Reentry Mechanism Research Articles

Monomorphic premature ventricular contractions in patients without cardiac structural changes: clinical and prognostic significance and evaluation of therapy effectiveness (clinical and experimental study)

Aim. To determine the individualized choice of therapy for monomorphic premature ventricular contractions (PVCs) in patients without structural cardiac changes by assessing the predictors of arrhythmogenic cardiomyopathy (ACM) and the clinical and prognostic significance of its course.Material and methods. Experimental study. Animals were used to model PVCs by the mechanism of early post-depolarization (EPD) (aconitine), re-entry (peroxide or H2O2 arrhythmia). In addition to the generally accepted parameters, the following ACMs were analyzed during electrocardiography (ECG): pre-ectopic interval, its variability, maximum index of internal deviation of PVCs, the QRS complex of PVC (QRSpvc), QRS of sinus rhythm (QRSsr), their ratio (QRSpvc/QRSsr), etc. Clinical study. A total of 343 patients with class IV-V PVCs aged 16 to 34 years were observed (B. Rayn, 1984). The same parameters were determined by ECG as in experimental arrhythmias. The follow-up duration was up to 10 years. The end point was the detection or absence of cardiovascular pathology.Results. Experimental study. When modeling ventricular arrhythmias using the EPD mechanism, early (R/T) monotopic PVCs were recorded, and re-entry — early and late monomorphic PVCs. ACM predictors were recorded only when modeling arrhythmia by the re-entry mechanism. Clinical study. In patients without structural cardiac changes, early (R/T) monotopic PVC highly correlated with ventricular ectopy induced by the EPD mechanism (aconitine) (r=0,92). These patients did not have cardiovascular diseases, and the most effective antiarrhythmic drugs for eliminating ventricular ectopy were class I drugs. In patients without structural cardiac changes, early and late monomorphic PVCs highly correlated with experimental ventricular ectopy caused by the re-entry mechanism (H2O2 arrhythmia). In these patients, on average, 7,2±0,5 years after inclusion in the study, various clinical forms of coronary artery disease were detected, and the positive clinical effect of PVC treatment was achieved mainly with the use of class III antiarrhythmic drugs.Conclusion. In patients with early monotopic ventricular ectopia, without detection of ACM predictors, the most effective were class I antiarrhythmic drugs. In other patients with early and late monomorphic ventricular ectopia and detected ACM predictors, class III agents were found to be effective.

Tumor Suppressor MicroRNAs in Clinical and Preclinical Trials for Neurological Disorders.

Cancers and neurological disorders are two major types of diseases in humans. We developed the concept called the "Aberrant Cell Cycle Disease (ACCD)" due to the accumulating evidence that shows that two different diseases share the common mechanism of aberrant cell cycle re-entry. The aberrant cell cycle re-entry is manifested as kinase/oncoprotein activation and tumor suppressor (TS) inactivation, which are associated with both tumor growth in cancers and neuronal death in neurological disorders. Therefore, some cancer therapies (e.g., kinase/oncogene inhibition and TS elevation) can be leveraged for neurological treatments. MicroRNA (miR/miRNA) provides a new style of drug-target binding. For example, a single tumor suppressor miRNA (TS-miR/miRNA) can bind to and decrease tens of target kinases/oncogenes, producing much more robust efficacy to block cell cycle re-entry than inhibiting a single kinase/oncogene. In this review, we summarize the miRNAs that are altered in both cancers and neurological disorders, with an emphasis on miRNA drugs that have entered into clinical trials for neurological treatment.

Unpacking the career transition process of returning women professionals in the Indian workplaces: a qualitative study

PurposeThis study aims to explore the career transition process of women professionals when they return to the workplace after a break and re-integrate with their career aspirations.Design/methodology/approachThis research used a qualitative approach with semi-structured interviews for data collection. All 20 women participants have returned to their careers after a break.FindingsThe data analysis reveals women’s career transition and re-integration process into the workplace after a career break. Supervisory support, work–life balance practices, role models, coworker support and career success emerged as factors enabling successful transition. The employing organisations’ diversity, equity and inclusion (DEI) hiring strategy emerged as an important mechanism for re-entry.Originality/valueAlthough previous research has studied women professionals returning after a break, the “transition process” that enables re-entry is missing.

Abstract B021: Influenza-induced inflammatory response reactivates and promotes dormant breast cancer cell outgrowth in lungs

Abstract Breast cancer is the most common form of cancer and the second cancer-causing death in females. Although remission rates are high if detected early, survival rates drop substantially when breast cancer becomes metastatic. Metastatic relapse can occur months to years after the initial diagnosis and treatment of the primary tumor. This relapse is mediated by awakening of dormant disseminated cancer cells (dDCCs). Studies have demonstrated that the relationship between the microenvironment and dDCCs is critical for maintaining both dormancy and for facilitating awakening to promote metastasis development. Prior studies have shown increased inflammation in the microenvironment can facilitate DCC awakening and outgrowth. Viral respiratory infections are also associated with massive inflammation and immune cell influx, typically in acute form. Respiratory infections affect millions of people worldwide, as is particularly evident in the ongoing SARS-CoV2 pandemic and variably severe annual influenza seasons. How the inflammatory response to viral respiratory infections impacts breast cancer metastasis remains unclear. Using FVB MMTV-erbB2/neu/HER2 mice as a model of breast dormancy in the lungs and influenza virus, we show that following influenza infection there is a significant increase in the number of disseminated cancer cells in the lungs of influenza infected mice with more than a 1000-fold expansion of carcinoma cells over a couple of weeks. Interestingly most of this expansion of DCCs takes place within 10 days following influenza infection. Strikingly, by 15 days post-infection, the lesions that expanded from solitary HER2+ DCCs almost homogeneously return to a quiescent state. Furthermore, we show interleukin-6 is required for the early phase of dormant cancer cells reawakening and proliferation and that CD4+ T cells are required for the maintenance of the expanded cancer cells post-infection at the late phase. Depletion of CD4 T cells (but not CD8 cells) during infection with influenza virus leads to the elimination of the expanded DCC population in the lung. Finally, single-cell RNA-seq analyses of DCC and microenvironmental cells in the lungs before and after infection reveals insight into underlying mechanisms for virus-induced awakening and reentry into dormancy. scRNA-seq analyses reveal that expanding DCC post-influenza infection reprogram CD4 and CD8 T-cells to a more immune suppressed state. These results support a model whereby pulmonary viral infections can increase the risk of metastatic relapse in the lungs for patients with a prior history of breast cancer. Thus, the immune response evolved to combat respiratory infections can be coopted and reprogrammed by dormant cancer cells to enable their expansion, thus increasing the odds of further metastatic cancer evolution. Ongoing work is currently being done to investigate this process in mouse models of SARS-CoV2 infection, as well as to examine clinical databases for epidemiological associations between respiratory viral infections and metastatic disease in the lung. Citation Format: Bryan J. Johnson, Shi Biao Chia, Vadym Zaberezhnyy, Varsha Sreekanth, Meher Boorgula, Michael Papanicolaou, James Costello, Andrew Goodspeed, Julio A. Aguirre-Ghiso, Mercedes Rincon, James V. DeGregori. Influenza-induced inflammatory response reactivates and promotes dormant breast cancer cell outgrowth in lungs [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B021.

Perioperative atrial fibrillation : Diagnosis with underestimated relevance

Atrial fibrillation (AF) is the most common cardiac arrhythmia in adults, both in general and perioperatively and is associated with significant morbidity and mortality. The age of the patients is amajor risk factor. The prevalence of AF in noncardiac surgery (NCS) varies widely from 0.4% to 30% and for cardiac surgery, especially major combined procedures, up to approximately 50%. Ectopic excitation centers and reentry mechanisms at the atrial level are favored as the main process of uncoordinated electrical atrial activity. The loss of atrial contraction can lead to areduction in cardiac output of up to 20-25%. The increased risk of thromboembolism due to AF extends beyond the perioperative period. Medication-based prevention strategies have not yet gained widespread acceptance. Treatment strategies include frequency and rhythm control as well as the avoidance of thromboembolisms through anticoagulation.

NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and its prevalence increases with age. The irregular and rapid contraction of the atria can lead to ineffective blood pumping, local blood stasis, blood clots, ischemic stroke, and heart failure. NADPH oxidases (NOX) and mitochondria are the main sources of reactive oxygen species in the heart, and dysregulated activation of NOX and mitochondrial dysfunction are associated with AF pathogenesis. NOX- and mitochondria-derived oxidative stress contribute to the onset of paroxysmal AF by inducing electrophysiological changes in atrial myocytes and structural remodeling in the atria. Because high atrial activity causes cardiac myocytes to expend extremely high energy to maintain excitation-contraction coupling during persistent AF, mitochondria, the primary energy source, undergo metabolic stress, affecting their morphology, Ca2+ handling, and ATP generation. In this review, we discuss the role of oxidative stress in activating AF-triggered activities, regulating intracellular Ca2+ handling, and functional and anatomical reentry mechanisms, all of which are associated with AF initiation, perpetuation, and progression. Changes in the extracellular matrix, inflammation, ion channel expression and function, myofibril structure, and mitochondrial function occur during the early transitional stages of AF, opening a window of opportunity to target NOX and mitochondria-derived oxidative stress using isoform-specific NOX inhibitors and mitochondrial ROS scavengers, as well as drugs that improve mitochondrial dynamics and metabolism to treat persistent AF and its transition to permanent AF.

PO-02-172 CONDUCTION VELOCITY AND CONDUCTION VELOCITY DYNAMICS IN THE LEFT ATRIUM ARE IMPACTED BY STRUCTURAL AND AUTONOMIC MODULATION AND SITES OF CONDUCTION VELOCITY HETEROGENEITY CORRELATE TO RE-ENTRY ACTIVITY IN ATRIAL FIBRILLATION

Structural and autonomic remodelling is proposed to drive atrial fibrillation (AF). Conduction velocity (CV) heterogeneity predisposes cardiac tissue to re-entry mechanisms. The impact of structural and autonomic remodelling on CV dynamics and re-entry formation is unclear. Evaluate the impact structural and autonomic modulation has on CV dynamics and re-entry activity in AF. Local activation times (LATs), voltage and geometry data were obtained from 20 patients undergoing catheter ablation for persistent AF. LATs were obtained at 3 pacing intervals (PI) (600, 400 and 250ms) with pacing from two pacing sites. LATs were used to determine CV dynamics and their relationship to voltage using an automated algorithm. Relationship between sites of enhanced CV heterogeneity defined as rate dependent CV slowing (RDCV) sites (sites exhibiting CV difference (CVd) between PI=600ms and PI=250ms of ≥20% of the mean CVd seen between these PIs for that voltage zone) and re-entry activity in AF was evaluated. Re-entry activity was identified using an automated algorithm and defined as ≥1.5 rotations of 360 degrees. The impact of autonomic modulation on CV dynamics both pharmacologically and with ganglionated plexi stimulation was assessed. A total of 512,082 LAT and voltage points were analysed. Voltage impacts CV (1.36±0.98 nLVZ ≥0.5mV, 1.05±1.03 LVZ 0.2-0.49mV and 0.58±0.37 vLVZ <0.2mV) (Figure 1A-B) and CV dynamics, whereby at nLVZ the curves are steeper (0.03±0.02ms CVd PI 600-400ms, 0.54±1.1ms CVd PI 400-250ms), broader at LVZ (0.16±0.09ms CVd PI 600-400ms, 0.23±1.1ms CVd PI 400-250ms) and flat at vLVZ (0.04±0.01ms CVd PI 600-400ms, 0.05±0.02ms CVd PI 400-250ms) (Figure 1C). Per patient, 5.6±1.1 RDCV sites and 3.4±1.3 sites of re-entry activity were identified. Of the RDCV sites, 72.3% (81/112) correlated to 94.1% (64/68) of re-entry activity sites which were mainly confined to LVZs (59/68, 86.8%). Autonomic modulation affected the CV dynamic curves through increasing rate dependency slowing (Figure 1D). The number of RDCV sites identified were enhanced following autonomic modulation (3.4±1.2 increase per patient). CVs and CV dynamics are impacted by structural remodelling and are influenced by autonomic modulation which enhances CV heterogeneity. CV heterogeneity sites correlate to re-entry activity in AF. Assessment of CV dynamics and heterogenity may help to determine the mechanistic importance of LVZs.

The performance of dipole charge density mapping integrated with robotic magnetic navigation in the treatment of atrial tachycardias

BackgroundCatheter ablation (CA) has become a well-established first-line therapy for a broad spectrum of arrhythmias, including atrial tachycardias (ATs). In this study we aimed to assess the performance of the integrated novel high-resolution new generation noncontact mapping system (AcQMap) with robotic magnetic navigation (RMN) system in CA procedures for patients with ATs including comparing patient subgroups based on the utilized mapping modality, arrhythmia mechanism, localization and type of procedure.MethodsAll patients undergoing CA for AT using the AcQMap-RMN system were included. Procedural safety and efficacy were characterized by intra- and post-procedural complications. Acute procedural success and the long-term outcome were assessed in the overall group and in the subgroups.ResultsA total number of 70 patients were referred for CA with atrial arrhythmias including 67 AT/AFL (mean age 57.1 ± 14.4 years), and 3 additional patients with inappropriate sinus tachycardia. Thirty-eight patients had de novo AT, 24 had post-PVI AT including 2 patients with perinodal AT, and 5 had post-MAZE AT. Two patients (2.9%) suffered post-procedural complications including 1 patient with groin hematoma and 1 patient with a transient ischemic attack. Acute success was achieved in 63/67 (94.0%) procedures. Thirteen patients (19.4%) had documented recurrence at the end of the 12-months follow-up period. The performance of AcQMap was equally good in focal vs. reentry mechanisms (p = 0.61, acute success), in the left and right atrium (p = 0.21).ConclusionsAcQMap-RMN integration might improve success rates in CA of ATs with low number of complications.

FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.

Cancers and neurological disorders are two major types of diseases. We previously developed a new concept termed "Aberrant Cell Cycle Diseases" (ACCD), revealing that these two diseases share a common mechanism of aberrant cell cycle re-entry. The aberrant cell cycle re-entry is manifested as kinase/oncogene activation and tumor suppressor inactivation, which are hallmarks of both tumor growth in cancers and neuronal death in neurological disorders. Therefore, some cancer therapies (e.g., kinase inhibition, tumor suppressor elevation) can be leveraged for neurological treatments. The United States Food and Drug Administration (US FDA) has so far approved 74 kinase inhibitors, with numerous other kinase inhibitors in clinical trials, mostly for the treatment of cancers. In contrast, there are dire unmet needs of FDA-approved drugs for neurological treatments, such as Alzheimer's disease (AD), intracerebral hemorrhage (ICH), ischemic stroke (IS), traumatic brain injury (TBI), and others. In this review, we list these 74 FDA-approved kinase-targeted drugs and identify those that have been reported in preclinical and/or clinical trials for neurological disorders, with a purpose of discussing the feasibility and applicability of leveraging these cancer drugs (FDA-approved kinase inhibitors) for neurological treatments.

Long-term prognosis of successful left ventricular substrate modification of electrical storm.

IntroductionThe Electrical storm (ES) subsumes a state of electrical instability of the heart, which manifests itself in repeated and potentially fatal ventricular arrhythmias (VA). We examine the long-term effects of substrate modification with regards to mortality, ventricular tachycardia (VT) recurrences and hospitalization depending on age, gender, heart function, scare location, VT documentation, postprocedural electrical stimulation (PES) and induced VTs.MethodsFrom 08/2008 and 09/2019 160 consecutive patients admitted for ES ablation via electroanatomical mapping were followed up until 04/2021.Results50/160 patients showed VT recurrences after 13.8 ± 21.7 (0.0–80.3) months, with a characteristic steep curve directly after ES and then a rapid decline leading to a plateau (first month 10/50 (20%), first year 35/50 VT recurrences (70%) Mortality rates followed a similar pattern also the initial decline was not as steep. 42 patients died during the observation period (26%) after 16.6 ± 16.1 (0.0-67.9) months after ablation day (first month (n = 7, 16.7%) first year (n = 21, 50%). Gender, age, scare localization, missing VT documentation did not worsen outcome. Induction of >3 VTs and lack of PES due to hemodynamic instability significantly decreased effectiveness. Finding the entry significantly increased long-term effects.ConclusionAblation of ES is safe and feasible independent of a variety of factors. Employing more sophisticated tools to understand the reentry mechanism will further improve the long-term outcome.

Detection of the origin of atrial tachycardia by 3D electro-anatomical mapping and treatment by radiofrequency catheter ablation in horses.

BackgroundAtrial tachycardia (AT) can be treated by medical or electrical cardioversion but the recurrence rate is high. Three‐dimensional electro‐anatomical mapping, recently described in horses, might be used to map AT to identify a focal source or reentry mechanism and to guide treatment by radiofrequency ablation.ObjectivesTo describe the feasibility of 3D electro‐anatomical mapping and radiofrequency catheter ablation to characterize and treat sustained AT in horses.AnimalsNine horses with sustained AT.MethodsRecords from horses with sustained AT referred for radiofrequency ablation at Ghent University were reviewed.ResultsThe AT was drug resistant in 4 out of 9 horses. In 8 out of 9 horses, AT originated from a localized macro‐reentrant circuit (n = 5) or a focal source (n = 3) located at the transition between the right atrium and the caudal vena cava. In these 8 horses, local radiofrequency catheter ablation resulted in the termination of AT. At follow‐up, 6 out of 8 horses remained free of recurrence.Conclusions and Clinical ImportanceDifferentiation between focal and macro‐reentrant AT in horses is possible using 3D electro‐anatomical mapping. In this study, the source of right atrial AT in horses was safely treated by radiofrequency catheter ablation.

Atypical atrial flutter in patients after cardiac surgery

Abstract Funding Acknowledgements Type of funding sources: None. Background Atypical atrial flutter (AFL) is often associated with cardiac surgery or extensive catheter ablation (CA) for the treatment of atrial fibrillation (AF) [1-2]. Therefore, the increase in the number of cardiac surgery procedures leads to the development of substrates for atypical AFL onset. Incisions after cardiac surgery are common substrates for macro re-entry tachycardia and one patient can suffer from several macro re-entry tachycardia mechanisms. Atrial flutter in this category of patients lead to heart failure. Objective The aim of our study was to access the effectiveness and safety of catheter ablation of atypical atrial flutter in patients after cardiac surgery. Methods 107 adult patients with AFL after cardiac surgery and catheter ablation were included in a single-center prospective study. The patient’s mean age was 57.8±11.1 years with the prevalence of male (56%). BMI was 27,8±5 kg/m 2. All patients underwent radiofrequency ablation (RFA) of atypical AFL with 3D navigation system Carto3 using the CLOSE protocol. The patients were discharged safely and were monitored for 12 months. Results According to basic characteristics of patients cardiac surgery performed in 19.6% for CABG, in 9.3% for congenital heart disease and in 58.9% for valvular heart diseases. RFA for pulmonary veins isolation (PVI) for AF was performed in 15.9% and cryoballoon isolation of PVI in 19.6%. The onset of atrial events after incision or catheter ablation was 12 (Q1-14; Q3-25) months. In 8.4% of patients, ejection fraction was less than 40%. The mean RFA time was 110,8±10,4 min, mean fluoroscopy time 2.2 min. There were two re-entry mechanisms in 22.4% of patients, three and more re-entry mechanisms in 8.4% of patients. During 12 months monitoring after RFA in 2 (1.9%) patients registered AFL and in 8 (7.5%) of patients noticed non-sustained palpitations. Conclusions RFA of AFL with the use of ablation index and CLOSE protocol lead to the high effect and safety in patients after cardiac surgery. AFL is most frequent in patients after valvular heart surgery and usually occurs 12 months after the surgery.

Automated quantification and identification of decremental response after extrastimulus: validation of a novel software

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Junta de Andalucia Background Automatic identification of myocardial electrograms (EGMs) with decremental conduction (DC) is a promising field in catheter ablation procedures, allowing the identification of the critical isthmus of tachycardias with re-entry mechanisms. In this work, a novel artificial intelligence (AI)-based software was developed for the automatic analysis of delays between evoked responses in the coronary sinus (CS), allowing signal quantification. Methods Atrioventricular (AV) and ventriculoatrial (VA) conduction was analysed in coronary sinus signals obtained from patients undergoing electrophysiological study. A simple pacing (S=400-600ms) and extra-stimulus protocol (S2=ERP + 20-60ms) were used in all cases. An AI-based algorithm was developed for EGM delineation with the objective of localising the onsets and offsets of each independent local and far field activations. The algorithm consisted in several steps. Firstly, an AI-based QRS detector was employed (Figure 1A). Secondly, the located QRS’ were used alongside another AI model to delineate the EGMs corresponding to all bipolar electrodes in the CS (Figure 1B). Thirdly, majority voting is performed on the delineations to obtain an overall prediction for all CS electrodes (Figure 1C). Fourthly, the predictions are cleaned and a rule-based algorithm is employed to automatically exclude faulty registries (e.g. loss of capture or AV/VA block after S2). Finally, the determination of decremental response is performed by computing the time difference between the last paced beat and the S2 extrastimulus. This was measured using the onsets of morphologically similar activations in the trace, correcting for misalignments. A decremental response was defined as a difference &amp;gt;10 ms between the AV/VA interval during the S1 drive and the same interval immediately after the S2. Four experts validated results of the automated analysis. Results 321 tracings from 50 patients were analysed. 81 tracings were automatically excluded due to loss of capture or AV/VA block after S2. The AV/VA interval was automatically annotated in 236 EGMs. 192 tracings exhibited decremental conduction properties, whereas 48 tracings showed non-decremental AV or VA conduction due to accessory pathways. Automatic analysis accurately classified 191 tracings as decremental (93.75% sensitivity, 91.47% specificity) and 45 tracings as non-decremental (85.42% sensitivity, 98.53% specificity). Conclusions AI-based algorithms are able to produce objective quantifications over real-world data, discriminating between local and far field signals and accurately identifying EGMs with decremental evoked response. Automated data analysis can accelerate research and reduce clinical workload. Moreover, a quantification-based approach can be employed in many other applications. Validation of this software on ventricular signals could facilitate ventricular tachycardia substrate ablation procedures.

Ablation of Left Atrial Tachycardia following Catheter Ablation of Atrial Fibrillation: 12-Month Success Rates.

The treatment of atrial tachycardia following catheter ablation of atrial fibrillation is often challenging. Electrophysiological studies using high-resolution 3D mapping systems have contributed significantly to their understanding, and new ablation approaches have shown high rates of acute terminations with low recurrences for the clinical AT. However, patient populations are very heterogeneous, and long-term data of the freedom from any atrial tachycardia or any arrhythmia are still sparse. To evaluate long-term success, a unified patient population and predefined ablation strategies are preferred. In this study, we present 12-month success and mean 30 month follow-up data of catheter ablation of left atrial tachycardia. All 35 patients had a history of pulmonary vein isolation (PVI), 71% of which had a previous substrate modification. A total of 54 ATs, with a mean cycle length 297 ± 86 ms, 31 macro-reentries, and 4 localized reentries, were targeted. The ablation strategy to be used was given by the study protocol, depending on the type of reentry and the number of critical isthmuses. All available ablation strategies were included: standard (anatomical) lines, individual lines, critical isthmuses, and focal ablation. All ATs were terminated by ablation. A total of 91% terminated upon the first ablation strategy. Freedom from any AT after 12 months was 82%, and from any arrhythmia, it was 77%. The multi-procedure success after 30 months was 65% for any AT and 55% for any arrhythmia. In conclusion, individual ablation strategies based on the reentry mechanism and the number of critical isthmuses seems promising and demonstrates a high long-term clinical success. Tachycardia comprising a single critical isthmus can be ablated by critical isthmus ablation only. These patients present with the highest 12-month and long-term success rates.

Rare variant of Remkheld syndrome

Introduction. Gastroesophageal reflux disease (GERD) can be accompanied by a triad of cardiac symptoms (arrhythmia, cardialgia, signs of autonomic dysfunction). This syndrome is called gastro-cardiac or Remheld syndrome. The most common rhythm disturbances in Remheld syndrome are atrial fibrillation, supraventricular extrasystole. In the clinical case we have described, a rare variant of Remheld’s syndrome is presented: paroxysmal ventricular tachycardia with GERD.Description of the clinical case. Patient V., 48 years old, applied to a cardiologist on 21.04.21 with complaints of attacks of sudden palpitations, disturbing for six months. From the anamnesis it is known that since 2017 he has been suffering from GERD, he does not take drugs for stopping reflux attacks for 6 months, canceling it on his own. According to Holter ECG monitoring from 03/20/21, paroxysmal ventricular tachycardia was revealed. According to echocardioscopy data from 04/26/21, no structural changes that could be the cause of this life-threatening rhythm disturbance were found. Video gastroscopy from 04/28/21: distal reflux esophagitis. Endoscopic signs of hiatal hernia. Lack of cardia 2 tbsp. Gastroesophageal prolapse. At the consultation with a gastroenterologist, the patient was prescribed both non-drug (lifestyle correction) and drug treatment: rabeprozole, clarithromycin, amoxicillin and others. In addition for the relief of paroxysmal ventricular tachycardia—amiodarone, telmisartan.Discussion. According to studies, one of the mechanisms of arrhythmia in GERD is associated with the excitation of the distal esophagus by refluctate with the development of viscero-visceral reflexes mediated through n. vagus. Increased activation of n. vagus creates an arrhythmogenic substrate for the re-entry mechanism, and thus increases the risk of arrhythmias. Antiarrhythmic therapy along with the treatment of GERD led to the elimination of VT paroxysms. Later, 2 months after the withdrawal of antiarrhythmic drugs against the background of ongoing GERD therapy, paroxysms of VT were not recorded. This was also a confirmation of the pathogenetic relationship between GERD and paroxysmal VT.Conclusion. The case is of interest to the development of a life-threatening rhythm disturbance: paroxysmal ventricular tachycardia against the background of GERD, which is a very rare variant of Remkheld’s syndrome and is not found in the available literature.

Electrophysiological Consequences of Cardiac Fibrosis.

For both the atria and ventricles, fibrosis is generally recognized as one of the key determinants of conduction disturbances. By definition, fibrosis refers to an increased amount of fibrous tissue. However, fibrosis is not a singular entity. Various forms can be distinguished, that differ in distribution: replacement fibrosis, endomysial and perimysial fibrosis, and perivascular, endocardial, and epicardial fibrosis. These different forms typically result from diverging pathophysiological mechanisms and can have different consequences for conduction. The impact of fibrosis on propagation depends on exactly how the patterns of electrical connections between myocytes are altered. We will therefore first consider the normal patterns of electrical connections and their regional diversity as determinants of propagation. Subsequently, we will summarize current knowledge on how different forms of fibrosis lead to a loss of electrical connectivity in order to explain their effects on propagation and mechanisms of arrhythmogenesis, including ectopy, reentry, and alternans. Finally, we will discuss a histological quantification of fibrosis. Because of the different forms of fibrosis and their diverging effects on electrical propagation, the total amount of fibrosis is a poor indicator for the effect on conduction. Ideally, an assessment of cardiac fibrosis should exclude fibrous tissue that does not affect conduction and differentiate between the various types that do; in this article, we highlight practical solutions for histological analysis that meet these requirements.

Protocolo diagnóstico de las taquiarritmias supraventriculares

Supraventricular tachycardias encompass tachycardias that originate in structures located above the bundle of His bifurcation. In general, supraventricular tachycardias can be atrial, of the AV node, or mediated by an accessory pathway. Most of them are due to reentry mechanisms, from focal to local to macro atrial reentries. For their proper diagnosis, first, a good graphical recording using a 12-lead ECG is fundamental, although sometimes a rhythm strip or a Holter can lead to a correct diagnosis. Second, once the recording has been obtained, it should be analyzed following a series of steps that includes verifying what it is like and the rate of the atrial activity as well as the relationship between the atria and the ventricles (P/QRS). An adenosine infusion or vagal maneuvers can help establish the final diagnosis.

Radiofrequency Catheter Ablation for Supraventricular Tachycardias: A Six-Year Single Centre Experience at NICVD

Pharmacological therapy is mostly employed in the management of supraventricular tachyarrhythmias in different part of the world including Bangladesh. However, Radiofrequency catheter ablation has been found to be highly effective and safe in the treatment of such tachyarrhythmias. Objective: The current study is aimed at sharing our experiences of 842 patients who presented with Supraventricular tachycardias and were diagnosed by EPS and treated with Radiofrequency catheter ablation. Methods: This descriptive study has been carried out in the cardiac electro physiology Department of NICVD, Dhaka, Bangladesh from 2nd January 2015 to 31st December, 2020. Electrophysiology study(EPS) was carried out to identity and diagnose the mechanism of different SVTs in 842 consecutive patients. RF catheter ablation was used to interrupt the tachycardia circuit. Results: Out of a total 842 patients who underwent Electrophysiology study, 435 were found to have atrioventricular nodal re-entry tachycardia (AVNRT) as underlying mechanism and 391 were having accessory pathway responsible for the reentry mechanism; of these accessory mediated tachycardia, 250 patients were manifested accessory pathway (WPWS); 141 were concealed accessory pathway (out of them 365 were presented with orthodromic and 26 as antidromic reciprocating tachycardia); moreover among the accessory pathway 231 patients were found having left sided accessory pathway whereas 155 having right sided pathway; 12 patients were having focal atrial tachycardia and 4 were found atrial flutter as the underlying cause for SVT. Radiofrequency catheter ablation was used with an overall success rate of 95%, recurrence rate of 2% without any significant complication. Complication: One patient developed pulmonary thrombo-embolism, 6 patients developed DVT of right lower limb, 4 patients developed complete heart block. Conclusion: RF catheter ablation is safe and highly effective mode of treatment of different types of supraventricular tachyarrhythmias which is emerging and becoming popular in our country. Bangladesh Heart Journal 2021; 36(2): 68-73

Cellular determinants of arrhythmic rysk in hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is the commonest inherited cardiac disease, with a prevalence of 1/500 in the general population. The most devastating consequence of HCM is sudden cardiac death (SCD) due to ventricular fibrillation, particularly common in children and young adults (age &amp;lt;30 years). The positive correlation between the extent of late gadolinium enhancement (LGE, reflecting myocardial fibrosis) and the arrhythmic risk in HCM suggests that ventricular arrhythmias are held to originate from the fibrotic regions, by a mechanism of electrical re-entry. However, recent data suggest that enhanced cellular automaticity (i.e. early- or delayed-afterdepolarizations, EADs or DADs-), rather than macro-reentry, may be clinically relevant in promoting ventricular arrhythmias in patients. Purpose Aiming to better understand the cellular and molecular mechanisms of arrhythmogenesis in HCM and to establish a reliable arrhythmic risk stratification in patients, we performed a translational study in HCM patients who underwent surgical myectomy, by combining a clinical follow-up study with in vitro assessments of cellular arrhythmogenicity in ventricular cardiomyocytes. Methods We retrospectively studied 61 HCM patients who underwent surgical interventricular-septum myectomy to relieve refractory obstruction-related symptoms. At the time of surgery, fresh ventricular tissue was collected and used to isolate single ventricular cardiomyocytes (CMs), which were used for patch-clamp measurements to assess the occurrence of EADs and DADs. Patients were followed up for a median time of 8 years and the occurrence of non-sustained ventricular tachycardia (NSVT) or life-threatening arrhythmic events (LAE) was monitored. Moreover, data from ECG and contract cardiac magnetic-resonance studies were collected. Results EADs occurred in CMs from 36% of patients and were associated with prolonged action potential duration. DADs occurred in 24% of patients and were associated with abnormalities of CM intracellular Ca2+ handling. The occurrence of NSVT/ LAE in patients was strongly associated with the presence of DADs in cardiomyocytes but not with the presence of EADs. Patients with NSVT/LAE were more likely to show specific “pro-arrhythmic” pathological ECG-patterns. Among patients with LGE, the presence of DADs in cells behaved as a necessary pre-requisite for NSVT/LAE, as none of the patients with evidence of fibrosis who were negative for DADs had arrhythmic events. Conclusions The presence of pro-arrhythmic changes appears to be necessary for arrhythmia generation in HCM and seems to be related with specific alterations at ECG level, that might be used as clinical arrhythmia predictors in HCM patients. Fibrosis per se is not a major predictor of arrhythmias in HCM but may contribute to generate sustained arrhythmias in the presence of substantial cellular triggers (DADs). Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU Horizon 2020. Grant number 777204 (silico FCM).

Studying droplet retention in porous media by novel microfluidic methods

Transport of oil droplets through porous media is an important topic in the oil and gas industry. Oil droplets that are present in produced water contribute to injectivity decline during re-injection due to retention in pores. In the literature, the retention phenomenon is typically studied by means of core/packed bed flooding, which struggles to provide a simple and inexpensive way to visualize retention events at the pore scale. This paper demonstrates a microfluidic method for studying the transport of dilute oil-in-water emulsions through porous media. The method allows identification of every single retention event at the capillary level and quantitative analysis of the spatial distribution of the retained droplets over pore volumes injected. Experiments were carried out for monodisperse and tailored polydisperse emulsions. Moreover, several droplet sizes, flow rates and dispersed phase concentrations were tested. The results showed that the droplet size has a dramatic effect on the pore clogging. Droplets that are larger than pore throats underwent complete retention, while droplets that are smaller than pore throats showed little to no retention in the monodisperse emulsion experiments. Additionally, the experiments with polydisperse emulsions showed that the larger droplets are facilitators for the retention of the smaller droplets, and the latter are unlikely to experience significant retention independently of the former. The flow rates affected flow re-entry mechanisms of the larger droplets, while for the smaller droplets it influenced only the number of retention events. It was identified that dispersed phase concentration has a significant effect in experiments with limited pore volumes injected. At low concentration, the obtained statistical sample was not sufficiently large to unravel the trends. The developed method presents a solid foundation for further experiments and developments in microfluidic studies of the emulsion transport.