[Mapping and ablation of a mechanically blocked concealed accessory pathway under repeated adenosine bolus infusions]. / Mapping und Ablation einer mechanisch blockierten akzessorischen Leitungsbahn unter wiederholten Adenosin-Bolusgaben.

During mapping and catheter ablation of an accessory pathway, a mechanically induced conduction block can occur. Adenosine is used to detect dormant conduction of incomplete ablation lesions. Presented in this article is the case of a patient with a left-sided accessory pathway, which was mechanically blocked during the mapping procedure and could only be successfully ablated after repeated adenosine bolus infusions, which resulted in intermittent restitution of conduction via the accessory pathway.

Reappraisal of the clinical implications of adenosine triphosphate in terms of the prediction of reconnection sites in cases with electrical isolation of the pulmonary veins.

PURPOSE: Dormant conduction (DC) induced by intravenous adenosine triphosphate (ATP) after pulmonary vein (PV) isolation (PVI) could predict subsequent PV reconnection (RC) sites. This study aimed to investigate the relationship between the DC and RC sites during the long-term follow-up. METHODS: Ninety-one consecutive patients (62 males; mean age, 62 ± 11 years) with symptomatic persistent (n = 18) or paroxysmal (n = 73) atrial fibrillation (AF) who underwent PVI were included in this study. After a successful PVI, we administered ATP to reveal the DC sites. In total, DC sites were observed in 46 (51%) patients, and all were left un-ablated after marking or tagging all of them using fluoroscopic images and a three-dimensional (3D) mapping system. After the follow-up period (14.8 ± 3.6 months), AF recurred in 29 (32%) patients, all of whom had a DC in the initial ablation session, and underwent redo sessions. We divided the DC sites into three groups; in group A, the RC sites differed from the DC sites, in group B, the RC sites were identical to the DC sites, and in group C, the RC sites involved both DC and other sites. RESULTS: As a result, 20 (69%), 3 (11.5%), and 6 (19.5%) patients belonged to groups A, B, and C, respectively. Statistical analyses comparing the agreement between DC and the RC sites yielded a weak relationship. CONCLUSIONS: DC sites implying RC sites had a weak agreement, and other options to predict RC sites will be required to improve the clinical benefit of CA of AF.

Mechanism-specific effects of adenosine on ventricular tachycardia.

INTRODUCTION: There is no universally accepted method by which to diagnose clinical ventricular tachycardia (VT) due to cAMP-mediated triggered activity. Based on cellular and clinical data, adenosine termination of VT is thought to be consistent with a diagnosis of triggered activity. However, a major gap in evidence mitigates the validity of this proposal, namely, defining the specificity of adenosine response in well-delineated reentrant VT circuits. To this end, we systematically studied the effects of adenosine in a model of canine reentrant VT and in human reentrant VT, confirmed by 3-dimensional, pace- and substrate mapping. METHODS AND RESULTS: Adenosine (12 mg [IQR 12-24]) failed to terminate VT in 31 of 31 patients with reentrant VT due to structural heart disease, and had no effect on VT cycle length (age, 67 years [IQR 53-74]); ejection fraction, 35% [IQR 20-55]). In contrast, adenosine terminated VT in 45 of 50 (90%) patients with sustained focal right or left outflow tract tachycardia. The sensitivity of adenosine for identifying VT due to triggered activity was 90% (95% CI, 0.78-0.97) and its specificity was 100% (95% CI, 0.89-1.0). Additionally, reentrant circuits were mapped in the epicardial border zone of 4-day-old infarcts in mongrel dogs. Adenosine (300-400 µg/kg) did not terminate sustained VT or have any effect on VT cycle length. CONCLUSION: These data support the concept that adenosine's effects on ventricular myocardium are mechanism specific, such that termination of VT in response to adenosine is diagnostic of cAMP-mediated triggered activity.

Correlation of intracardiac electrogram with surface electrocardiogram in Brugada syndrome patients.

AIMS: The objective of this study was to correlate the electrocardiogram (ECG) modification during an Ajmaline challenge in patients affected by the Brugada syndrome and implanted with an implantable cardioverter-defibrillator (ICD) with the morphological changes of their ICD's intracardiac electrogram (IEGM). METHODS AND RESULTS: Sixteen type 1 Brugada syndrome patients implanted with a St Jude Medical AnalyST(®) ICD were enrolled and underwent ajmaline challenge. Intracardiac electrograms and 12 lead ECG signals were collected over the duration of the study and analysed off-line. The right precordial ECG leads were in both the third and fourth intercostal space by putting V5 and V6 in V1 and V2 at the third intercostal space. Two patients were excluded from the analysis due to signal noise issues. Of the remaining 14 patients, 12 and 2 patients were adjudicated to have positive and negative ajmaline challenges, respectively, based on standard ECG criteria. In the ajmaline positive patients, the IEGM T wave amplitude changes were more prominent than those of the IEGM ST segment (-898 ± 463 vs. -55 ± 381 µV, P < 0.05). Furthermore, all of these T wave amplitude changes were in the negative polarity, whereas the change in polarity of the ST segment was mixed. The changes in the IEGM T wave amplitude and ST segment were significantly smaller in the ajmaline negative patients compared with those in the ajmaline positive patients [211 ± 158 (P < 0.05) and 107 ± 54 (P < 0.05) µV, respectively). Over all 14 analysable patients, the change in the ECG ST segment over the timecourse of the ajmaline challenge correlated better with the IEGM T wave amplitude change (R = 0.72 ± 0.33) than the IEGM ST segment change (R = 0.63 ± 0.33). Applying an IEGM T wave amplitude change cut-off of 400 µV for predicting the outcome of the ajmaline challenge yielded 92% sensitivity (11/12) and 100% specificity (2/2). CONCLUSION: In Brugada patients, ajmaline challenge elicits significant T wave amplitude changes within the ICD IEGM, greater than those of the IEGM ST segment. This study is the first step to provide new tools able to continuously monitor the type I Brugada aspect in patients affected by the Brugada syndrome.

Electrophysiologic mechanism of typical atrial flutter termination by nifekalant: effect of a pure IKr -selective blocking agent.

BACKGROUND: Little is known about the effect of nifekalant, a pure I(Kr) -selective blocker, on typical atrial flutter (AFL) and its termination mechanism. METHODS: The effects of nifekalant on AFL were elucidated in 17 patients. During AFL, the conduction time from the lateral to septal cavotricuspid isthmus (IS) and that through the reminder of the right atrium (nIS); AFL-cycle length (CL) variability, which was quantified by the standard deviation; and the maximum difference in AFL-CL were measured before and after administration of nifekalant (0.2-0.3 mg/kg). A single extrastimulus was delivered from the lateral cavotricuspid isthmus to elucidate the resetting response curves and atrial effective refractory period (AERP) before and after administration of nifekalant. RESULTS: There was no significant difference in AFL-CL, IS, and nIS before and after nifekalant; however, AERP was increased after nifekalant (155 ± 22 ms vs 184 ± 32 ms, P < 0.001). The standard deviation and the maximum difference in AFL-CL were both increased after nifekalant (1.7 ± 0.7 ms vs 3.6 ± 2.3 ms, P < 0.001 and 4.1 ± 1.9 ms vs 8.5 ± 5.2 ms, P < 0.001). The total excitable gap decreased (94 ± 17 ms vs 66 ± 21 ms, P < 0.001) with rightward shift of the resetting response curves and loss of full excitability after nifekalant. In 11 patients (65%), AFL was terminated spontaneously (n = 7) or by a single extrastimulus (n = 4), which was not observed before nifekalant. Termination was associated with orthodromic block in the cavotricuspid isthmus in all patients. CONCLUSIONS: Nifekalant increases AERP and AFL-CL variability by abolishing a fully excitable gap, without prolongation of AFL-CL. These unique effects facilitate the termination of AFL.

Optical mapping study of blebbistatin-induced chaotic electrical activities in isolated rat atrium preparations.

We have studied the spatiotemporal pattern of blebbistatin-induced anomalous electrical activities in isolated rat atrial preparations using the optical mapping of excitation spread. Atrial preparations including the right or left auricle were dissected from adult rat hearts. Each preparation was then stained with a fast merocyanine-rhodanine voltage-sensitive dye (NK2761). Using a multi-element (16 x 16) photodiode array, we assessed the spread of excitation optically by timing the initiation of the action potential-related extrinsic absorption changes. The contraction-related optical signals were suppressed by adding (S)-(-)-blebbistatin (10-100 miocroM) to the bathing solution. Blebbistatin had an effective delay time of about 1.5 h following its application, at which time anomalous electrical activities occurred. These took the form of triggered activities and rhythmical spontaneous excitations. We optically mapped the spatiotemporal patterns of the excitation spread during these anomalous electrical activities. When the triggered activities occurred, the site of ectopic focus, where the triggered action potential first appeared, and the area of excitation spread varied in every event. When the rhythmical spontaneous excitations occurred, the excitation spread from the anomalous pacemaker and, occasionally, their spatial shift was observed. In addition, the combination pattern of the spontaneous excitations and triggered activities was also observed. We suggest that these phenomena are due to the disturbed intracellular calcium dynamics induced by the application of blebbistatin.

Spatially divergent cardiac responses to nicotinic stimulation of ganglionated plexus neurons in the canine heart.

Ganglionated plexuses (GPs) are major constituents of the intrinsic cardiac nervous system, the final common integrator of regional cardiac control. We hypothesized that nicotinic stimulation of individual GPs exerts divergent regional influences, affecting atrial as well as ventricular functions. In 22 anesthetized canines, unipolar electrograms were recorded from 127 atrial and 127 ventricular epicardial loci during nicotine injection (100 mcg in 0.1 ml) into either the 1) right atrial (RA), 2) dorsal atrial, 3) left atrial, 4) inferior vena cava-inferior left atrial, 5) right ventricular, 6) ventral septal ventricular or 7) cranial medial ventricular (CMV) GP. In addition to sinus and AV nodal function, neural effects on atrial and ventricular repolarization were identified as changes in the area subtended by unipolar recordings under basal conditions and at maximum neurally-induced effects. Animals were studied with intact AV node or following ablation to achieve ventricular rate control. Atrial rate was affected in response to stimulation of all 7 GPs with an incidence of 50-95% of the animals among the different GPs. AV conduction was affected following stimulation of 6/7 GP with an incidence of 22-75% among GPs. Atrial and ventricular repolarization properties were affected by atrial as well as ventricular GP stimulation. Distinct regional patterns of repolarization changes were identified in response to stimulation of individual GPs. RAGP predominantly affected the RA and posterior right ventricular walls whereas CMVGP elicited biatrial and biventricular repolarization changes. Spatially divergent and overlapping cardiac regions are affected in response to nicotinic stimulation of neurons in individual GPs.

[Effect of nibentan on dispersion of repolarization of ventricular myocardium in the rabbit].

Among factors determining development of polymorphic ventricular tachycardia torsades de pointes under influence of class III antiarrhythmic drugs great value is attributed to enhanced heterogeneity of repolarization of ventricular myocardium which can cause functional conduction blocks and development of re-entry of excitation. In this work with the help of optical mapping of electrical activity of the heart we investigated effect of nibentan (0.3 and 1 mM) on chronotopography of repolarization of epicardial surface of ventricles of isolated after Langendorf rabbit heart (n=5). For assessment of heterogeneity of repolarization we measured the following parameters: standard deviation of mean action potential duration (APDm) along mapped region (SD-APD), dispersion index (DI=1000 SD-APDm), maximal dispersion (Dmax=APDmax-APDmin). Nibentan in concentrations 0.3 and 1 mM increased APD at the level of 90% repolarization (APD90%) from 231 +/- 12 to 277 +/- 7 ms (p < 0.05) 318 +/- 7 ms (p < 0.001), respectively, but in concentration 1 mM it practically did not affect parameters of heterogeneity of repolarization (SD-APD: from 4.4 +/- 0.9 to 5.7 +/- 1.1 ms, p=0.4; DI: from 19.1 +/- 4.2 to 18.0+3.5, p=0.8; Dmax: from 16.6 +/- 2.5 to 24.8 +/- 4.3 ms, < 0.05). These results show that nibentan in the range of clinically used doses does not effect heterogeneity of ventricular myocardium. This can explain low proarrhythmic effect of nibentan.

[Changes in parameters of orthogonal ECG in hypertensive patients given combined antihypertensive treatment].

AIM: To evaluate changes in parameters of orthogonal ECG in hypertensive patients on trandolapril+verapamil combination. MATERIAL AND METHODS: Eighteen patients before and after 8-week therapy were examined using orthogonal ECG and 24-h monitoring of blood pressure. Computer processing of orthogonal ECG was made with calculation of some vectorcardiography (VCG) and d mapping parameters. Also, 24-h blood pressure monitoring was made. RESULTS: 8-week therapy significantly reduced mean diurnal and nocturnal systolic and diastolic blood pressure (SBP, DBP), improved their variability. In patients with VCG signs of left ventricular hypertrophy the treatment significantly diminished some VCG parameters. A direct correlation was found between initial diurnal SBP variability and SQRSxyz, SQRSxz; dynamics of nocturnal SBP variability and dynamics of SQRSxyz, SQRSxz and Rx+Sz (r = 0.7; p < 0.05). A direct correlation was between dynamics of SBP and IADI (r = 0.7; p < 0.05). CONCLUSION: Hypertensive patients treated with a fixed combination trandolapril/verapamil exhibit a positive trend not only in parameters of 24-h monitoring of blood pressure but also in parameters of orthogonal ECG.

The effects of losartan on signal-averaged P wave in patients with atrial fibrillation.

BACKGROUND: Losartan has recently been reported to suppress atrial structural remodeling. However, few reports exist on signal-averaged electrocardiography (ECG) for preventing atrial electrical remodeling. We examined the effect of losartan on atrial electricity by using signal-averaged ECG of P waves. METHODS: The subjects comprised 40 patients with essential hypertension complicated with symptomatic paroxysmal atrial fibrillation. The patients received pilsicainide for the complication; they were defibrillated and divided into two subgroups for antihypertensive therapy: calcium antagonist-administrated (CB) and losartan-administrated (LOS) groups. We recorded the signal-averaged electrocardiography of P waves and calculated (1) filtered P wave duration (PD), (2) the voltage integral for the entire P wave (integral-p), and (3) the root mean square voltages of the terminal 40, 30, and 20 ms (RMS-40, RMS-30, and RMS-20). Procollagen C propeptide type I (PIP) and A- and B-type natriuretic peptide (ANP and BNP, respectively) levels in the groups were measured before and after antihypertensive agent administration. RESULTS: RMS-20 increased significantly and PD decreased significantly in the LOS group 24 weeks after antihypertensive drug administration; however, they remained unchanged in the CB group. Integral-p decreased significantly in both groups, and the decrease rate was significantly higher in the LOS group. Serum BNP levels decreased significantly only in the LOS group. CONCLUSIONS: Losartan inhibits atrial remodeling by inhibiting left atrial fibrosis as indicated by the procollagen C propeptide type I, ANP, and BNP levels. Signal-averaged ECG demonstrated that losartan suppresses atrial fibrillation recurrence by improving atrial conduction disturbance.

Adenosine-insensitive focal atrial tachycardia: evidence for de novo micro-re-entry in the human atrium.

OBJECTIVES: The purpose of this work was to describe the entity and mechanism of adenosine-insensitive focal atrial tachycardia (AT). BACKGROUND: The majority of regular focal ATs demonstrate properties consistent with triggered activity, including termination by adenosine. Less commonly, AT may be due to enhanced automaticity, which is transiently suppressed by adenosine. Small re-entrant circuits may also give rise to focal AT, but limited data exist regarding this entity as a de novo arrhythmia in the human atrium. METHODS: Eighty cases of focal AT were mapped in the electrophysiology laboratory and challenged with adenosine. Adenosine-sensitive and -insensitive groups were compared with regard to demographics, anatomical distribution, and electrogram characteristics at the tachycardia origin. RESULTS: In response to adenosine, termination occurred in 67 cases (84%), transient suppression in 5 (6%), 6 were insensitive (8%), and 2 exhibited nonspecific responses. Adenosine-insensitive AT arose near the pulmonary vein ostia (4) and from the right atrium (2), whereas adenosine-sensitive AT arose from a wide distribution in both atria. Electrograms at the site of origin for adenosine-insensitive AT were highly fractionated, with longer durations and lower amplitudes compared with AT that terminated or was transiently suppressed. The electrograms at the origin of adenosine-insensitive ATs comprised 22% to 69% of the tachycardia cycle length, compared with 4% to 21% for adenosine-sensitive ATs. In 3 adenosine-insensitive ATs, entrainment was demonstrated with post-pacing intervals equivalent to the tachycardia cycle length. CONCLUSIONS: The characteristics of adenosine-insensitive focal AT differ from adenosine-sensitive AT and are consistent with small re-entrant circuits. These data provide evidence that focal re-entry is a mechanism of AT and has an electropharmacologic profile that differs from AT due to automaticity and triggered activity.

Spatial distribution of repolarization and depolarization abnormalities evaluated by body surface potential mapping in patients with Brugada syndrome.

BACKGROUND: Mutations in sodium channel gene, SCN5A, have been identified in Brugada syndrome, but it is still unclear as to how sodium channel dysfunction relates to arrhythmogenesis. We examined spatial distribution of both repolarization and depolarization abnormalities in patients with Brugada syndrome by using 87-leads body surface potential mapping (BSPM). METHODS: BSPM was recorded under baseline condition and after pharmacological interventions in 28 patients with Brugada syndrome (27 males, 49 +/- 14 years). The ST-segment amplitude 20 ms after the end of QRS (ST20), QRS duration, and corrected recovery time (RTc) were measured in all 87-leads, and averaged among 6-leads (D-F, 5-6) reflecting right ventricular outflow tract (RVOT) potentials and the other 81-leads. RESULTS: The ST20 was elevated at baseline, normalized by isoproterenol, and augmented by pilsicainide in only the RVOT. The RTc was longer at baseline and increased by pilsicainide in only the RVOT. On the other hand, the QRS duration was slightly widened at baseline, further increased by pilsicainide, but not changed by isoproterenol in both leads. CONCLUSIONS: The ST-segment elevation and the RTc prolongation were localized and modulated by agents only in the RVOT region, while the slight QRS widening at baseline and further increase by pilsicainide were observed homogeneously. Our data suggest that depolarization abnormalities are distributed homogeneously, whereas repolarization abnormalities are localized in the RVOT.

Changes in body surface potential distributions induced by isoproterenol and Na channel blockers in patients with the Brugada syndrome.

BACKGROUND: The characteristics of unique ECG findings in the Brugada syndrome have not been well explained. METHODS: To clarify their characteristics and mechanisms, body surface maps (BSM) were recorded from patients with the Brugada syndrome (13 cases; a mean age of 48 years) before and after administration of isoproterenol (ISP) or Na channel blockers (12 cases). RESULTS: ST elevation in V1-V3 was decreased by 0.1 mV or more after ISP infusion in 8 of 11 cases and elevated after Na channel blockers in 8 of 12. In ventricular activation time (VAT) isochronal map, delayed conduction was noted on upper anterior chest in 11 and on anterior left chest in two. Delayed conduction areas were decreased by ISP and expanded by Na channel blockers. QRST isointegral map showed normal findings in baseline with minimal changes after ISP or Na channel blockers. Activation recovery interval (ARI) isochronal map showed prolonged area on upper anterior chest in baseline, being reduced by ISP and expanded by Na channel blockers. ARI dispersion (ARI-d), defined as difference between the maximum and minimum value of ARI, was larger in Brugada patients than that of normal subjects in baseline, and decreased after ISP and increased after Na channel blockers. CONCLUSION: ST elevation in the Brugada syndrome is primarily caused by abnormality in depolarization rather than in repolarization. BSM can provide better information to clarify a mechanism of ECG changes adding its diagnostic value for this unique syndrome.

Fractionation of electrograms and linking of activation during pharmacologic cardioversion of persistent atrial fibrillation in the goat.

INTRODUCTION: During atrial fibrillation (AF), there is fractionation of extracellular potentials due to head-to-tail interaction and slow conduction of fibrillation waves. We hypothesized that slowing of the rate of AF by infusion of a Class I drug would increase the degree of organization of AF. METHODS AND RESULTS: Seven goats were instrumented with 83 epicardial electrodes on the left atrium, left atrial appendage, Bachmann's bundle, right atrium, and right atrial appendage. AF was induced and maintained by an automatic atrial fibrillator. After AF had persisted for 4 weeks, the Class IC drug cibenzoline was infused at a rate of 0.1 mg/kg/min. AF cycle length (AFCL), the percentage of fractionated potentials, conduction velocity (CV), and direction of propagation of the fibrillation waves were measured during baseline, after AFCL was increased by 20, 40, 60, and 80 ms, and shortly before cardioversion. Infusion of cibenzoline increased the mean of the median AFCLs from 96 +/- 6 ms to 207 +/- 43 ms (P < 0.0001). The temporal variation in AFCL in different parts of the atria was 8% to 20% during control and, with the exception of Bachmann's bundle, was not significantly reduced during cibenzoline infusion. CV decreased from 76 +/- 14 ms to 52 +/- 9 cm/s (P < 0.01). Cibenzoline increased the percentage of single potentials from 81%+/- 4% to 91%+/- 4% (P < 0.01) and decreased the incidence of double potentials from 14%+/- 4% to 7 +/- 5% (P < 0.01) and multiple potentials from 5%+/-% to 1%+/- 2% (P < 0.001). Whereas during control, linking (consecutive waves propagating in the same direction) during seven or more beats occurred in 9%+/- 15% of the cycles, after cibenzoline the degree of linking had increased to 40%+/- 33% (P < 0.05). During the last two beats before cardioversion, there was a sudden prolongation in AFCL from 209 +/- 37 ms to 284 +/- 92 ms (P < 0.01) and a strong reduction in fractionated potentials (from 22%+/- 12% to 6%+/- 5%, P < 0.05). CONCLUSION: The Class IC drug cibenzoline causes a decrease in fractionation of fibrillation electrograms and an increase in the degree of linking during AF. This supports the observation that Class I drugs widen the excitable gap during AF.

Electrocardiographic dose-dependent changes in prophylactic doses of dosulepine, lithium and citalopram.

Tricyclic antidepressant drugs dosulepine (TCA), serotonin selective reuptake inhibitor (SSRI) and prophylactic agent with antidepressant effect lithium carbonicum (Li) have different cardiovascular side-effects. We compared them in the prophylactic therapy of periodic affective disorder in remission with TCA, SSRI and Li. Our previous papers confirmed the most prominent effects of heart electric field parameters in TCA patients (Slavícek et al., 1998). In the present work we studied for the first time the dose-dependent changes of ECG, body surface potential maps (BSPM - parameter DIAM 30, 40) in 43 TCA dosulepine, 40 SSRI citalopram and 30 Li outpatients (Hamilton scale: HAMDL10; age 40+/-5 years; treated for depressive disorders or bipolar disorders). The daily doses of dosulepine were 50-250 mg, citalopram 20-80 mg, Li plasma levels 0.66+/-0.08 meq/l. The electrocardiogram (ECG), vectorcardiogram (VCG), and BSPM were measured and calculated by the Cardiag 112.1 diagnostic system. The results have shown a relation between the dose of dosulepine and extremum (maximum and minimum) of depolarization isoarea map in dosulepine, but not in citalopram patients. The repolarization BSPM changes were most pronounced in SSRI patients. Lithium in long-term prophylaxy (1-22 years) caused only minimal ECG BSPM changes. The present results correspond with our previous observations.

Plasma levels of dosulepine and heart electric field.

Antidepressants, particularly tricyclic (TCA) antidepressants, may have cardiotoxic effects, such as cardiac arrhythmias, especially in patients with cardiovascular diseases. For most of TCA, no exact correlation between dosage, plasma levels and changes of ECG parameters of standard ECG has been found. So far, no relationship between dosulepine plasma levels and heart electric field parameters has been studied. We selected 18 female outpatient subjects diagnosed with recurrent depressive disorders, currently in the remission phase (HAMD < 10), without any cardiovascular disease. Patients were treated with daily dosulepine doses of 25-125 mg for 4-8 weeks. 30 heart electric field parameters were analyzed by Cardiag 128.1 diagnostic system as part of BSPM (Body Surface Potential Mapping). Acquired data were correlated with dosulepine plasma levels by means of Spearman's rank order correlation test. Four ECG parameters showed a significant correlation with dosulepine plasma levels: QRS axis deviation in frontal plane (p=0.01), DIAM 40 max (p<0.05), QRS-STT angle in transversal and left sagittal plane (p<0.05). The demonstrated changes confirmed dosulepine influence on the early myocardium depolarization phase and the correlation of this effect with dosulepine dose (its plasma concentration). The higher the dosulepine level, the more marked are the changes of the QRS-STT angle in transversal and sagittal planes and the changes in the QRS axis deviation in frontal plane. Repeatedly recorded changes in the heart electric field were dosulepine-specific and dependent on its plasma levels.

Dipyridamole body surface potential mapping: noninvasive differentiation of syndrome X from coronary artery disease.

Up to 20% to 30% of patients with angina and abnormal stress test have normal coronary arteries at angiography or syndrome X (Sy X). We tested whether body surface potential mapping (BSPM) with intravenous dipyridamole could differentiate patients with Sy X from patients with coronary artery disease (CAD). We compared the effects of intravenous dipyridamole (0.28 mg/kg over 4 min) on BSPM in 17 healthy volunteers (controls) and in 2 groups of patients with angina and abnormal ergometric tests who were referred for angiography: 27 patients with obstructive disease (> or =70% diameter stenosis) in the CAD group, and 17 patients with Sy X. Control subjects were easily differentiated from patients with CAD or Sy X by markedly smaller baseline BSPM DeltaST-T < or = LSD departure areas (P <.001), but the Sy X and CAD groups had similar ST-T departure areas. The average potential integral difference after dipyridamole (APID) differentiated Sy X and CAD patients: the mean APID increased in patients with Sy X and trended negative in the CAD group. The APID(20%-40%) (integrated over 20% to 40% of the ST-T interval) mean value was 0.59 +/- 0.67 microVs in the Sy X group and -0.18 +/- 0.59 microVs in the CAD group (P <.01). At a threshold APID(20%-40%) > 0.17 microVs, the sensitivity and specificity for Sy X was 71% and 78%, respectively; the area under the receiver operating characteristic curve was 0.79 (95% CI 0.64, 0.93). Dipyridamole BSPM is a promising noninvasive diagnostic modality to differentiate patients with Sy X from those with CAD.

Body surface distribution and response to drugs of ST segment elevation in Brugada syndrome: clinical implication of eighty-seven-lead body surface potential mapping and its application to twelve-lead electrocardiograms.

INTRODUCTION: Body surface distribution and magnitude of ST segment elevation and their reflection in 12-lead ECGs have not been clarified in Brugada syndrome. METHODS AND RESULTS: Eighty-seven-lead body surface potential mapping and 12-lead ECGs were recorded simultaneously in 25 patients with Brugada syndrome and 40 control patients. The amplitude of the ST segment 20 msec after the end of QRS (ST20) was measured from all 87 leads, and an ST isopotential map was constructed. The maximum ST elevation (maxST20) was distributed in an area of the right ventricular outflow tract in all Brugada patients, and it was larger than that in control patients (0.37 +/- 0.13 vs 0.12 +/- 0.04 mV; P < 0.0005). The maximum was observed on the level of the parasternal fourth intercostal space, on which the V1 and V2 leads of the standard 12-lead ECG were located, in 18 of the 25 Brugada patients in whom typical coved- or saddleback-type ST elevation was seen in leads V1 and V2. The maximum was located on the second intercostal space in the remaining seven Brugada patients in whom only a mild saddleback-type ST elevation was seen in leads V1 and V2 of the 12-lead ECG. Typical ST segment elevation was recognized in leads V1 and V2, which were recorded on the second or third intercostal space. ST elevation in Brugada patients was dramatically normalized by isoproterenol, a beta-adrenergic agonist (maxST20 = 0.17 +/- 0.08 mV; P < 0.0005 vs control conditions), and accentuated by disopyramide, an Na+ channel blocker (maxST20 = 0.50 +/- 0.15 mV; P < 0.0005 vs control conditions), without any change in the location of the maxST20. CONCLUSION: Our data indicate that recordings of leads V1-V3 of the 12-lead ECG on the parasternal second or third intercostal space would be helpful in diagnosing suspected patients with Brugada syndrome. The data suggest that Na+ channel blockers are capable of accentuating ST elevation in leads V1-V3.

Preferential depression of conduction around a pivot point in rabbit ventricular myocardium by potassium and flecainide.

INTRODUCTION: During reentrant arrhythmias, the circulating wavefront often makes a sharp turn around a functional or anatomic barrier. We tested the hypothesis that lowering the safety factor for conduction by high K+ or flecainide preferentially depresses conduction of sharply turning wavefronts. METHODS AND RESULTS: In 16 Langendorff-perfused rabbit hearts, a thin layer of anisotropic ventricular myocardium was made using a cryoprocedure. In this layer, a linear radiofrequency lesion was made parallel to the fiber orientation. The tip of the lesion was extended by a short incision. U-turning wavefronts were initiated by pacing at one side of the lesion. A mapping electrode (240 electrodes, resolution 350 to 700 microm) was used to measure conduction times and velocity of planar waves (longitudinal and transverse) and U-turning wavefronts. The safety factor for conduction was lowered by high potassium (8, 10, and 12 mmol/L) and flecainide (1 and 2 mg/L). On average, high potassium and flecainide increased the conduction times of U-turning wavefronts 1.6 times more than longitudinal or transverse planar wavefronts (P < 0.01). At a critical lowering of the excitatory current, functional conduction block occurred at the pivot point, which forced the wavefront to make a longer U-turn. In these cases, the total U-turn conduction time increased from 27+/-9 msec to 75+/-37 msec. About 40% of this delay was caused by a shift of the pivot point and consequent lengthening of the returning pathway. CONCLUSION: Lowering the amount of excitatory current by potassium or flecainide preferentially impairs U-turn conduction. The occurrence of long delays and conduction block at pivot points may explain the mode of action of Class I drugs.