Treatment Of Various Arrhythmias Research Articles

Prokaryotic voltage-gated sodium channels are more effective than endogenous Nav1.5 channels in rescuing cardiac action potential conduction: an in silico study.

Methods to augment Na+ current in cardiomyocytes hold potential for the treatment of various cardiac arrhythmias involving conduction slowing. Because the gene coding cardiac Na+ channel (Nav1.5) is too large to fit in a single adeno-associated virus (AAV) vector, new gene therapies are being developed to enhance endogenous Nav1.5 current (by overexpression of chaperon molecules or use of multiple AAV vectors) or to exogenously introduce prokaryotic voltage-gated Na+ channels (BacNav) whose gene size is significantly smaller than that of the Nav1.5. In this study, based on experimental measurements in heterologous expression systems, we developed an improved computational model of the BacNav channel, NavSheP D60A. We then compared in silico how NavSheP D60A expression vs. Nav1.5 augmentation affects the electrophysiology of cardiac tissue. We found that the incorporation of BacNav channels in both adult guinea pig and human cardiomyocyte models increased their excitability and reduced action potential duration. When compared with equivalent augmentation of Nav1.5 current in simulated settings of reduced tissue excitability, the addition of the BacNav current was superior in improving the safety of conduction under conditions of current source-load mismatch, reducing the vulnerability to unidirectional conduction block during premature pacing, preventing the instability and breakup of spiral waves, and normalizing the conduction and ECG in Brugada syndrome tissues with mutated Nav1.5. Overall, our studies show that compared with a potential enhancement of the endogenous Nav1.5 current, expression of the BacNav channels with their slower inactivation kinetics can provide greater anti-arrhythmic benefits in hearts with compromised action potential conduction.NEW & NOTEWORTHY Slow action potential conduction is a common cause of various cardiac arrhythmias; yet, current pharmacotherapies cannot augment cardiac conduction. This in silico study compared the efficacy of recently proposed antiarrhythmic gene therapy approaches that increase peak sodium current in cardiomyocytes. When compared with the augmentation of endogenous sodium current, expression of slower-inactivating bacterial sodium channels was superior in preventing conduction block and arrhythmia induction. These results further the promise of antiarrhythmic gene therapies targeting sodium channels.

Outcome of catheter ablation in the very elderly-insights from a large matched analysis.

BackgroundAblation emerged as first line therapy in the treatment of various arrhythmias. Nevertheless, in older patients (pts), decision is often made pro drug treatment as more complications and less benefit are suspected.HypothesisWe hypothesized that different kind of ablations can be performed safely regardless of the pts age.MethodsWe enrolled all pts aged >80 years (yrs) who underwent ablation for three different arrhythmias (atrial flutter [AFL], atrioventricular nodal re‐entry tachycardia [AVNRT], ventricular tachycardia [VT]) between August 2002 and December 2018. Procedural data and outcome were compared with matched groups aged 60 to 80 years and 40 to 60 years, respectively. Periprocedural and in‐hospital complications were analyzed.ResultsThe analysis included 1191 patients (397 pts per group: 63% AFL, 23% AVNRT, 14% VT) who underwent ablation. Acute success was high in all types of arrhythmias irrespective of age (>80, 60‐80, 40‐60 years: AFL 97%/98%/98%, AVNRT 97%/95%/97%, VT 82%/86%/93%). Rate of periprocedural complications were similar in all groups treated for AFL and AVNRT. For VT ablations significant differences were noted between pts > 80 or 60 to 80 years and those aged 40‐60 years (16.1%/14.3%/3.6%). Most complications were infections and groin haematoma. No strokes, iatrogenic atrioventricular blocks and deaths related to the ablation occurred.ConclusionAblation appears safe in pts > 80 years. Success rates were comparable to matched younger cohorts. A significant difference was observed for VT patients.

Isolated Neutropenia: An Unexplored Side Effect of Amiodarone

Amiodarone has been widely used for the treatment of various arrhythmias. It is a potent P450 inhibitor leading to interaction with many commonly prescribed drugs. Also, due to its long half-life, lipophilicity, and broad tissue distribution, it can cause a wide range of toxicities. A 62-year-old male with the unknown past medical history presented to the emergency department following a grand mal seizure. The patient initially presented with atrial flutter, which was controlled with beta blockers but was switched to amiodarone after 2 weeks when he developed atrial fibrillation with the rapid ventricular response. Approximately 1 month into his hospital stay, the patient developed severe isolated neutropenia. After ruling out other etiologies, amiodarone was withdrawn. The patient’s absolute neutrophil count recovered 3 days after discontinuation of amiodarone. J Med Cases. 2020;11(1):1-5 doi: https://doi.org/10.14740/jmc3394

Real-time contact force measurement: a key parameter for controlling lesion creation with radiofrequency energy.

Radiofrequency (RF) energy, the dominant energy source for the treatment of various arrhythmias by catheter ablation, has replaced most other treatments for the effective suppression of supraventricular and ventricular arrhythmias.1 With expanding indications, it has become increasingly clear that the success and sustainable effect of RF ablation depends on a critical understanding of the biophysics of lesion creation and its control. RF current at the electrode tissue (ET) interface is the key to RF lesion creation by virtue of its tissue heating capability2 but cannot be measured directly, and therefore, delivered RF power and duration are typically manipulated to control lesion creation.3 Despite such manipulation, there is significant variability in lesion size, which is thought to be responsible for both inefficacy and complications. Contact between electrode and tissue may be the key parameter to control lesion size because it is essential for the passage of current into the target tissue, but has until recently remained intangible and unmeasurable. RF energy delivery creates tissue coagulation and necrosis by producing targeted tissue hyperthermia. This hyperthermia is the consequence of resistive heating of a thin rim of tissue in direct contact with the RF energy delivering electrode, with surrounding tissue being heated by conduction. Direct resistive heating is produced by a high density of alternating current, the magnitude of which declines with the inverse of the square of the distance; therefore, target tissue contact is essential for effective lesion formation.3 The key to effective and safe treatment with RF catheter ablation is controlling lesion size, that is, increasing or decreasing lesion size as desired. Precise control of lesion size is particularly important for treatment strategies requiring multiple coalescent ablations, for example, linear lesions making strategies, such as for atrial flutter, atrial fibrillation (AF), and reentrant ventricular tachycardia.4 The …

Feasibility of Implementation of a “Simplified, No‐X‐Ray, No‐Lead Apron, Two‐Catheter Approach” for Ablation of Supraventricular Arrhythmias in Children and Adults

Although the "near-zero-X-Ray" or "No-X-Ray" catheter ablation (CA) approach has been reported for treatment of various arrhythmias, few prospective studies have strictly used "No-X-Ray," simplified 2-catheter approaches for CA in patients with supraventricular tachycardia (SVT). We assessed the feasibility of a minimally invasive, nonfluoroscopic (MINI) CA approach in such patients. Data were obtained from a prospective multicenter CA registry of patients with regular SVTs. After femoral access, 2 catheters were used to create simple, 3D electroanatomic maps and to perform electrophysiologic studies. Medical staff did not use lead aprons after the first 10 MINI CA cases. A total of 188 patients (age, 45 ± 21 years; 17% <19 years; 55% women) referred for the No-X-Ray approach were included. They were compared to 714 consecutive patients referred for a simplified approach using X-rays (age, 52 ± 18 years; 7% <19 years; 55% women). There were 9 protocol exceptions that necessitated the use of X-rays. Ultimately, 179/188 patients underwent the procedure without fluoroscopy, with an acute success rate of 98%. The procedure times (63 ± 26 vs. 63 ± 29 minutes, P > 0.05), major complications (0% vs. 0%, P > 0.05) and acute (98% vs. 98%, P > 0.05) and long-term (93% vs. 94%, P > 0.05) success rates were similar in the "No-X-Ray" and control groups. Implementation of a strict "No-X-Ray, simplified 2-catheter" CA approach is safe and effective in majority of the patients with SVT. This modified approach for SVTs should be prospectively validated in a multicenter study.

The role of magnesium in cardiac arrhythmias

Magnesium plays an essential role in many fundamental biological reactions, as it is involved in more than 300 metabolic reactions. Deficiency of magnesium may result in many disorders, including cardiac arrhythmias. As intravenous magnesium has a high therapeutic to toxic ratio and a minimal negative inotropic effect, it has long been used in treatment and prevention of cardiac arrhythmias. Several studies have shown the beneficial effect of intravenous infusion of Mg during an attack of supraventricular tachycardia, indicating that the effectiveness of magnesium depends on the type of tachycardia. Magnesium has also an advantageous effect in the case of atrial fibrillation, considered a criterion of the effectiveness of atrial fibrillation acute treatment at the ventricular rate ≤ 100 min–1. As intravenous magnesium seems to be useful in prevention and treatment of various cardiac arrhythmias, it is a common component of a complex antiarrhythmic therapy.

Redox Control of Cardiac Excitability

Reactive oxygen species (ROS) have been associated with various human diseases, and considerable attention has been paid to investigate their physiological effects. Various ROS are synthesized in the mitochondria and accumulate in the cytoplasm if the cellular antioxidant defense mechanism fails. The critical balance of this ROS synthesis and antioxidant defense systems is termed the redox system of the cell. Various cardiovascular diseases have also been affected by redox to different degrees. ROS have been indicated as both detrimental and protective, via different cellular pathways, for cardiac myocyte functions, electrophysiology, and pharmacology. Mostly, the ROS functions depend on the type and amount of ROS synthesized. While the literature clearly indicates ROS effects on cardiac contractility, their effects on cardiac excitability are relatively under appreciated. Cardiac excitability depends on the functions of various cardiac sarcolemal or mitochondrial ion channels carrying various depolarizing or repolarizing currents that also maintain cellular ionic homeostasis. ROS alter the functions of these ion channels to various degrees to determine excitability by affecting the cellular resting potential and the morphology of the cardiac action potential. Thus, redox balance regulates cardiac excitability, and under pathological regulation, may alter action potential propagation to cause arrhythmia. Understanding how redox affects cellular excitability may lead to potential prophylaxis or treatment for various arrhythmias. This review will focus on the studies of redox and cardiac excitation.

Arrhythmogenic Ion-Channel Remodeling in Heart Failure and Upstream Approach

Class I antiarrhythmic drugs with Na+ channel blocking action cannot be readily used for the treatment of various arrhythmias associated with heart failure because the antiarrhthmic drugs may worsen cardiac function. In failing hearts ion-channel remodeling, such as downregulation of K channels and connexin 43, upregulation of Na-Ca exchanger and HCN channels, and instability of Ca release channels in sarcoplasmic reticulum, can be observed. These electrophysiological abnormalities can produce severe ventricular tachyarrhythmias through reentrant and automatic mechanisms. Neurohumoral factors such as renin-angiotensin system, endothelin system and sympathetic nervous system play an important role in the establishment of the ion-channel remodeling. Upstream approach with blockade of the neurohumoral factors may prevent lethal ventricular arrhythmias. In congestive heart failure atrial tissues are expanded and susceptibility to atrial fibrillation is increased. Control of neurohumoral factors may be also beneficial for the prevention of atrial fibrillation. Recently it has been suggested that inflammatory mechanisms may be also involved in not only the deterioration of heart failure but also induction of atrial fibrillation and ventricular tachyarrhythmias. Drugs with anti-inflammatory action, including the antiarrhythmic drug amiodarone, may be effective for the treatment of arrhythmias associated with heart failure. Current perspective of upstream approach to preventing atrial and ventricular arrhythmias associated with heart failure will be discussed.

Effects of Antiarrhythmic Drugs on the Hyperpolarization-Activated Cyclic Nucleotide–Gated Channel Current

After the report of the Cardiac Arrhythmia Suppression Trial, a tabular framework of the Sicilian Gambit has been proposed to display actions of antiarrhythmic drugs on ion channels and receptors and to provide more rational pharmacotherapy of arrhythmias. However, because effects of antiarrhythmic drugs on If have not been thoroughly examined, we used patch clamp techniques to determine the effects of various antiarrhythmic drugs on the HCN (hyperpolarization-activated cyclic nucleotide-gated) channel currents. HCN4 channels, a dominant isoform of HCN channels in the heart, were expressed in HEK293 cells. Amiodarone and bepridil potently inhibited the HCN4 channel current with IC50 values of 4.5 and 4.9 microM, respectively, which were close to their therapeutic concentrations. The inhibitory effects of quinidine, disopyramide, cibenzoline, lidocaine, mexiletine, aprindine, propafenone, flecainide, propranolol, and verapamil on the HCN4 channel current were weak in their therapeutic concentrations, with IC50 values of 78.3, 249, 46.8, 276, 309, 43.7, 14.3, 1700, 50.5, and 44.9 microM, respectively, suggesting that the inhibitory effects on If would be clinically small. D,L-Sotalol hardly affected the HCN4 channel current. Information about the HCN4-channel effects of many antiarrhythmic drugs may be useful for determining the appropriate drug for treatment of various arrhythmias while minimizing adverse effects.

Amiodarone Induced Thyrotoxicosis (Type II)

Amiodarone is an iodinated benzofuran derivative, that is highly effective as an agent for the treatment of various cardiac arrhythmias; these arrthymias, range from paroxysmal atrial fibrillation to life-threatening ventricular tachyarrhythmias. Yet amiodarone is associated with several side effects that include dysfunction of liver, thyroid or various other organs. Two main forms of amiodarone induced thyrotoxicosis (AIT) have been described; type I AIT develops in an abnormal thyroid gland (nodular goiter, latent Graves' disease) and it is due to amiodarone-induced true hyperthyroidism; type II AIT occurs in an apparently normal thyroid gland and it is due to amiodarone-induced destructive thyroiditis. We recently experienced a case of type II thyrotoxicosis that was induced by amiodarone treatment for ventricular tachycardia after acute myocardial infarction. The symptoms of thyrotoxicosis were relieved after withdrawal of amiodarone and administering steroid. Type I AIT has often been reported on but type II AIT is relatively rare. We report here on a case of type II amiodarone induced thyrotoxicosis along with a literature review.

Characterization of Radiofrequency Ablation Lesions With Gadolinium-Enhanced Cardiovascular Magnetic Resonance Imaging

This study was designed to evaluate the characteristics of gadolinium-enhanced imaging of radiofrequency ablations. Gadolinium-enhanced magnetic resonance imaging (MRI) has been used successfully to evaluate tissue necrosis after myocardial infarction. In electrophysiology, radiofrequency energy is used to create a targeted myocardial necrosis for the treatment of various arrhythmias. Using a power-controlled, cooled-tip 7-F catheter system, radiofrequency lesions (10 to 40 W for 30 s) were created on the epicardium of the right ventricle in eight mongrel dogs. After injection of 0.225 mmol/kg gadolinium, T1-weighted fast gradient echo images were obtained during a follow-up of 10 h using an intrathoracic high-resolution coil. Radiofrequency ablations were analyzed on the MR images and compared with gross anatomy and histopathology. Four distinct phases of signal enhancement were observed. After gadolinium injection, radiofrequency lesions were delineated clearly as contrast-free areas of low signal intensity (contrast-to-noise ratio [CNR] = -21.1 +/- 19.8). Signal enhancement in the lesion periphery started 4.0 +/- 1.8 min after injection and progressively extended toward the lesion center at a rate of 0.02 mm/min. Full delayed enhancement was observed after 98 +/- 21 min (CNR = +17.8 +/- 9.0). During the follow-up period, CNR started to decrease, but the lesions were detectable for as long as 10 h of follow-up. During the first three phases of enhancement, MRI correlated well with the pathological findings (r = 0.88, r = 0.88, and r = 0.86 [p < 0.001], respectively). Radiofrequency ablation can be evaluated accurately by using gadolinium-enhanced MRI, which may allow the noninvasive assessment of procedural success. The dissimilar wash-in and wash-out kinetics compared with myocardial infarction suggest a different pathophysiological process with complete loss of microvasculature.

Catheter ablation using very high frequency current: effects on the atrioventricular junction and ventricular myocardium in sheep.

Radiofrequency ablation is currently used in the treatment of various cardiac arrhythmias. However, this technique is limited by impedance rise, leading to coagulum formation and desiccation of tissue. We developed a new generator, providing very high frequency (27 MHz) current, which is in the intermediate range between radiofrequency and microwave energy. The aim of this study was to evaluate the results for catheter ablation of the atrioventricular junction and characteristics of the lesions obtained at ventricular sites. The generator was coupled to a specially designed 7-French coaxial catheter. The study included experiments performed on 10 sheep (Wt. 31- 42 kg). In seven sheep, the catheter was introduced into the femoral vein and advanced across the tricuspid annulus to record the largest possible His electrogram. VHF current was applied for 25 s, with increasing energies. The energy needed to obtain complete atrioventricular (AV) block ranged from 60 to 100 Watts. Six animals were observed for 6 to 21 days. Complete AV block was found to be persistent. In those seven sheep in whom AV junction was ablated and in three additional sheep, the ablation catheter was positioned toward the right ventricular apex using the same approach and into the left ventricle via the femoral artery, and 20 to 90 Watts energy was delivered in order to assess the size of the induced lesions. Side effects included ventricular tachycardia degenerating into ventricular fibrillation in six cases, but the same effect was observed in this animal model with radiofrequency energy. No cardiac perforation was noted. No thrombus was observed at the catheter tip. The size of the lesion ranged from 3 to 45 mm in width and 1 to 15 mm in depth. Catheter ablation using VHF current is feasible and appears effective in producing stable AV block when applied at the AV junction and results in substantial myocardial lesions. Further studies are needed to define its clinical interest and side effects.

Reproductive issues in adults with congenital heart disease: arrhythmias during pregnancy: importance, diagnosis and therapy.

Even in healthy women, increased ectopic activity is commonly seen during pregnancy. Congenital heart defects--whether nonoperated or operated--are, in general, associated with an increased risk of arrhythmias to a greater or lesser extent. During pregnancy, congenital heart disease patients are at increased risk of presenting first time with a symptomatic arrhythmia or, if previously diagnosed, the risk of recurrence of their arrhythmia is increased. Antiarrhythmic therapy should in general be restricted to the presence of intolerable symptoms, hemodynamic compromise or threat to the fetus and to patients in whom the arrhythmia may be life-threatening. The risk/benefit ratio must be considered for both the mother and the fetus. Considerations include the stage of pregnancy as well as possible effects of therapy on labor, delivery, and lactation. Nearly all of the presently available antiarrhythmic drugs are classified as Category C drugs in pregnancy. Thus, we rely on observational reports. Safety data are discussed for various drugs, and recommendations for the treatment of various arrhythmias are presented in this review.

Electromechanical mapping of the heart.

Electromechanical endocardial mapping of the heart using a nonfluoroscopic catheter-based system is a new imaging modality that has been studied recently in the experimental setting as well as in patients. Besides its original application in the diagnosis and treatment of various cardiac arrhythmias, it has also been used as an investigational tool for assessing left ventricular function and viability. Finally, the mapping system may be a valuable platform for direct myocardial revascularization using either laser treatment or injection of pharmacologic agents.

10] In vitro assessment of various cytochromes P450 and glucuronosyltransferases using the antiarrhythmic propafenone as a probe drug

Publisher Summary The antiarrhythmic propafenone is used in the treatment of various cardiac arrhythmias. The drug undergoes extensive metabolism in man by both P450 enzymes (formation of 5-hydroxypropafenone and N -desalkylpropafenone) and glucuronosyltransferases (formation of propafenone glucuronide and 5-hydroxypropafenone glucuronide). The chapter describes the experimental conditions for in vitro assessment of each metabolite. The phase I and phase II metabolism of the antiarrhythmic propafenone are subjected to detailed investigations. The P450 enzymes involved in the formation of 5-hydroxypropafenone and N -desalkylpropafenone have been identified; the in vitro system enables monitoring of the activity of these enzymes. Development and validation of a combined in vitro assay for the oxidative and phase II metabolism of propafenone will allow investigations of a coregulation of both enzyme systems that have been suggested for other substrates based on in vivo experiments.

Electrophysiologic effects of intravenous magnesium in patients with normal conduction systems and no clinical evidence of significant cardiac disease

Parenteral magnesium has been used for several decades in the empiric treatment of various arrhythmias, but the data on its electrophysiologic effects in man are limited. We evaluated the electrophysiologic effects of magnesium sulfate (MgSO 4) administration in eight normomagnesemic patients with normal mononuclear cell magnesium content, who had no clinically significant heart disease and had normal baseline electrophysiologic properties. After administration of intravenous MgSO 4, serum magnesium rose significantly from 1.9 ± 0.1 to 4.4 ± 1.7 mg/dl ( p < 0.02). During a maintenance magnesium infusion, we observed significant prolongation of the ECG PR interval (145 ± 18 to 155 ± 26 msec, p < 0.05), AH interval (77 ± 27 to 83 ± 26 msec, p < 0.002), antegrade atrioventricular (AV) nodal effective refractory period (278 ± 67 to 293 ± 67 msec, p < 0.05), and sinoatrial conduction time (60 ± 34 to 76 ± 32 msec, p < 0.02). No significant effect was observed on sinus cycle length, sinus node recovery time, intra-atrial or intraventricular conduction times, QRS duration (during both sinus rhythm and ventricular pacing), QT interval, HV interval, paced cycle length resulting in AV nodal Wenckebach block, AV nodal functional refractory period, retrograde ventriculoatrial (VA) effective refractory period, or atrial and ventricular refractory periods. These findings, in conjunction with the demonstrated ability of magnesium to block slow channels for sodium movement, may provide an explanation of the mechanism by which magnesium exerts its effect in the treatment of atrial and junctional arrhythmias.

Quinidine-induced hepatitis

To the Editor. —The article on quinidine-induced hepatitis by Knobler et al 1 is interesting and important. Curiously, no mention is made of the reason why quinidine was given to 1500 patients in a ten-year period at their hospital. Hopefully, the recovery that occurred after cessation of the drug will not encourage its use. Indeed, although quinidine is widely used (and has been for a long time) in the prevention and treatment of various arrhythmias, it use remains moot, and adverse effects continue to be emphasized. 2 Yet, it is certain that in most, if not all, instances the use of quinidine can be avoided.

Optimal mode of transesophageal atrial pacing

The optimal mode of transesophageal atrial pacing was determined by clinical electrophysiologic studies in 15 healthy adult volunteers. The point at which the unipolar atrial electrogram was biphasic and largest in amplitude (35.4 ± 1.6 cm from the incisors) was considered the best stimulation site for atrial pacing. The stimulation threshold on bipolar pacing (using the proximal pole as cathode and the distal pole as anode) at this site was 27 ± 7 mA, which was significantly lower (p < 0.001, n = 10) than that on unipolar cathodal stimulation (41 ± 8 mA). Although the stimulation threshold tended to be higher with a No. 10Fr electrode catheter (30 ± 5 mA) than with a No. 6Fr catheter (27 ± 7 mA), the difference was statistically insignificant (n = 9). When the interpolar distance in bipolar stimulation was varied in 5 steps from 12 to 80 mm, the threshold was lowest at the distance of 24 mm. Of the 10 pulse durations tested, ranging from 0.25 to 128 ms, 8 ms appeared most desirable in minimizing the total amount of current and chest discomfort accompanying the pacing. With the optimal site, interpolar distance and pulse duration, transesophageal atrial pacing was successfully performed in all patients, without producing significant complications such as chest pain. Transesophageal atrial pacing is noninvasive, technically simple and efficient, and may be valuable in the diagnosis and treatment of various cardiac arrhythmias.

Intravenous amiodarone in the treatment of various arrhythmias following cardiac operations

In a group of 95 patients having cardiac operations with extracorporeal circulation, intravenous (IV) amiodarone, administered in doses of 2.5 to 5 mg/kg, was used in the treatment of various perioperative arrhythmias. Conversion to sinus rhythm was achieved in 55 (61%) of 90 patients with supraventricular arrhythmias, the other patients showing a satisfactory slowing of their heart rate. Total suppression and control was obtained in 18 patients with persistent ventricular extrasystoles associated with various supraventricular arrhythmias. Amiodarone was administered in five patients with life-threatening ventricular arrhythmias resistant to other antiarrhythmic agents: Suppression was obtained in one of two patients with recurrent ventricular tachycardias and control was achieved in three patients with repetitive ventricular tachycardia and ventricular fibrillation, allowing the effective use of intra-aortic balloon counterpulsation (IABP) needed for hemodynamic support. Seven patients experienced minor side effects such as nausea or flushing. No complete atrioventricular (AV) block was noted. Significant hypotension occurred at the end of the IV injection in 17 (18%) patients. In all but five patients, hypotenion was transient, without clinical complications. In the five others, adrenergic drugs in four cases and IABP in one case were necessary. Those five patients had marked cardiomegaly with poor myocardial contractility. IV bolus injection of amiodarone seems prohibited in such patients; constant infusion would be preferable.

人工ペースメーカと不整脈の治療 : III. ペースメーカと電極の選択,植込み術式,および合併症と対策

人工ペースメーカと不整脈の治療 : III. ペースメーカと電極の選択,植込み術式,および合併症と対策