Characteristics of successful termination of atrial fibrillation by atrial antitachycardia pacing in patients with cardiac implantable electronic devices.

Asymptomatic paroxysmal atrial fibrillation (AF) is often found in patients implanted with cardiac implantable electronic devices (CIEDs). Second-generation atrial antitachycardia pacing (A-ATP) is effective in managing AF in patients implanted with CIEDs. The purpose of this study was to evaluate the efficacy and safety of A-ATP in patients implanted with CIEDs. This was a single-center retrospective study involving 91 patients (male 46 patients, mean age 74 ± 9 years) implanted with Reactive A-ATP equipped devices (84 patients with pacemakers, 6 with ICDs, and 1 with a CRT-D). The AF burden, rate of AF termination, and details of the activation of the A-ATP were analyzed in each patient. During a mean follow-up period of 21 ± 13 months, A-ATP was activated in 45 of 91 patients (49.5%). No patients had adverse events. Although the efficacy of the A-ATP varied among the patients, the median rate of AF termination was 44%. In comparison to the A-ATP start time, "0 min" had a higher AF termination rate by the A-ATP (39.4% vs. 24.4%, P = 0.011). The rate of termination by the A-ATP was high for AF with a long cycle length and a relatively regular rhythm. A-ATP successfully terminated AF episodes in some patients implanted with CIEDs. The optimal settings of the A-ATP will be determined in future studies.

Prevention of long-lasting atrial fibrillation through antitachycardia pacing in DDDR pacemakers.

OBJECTIVE: The MINERVA trial showed that in pacemaker patients with atrial fibrillation (AF) history, DDDRP pacing combining three algorithms - (a) atrial antitachycardia pacing with Reactive ATP enabled, (b) atrial preventive pacing and (c) managed ventricular pacing (MVP)-may effectively delay progression to persistent/permanent AF compared with standard DDDR pacing. We performed a comparative non-randomised evaluation to evaluate if Reactive ATP can be the main driver of persistent/permanent AF reduction independently on preventive pacing. METHODS: Thirty-one centres included consecutive dual-chamber pacemaker patients with AF history. Reactive ATP was programmed in all patients while preventive atrial pacing was not enabled. These patients were compared with the three groups of MINERVA randomised trial (Control DDDR, MVP, and DDDRP). The main endpoint was the incidence of AF longer than 7 consecutive days. RESULTS: A total of 146 patients (73 years old, 54% male) were included and followed for a median observation period of 31 months. The 2-year incidence of AF > 7 days was 12% in the Reactive ATP group, very similar to that found in the DDDRP arm of the MINERVA trial (13.8%, P = .732) and significantly lower than AF incidence found in the MINERVA Control DDDR arm (25.8%, P = .012) and in the MINERVA MVP arm (25.9%, P = .025). CONCLUSIONS: In a real-world population of dual-chamber pacemaker patients with AF history, the use of Reactive ATP is associated with a low incidence of persistent AF, highlighting that the positive results of the MINERVA trial were related to the effectiveness of Reactive ATP rather than to preventive pacing.

Endocardial arrhythmogenic mechanisms of torsades de pointes in patients with the congenital long QT syndrome.

We injected acetylcholine (Ach) into the coronary artery to ascertain whether coronary vasospasm contributed to the syncopal events or chest oppression suffered by 3 patients with long QT syndrome (LQTS). During the test, a quadripolar electrode catheter was placed in the right ventricle and the activation-recovery interval was reanalyzed from the stored data. Intracoronary Ach transiently prolonged the QT intervals in all 3 patients without inducing coronary vasospasm. The Ach-induced QT prolongation was associated with enhanced spatial and temporal dispersion of intra-ventricular repolarization. The electrophysiological abnormalities were consistent with the putative arrhythmogenic mechanisms identified in experimental studies of LQTS.

Effects of bepridil versus E-4031 on transmural ventricular repolarization and inducibility of ventricular tachyarrhythmias in the dog.

BACKGROUND: Bepridil (a multiple channel blocker) may markedly prolong the QT interval and induce polymorphic ventricular tachyarrhythmias (VTA). We compared the transmural ventricular repolarization characteristics and inducibility of polymorphic VTA after administration of bepridil versus the pure I(Kr) blocker, E-4031, each administered to five open-chest dogs. METHODS: We used plunge needle electrode to record transmural left ventricular (LV) repolarization and activation-recovery interval (ARI) to estimate local repolarization. The correlation between paced cycle length and ARI was separately examined in the LV endocardium, mid-myocardium (Mid), and epicardium. Attempts to induce VTA were made during bradycardia and sympathetic stimulation. RESULTS: Bepridil and E-4031 prolonged QT interval and ARI in all LV layers, though the magnitude of prolongation was greatest in Mid, increasing the transmural ARI dispersion, particularly during bradycardia. Compared with E-4031, bepridil caused mild, reverse use-dependent changes in ventricular repolarization, and less ARI dispersion than E-4031 during slow ventricular pacing. Both drugs increased ARI(max) and cycle length at 50% of ARI(max), though the changes were smaller after bepridil than after E-4031 administration. Bradycardia after the administration of each drug induced no VTA; however, sympathetic stimulation induced sustained polymorphic VTA in two of five dogs treated with E-4031 versus no dog treated with bepridil. CONCLUSIONS: Unlike the pure I(kr) blocker, E-4031, bepridil exhibited weak properties of reverse use-dependency and protected against sympathetic stimulation-induced VTA. It may be an effective supplemental treatment for recipients of implantable cardioverter defibrillator.

Effect of bepridil in atrial fibrillation inducibility facilitated by vagal nerve stimulation. - Prevention of vagal nerve activation-induced shortening of the atrial action potential duration -.

BACKGROUND: Because bepridil blocks multiple myocardial ionic channels, including the muscarinic acetylcholine receptor-operated potassium current (I(KAch)), bepridil is expected to suppress atrial fibrillation (AF) mediated by vagal nerve stimulation (VNS). METHODS AND RESULTS: The therapeutic effects of bepridil were studied with a special focus on heart rate variability (HRV) in a canine model of AF. During VNS, AF was induced in 9 of 9 experiments before, vs 3 of 9 experiments after administration of bepridil (P<0.01). During 350 ms atrial pacing, VNS shortened the right and left atrial monophasic action potentials at 90% repolarization (MAP90) by -31+/-8% and -22+/-12%, respectively, vs -10+/-13% and -6+/-8%, respectively, after bepridil (P<0.01, N=9). Bepridil prolonged the sinus cycle length, although it had no significant effect on the conduction time measured at 300 ms pacing. Statistically insignificant change was observed in the VNS-induced slowing of the sinus cycle length and in the VNS-induced increase in high frequency amplitude of HRV before (1.2+/-0.7 to 5.3+/-4.0 ms) vs after (1.7+/-0.8 to 5.4+/-2.3 ms) bepridil administration. CONCLUSIONS: Bepridil prevented the VNS-induced shortening of atrial MAP90 and suppressed the inducibility of AF during VNS in two-thirds of the experiments. As far as this study shows, it may be possible that inhibition of I(KAch) played a part in this antifibrillatory effect.

Efficacy of procainamide and lidocaine in terminating sustained monomorphic ventricular tachycardia.

BACKGROUND: The efficacy of antiarrhythmic drugs in terminating sustained monomorphic ventricular tachycardia (SMVT) was assessed in a retrospective manner to provide a basis for recommending their use. METHODS AND RESULTS: The 90 patients were included in this study to evaluate the efficacy to terminate SMVT using procainamide or lidocaine. All patients were alert and responsive. The mean systolic blood pressure was 91+/-25 mmHg (range, 40-150 mmHg). SMVT was diagnosed from ECG recordings and later in an electrophysiologic study. VTs with a cycle length of 329+/-55 and 324+/-61 ms were treated with the mean doses of 358+/-50 mg and 81+/-30 mg of procainamide and lidocaine and were terminated in 53/70 (75.7%) and in 7/20 (35.0%) respectively. The drugs were discontinued if there was no rise in blood pressure after slowing of the tachycardia rate or if there were signs of impending deterioration in consciousness. Though procainamide was effective, blood pressure was often low and DC shock should be available at all times during administration of the drug. CONCLUSIONS: Procainamide, the relatively older drug, was more effective than lidocaine in terminating SMVT associated with structural heart diseases. This is a retrospective analysis but can form the basis for formulating guidelines for initial management of SMVT.

Inducibility of atrial fibrillation depends not on inflammation but on atrial structural remodeling in rat experimental autoimmune myocarditis.

INTRODUCTION: There is increasing evidence to support a link between inflammation and atrial fibrillation (AF). However, the role of inflammation on new-onset AF is still to be elucidated. METHODS: Rats underwent induction of experimental autoimmune myocarditis (EAM). Atrial structural change was evaluated by echocardiography and histological analysis. Electrophysiological data and the in vivo atrial response to burst atrial pacing were evaluated in the acute (2 weeks after EAM induction) and chronic phases (8 weeks after induction). In addition, atrial pacing after 2, 4, and 6 h after lipopolysaccharide (LPS) infusion, when the expression of gap junctions was modified, were challenged with young healthy rats. RESULTS: AF was induced in 11 of 15 chronic phase EAM rats but not in either acute phase EAM rats or LPS infusion rats (P<.01). Echocardiography showed dilatation of both atrium and ventricle and a decrease in the ejection fraction in the chronic phase. Histology revealed severe inflammatory lesions only in the acute phase. Interstitial atrial fibrosis as well as the area of atrial myocyte increased in the chronic phase but not in the acute phase. CONCLUSIONS: AF could be induced in the chronic phase of myocarditis rats, but not in the acute phase of myocarditis rats or in rats with LPS infusion. Acute inflammation per se did not increase the occurrence of AF induction. Atrial structural remodeling caused by inflammation and hemodynamic effects is necessary to induce AF.

Segmental conduction block in a low-voltage area suppressed macro-reentrant ventricular tachycardia after surgical repair of tetralogy of Fallot.

Macro-reentrant ventricular tachycardia (VT) developed in a 20-year-old man, 17 years after surgical repair of tetralogy of Fallot. Activation mapping of the VT revealed its counterclockwise propagation around the right ventricle, and through a critical pathway between a transannular patch and the tricuspid annulus. This critical pathway was 6 cm long and contained myocardium with a normal amplitude, while the area of low voltage was limited adjacent to the transannular patch. A linear lesion was created by radiofrequency energy delivered only to the low voltage area. After ablation, the activation wavefront through the low voltage area was blocked, and VT became non-inducible.

Effects of verapamil on anterior ST segment and ventricular fibrillation cycle length in patients with Brugada syndrome.

PURPOSE: This study examined the effects of verapamil (5-10 mg intravenous) on the cardiac electrical activity of 10 Brugada syndrome (BS) patients having vasospastic angina, atrial fibrillation, and/or hypertension. RESULTS: Verapamil showed no significant change in the ST-segment elevation. Likewise, there was no significant change in the lengths of QRS complex, HV and corrected QT intervals, or effective refractory period at the right ventricle. The conduction time between right ventricular apex and outflow tract, measured at 400-millisecond pacing, was mildly prolonged by verapamil. At baseline, induced ventricular fibrillation (VF) was terminated by a 200-J shock in all patients. After verapamil, VF was reinduced in 7, was noninducible in 2, and self-terminated in 1 patient. Mean F-F interval was shorter after than before verapamil, and a 360-J shock was required in 2 of the 7 patients. CONCLUSION: In some BS patients, calcium channel blockade may modify the electrical characteristics of VF.

Preservation of renal function in response to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) has recently been introduced as a new option for patients with severe heart failure, but its effect on renal function remains unclear. METHODS AND RESULTS: Twenty-three patients receiving CRT were studied. Responders were those who showed >0% increase in left ventricular ejection fraction after CRT by echocardiography. Clinical parameters, echocardiographic measurement, renal function, and prescriptions were examined before and 3 months after CRT, and the relationship between the response to CRT and renal function was examined. The responders had a better prognosis than the non-responders (p<0.05). There was a significant difference in the change in the estimated glomerular filtration rate between the responders and non-responders (p<0.05), even in patients with renal dysfunction before CRT (p<0.01). Prescriptions of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB) were 100% in the CRT responders and 60% in the non-responders (p<0.05). Up-titration of beta-blockers could be significantly achieved in the CRT responders compared with the non-responders (p<0.05). CONCLUSIONS: Preservation of renal function was observed in the responders to CRT, even in patients with renal dysfunction. Prescription of ACEI/ARB and up-titration of beta-blockers increased in the CRT responders. These results may contribute to the beneficial effects of CRT.

A double-point mutation in the selectivity filter site of the KCNQ1 potassium channel results in a severe phenotype, LQT1, of long QT syndrome.

INTRODUCTION: Slowly activating delayed-rectifier potassium currents in the heart are produced by a complex protein with alpha and beta subunits composed of the potassium voltage-gated channel KQT-like subfamily, member 1 (KCNQ1) and the potassium voltage-gated channel Isk-related family, member 1 (KCNE1), respectively. Mutations in KCNQ1 underlie the most common type of hereditary long QT syndrome (LQTS). Like other potassium channels, KCNQ1 has six transmembrane domains and a highly conserved potassium selectivity filter in the pore helix called "the signature sequence." We aimed to investigate the functional consequences of a newly identified mutation within the signature sequence. METHODS AND RESULTS: Potassium channel genomic DNA from a family with clinical evidence of LQTS was amplified by polymerase chain reaction (PCR), and the resulting products were then sequenced. Three family members had a double-point mutation in KCNQ1 at nucleotides 938 (T-to-A) and 939 (C-to-A), resulting in an isoleucine-to-lysine change at amino acid position 313. These patients displayed prolonged QTc intervals (629, 508, and 500 ms(1/2,) respectively) and repetitive episodes of syncope, but no deafness. Three-dimensional structure modeling of KCNQ1 revealed that this mutation is located at the center of the channel pore. COS-7 cells displayed a lack of current when transfected with a plasmid expressing the mutant. In addition, the mutant displayed a dominant negative effect on current but appeared normal with respect to plasma membrane integration. CONCLUSION: An I313K mutation within the selectivity filter of KCNQ1 results in a dominant-negative loss of channel function, leading to a long QT interval and subsequent syncope.

Antiarrhythmic vs. pro-arrhythmic effects depending on the intensity of adrenergic stimulation in a canine anthopleurin-A model of type-3 long QT syndrome.

AIMS: The effects of adrenergic activity and beta-blockade were studied in a canine experimental model of type-3 long QT syndrome (LQT3) induced by application of anthopleurin-A. METHODS AND RESULTS: Boluses of epinephrine at 0.5 and/or 1.0 microg/kg were administered before and after propranolol, 0.3 mg/kg, and the distribution of the ventricular repolarization and the development of polymorphic ventricular tachyarrhythmia (VA) were assessed. Using needle electrodes, transmural unipolar electrograms were recorded across the left ventricle (LV) and right ventricle (RV). Activation-recovery interval (ARI) was measured in each electrogram to estimate local repolarization during RV pacing at the cycle length of 750 ms after the creation of complete atrioventricular block. Before propranolol, epinephrine, 0.5 microg/kg, did not induce VA in any experiment. However, a dose of 1.0 microg/kg induced polymorphic VA following multiple premature ventricular complex (PVC) in four of six experiments. Epinephrine, 0.5 microg/kg, shortened ARI at all sites and lessened LV transmural ARI dispersion. Neither ARI nor its dispersion could be determined after 1.0 microg/kg of epinephrine because of the induction of PVC, polymorphic VA, or both. Propranolol (i) prevented epinephrine-induced PVC and polymorphic VA in all experiments, (ii) slightly prolonged ARI at all sites, along with a decrease in LV transmural ARI dispersion, and (iii) reversed the epinephrine-induced shortening of ARI. CONCLUSION: In this LQT3 model, an increase in adrenergic activity by epinephrine had dose-dependent, opposite effects on ventricular electrical stability. Since beta-adrenergic blockade suppressed epinephrine-induced PVC and polymorphic VA, it might be considered for supplemental therapy to suppress VA in patients presenting with LQT3.

Effect of dl-sotalol on mortality and recurrence of ventricular tachyarrhythmias: ischemic compared to nonischemic cardiomyopathy.

OBJECTIVE: We compared the effectiveness of sotalol on mortality and the recurrence of ventricular tachyarrhythmia (VTA) between idiopathic dilated cardiomyopathy (IDCM) and coronary artery disease (CAD). PATIENTS: Forty patients with spontaneous VTA and induced VTA associated with CAD (n = 23) and IDCM (n = 17) were studied. In all patients, sotalol was prescribed and an electrophysiologic study (EPS) was performed to evaluate its effect on the induction of VTA. There were no significant differences in left ventricular ejection fraction (LVEF) between CAD and IDCM (35%+/- 10% vs. 35%+/- 12%). RESULTS: After sotalol, there were no significant differences in the QTc interval on electrocardiogram (ECG) or in the effective refractory period in the apex of the right ventricle between the two groups, but sotalol was more effective in preventing the induction of VTA in CAD than in IDCM (65% vs. 29%; P < 0.05). During a mean follow-up period of 47 +/- 27 months, the overall VTA recurrence rate was significantly lower in CAD than in IDCM (P < 0.01). The all-cause mortality rate tended to be lower in CAD than in IDCM, but the difference was not significant (P = 0.07). Electrical storm (ES) occurred more frequently in IDCM than in CAD, (41% vs. 13%; P < 0.05), and all patients with ES (n = 10) failed to respond to sotalol as assessed by EPS. CONCLUSION: Sotalol reduced the overall VTA recurrence rate and all-cause mortality more in CAD than in IDCM.

Comparison of conduction delay in the right ventricular outflow tract between Brugada syndrome and right ventricular cardiomyopathy: investigation of signal average ECG in the precordial leads.

BACKGROUND: In both Brugada syndrome (BS) and arrhythmogenic right ventricular cardiomyopathy (ARVC), electrical abnormalities in the right ventricular outflow tract (RVOT) are important for arrhythmogenesis. OBJECTIVES: The aim of this study was to compare conduction delay in the right ventricular in BS with that in ARVC using the signal-averaged electrocardiogram. METHODS: Twenty patients with BS (18 men and 2 women; 55 +/- 12 years old; 9 symptomatic and 11 asymptomatic) and eight patients with ARVC (six men and two women; 53 +/- 16 years old) were included. We assessed the presence of late potentials (LPs) and the filtered QRS duration (fQRSd) in V(2) and V(5) using a high-pass filter of 40 Hz (fQRSd:40) and 100 Hz (fQRSd:100). RESULTS: In ARVC, there was no significant difference in fQRSd:40 between V2 and V5 (158 +/- 19 vs. 145 +/- 17 ms, respectively): however, in BS, fQRSd:40 in V2 was significantly longer than fQRSd:40 in V5 (147 +/- 15 vs. 125 +/- 10 ms, P < 0.001). In ARVC, there was no significant difference between fQRSd:40 and fQRSd:100 in V(2) and V(5) (158 +/- 19 vs. 142 +/- 23 ms and 145 +/- 17 vs. 132 +/- 9 ms, respectively). In contrast, in BS, fQRSd:100 was significantly shorter than fQRSd:40 in V2 (110 +/- 8 ms vs. 147 +/- 15, P < 0.001). The relative decrease in fQRSd:100 compared with fQRSd:40 in V2 was significantly greater in BS than in ARVC. CONCLUSION: The dominant prolongation of the fQRSd in the right precordial lead in BS was different from the characteristics of ARVC, which may be caused by the conduction delay due to fibro-fatty replacement in RV.

Incidence and initial characteristics of pilsicainide-induced ventricular arrhythmias in patients with Brugada syndrome.

BACKGROUND: In patients with Brugada syndrome, class I antiarrhythmic drugs can trigger ventricular arrhythmias (VA). The incidence and initial characteristics of VA that developed after pilsicainide was examined in 28 patients with Brugada-type electrocardiographic (ECG) abnormalities and with a positive response in the pilsicainide test. The clinical outcome was also compared between patients with and without pilsicainide-induced VA. METHODS AND RESULTS: In all patients, pilsicainide increased ST segment elevation and accentuated type 1 ECG changes. Ventricular tachycardia (VT) developed in 3 patients and premature ventricular complexes (PVC) in 2 other patients. These 5 patients (group I) had higher ST segment elevation in lead V2 on the ECG at baseline and after pilsicainide and showed a longer QTc interval after pilsicainide than the other 23 patients (group II). However, there was no difference between the 2 groups regarding incidence of prior cardiac events, results of signal-averaged ECG, HV interval, inducibility of ventricular fibrillation by programmed electrical stimulation, or QRS duration. In 1 patient, PVC originated from 3 sites, 2 of which triggered polymorphic VT. The right ventricular (RV) outflow tract was the origin of 2 types of PVC, and other RV sites of 5 other types. During a 45 +/- 37 months follow-up, polymorphic VT recurred in 2 patients in group II. CONCLUSIONS: Pilsicainide induced VA in some patients with Brugada syndrome, but this result may not be used as a parameter of the risk stratification of Brugada syndrome. Multiple PVC induced by pilsicainide and triggering polymorphic VT originated from several RV sites is an important factor when considering patients for treatment with catheter ablation.

Bepridil for drug-refractory ventricular tachyarrhythmias.

AIMS: To avoid frequent discharges of implantable cardioverter defibrillators, antiarrhythmic drugs may be needed in some patients with ventricular tachyarrhythmias. For ventricular tachyarrhythmias refractory to conventional antiarrhythmic drugs, we evaluated the efficacy of bepridil, a multiple ion-channel blocker. METHODS AND RESULTS: Sixteen patients with structural heart disease and ventricular tachyarrhythmias refractory to multiple antiarrhythmic drugs (4.1+/-1.6 drugs including class III drugs) were enrolled. Bepridil was prescribed at a mean dose of 156+/-40 mg/day. Bepridil prolonged the QT/QTc interval without affecting heart rate or the QRS duration. During a mean follow-up of 52+/-44 months, bepridil completely suppressed ventricular tachyarrhythmias in 6 of the 16 patients (38%) and the drug decreased the frequency of ventricular tachyarrhythmia recurrences by >75% in 3 of the other 10 patients. The markers of complete suppression of ventricular tachyarrhythmias during bepridil treatment included a smaller number of VT morphologies, a better NYHA functional class, and a greater drug-induced prolongation of the QT/QTc interval. The result of electrophysiologic study-guided evaluation of bepridil was closely associated with the clinical efficacy of bepridil in 7 of 8 patients. CONCLUSION: Bepridil appears to be useful to suppress drug-refractory ventricular tachyarrhythmia recurrence.

Human cardiac ryanodine receptor mutations in ion channel disorders in Japan.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by adrenergic induced bidirectional or polymorphic ventricular tachycardias. Some of CPVT families were reported to be associated with cardiac ryanodine receptor gene (RyR2) mutations. However, association between RyR2 and other arrhythmogenic disorders is not clarified. In this study, we analyzed 83 Japanese patients including patients with long-QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, arrhythmogenic right ventricular cardiomyopathy and CPVT. Genetic screening of RyR2 revealed 3 distinct mutations among 4 families with CPVT (75% of incidence). However, no mutation was found in other groups. This is the first report to demonstrate prevalence of RyR2 mutations in various arrhythmogenic disorders in Japan. RyR2 mutations were detected frequently in CPVT but not in other diseases.

Role of autonomic nervous activity in the antiarrhythmic effects of magnesium sulfate in a canine model of polymorphic ventricular tachyarrhythmia associated with prolonged QT interval.

This study was performed to examine the role played by the autonomic nervous system in the antiarrhythmic effects of magnesium sulfate (Mg) in a canine model of polymorphic ventricular tachyarrhythmia facilitated by anthopleurin-A and a slower heart rate induced QT interval prolongation. In 6 experiments, complete atrioventricular block was created to control the heart rate and bradycardia at 800- to 1500-ms cycle lengths was applied for 60 sec before and after drug-induced autonomic block. Transmural unipolar electrograms were recorded from multipolar needle electrodes, and activation-recovery intervals (ARI) were measured. Before drug-induced autonomic block, polymorphic ventricular tachyarrhythmia developed in all 6 experiments during bradycardia before but not after the administration of Mg (0.2 ml/kg intravenous bolus). During drug-induced autonomic block, triggered premature activity decreased without significant changes in underlying dispersion of repolarization and polymorphic ventricular tachyarrhythmia developed during bradycardia in 1 experiment. Administration of Mg during drug-induced autonomic block eliminated premature activity and polymorphic ventricular tachyarrhythmia during bradycardia. The distribution of left ventricular (LV) and right ventricular repolarization and dispersion of transmural repolarization were analyzed before and 60 sec after Mg administration during ventricular pacing at 80 bpm. Mg caused a modest shortening of ARI at all sites before and after drug-induced autonomic block. Since ARI shortening was greater at the mid-myocardial sites than at other LV sites, Mg decreased transmural ARI dispersion from 77 +/- 16 to 46 +/- 21 ms before drug-induced autonomic block and from 79 +/- 7 to 51 +/- 16 ms after drug-induced autonomic block. The antiarrhythmic effects of Mg in this model of long QT syndrome were attributable to its direct pharmacological properties and not to changes in ambient autonomic nervous activity. The blockade of sympathetic activity decreased the incidence of premature events and partially suppressed polymorphic ventricular tachyarrhythmia in this model.

Decrease in amplitude of intracardiac ventricular electrogram and inappropriate therapy in patients with an implantable cardioverter defibrillator.

Intracardiac electrograms are important for discrimination of tachyarrhythmia by implantable cardioverter defibrillators (ICD). A low R-wave can cause not only undersensing of ventricular tachyarrhythmia but also inappropriate discharges due to oversensing of unexpected signals because of its characteristic sensing algorithm. Therefore, this study aimed to investigate adverse events associated with R-wave amplitude. We included 115 consecutive patients followed-up over one year after implantation of a transvenous ICD system. The status of the ICD was checked every 3 months and intracardiac ventricular electrograms were analyzed. The decrease in R-wave amplitude was high in arrhythmogenic hypertrophy cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy (ARVC), and sarcoidosis. Low R-waves (< 5.0 mV) were observed in 13 patients at a follow-up of 15 +/- 16 months after implantation, and the mean R-wave was 3.0 +/- 0.8 mV. The frequency of low R-waves was high in ARVC (38%), sarcoidosis (33%), and dilated cardiomyopathy (17%). All of the dilated cardiomyopathy patients with low R-waves had severe left ventricular dysfunction. Inappropriate ICD therapy resulting from T-wave oversensing occurred in 7 patients and the R-wave was < 5.0 mV in 6 of the patients. The frequency of inappropriate therapy was high in patients with sarcoidosis. In 3 patients, inappropriate therapy caused ventricular tachyarrhythmia. In conclusion, decreases in R-wave amplitude occurred in some progressive cardiac disorders and caused inappropriate ICD discharges having arrhythmogenicity. Physicians should attempt to obtain a high R-wave amplitude during ICD implantation and careful follow-up is required, especially in patients with ARVC or sarcoidosis.