmal AF, could be identified and safely eliminated by focal radiofrequency ablation. Ectopic beats originating from the IVC presented with narrow P'-wave duration and negative P' waves in all inferior leads.

Slow antegrade excitation and delayed retrograde activation through an "inexcitable zone": A basis for arrhythmia formation in infarcted myocardium ex vivo.

INTRODUCTION: The electrophysiologic mechanism for rate-dependent PVBs associated with double potentials (DPs) was investigated in infarcted canine hearts using bipolar and intracellular microelectrode recordings. METHODS AND RESULTS: Dogs exhibiting rate-related ventricular ectopic beats (coupling interval, 390 ± 54 milliseconds) during sinus rhythm or atrial pacing were studied 4-5 days (N = 63) or 25 days (N = 16) following anterior descending coronary artery ligation. Sites of DP and rate-dependent arrhythmia formation were identified in vivo using bipolar recordings for subsequent ex vivo studies. Rate-dependent conduction delays with increasing duration isoelectric intervals representing very slow conduction were observed at sites of DP formation, frequently provoking both manifest and concealed reentry (non-stimulated beats) over a narrow range of paced cycle lengths. Both slow antegrade and retrograde activation across an inexcitable gap (reflection) were integral components of extrasystole formation. Retrograde reflection to a region of very slow conduction (mid-potential) during antegrade activation was routinely observed at 4-5 days (42 of 63 preparations, 67%) and 25 days (22 of 26 preparations, 85%) postcoronary artery ligation. Reflection and premature re-activation of the proximal site was then observed in 6 of 63 (9%), and 3 of 26 preparations (12%). CONCLUSION: The present experiments demonstrate DP formation and rate-dependent constant-coupled late epicardial premature beats in infarcted dog hearts. Microelectrode recordings at DP sites demonstrating prolonged isoelectric intervals display very slow conduction preceding distal activation and "reentrant" re-activation of more proximal sites, representing reflection as an arrhythmia mechanism in ischemically injured epicardium during subacute myocardial infarction.

Different Impacts of Atrial Fibrillation and Cardiac Premature Contractions on the Health-Related Quality of Life in Elderly People: The Yilan Study.

Atrial fibrillation (AF) is currently recognized as one of the most common cardiac arrhythmias worldwide, with the increasing prevalence that has been estimated to be as high as 9% among the elderly. Health-related quality of life (HRQoL) has become an important patient-centered health outcome measurement, but the impacts created by AF and other arrhythmias with similar symptoms, such as frequent atrial and ventricular premature contractions (APCs and VPCs, defined as ≥ 3 beats/5 minutes), have not been extensively evaluated. The Yilan Study is a population-based community health survey, which in part aims to evaluate the prevalence and impacts of these arrhythmias on the HRQoL in a community dwelling elderly population. A total of 1,732 citizens from the Yilan, Taiwan, aged 65 years or older (45.8% male) were enrolled and visited at their homes, where HRQoL was measured utilizing the Short Form-12 Health Survey. Each participant's heart rhythm was recorded with an electrocardiographic monitor for 5 minutes. The results disclosed that the prevalence of AF of this aged population was 5.8%, similar to the mean global prevalence. Besides, the prevalence of frequent APCs and frequent VPCs in these elderly people were 7.1% and 5.5%, respectively. After multiple regression analysis, elderly people with AF had lower scores in the physical component of HRQoL, while those elderly people with frequent VPCs had lower scores in the mental component. Ultimately, these findings can provide additional useful and population-specific information about AF, and assist medical professionals in designing more effective strategies for cardiac arrhythmia treatments.

Optogenetic determination of the myocardial requirements for extrasystoles by cell type-specific targeting of ChannelRhodopsin-2.

Extrasystoles lead to several consequences, ranging from uneventful palpitations to lethal ventricular arrhythmias, in the presence of pathologies, such as myocardial ischemia. The role of working versus conducting cardiomyocytes, as well as the tissue requirements (minimal cell number) for the generation of extrasystoles, and the properties leading ectopies to become arrhythmia triggers (topology), in the normal and diseased heart, have not been determined directly in vivo. Here, we used optogenetics in transgenic mice expressing ChannelRhodopsin-2 selectively in either cardiomyocytes or the conduction system to achieve cell type-specific, noninvasive control of heart activity with high spatial and temporal resolution. By combining measurement of optogenetic tissue activation in vivo and epicardial voltage mapping in Langendorff-perfused hearts, we demonstrated that focal ectopies require, in the normal mouse heart, the simultaneous depolarization of at least 1,300-1,800 working cardiomyocytes or 90-160 Purkinje fibers. The optogenetic assay identified specific areas in the heart that were highly susceptible to forming extrasystolic foci, and such properties were correlated to the local organization of the Purkinje fiber network, which was imaged in three dimensions using optical projection tomography. Interestingly, during the acute phase of myocardial ischemia, focal ectopies arising from this location, and including both Purkinje fibers and the surrounding working cardiomyocytes, have the highest propensity to trigger sustained arrhythmias. In conclusion, we used cell-specific optogenetics to determine with high spatial resolution and cell type specificity the requirements for the generation of extrasystoles and the factors causing ectopies to be arrhythmia triggers during myocardial ischemia.

Dantrolene suppresses ventricular ectopy and arrhythmogenicity with acute myocardial infarction in a langendorff-perfused pacing-induced heart failure rabbit model.

INTRODUCTION: Dantrolene prevents arrhythmogenic Ca(2+) release during heart failure (HF). However, direct evidence to support its antiarrhythmic effects in failing hearts with acute myocardial infarction (AMI) is lacking. METHODS AND RESULTS: HF was induced by right ventricular pacing (312 beats/min, 4 weeks) in 19 rabbits. AMI was induced by coronary artery ligation in rabbits surviving chronic pacing (n = 17). The hearts were quickly excised and Langendorff-perfused for simultaneous membrane potential and intracellular Ca(2+) (Cai ) optical mapping when ventricular fibrillation (VF) occurred or 4 hours after AMI. The VF inducibility was defined as the ability to provoke sustained VF (>2 minutes) by pacing. Dantrolene (10 µM) was administered after baseline studies. Spontaneous VF occurred in 5 rabbits (SVF group). The ventricular premature beat (VPB) burden was significantly higher in the SVF group than the non-SVF group (P < 0.05). Dantrolene suppressed VPB burden (P = 0.03) and prolonged action potential duration (APD; P < 0.05) to reduce VF inducibility (P < 0.05). However, dantrolene shortened immediate postshock APD50 even if VF storm was suppressed. CONCLUSION: In failing hearts with AMI, VPB burden plays a pivotal role in SVF occurrence. Dantrolene suppresses VPBs and/or prolongs repolarization to inhibit spontaneous VF and reduce VF inducibility.

[Concealed His bundle extrasystoles causing atrioventricular block]. / Utajona ekstrasystolia z peczka Hisa przyczyna bloku przedsionkowo-komorowego.

We present electrocardiograms of a 37 year-old male with frequent extrasystoles and second-degree atrioventricular block. Electrophysiological study confirmed the initial diagnosis of manifest and concealed His bundle ectopy as the cause of his brady- and tachyarrhythmia.

Usefulness of frequent supraventricular extrasystoles and a high CHADS2 score to predict first-time appearance of atrial fibrillation.

Frequent supraventricular extrasystoles (SVEs) are associated with the subsequent first-time appearance of atrial fibrillation (AF) and ischemic stroke. The aim of this study was to investigate the combined role of SVEs and an AF-related risk score for ischemic stroke, the CHADS2 score, on the occurrence of new AF in patients in sinus rhythm. The Shinken Database 2004-2010 lists 3,263 patients who underwent 24-hour Holter monitoring. A total of 2,589 patients were analyzed, after excluding 674 patients previously diagnosed with AF. Frequent SVEs were defined as ≥102 beats/day (the top quartile) and the presence of a clinical background for a CHADS2 score ≥2 points as a high CHADS2 score. During the mean follow-up period of 571.4 ± 606.4 days, new AF occurred in 38 patients (9.4 per 1,000 patient-years). The incidence of new AF was 2.7 and 37.7 per 1,000 patient-years for patients with nonfrequent SVEs (<102 beats/day) and low CHADS2 scores and those with frequent SVEs and high CHADS2 scores, respectively. Multivariate Cox regression analysis showed that the hazard ratio for frequent SVEs and a high CHADS2 score compared with nonfrequent SVEs and a low CHADS2 score was 9.49 (95% confidence interval 3.20 to 28.15, p <0.001), even after adjustment for gender, age, medications, and echocardiographic parameters. In conclusion, frequent SVEs and a high CHADS2 score independently and synergistically predict the first-time appearance of AF in patients in sinus rhythm, indicating an approximately 10-fold higher risk. Patients meeting these criteria should have more aggressive early intervention for preventing AF.

Cardiologia intervencionista das arritmias ventriculares / Interventional Cardiology of ventricular arrhythmias

A ablação por radiofrequência (RF) das arritmias ventriculares visa, principalmente, melhorar a qualidade de vida dos pacientes. Tem recomendação precisa nos pacientes recebendo choques dos cardiodesfibriladores implantáveis (CDI) e, em particular, naqueles com taquicardias incessantes com função ventricular em franca deterioração. As técnicas de ablação atuais permitem que os procedimentos sejam bastante eficazes e realizados em ambiente de muita segurança. Os benefícios da sua realização dependem do tipo de arritmia e das características clínicas dos paciente.

The ablation of ventricular arrhythmias with RF aims chiefly to improve the quality of life of patients. It is recommended for patients receiving shocks of IDUs and in particular those with incessant tachycardia with ventricular function in full decay. Current ablation techniques allow procedures to be quite effective and carried out in a safe environment. The benefits of its implemention will depend on the type of arrhythmia and the clinical characteristics of the patients.

Successful catheter cryoablation of Hisian ectopy using 2 new diagnostic criteria based on unipolar and bipolar recordings of the His electrogram.

We describe the case of a 61-year-old woman who underwent successful catheter cryoablation of a symptomatic Hisian ectopy. Diagnosis was based on features of the HV interval assessed from a bipolar recording during mapping. The location of the arrhythmic focus was identified using simultaneous unipolar and bipolar recordings of the His electrogram. This case report highlights the use of 2 new criteria for the diagnosis and mapping of Hisian ectopy, and the successful use of cryothermia for the ablation of extrasystoles arising from the His bundle.

A His bundle extrasystole can both induce and reverse 2:1 atrioventricular block.

An 84 year-old man with history of recurrent dizziness presented with first degree atrio-ventricular block (1° AVB) and periods of 2:1 AVB. An electrophysiological study revealed a predominant 1:1 AV conduction with markedly prolonged AH interval and frequent His bundle extrasystoles (H). A properly timed H could induce periods of 2:1 AV nodal block and 1:1 AV conduction could only resume following another properly timed H. Procainamide suppressed H. However, because of persistence of the patient symptoms, a permanent pacemaker was eventually inserted. The case illustrates a hitherto not described manifestation of H.

Circa(ultra)dians of single extrasystoles in chronic respiratory failure versus health at lowland.

BACKGROUND: The circa- and ultradians of the single extrasystoles' frequency in patients with chronic respiratory insufficiency (CRI) in lowlands (Kosice 210 m) were studied by the testing of following null hypotheses: their average frequency as well as rhythmicity is the same as at health. METHODS: In 54 elderly males with CRI, mean numbers of supraventricular (SV) and ventricular (VE) extrasystoles were calculated for each 24 hours. The Halberg cosinor regression was used to test the presence of the 24-hour rhythm and its 2nd to 10th harmonics, i.e. ultradians with the period lengths of 12 to 2.4 hours. The resulting approximating function for either extrasystole type included its point, 95% confidence for mean and 95% tolerance for one individual. The results were compared with those obtained at health at alpha = 0.05. RESULTS: The daily mesors in CRI were 20.9 for SV, for VE 17.6 extrasystoles per hour and subject. This was significantly (20.3 (SV) and 17.0 (VE)) higher than at health. Significant periodic harmonic components were 3 in CRI versus 6 at health for SV and 6 in CRI versus 1 at health for VE. The dominating CRI rhythm was the 8 hour ultradian for SV and circadian for VE while at health the circadian rhythm was leading for every type of extrasystoles. CONCLUSION: The most remarkable effect of CRI versus health at lowlands is a marked increase of the frequency of every type of extrasystoles. SV extrasystoles exert more rhythmicity at health while the VE in disease (Tab. 1, Fig. 1, Ref. 20).