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Background: Cardiovascular diseases represent the most common non-oncologic cause of death in patients following radiotherapy (RT) in the thoracic region. Radiation-induced heart disease (RIHD) can manifest as various heterogeneous clinical entities. However, the influence of RT on the cardiac conduction system has only recently gained more attention. Arrhythmogenic toxicity, i.e., conduction disorders and arrhythmias, constitutes a significant part of these adverse effects. The cardiac conduction system is not routinely monitored as an organ at risk (OaR). Its specific histological nature and function suggest different sensitivity and response to radiation. The heart is a highly heterogeneous organ, and the routinely monitored dose to the whole heart may not adequately characterize the risk of increased arrhythmogenic toxicity from RT. Cardiac structures, including the conduction system, appear to be additional OaRs for which dose distribution should be monitored., Material and Methods: For the systematic selection of studies, we utilized the PubMed database with keywords derived from the analysis of existing literature. The search was limited to English-language publications, and the selection criteria included relevance to the topic and the quality of methodology., Purpose: This article summarizes the impact of RT on the cardiac conduction system., Conclusion: Radiotherapy-induced cardiotoxicity significantly affects morbidity and mortality. The heart exhibits heterogeneity in terms of radiosensitivity. Certain cardiac subregions in the dose distribution show a higher correlation with poorer overall survival than routinely monitored doses to the whole heart and derived parameters (the volumes irradiated with the doses of 5 or 30 Gy - V5 or V30, respectively). The most radiosensitive subregions appear to be the base of the heart, including the beginning of the conduction system. Higher doses to the conduction system, especially the sinoatrial (SA) node, are associated with a higher incidence of a wide range of arrhythmias and poorer overall survival. However, dose limits (Dmean and Dmax) for the conduction system have not yet been established. Dosimetric studies have identified cutoff doses to the SA node, exceeding which there is a significant increase in mortality and the occurrence of arrhythmias.

Ventricular arrhythmias are the leading cause of sudden cardiac death. Current treatment strategies for ventricular tachycardia, including antiarrhythmic drugs and catheter ablation, have limited efficacy in patients with structural heart disease. Noninvasive ablation with the use of externally applied radiation (cardiac radioablation) has emerged as a promising and novel approach to treating recurrent ventricular tachycardias. However, the heart is generally an "organ at risk" for radiation treatments, such that very little is known on the effects of radiotherapy on cardiac ultrastructure and electrophysiologic properties. Furthermore, there has been limited interaction between the fields of cardiology and radiation oncology and physics. The advent of cardiac radioablation will undoubtedly increase interactions between cardiologists, cardiac electrophysiologists, radiation oncologists and physicists. There is an important knowledge gap separating these specialties, but scientific developments, technical optimisation, and improvements depend on intense multidisciplinary collaboration. This manuscript seeks to review the basic of radiation physics and biology for cardiovascular specialists in an effort to facilitate constructive scientific and clinical collaborations to improve patient outcomes., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Interruptions in nonlinear wave propagation, commonly referred to as wave breaks, are typical of many complex excitable systems. In the heart they lead to lethal rhythm disorders, the so-called arrhythmias, which are one of the main causes of sudden death in the industrialized world. Progress in the treatment and therapy of cardiac arrhythmias requires a detailed understanding of the triggers and dynamics of these wave breaks. In particular, two very important questions are: 1) What determines the potential of a wave break to initiate re-entry? and 2) How do these breaks evolve such that the system is able to maintain spatiotemporally chaotic electrical activity? Here we approach these questions numerically using optogenetics in an in silico model of human atrial tissue that has undergone chronic atrial fibrillation (cAF) remodelling. In the lesser studied sub-threshold illumination régime, we discover a new mechanism of wave break initiation in cardiac tissue that occurs for gentle slopes of the restitution characteristics. This mechanism involves the creation of conduction blocks through a combination of wavefront-waveback interaction, reshaping of the wave profile and heterogeneous recovery from the excitation of the spatially extended medium, leading to the creation of re-excitable windows for sustained re-entry. This finding is an important contribution to cardiac arrhythmia research as it identifies scenarios in which low-energy perturbations to cardiac rhythm can be potentially life-threatening., Competing Interests: The authors have declared that no competing interests exist.

Cardiac radiotherapy (RT) may be effective in treating heart failure (HF) patients with refractory ventricular tachycardia (VT). The previously proposed mechanism of radiation-induced fibrosis does not explain the rapidity and magnitude with which VT reduction occurs clinically. Here, we demonstrate in hearts from RT patients that radiation does not achieve transmural fibrosis within the timeframe of VT reduction. Electrophysiologic assessment of irradiated murine hearts reveals a persistent supraphysiologic electrical phenotype, mediated by increases in Na V 1.5 and Cx43. By sequencing and transgenic approaches, we identify Notch signaling as a mechanistic contributor to Na V 1.5 upregulation after RT. Clinically, RT was associated with increased Na V 1.5 expression in 1 of 1 explanted heart. On electrocardiogram (ECG), post-RT QRS durations were shortened in 13 of 19 patients and lengthened in 5 patients. Collectively, this study provides evidence for radiation-induced reprogramming of cardiac conduction as a potential treatment strategy for arrhythmia management in VT patients., (© 2021. The Author(s).)

Background: It is still difficult to create a secure linear conduction block on a beating heart from the epicardial side. To overcome this drawback we developed an infrared coagulator equipped with a cuboid light-guiding quartz rod. This study was designed to electrophysiologically confirm the efficacy of a new ablation probe using infrared energy in a clinical case., Methods: The infrared light from a lamp is focused into the newly developed cuboid quartz rod, which has a rectangular distal exit-plane that allows 30 mm × 10 mm linear photocoagulation. Two pairs of electrodes were attached to the right atrium of a patient who was undergoing surgery. Each pair of electrodes was placed 10 mm from an ablation line. The change in conduction time between the two pairs of electrodes was measured during ablation. The predicted conduction time delay ratio was 1.54., Results: The actual conduction time after ablation was 1.38-1.43 times longer than the pre-ablation conduction time., Conclusions: The infrared ablation using a newly developed cuboid probe made it possible to create a linear conduction block on the beating right atrial free wall clinically.

Background: Stereotactic radioablation (SR), a commonly used therapy to treat malignant tumors, has been used to treat refractory ventricular tachycardia, but the feasibility of treating atrial fibrillation with SR is unknown., Objective: We evaluated the safety and efficacy of SR targeting pulmonary vein (PV) antral tissues as a potential therapy for atrial fibrillation., Methods: Seventeen adult canines and 2 adult swine underwent surgical fiducial marker placement, 3-dimensional anatomic rendering computed tomography angiogram of the left atrium, and creation of a treatment plan targeting the right superior PVs. Four treatment doses (15, 20, 25, and 35 Gy) were administered to 4 cohorts. Subjects were monitored for 3-6 months, followed by electrophysiological testing, gross pathological examination, and histopathology in 2 subjects., Results: All subjects received SR treatment without complication. Electrophysiology study and gross pathological analysis demonstrated treatment effect in all treated PVs at 35 Gy and 25 Gy (n = 11 of 11 [100%]), with a partial effect at 20 Gy (n = 4 of 5 [80%]; 1 did not undergo repeat electrophysiology study) and 15 Gy (n = 1 of 2 [50%]). No evidence of collateral injury was found in tissues directly adjacent to the treated PVs. In 2 subjects, detailed histopathology demonstrated evidence of circumferential, transmural scar at the PV ablation sites, with sparing of the surrounding structures., Conclusions: SR is safe and effective for creating precise circumferential scar and electrical isolation of the right superior PV in an experimental model, with dose dependence between delivered radioablative energy and observed electrical effects., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

We studied the effects of low-intensity broadband red light on electrical activity of the heart and oxidative modification of proteins in the myocardium of rats after asphyxia. It was shown that low-intensity red light reduced the content of oxidatively modified proteins in rat heart after oxidative stress caused by asphyxia. Exposure to low-intensity red light normalized ECG parameters in rats after asphyxia.

This article provides a contemporary review of the current role of amiodarone and dronedarone in patients with atrial fibrillation who need to undergo rhythm control therapy for relief of symptoms. Amiodarone is the most widely prescribed antiarrhythmic drug for this indication. Recent findings show that its use is not associated with increased mortality even in patients with advanced structural heart disease. However, its extracardiac side effect profile may limit its widespread use. Dronedarone appears to be a useful drug in patients with paroxysmal or persistent atrial fibrillation. However, the compound cannot be used in patients with heart failure. In permanent atrial fibrillation, dronedarone is likewise contraindicated based on findings from the PALLAS trial., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Long-term clinical outcomes for atrial fibrillation ablation depend on the creation of durable transmural lesions during pulmonary vein isolation and on substrate modification. Focal conventional radiofrequency (RF) ablation studies have demonstrated that tissue temperature and power are important factors for lesion formation. However, the impact and predictability of temperature and power on contiguous, transmural lesion formation with a phased RF system has not been described., Objective: The purpose of this study was to determine the sensitivity, specificity, and predictability of power and temperature to create contiguous, transmural lesions with the temperature-controlled, multielectrode phased RF PVAC GOLD catheter., Methods: Single ablations with the PVAC GOLD catheter were performed in the superior vena cava of 22 pigs. Ablations from 198 PVAC GOLD electrodes were evaluated by gross examination and histopathology for lesion transmurality and contiguity. Lesions were compared to temperature and power data from the phased RF GENius generator. Effective contact was defined as electrodes with a temperature of ≥50°C and a power of ≥3 W., Results: Eighty-five percent (168 of 198) of the lesions were transmural and 79% (106 of 134) were contiguous. Electrode analysis showed that >30 seconds of effective contact identified transmural lesions with 85% sensitivity (95% confidence interval [CI] 78%-89%), 93% specificity (95% CI 76%-99%), and 99% positive predictive value (95% CI 94%-100%). Sensitivity for lesion contiguity was 95% (95% CI 89%-98%), with 62% specificity (95% CI 42%-78%) and 90% positive predictive value (95% CI 83%-95%). No char or coagulum was observed on the catheter or tissue., Conclusion: PVAC GOLD safely, effectively, and predictably creates transmural and contiguous lesions., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the correlation between pulmonary venous (PV) anatomy and acute and long-term success of PV isolation (PVI) with two balloon-based ablation catheter techniques., Methods: One hundred consecutive patients were analyzed in two equal groups treated with either the second-generation cryoballoon (CRYO) catheter or the visually guided laser ablation (VGLA) catheter. All patients underwent multi-detector computed tomography (CT) imaging. The primary and secondary efficacy endpoints were the procedural achievement of proven electrical isolation of all veins and freedom from atrial fibrillation (AF) within a 1-year follow-up period, respectively., Results: Variant PV anatomy was observed in 32% of patients in the CRYO group and in 40% of patients in the VGLA group. All PVs were targeted with either the CRYO catheter (n = 199) or the VGLA catheter (n = 206). One hundred ninety-three of 199 PVs (97%) were successfully isolated in the CRYO group and 194 of 206 PVs (94%) in the VGLA group (p = 0.83). Over a 12-month follow-up, AF recurrence was documented in 11/45 (24%) and 7/43 (16%) patients in the CRYO and the VGLA groups, respectively (p = 0.21). In the CRYO group, a larger left inferior PV size was associated with worse long-term outcome (p = 0.001). In the VGLA group, a larger left superior PV size (p = 0.003) and more oval right inferior PV were associated with worse acute success (p = 0.038). There was no absolute cutoff between PV anatomy and clinical success., Conclusions: The variability of PV anatomy did not significantly compromise acute success of PVI or patient outcomes.

Ultrasound has been shown to produce Premature Ventricular Contractions (PVC's). Two clinical applications in which acute cardiac pacing by ultrasound may be valuable are: (1) preoperative patient screening in cardiac resynchronization therapy surgery; (2) Emergency life support, following an event of sudden death, caused by cardiac arrest. Yet, previously the demonstrated mean success rate of extra-systole induction by High Intensity Focused Ultrasound (HIFU) in rats is below 4.5% (Miller et al., 2011). This stands in contrast to previous work in rats using ultrasound (US) and ultrasound contrast agents (UCAs), where success rates of close to 100% were reported (Rota et al., 2006). Herein, bi-stage temporal sequences of accentuated negative pressure (rarefaction) and positive pressure HIFU transmission (insonation) patterns were applied to anaesthetized rats under real-time vital-signs monitoring and US imaging. This pattern of insonation first produces a gradual growth of dissolved gas cavities in tissue (cavitation) and then an ultrasonic impact. Results demonstrate sequences of successive successful HIFU pacing. Triggering insonation at different delays from the preceding ECG R-wave demonstrated successful HIFU pacing induction from mid ECG T-wave till the next ECG complex's PR interval. Spatially focusing the beam at different locations allows cumulative coverage of the whole left ventricle. Analysis of the acoustic wave patterns and temporal characteristics of paced PVCs is suggested to provide new insight into the mechanisms of HIFU cardiac pacing. Specifically, the observed HIFU pacing temporal success rate distribution suggests against sarcomere length modulation current being the dominant cellular level mechanism of HIFU cardiac pacing and may allow postulating that membrane deformation currents are dominant at the applied insonation conditions., (Copyright © 2014. Published by Elsevier Ltd.)

We developed a novel cardiomyocyte electrical conduction line. We studied electrical conduction block by extra-cellular photosensitization reaction with this conduction line to study electrical blockade by the photosensitization reaction in vitro.

Tachycardia and fibrillation are potentially fatal arrhythmias associated with the formation of rotating spiral waves in the heart. Presently, the termination of these types of arrhythmia is achieved by use of antitachycardia pacing or cardioversion. However, these techniques have serious drawbacks, in that they either have limited application or produce undesirable side effects. Low-energy far-field stimulation has recently been proposed as a superior therapy. This proposed therapeutic method would exploit the phenomenon in which the application of low-energy far-field shocks induces a large number of activation sites ("virtual electrodes") in tissue. It has been found that the formation of such sites can lead to the termination of undesired states in the heart and the restoration of normal beating. In this study we investigate a particular aspect of this method. Here we seek to determine how the activation site density depends on the applied electric field through in vitro experiments carried out on neonatal rat cardiac tissue cultures. The results indicate that the activation site density increases exponentially as a function of the intracellular conductivity and the level of cell isotropy. Additionally, we report numerical results obtained from bidomain simulations of the Beeler-Reuter model that are quantitatively consistent with our experimental results. Also, we derive an intuitive analytical framework that describes the activation site density and provides useful information for determining the ratio of longitudinal to transverse conductivity in a cardiac tissue culture. The results obtained here should be useful in the development of an actual therapeutic method based on low-energy far-field pacing. In addition, they provide a deeper understanding of the intrinsic properties of cardiac cells.

Background: It has long been speculated that mobile phones may interact with the cardiac devices and thereby cardiovascular system may be a potential target for the electromagnetic fields emitted by the mobile phones. Therefore, the present study was designed to test possible effects of radiofrequency waves emitted by digital mobile phones on cardiac autonomic modulation by short-time heart rate variability (HRV) analysis., Methods and Results: A total of 20 healthy young subjects were included to the study. All participants were rested in supine position at least for 15 minutes on a comfortable bed, and then time and frequency domain HRV parameters were recorded at baseline in supine position for 5 minutes. After completion of baseline records, by using a mobile GSM (Global System for Mobile Communication) phone, HRV parameters were recorded at turned off mode, at turned on mode, and at calling mode over 5 minutes periods for each stage., Conclusion: Neither time nor frequency domain HRV parameters altered significantly during off mode compare to their baseline values. Also, neither time nor frequency domain HRV parameters altered significantly during turned on and calling mode compared to their baseline values. Short-time exposure to electromagnetic fields emitted by mobile phone does not affect cardiac autonomic modulation in healthy subjects.

Minimally invasive surgical (MIS) ablation, with pulmonary vein (PV) isolation and ganglionated plexi (GP) ablation, has proven highly successful for paroxysmal atrial fibrillation but has limited success in patients with persistent and long-standing persistent (P-LSP) AF. A set of linear left atrial (LA) lesions has been added to interrupt some macroreentrant components of P-LSP AF. This includes a Transverse Roof Line and Left Fibrous Trigone Line (from Roof Line to mitral annulus at the left fibrous trigone). With complete conduction block (CCB), these lesions should prevent single- or double-loop macroreentrant LA tachycardias from propagating around the PVs or mitral annulus. It is critical to identify whether CCB has been achieved and, if not, to locate the gap for further ablation, since residual gaps will support macroreentrant atrial tachycardias. Confirming CCB involves pacing close to one side of the ablation line and determining the direction of activation on the opposite side, by recording close bipolar electrograms at multiple paired sites (perpendicular and close to the ablation line) along the entire length of the line. Simpler approaches have been used, but all have limitations, especially when the conduction time across a gap is long. The extended lesion set was created after PV isolation and GP ablation in 14 patients with P-LSP AF. Mapping after the first set of radiofrequency applications for the Transverse Roof and Left Trigone Lines confirmed CCB in only 3/14 (21%) patients for each line, showing the importance of checking for CCB. During follow-up (median 8 months), 10/14 (71%) patients had no symptoms of atrial arrhythmia (7/10 off antiarrhythmic drugs). Of the remaining four patients, three have only infrequent episodes (self-terminating in 2/3). These preliminary results suggest that adding Roof and Trigone Lines may increase MIS success in patients with P-LSP AF. Accurate mapping techniques verify CCB and effectively locate gaps in ablation lines for further ablation.

The Cox maze surgical ablation operation is a highly effective treatment for patients with atrial fibrillation, but adoption has been limited by procedure complexity and invasiveness. Minimally invasive approaches using nonsternotomy limited access and eliminating cardiopulmonary bypass have been developed. All published series of minimally invasive surgical ablation for isolated, atrial fibrillation were reviewed. Series were analyzed for method of access, energy source, procedure success, and complications. Outcomes were compiled based on type of atrial fibrillation, method and length of follow-up, and freedom from atrial fibrillation with and without antiarrhythmic drugs. There are 14 published series with outcomes reported in 604 unique patients. Most procedures are performed through bilateral minithoracotomies with video assistance, although in later series a totally thoracoscopic approach is more commonly used. Bipolar radiofrequency is the predominant energy source used, and bilateral pulmonary vein isolation the most common lesion set, with some reports adding ganglionic plexi ablation and more extensive ablation lines. Approximately 53% of the procedures were performed for paroxysmal and 47% for persistent/long-standing persistent atrial fibrillation. Overall freedom from atrial fibrillation at 6-12 months is 84% (59%-91%), with 89% (79%-100%) in paroxysmal and 62% (25%-87%) in persistent/long-standing persistent patients. Overall freedom from atrial fibrillation off of antiarrhythmic drugs is 65% (57%-87%). Results approximating those of the Cox maze procedure are achieved with minimally invasive surgical ablation of atrial fibrillation in patients with paroxysmal atrial fibrillation. Further developments are necessary to further simplify and standardize the procedure, to replicate the results in larger series from more centers, to standardize the reporting of results, and to define a more effective procedure for persistent and long-standing persistent atrial fibrillation.

Introduction: Although life-saving, a strong internal defibrillation shock may temporarily or permanently damage the heart via disruption of cell membranes (electroporation). Spatial extent of electroporation in intact, normal, or infarcted hearts has not been investigated. In this study, shock-induced electroporation in intact rabbit hearts with and without chronic (>4 weeks) left ventricular myocardial infarction (MI) was characterized., Methods and Results: A coil shock electrode was inserted in the right ventricle of Langendorff-perfused hearts. One truncated exponential monophasic shock (+300 V, 8 ms) was delivered by a 150 microF capacitor clinical defibrillator while the heart was perfused with membrane-impermeant dye propidium iodide (PI). The heart was sectioned transversely, and uptake of PI into ventricular myocardium through electropores was quantified. Histological evaluation was performed via Masson's trichrome staining. PI accumulation was minimal in the control (n = 3) and MI (n = 3) hearts without shock. Following shock delivery, (1) in control (n = 5) and MI (n = 5) hearts, electroporation mostly occurred near the shock electrode and was longitudinally distributed along the active region of the shock electrode; (2) in MI group, electroporation was significantly increased (P < 0.05) in the surviving anterior epicardial layers of the infarcted region; and (3) between the control and MI groups, the overall extent of electroporation was similar., Conclusion: Shock-induced electroporation was spatially dependent on the location and dimension of the active region of the shock electrode. The overall extent of electroporation in the MI heart was comparable with the control heart, but the surviving anterior epicardial layers in the infarcted region were more susceptible to electroporation.

Reentrant spiral waves can become pinned to small anatomical obstacles in the heart and lead to monomorphic ventricular tachycardia that can degenerate into polymorphic tachycardia and ventricular fibrillation. Electric field-induced secondary source stimulation can excite directly at the obstacle, and may provide a means to terminate the pinned wave or inhibit the transition to more complex arrhythmia. We used confluent monolayers of neonatal rat ventricular myocytes to investigate the use of low intensity electric field stimulation to perturb the spiral wave. A hole 2-4 mm in diameter was created in the center to pin the spiral wave. Monolayers were stained with voltage-sensitive dye di-4-ANEPPS and mapped at 253 sites. Spiral waves were initiated that attached to the hole (n = 10 monolayers). Electric field pulses 1-s in duration were delivered with increasing strength (0.5-5 V/cm) until the wave terminated after detaching from the hole. At subdetachment intensities, cycle length increased with field strength, was sustained for the duration of the pulse, and returned to its original value after termination of the pulse. Mechanistically, conduction velocity near the wave tip decreased with field strength in the region of depolarization at the obstacle. In summary, electric fields cause strength-dependent slowing or detachment of pinned spiral waves. Our results suggest a means to decelerate tachycardia that may help to prevent wave degeneration.

Introduction: TASER devices deliver electrical pulses that temporarily incapacitate suspects. This study analyzes the theoretical possibility of ventricular fibrillation (VF) induction by TASER currents., Methods and Results: Using finite element models (FEM), the results found that the skin, fat and anisotropic skeletal muscle layers attenuated a large portion of TASER currents, allowing just a fractional amount to penetrate transversally into deeper layers of tissue. The TASER current density reached 91 mA/cm(2), the threshold required to induce VF, at less than 14.7 mm away from the skin surface. This distance is significantly lower than the average skin-heart distance of 35 mm, as measured in subjects with a body-mass index (BMI) matched to that of typical in-custody suspects. The theoretical probability of inducing VF is significantly lower than 0.0000008, or 1:1,270,000. By comparison, the standard for basic safety and essential performance of medical electrical equipment, EN 60601-1, accepts as satisfactory a VF induction probability of 0.002, or 1:500., Conclusion: The results indicated that TASER devices, while not risk free, have a very low cardiac risk profile when used for suspect temporary incapacitation.

Aims: In this study, we evaluated the effects of atrial shock delivered via diagnostic electrophysiology catheters., Methods and Results: In 11 anaesthetized goats, decapolar catheters were positioned in the right atrial appendage (RAA) and coronary sinus (CS). Three different catheters and two cardioversion protocols were evaluated. In four goats, 50 J shocks were delivered using catheters with 1 mm electrodes (surface area 70 mm(2)). In 6 goats, catheters with 2 mm electrodes (area 140 mm(2)) were used. In three of the six goats, 50 J shocks were given while in the other 3, 10 J shocks were delivered. In 1 goat 50 J shocks were delivered via 5 mm electrode catheters (area 310 mm(2)). No persisting adverse effects occurred. However, the electrogram amplitude at the RAA and CS decreased by >50-98% (P > 0.01). The amount of amplitude decrease was most pronounced at the CS site and for 50 J shocks. Goats were sacrificed after 9 +/- 1 days. Macroscopy revealed endocardial lesions at the electrode locations. Microscopy showed endocardial thrombosis, and necrosis with formation of granulation tissue. Changes were most marked with diagnostic catheters and 50 J shocks., Conclusions: Atrial shock delivery via diagnostic catheters causes local ablation lesions. The amount of amplitude decrease, macroscopic and microscopic damages were related to the energy applied and electrode surface area.

This case report describes a 51-year-old man who presented with syncope. His electrocardiogram showed an abnormally long pause and the electrophysiology study revealed a prolonged H-V interval. This was attributed to the radiation therapy he received to the chest. He was successfully treated with implantation of a permanent pacemaker. This case highlights this rare complication of radiation-induced conduction system disease and management of this potentially life-threatening condition.

Static magnetic fields induce flow potentials in arterial flows in and around the heart, that have been detected as distortions in the ECG. The resultant currents flowing through the myocardium could alter the rate or rhythm of the heart. No such changes have been seen in animal experiments, or with humans, in static fields up to 8 T. The possible effects of such currents induced by fields larger than 8 T on cardiac pacemaker rate, and arrhythmogenesis are reviewed, using virtual cardiac tissues-computational models of cardiac electrophysiology. Arrhythmogenesis can be by the initiation of ectopic beats, or by re-entry, whose probability of occurrence is increased by any increase in the electrical heterogeneity, in particular, the action potential duration heterogeneity of the ventricle. Focal ectopic activity would be readily detectable, but since re-entrant arrhythmias are very rare events, even a large increase in their probability of occurrence still leaves them unlikely to be observed. Both of these two arrhythmogenic mechanisms would show a steep sigmoidal, or threshold dependence on induced current intensity, with the threshold for increasing the vulnerability to re-entry less than the threshold for initiating activity. Failure to observe them at fields less than 8 T provides only a lower bound for any threshold for arrhythmogenesis.

Blood flow in an applied magnetic field gives rise to induced voltages in the aorta and other major arteries of the central circulatory system that can be observed as superimposed electrical signals in the electrocardiogram (ECG). The largest magnetically induced voltage occurs during pulsatile blood flow into the aorta, and results in an increased signal at the location of the T-wave in the ECG. Studies involving the measurement of blood pressure, blood flow rate, heart sounds, and cardiac valve displacements have been conducted with monkeys and dogs exposed to static fields up to 1.5 tesla (T) under conditions producing maximum induced voltages in the aorta. Results of these studies gave no indication of alterations in cardiac functions or hemodynamic parameters. Cardiac activity monitored by ECG biotelemetry during continuous exposure of rats to a 1.5-T field for 10 days gave no evidence for any significant changes relative to the 10 days prior to and following exposure. Theoretical modeling of magnetic field interactions with blood flow has included a complete solution of the equation describing the flow of an electrically conductive fluid in the presence of a magnetic field (the Navier-Stokes equation) using the finite element technique. Magnetically induced voltages and current densities as a function of the applied magnetic field strength have been calculated for the aorta and surrounding tissues structures, including the sinoatrial node. Induced current densities in the region of the sinoatrial node are predicted to be >100 mA/m2 at field levels >5 T in an adult human under conditions of maximum electrodynamic coupling with aortic blood flow. Magnetohydrodynamic interactions are predicted to reduce the volume flow rate of blood in the human aorta by a maximum of 1.3%, 4.9%, and 10.4% at field levels of 5, 10, and 15 T, respectively.

Irradiation of the heart begets different complications in which pericardial disease is the most common manifestation. Thoracic irradiation of lymphoma, Hodgkin's disease, lung and breast cancer could be complicated by adverse effects to every structure of the heart. Potential injury of mediastinal irradiation can include acute and late pericarditis, cardiomyopathy, valvular disease and conduction abnormalities. The pathophysiology of these various syndromes is probably similar, starting by prior microvascular injury that leads to subsequent myocardium ischemia, all of which cause late fibrous scars. Acute pericarditis is often asymptomatic and clear spontaneously. Late pericarditis affects approximately 5% of the patients when the irradiation dose exceeds 40 Gy. At this dose, the mortality rate is below than 1%. Cardiomyopathy is rare and often asymptomatic. A long time unrecognized, coronary artery disease, diagnosed in 5 to 10% of the patients, begets multifarious sequelae like myocardial infarction, valvular abnormalities and cardiac rhythm changes. This coronary artery disease is more likely to occur if the patient was young at the time of the irradiation (< or = 21 years) and/or if other cardiovascular risk factors are associated. Incidence and mortality rates of valvular defects are about 20 and 0.5%, respectively. Conduction dysfunctions can also be seen in 5% of the patients. Radiation-induced heart complications seem to be related to total dose (> 30 Gy), irradiated tissue volume and fraction size. Since cardiac complications appear months to years following incidental irradiation of the heart, appropriate screening and long-term cardiac follow-up of these patients is essential.

Background: Creating linear lesions is important for the treatment of arrhythmias such as atrial flutter and fibrillation. Making these lesions with standard radiofrequency catheters can be difficult and may result in charring and thrombosis. The purpose of this study was to evaluate beta-radiation as a novel energy source for creating linear myocardial lesions., Methods and Results: Eight dogs with intact conduction across the cavotricuspid isthmus were studied. The isthmus was irradiated (25 to 50 Gy) with strontium/yttrium-90 delivered via a deflectable 7F catheter (Novoste Corporation). There were no immediate effects, but bidirectional conduction block developed during follow-up studies in 7 of 8 dogs. The dog without conduction block received 25 Gy. After the animals were euthanized, histology revealed transmural, linear areas of fibrosis without any thrombus., Conclusions: Beta-radiation can safely and effectively create linear lesions that are contiguous and nonthrombogenic. This energy source may become an interesting adjunct to radiofrequency for the treatment of atrial flutter and fibrillation.

Purpose: Cardiovascular status was assessed in 48 Hodgkin's disease (HD) survivors at a median of 14.3 years (range, 5.9 to 27.5 years) after diagnosis because they may be at increased risk for cardiovascular abnormalities., Patients and Methods: Patients completed the Short-Form 36 quality-of-life instrument and were screened by echocardiography, exercise stress testing, and resting and 24-hour ECG., Results: All patients received mediastinal irradiation (median, 40.0 Gy; range, 27.0 to 51.7 Gy) at a median age of 16.5 years (range, 6.4 to 25.0 years). Four patients received an anthracycline. Although every patient described their health as good or better, and none had symptomatic heart disease at screening, all but one had cardiac abnormalities on screening. Restrictive cardiomyopathy was suggested by reduced average left ventricular (LV) dimension (P < .001) and mass (P < .001), without increased LV wall thickness. Significant valvular defects were present in 42%; 75% had conduction defects. One survivor developed complete heart block shortly after the study visit. Autonomic dysfunction was suggested by a monotonous heart rate in 57%, persistent tachycardia in 31%, and blunted hemodynamic responses to exercise in 27%. Peak oxygen uptake (VO2max) during exercise, a predictor of mortality in heart failure, was significantly reduced (< 20 mL/kg/m2) in 30% of survivors. VO2max was correlated with increasing fatigue, increasing shortness of breath (both, r = -0.35; P =. 02), and decreasing physical component score on the SF-36 (r = 0.554; P = .00017)., Conclusion: A variety of unsuspected, clinically significant cardiovascular abnormalities are common in long-term survivors of HD who are treated at a young age with mediastinal irradiation. We recommend serial, comprehensive cardiac screening of HD survivors who fit this profile., (Copyright 2004 American Society of Clinical Onocology)

In this work the effect of sinusoidal 50 Hz, 0.2 mT magnetic fields on the red blood cells (RBCs) and heart functions of Albino rats were investigated. Twenty-four male Albino rats were equally divided into four groups, A, B, C, and D. Animals from groups B were continuously exposed to the magnetic field for 15 days; and groups C and D, for 30 days. Group A was used as control. Animals from group D were kept after exposure to the magnetic field for a period of 45 days for delayed effect studies. The osmotic fragility and shape of RBCs' membrane and hemoglobin (Hb) structure tests were carried out for all groups. The dielectric relaxation of Hb molecules was measured in the frequency range of 0.1-10 MHz and the dielectric increment (Deltaepsilon), relaxation time (tau), molecular radius (r), and Cole-Cole parameter (alpha) were calculated for all groups. The ECG was measured for all animals before and after exposure to the magnetic field. The results indicated that exposure of the animals to 50 Hz, 0.2 mT magnetic fields resulted in the decrease of RBCs membrane elasticity and permeability and changes in the molecular structure of Hb. The ECG of the exposed animals was considerably altered. The data also indicated that there was no sign of repair in the newly generated RBCs structure and the ECG after removing the animals from the magnetic field, which indicates that the blood generating system was severely injured. The injuries in the heart of the animals were attributed to the loss of some physiological functions of the RBCs as a result of exposures of the rats to the magnetic field., (Copyright 2003 Wiley-Liss, Inc.)

This article investigates the quantitative predictive capabilities of region-specific models by comparing experimental electrograms obtained from in vivo mapping of the ventricular free wall with those obtained through simulation of a region specific three-dimensional bidomain model that incorporates measured fiber orientations. Epicardial electrograms were recorded from canine left ventricles during and after unipolar pacing using a 528-channel electrode plaque. Fiber directions throughout the tissue were estimated from diffusion-weighted MRI and from pace mapping. Electrograms were computed in the bidomain model with experimentally derived properties during paced activations at the same spatiotemporal resolution as those recorded experimentally. Epicardial potentials from model and experiment were directly compared, and sensitivities of these comparisons to reference electrode location and to the choice of material properties were analyzed. The comparisons performed here demonstrate, that (1) the stimulus artifact can be used to estimate the in vivo myocardial fiber architecture, (2) the correlation between simulated and experimental electrograms decreases with increasing pacing depth, and (3) the quantitative comparisons between bidomain model and experimental data are sensitive to both the description of the fiber architecture, and the location of the unipolar reference electrode, but relatively insensitive to moderate changes in the bidomain conductivities.

Background: A method of atrial ablation was developed with the aim of shortening the aortic cross-clamp time during MAZE surgery. The IRK-151 infrared coagulator (Infrarot-Kontaktkoagulator: MBB: Messerschmidt-Bolkow-Blohn, Germany) was employed. Our aim was to electrophysiologically confirm the efficacy of this device., Methods: The MAZE-III procedure was performed in four mongrel dogs. Instead of a pulmonary vein-encircling incision, IRK-151 was applied several times to create a continuously overlapping circular lesion. After aortic declamping, the potentials of both atria were recorded using 18 bipolar electrodes implanted in the atrial wall. The recording conditions were: 1) sinus rhythm, 2) overdrive pacing from outside the encircling coagulation, and 3) overdrive pacing from inside the encircling coagulation., Results: 1) There was no detectable potential within the pulmonary vein-encircling coagulation. 2) There was no conduction of paced atrial potential inside the encircling coagulation. 3) Only the area within the encircling coagulation was activated by the stimulus. Other parts of the atrium showed sinus rhythm simultaneously., Conclusions: The left atrium within the pulmonary vein-encircling coagulation was isolated electrophysiologically.

Clinical and epidemiological studies attest that alterations in heart rate variability (HRV) are predictive of specific types of cardiovascular morbidity and mortality in otherwise healthy persons. Recent reports also suggest that changes in HRV may be associated with exposure to intermittent magnetic fields (60 Hz, 28.3 microT) in the laboratory and that mortality is increased in cardiac disease categories related to altered HRV for utility workers whose jobs involve longer exposure to elevated magnetic fields. This study combined three approaches to learn more about the specific exposure circumstances under which changes in HRV occur. First, cardiac autonomic control, as indexed by HRV spectral analysis measures, was measured in 24 men during exposure to a much higher intensity field than any previously examined (resultant flux density = 127.3 microT [1273 milliGauss, mG]). Second, HRV measures from the same individual were compared across three relevant test conditions: intermittent and continuous field exposure and during a no-exposure, control condition. Third, electrocardiographic data were analyzed to determine if the precise timing of when the magnetic field switched on or off in relation to the cardiac cycle results in phase-resetting of the human cardiac rhythm. HRV measures were not altered by either field exposure condition compared to the control condition, and no evidence for a phase-resetting mechanism was found. Further research is needed to resolve the differences between the present and the earlier laboratory-based studies of HRV and to determine if cardiac rhythm disturbances are associated with exposure to the more complex magnetic fields found in the man-made environment., (Copyright 2000 Wiley-Liss, Inc.)

Background: With the increasing population of patients with prior mediastinal irradiation, cardiac surgeons will encounter patients with radiation-induced damage to the heart and the great vessels. Awareness of the pathology and the surgical management is essential to provide optimal care for these patients., Methods: Eight patients with radiation-induced heart disease were encountered in the last 10 years. After a brief clinical presentation, the surgical management of radiation-induced heart disease is reviewed., Results: Radiation can affect all the structures in the heart, including the coronary arteries, the valves, and the conduction system. The pericardium is the most commonly involved, and the conduction system is the least involved. Pericardiectomy is quite effective in patients with symptomatic pericardial effusion or constriction. The coronary lesions are located predominantly in the ostial or proximal regions of the epicardial vessels. Percutaneous transluminal coronary angioplasty alone appears to have a high rate of restenosis. Surgical revascularization has good long-term results, and the internal mammary artery should be used if it is satisfactory. The aortic and mitral valves are more commonly involved than the tricuspid and pulmonary valves. Myocardial dysfunction predominantly affects the right ventricle and requires particular attention during cardiopulmonary bypass and in the postoperative period. Restoration of sinus rhythm is essential in view of stiffness of the ventricles. Flexibility in the surgical approach with selective use of thoracotomy will facilitate the surgical procedure in certain patients., Conclusions: Surgeons should be well versed in all the manifestations and the management of radiation-induced heart disease.

This report describes an unusual arrhythmia due to partial damage of an accessory pathway by radiofrequency energy delivered during a catheter ablation procedure. The following phenomena were observed after the first radiofrequency current application: a) manifest anterograde conduction over the Kent bundle was abolished, so that preexcitation disappeared; b) concealed anterograde conduction over the accessory pathway was interrupted, resulting in initiation of orthodromic re-entrant tachycardia by any sinus impulse; c) retrograde conduction through the accessory pathway was impaired, but still present, and a pattern of longitudinal dissociation manifested; this was suggested by alternation of the R-P intervals, that during orthodromic tachycardia were alternatively long and short. Following a second radiofrequency application, the R-P interval during orthodromic tachycardia became markedly prolonged (0.36 sec), to the extent that the pattern mimicked a form of atrial or sinus tachycardia. Retrograde accessory pathway conduction was totally interrupted following a third radiofrequency energy application.

Extremely low frequency magnetic fields interact with an animal by inducing internal electric fields, which are in addition to the normal endogenous fields present in living animals. Male rats weighing about 560 g each were anesthetized with ketamine and xylazine. Small incisions were made in the ventral body wall at the chest and upper abdomen to position a miniature probe for measuring internal electric fields. The calibration constant for the probe size was 5.7 mm, with a flat response from at least 12 Hz to 20 kHz. A cardiac signal, similar to the normal electrocardiogram with a heart rate of about 250 bpm, was readily obtained at the chest. Upon analysis of its spectrum, the cardiac field detected by the probe had a broad maximum at 32-95 Hz. When the rats were exposed to a 1 mT, 60 Hz magnetic field, a spike appeared in the spectrum at 60 Hz. The peak-to-peak magnitudes of electric fields associated with normal heart function were comparable to fields induced by a 1 mT magnetic field at 60 Hz for those positions measured on the body surface (where induced fields were maximal). Within the body, or in different directions relative to the applied field, the induced fields were reduced (reaching zero at the center of the animal). The cardiac field increased near the heart, becoming much larger than the induced field. Thus, the cardiac electric field, together with the other endogenous fields, combine with induced electric fields and help to provide reference levels for the induced-field dosimetry of ELF magnetic field exposures of living animals.

Thirty-two frog hearts were divided into four groups and placed individually in temperature-controlled waveguides filled with Ringer's solution. The pacemaker was removed, and stimulation was provided at 0.3 Hz by three carbon-loaded Teflon electrodes located on the aorta and the ventricular muscle. Conduction velocity was measured from the difference between two action potentials. One group served as control; the three other groups were exposed for 2 h to pulsed 2,450 MHz microwave fields (10 microseconds, 0.001 duty cycle, 16 Hz modulation) at specific absorption rates (SARs) of 0.003, 2, and 6 W/kg, respectively. No significant difference in conduction velocity was found between the control and the exposed groups.

Background: High rates of success using radiofrequency ablation energy have rapidly transformed catheter ablation from an investigational procedure to the nonpharmacological therapy of choice for symptomatic Wolff-Parkinson-White syndrome. Prior studies of radiofrequency accessory pathway ablation were based on a ventricular approach. Risks associated with prolonged arterial catheter manipulation, retrograde left ventricular catheterization, and production of ventricular lesions required for successful ventricular insertion ablation can be avoided using atrial insertion ablation procedures. The purpose of the present study was to define the safety and efficacy of accessory pathway ablation using radiofrequency energy delivered solely to accessory atrioventricular pathway atrial insertion sites., Methods and Results: One hundred fourteen patients with accessory pathway-mediated tachycardia underwent attempted radiofrequency current ablation at the accessory pathway atrial insertion site. All catheters were introduced transvenously. Left-sided accessory pathways were approached using transseptal left atrial catheterization techniques. Retrograde localization of the atrial insertion site during reentrant tachycardia was characterized by 40 +/- 15-msec local ventriculoatrial and 79 +/- 17-msec surface QRS to local atrial electrogram intervals. Presumed accessory pathway potentials were present in only 30% of ablation site electrograms. Successful ablation required 6.2 +/- 5.3 radiofrequency energy applications. Cumulative energy dose required for success was 2,341 +/- 2,233 J. There were no complications associated with transseptal catheterization. Energy delivery to accessory pathway atrial insertion sites was associated with non-life-threatening complications in two patients. Recurrent conduction requiring repeat ablation occurred in 10 of 115 (9%) successfully ablated accessory pathways, all within 1 month of the ablation procedure. After 21.2 +/- 4.6 months of follow-up, 108 of 114 (95%) patients are asymptomatic and without evidence of accessory pathway conduction., Conclusions: The atrial insertion approach to accessory pathway ablation is safe and highly effective. This approach compares favorably with the retrograde ventricular insertion ablation technique. Atrial insertion ablation eliminates the need to produce ventricular lesions and avoids the risks of prolonged arterial catheter manipulation and retrograde left ventricular catheterization.

Intracardiac defibrillation to produce complete heart block is a modern and effective method for treatment of refractory supraventricular arrhythmias. The main drawback of this technique is the necessity of implantation of permanent pacemaker. There is however a growing interest in modification of atrio-ventricular (A-V) conduction to prevent arrhythmias without producing complete heart block. A new energy source used for this purpose is the radiofrequency (RF) current. Preliminary clinical results of modification of antegrade conduction in 5 patients with recurrent supraventricular arrhythmias are presented. HAT 100 (Dr Osypka GmbH, Germany) a high frequency generator was used for modification. Electrophysiological studies showed slow/fast type of junctional reentry tachycardia in 4 patients and paroxysmal atrial flutter with rapid ventricular response in 1. Since RF current produces much smaller and more discrete lesion, the precise localization of the active electrode was of primary importance. We manipulated the catheter, used for modification, in AV region until a relatively large atrial potential with only barely visible His bundle deflection was obtained. During reentry tachycardia the place of the earliest retrograde atrial depolarization was searched for. Current and voltage were monitored during the modification procedure. It was possible to titrate the HF energy to achieve the desired effect changing the power and the time of current application. The modification was repeated several times since PQ and AH interval increased > 50%. No prolongation of HV was noted. The modification was effective in all patients and allowed to avoid the induction of reentry despite the persistence of 1:1 AV conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Isolated pacemaker of the frog's heart served as a sensitive model to study the combined action of the low intensity electromagnetic and mechanic factors. Critical energy levels of factors, their relative efficiency in direct action on the cell were estimated. Additive effects of microwaves and ultrasound were examined. The data can be valuable for the further investigations concerning the effects of different nonionizing rays.

Precise location of the endocardial site of origin of ventricular tachycardia may facilitate surgical and catheter ablation of this arrhythmia. The endocardial catheter mapping technique can locate the site of ventricular tachycardia within 4-8 cm2 of the earliest site recorded by the catheter. This report describes an orthogonal electrode catheter array (OECA) for mapping and radiofrequency ablation (RFA) of endocardial focal site of origin of a plunge electrode paced model of ventricular activation in dogs. The OECA is an 8 F five pole catheter with four peripheral electrodes and one central electrode (total surface area 0.8 cm2. In eight mongrel dogs, mapping was performed by arbitrarily dividing the left ventricle (LV) into four segments. Each segment was mapped with OECA to find the earliest segment. Bipolar and unipolar electrograms were obtained. The plunge electrode (not visible on fluoroscopy) site was identified by the earliest wave front arrival times of -30 msec or earlier at two or more electrodes (unipolar electrograms) with reference to the earliest recorded surface ECG (I, AVF, and V1). Validation of the proximity of the five electrodes of the OECA to the plunge electrode was performed by digital radiography and RFA. Pathological examination was performed to document the proximity of the OECA to the plunge electrode and also for the width, depth, and microscopic changes of the ablation. To find the segment with the earliest LV activation a total of 10 +/- 3 (mean +/- SD) positions were mapped. Mean arrival times at the two earlier electrodes were -39 +/- 4 msec and -35 +/- 3 msec. Digital radiography showed the plunge electrode to be within the area covered by all five electrodes in all eight dogs. The plunge electrode was within 1 cm2 area of the region of RFA in all eight dogs. The width and depth of ablation were 5 +/- 3.5 and 7 +/- 3.5 mm, respectively. Microscopic changes revealed coagulative necrosis, hemorrhage, and inflammatory changes in all RFAs. In conclusion, the OECA can map the endocardial focal site of origin of paced ventricular activation within 1 cm2 area in a canine model. RFA from the OECA can cause discrete ablations representing all five electrodes or cross-shaped ablation connecting central electrode to all four peripheral electrodes. This catheter holds promise for extending surgical and clinical catheter ablation procedures.

Systematic ECG-analysis were performed in 13 patients (mean age 55.1 years) with mammary carcinoma on the left, prior to, during, and 4 months after postoperative radiation therapy. Treatment was done with a gammatron, the average load to the anterior cardiac wall amounted to 36 Gy. All patients exhibited ST-T segment changes, flat, isoelectric or coronary negative T-waves in the precordial leads demonstrating radiation-induced perimyocarditis. Prolongation of QT-interval corrected with Bazett's formula (QTc) was observed in 6 patients showing myocardial damage. Sinus tachycardia in 9 patients and lower voltage in 3 patients gave a hint to early appearance of pericardial effusions. Pulmonary P-waves in 6 patients and shift of QRS-axis to the right in 5 patients demonstrated early damage of the right heart. Clinical deterioration could not be seen in any patient.

Using computerized tomography (CT) in which cardiac anatomy was defined, doses delivered to the cardiac compartments, vascular and conduction systems were assessed for various standard techniques of primary breast irradiation. Included in the analysis were 6 MV photon tangents (T) alone, or in conjunction with a separate internal mammary field (IMF). Beams evaluated in the IMF were 6 MV photons, 12 MeV electron beam, and mixed photon/electron beam; Cobalt 60 was also analyzed as an alternate photon beam. Treatment of the IMF with photons, either alone or in combination with electron beam, delivered doses ranging between 30 Gy to 50 Gy to all chambers of the heart, coronary arteries and branches of the conduction system. Complete sparing of the posterior cardiac structures and volume is accomplished with treatment plans using tangents alone or in combination with 12 MeV electron beam irradiation to the IMF. Sparing of the anterior wall of the left ventricle, Bundle of His and left anterior descending coronary artery is also achieved in treatment with tangents and 12 MeV electron beam IMF. Doses to this region with tangents alone ranged from 20 Gy to 45 Gy compared to 0 to 30 Gy with tangents and 12 MeV electron beam IMF. Clinical significance of these findings will be discussed.