Population differences in S-warfarin pharmacokinetics among African Americans, Asians and whites: their influence on pharmacogenetic dosing algorithms.

Using population pharmacokinetic analysis (PPK), we attempted to identify predictors of S-warfarin clearance (CL(S)) and to clarify population differences in S-warfarin pharmacokinetics among a cohort of 378 African American, Asian and white patients. Significant predictors of CL(S) included clinical (age, body weight and sex) and genotypic (CYP2C9*2,*3 and *8) factors, as well as African American ethnicity, the median CL(S) being 30% lower in the latter than in Asians and whites (170 versus 243 and 250 ml h-1, P<0.01). The plasma S-warfarin (Cp(S)) time courses following the genotype-based dosing algorithms simulated using the PPK estimates showed African Americans with CYP2C9*1/*1 and any of the VKORC1 genotypes would have an average Cp(S) at steady state 1.5-1.8 times higher than in Asians and whites. These results indicate warfarin dosing algorithms should be evaluated in each respective ethnic population. Further study of a large African American cohort will be necessary to confirm the present findings.

Evaluation of a novel index by tissue Doppler imaging in patients with advanced heart failure: relation to functional class and prognosis.

BACKGROUND: Despite the ability of tissue Doppler imaging (TDI) to detect left ventricular (LV) systolic and diastolic myocardial functions in patients with heart failure, the added value of TDI to clinical variables and conventional echocardiography in predicting the symptoms and outcome of advanced heart failure has not been clearly defined. METHODS AND RESULTS: Two hundred and thirty adult patients diagnosed with congestive heart failure were assigned to study groups based on the New York Heart Association functional classes. Pulsed-wave TDI (PWTDI), including average of peak systolic (Sm), early (Em) and late diastolic (Am) velocities from six mitral annular sites was evaluated. PWTDI was also calculated to create a combined index (EAS index) of diastolic and systolic performances. All patients were followed up for cardiac-related death and hospitalisation as a result of heart failure. Patients with functional class III-IV had a significantly higher EAS index (0.21 ± 0.19 vs. 0.13 ± 0.08, p < 0.05) than those with class I-II and the control (0.10 ± 0.04, p < 0.05). Except for Sm and Em, all conventional echocardiographic Doppler parameters and TDI variables significantly correlated with functional class. Moreover, according to multiple stepwise analysis, EAS index and percentage of chronic renal insufficiency (CRF) were the only two independent predictors of functional class (EAS index, p = 0.006; CRF, p = 0.019). During follow-up (median, 30 months), 93 participants had cardiac events. EAS index, LV mass index and CRF were significant predictors of cardiac mortality and hospitalisation [EAS index, hazard ratio (HR) 4.962, p = 0.006; LV mass index, HR 1.007, p = 0.003; CRF, HR 1.616, p = 0.040]. CONCLUSIONS: The EAS index, which reflects systolic and diastolic performances, is a highly effective means of differentiating between patients with functional class I-II and those with III-IV. The index also correlates with cardiac mortality and hospitalisation for worsening heart failure, thus providing additional value to conventional echocardiographic measures.

Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes.

Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han-Chinese patients without prior warfarin treatments. Using the genotype-based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR > 4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R(2) of 0.62). This study demonstrated that pharmacogenetics-based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.

Lactococcus garvieae infections in humans: possible association with aquaculture outbreaks.

Lactococcus garvieae is an important pathogen in aquaculture, outbreaks of which significantly affect production. It is a rare pathogen with a low virulence in human infection. The relation between the aquaculture outbreak and the human infection has not been clarified. Prospective and retrospective epidemiologic surveillance of the four patients with L. garvieae infection between 2000 and 2003 and their relations to the aquaculture outbreaks of L. garvieae were conducted. All the four patients with L. garvieae infection were associated with gastrointestinal disorders. Three of the four patients gave a history of consuming raw fish and in three of the four patients, the infection occurred in summer between June and August while there is a decrease of fisheries production and an increase in L. garvieae infection in aquaculture farms. There was a 100% identity of 16S rDNA sequence of L. garvieae isolates from patient 1 and from the squid muscle obtained from the restaurant where patient 1 consumed the raw fish. Sporadic occurrence of L. garvieae infection in human appears to correlate with the seasonal aquaculture outbreaks of L. garvieae infection. The presence of gastro-intestinal disorder may facilitate L. garvieae infection.

Aortic valve sclerosis is an echocardiographic indicator of significant coronary disease in patients undergoing diagnostic coronary angiography.

Aortic valve sclerosis (AVS) is considered to be a manifestation of generalised atherosclerosis that involves the aortic valve. It has been associated with higher cardiovascular morbidity and mortality in a population-based study. This investigation used transthoracic echocardiography (TTE) to evaluate the prevalence and significance of AVS in 357 Chinese patients with suspected coronary artery disease (CAD). This work reveals that AVS is an independent echocardiographic predictor of significant CAD in such clinical setting (O.R.=3.18; 95% confidence interval 1.52-6.7; p=0.002). Other independent predictors include male gender, diabetes mellitus and hypertriglyceridemia. The predictive value of AVS for the presence of CAD is more prominent in females and in subjects aged <65 years. The recognition of AVS on TTE should alert the physicians to the possibility of underlying significant CAD, and further evaluation with aggressive management is indicated, even though no angiographic documentation is available.

Further characterization of apolipoprotein B genetic variations in Taiwanese.

Apolipoprotein B (apoB, protein; APOB, gene) is the main protein component of low-density lipoprotein (LDL) and plays an important role in blood lipid metabolism. Previously, we have reported four APOB coding regions, 5' signal peptide, and 3' repeat sequence polymorphisms in our population. In this report, we further characterize other APOB genetic variations. The results illustrate that the mutation frequencies for Arg3500Gln (1/846 alleles), Arg4019Trp (2/786 alleles), -265 C/T promoter region (0/264 alleles), and intron 2 A/G (0/450 alleles) are very low. Our population showed a frequency of 68.9% for the B4311 Ser allele. The B4311 Asn allele was associated with a higher apoB level than the Ser group (p < 0.05) in normal controls. In the normal controls, a higher B4311 Asn/Asn genotype frequency was found in the group with total cholesterol (TC) > 200 mg/dL and apoB concentration > 85 mg/dL than in the group with a TC < 200 mg/dL and apoB < 85 mg/dL (p = 0.03 for TC comparison).

DNA polymorphisms at the apolipoprotein A1-CIII loci in Taiwanese: correlation of plasma APOCIII with triglyceride level and body mass index.

BACKGROUND AND PURPOSE: Apolipoprotein (APO) A1-CIII genes are linked within a 2.6-kb region on human chromosome 11. ApoA1 is the main component of high-density lipoprotein (HDL), and apoCIII inhibits lipoprotein lipase activity. Genetic variations in APOA1-CIII may affect the function of apoA1/apoCIII and plasma lipid/lipoprotein levels, and thus, the risk of developing atherosclerosis. This study compared the frequency distributions of genetic variations in APOA1-CIII genes and their influence on plasma lipid concentrations in Taiwanese patients with coronary artery disease (CAD) and in healthy controls. METHODS: Six restriction site variations (RSVs) of the APOA1-CIII gene complex were investigated by DNA amplification using polymerase chain reaction and restriction enzyme digestion in 229 control subjects and 131 CAD patients during the period from 1992 through 1996. The blood lipid profiles of these subjects were also determined. RESULTS: Thirty-seven distinct six-RSV genotypes were observed. Separate comparisons of the frequency distributions of the six genetic variations showed no significant differences between CAD patients and controls subjects, but the combined six-RSV-genotypes showed different frequency distributions between these two groups. Nine of the 37 six-RSV genotypes were found only in the CAD patients and higher frequencies of two of these types were observed in the CAD patients than in healthy controls. The effects of these genetic variations were on high-density lipoprotein cholesterol in women (for MspIB, PstI, SstI and PvuII RSV) and total cholesterol (for PvuII RSV), low-density lipoprotein cholesterol (for XmnI RSV), and apolipoprotein B (for MspI and SstI RSV) levels in men in the control group. Elevated plasma apoCIII concentration was significantly associated with an increased plasma triglyceride level and body mass index in the control group (P < 0.0001). CONCLUSIONS: Analysis of the frequency distribution of six RSVs of the APOA1-CIII gene complex in Taiwanese CAD patients and control subjects showed that the effect of genotype on plasma lipid levels was gender-specific and that the apoCIII level was closely associated with plasma triglyceride level and body mass index.

Comparison of antihypertensive efficacy and tolerability of losartan and extended-release felodipine in patients with mild to moderate hypertension.

Appropriate control of blood pressure has been shown to reduce morbidity and mortality in patients with hypertension. Losartan potassium, a selective antagonist of the angiotensin II type 1 (AT1) receptor, has been shown to lower blood pressure in patients with hypertension. The purpose of this study was to compare the efficacy and tolerability of losartan and extended-release (ER) felodipine in Taiwanese patients with mild to moderate hypertension. Patients with mild to moderate hypertension (sitting diastolic blood pressure, 95-115 mm Hg) were enrolled in this prospective, randomized, parallel study. Sitting blood pressure, heart rate, adverse reactions, and serum biochemistry values were assessed during 2 weeks of placebo and 12 weeks of active treatment. Each patient received 50 mg of losartan or 5 mg of felodipine ER once daily, and the dosage was adjusted to double the initial level at week 6 if necessary. Of the 44 patients randomly allocated to receive losartan (n = 23) or felodipine (n = 21) therapy, 37 completed the study; three patients in the losartan group and four in the felodipine group withdrew because of adverse experiences, or were lost to follow-up. The mean reductions in sitting diastolic blood pressure at 6 and 12 weeks were significant with both losartan (-8.6 and -11.38 mm Hg, respectively) and felodipine (-9.2 and -10.69 mm Hg, respectively), and did not differ significantly between the two groups. Both losartan and ER felodipine were well tolerated by patients. However, the ER felodipine group had a significantly higher rate of drug-related flushing than the losartan group (24% vs 0%, p = 0.022). The results indicate that once-daily administration of losartan is as effective and well tolerated as once-daily ER felodipine in blood pressure reduction.

Variation of P-QRS relation during atrioventricular node reentry tachycardia.

OBJECTIVES: The main objective of this study was to characterize the phenomenon of variation in the P-QRS relation during atrioventricular node reentry tachycardia. BACKGROUND: Variation of P-QRS relation during tachycardia has been observed occasionally in atrioventricular node reentry tachycardia. However, the incidence, the characteristics and the mechanisms of this phenomenon have not been investigated previously. METHODS: Retrospective analysis was performed in 311 consecutive patients with slow-fast form and 108 patients with atypical or multiple form of atrioventricular node reentry tachycardia to examine whether variation of P-QRS relation with changes in AH, HA and AH/HA (A = atria; H = His bundle) ratio occurred during tachycardia. RESULTS: A total of 28 patients, 8 with slow-fast and 20 with atypical or multiple tachycardias, were found to manifest this phenomenon. There were 6 males and 22 females, with an average age of 38+/-16 years. In 10 patients, this phenomenon occurred transiently following electrical induction of the tachycardia. In 15 patients, changes in AH, HA and AH/HA ratio were associated with the occurrence of Wenckebach or 2:1 block proximal to the His bundle (H) recording site without interruption of the tachycardia. In nine patients, three with nonsustained tachycardia and six after administration of adenosine triphosphate, this phenomenon was observed at the termination of the tachycardia. This phenomenon was usually accompanied by a mild lengthening of the tachycardia cycle length. CONCLUSIONS: Variation of P-QRS relation with or without block may occur during atrioventricular node reentry tachycardia, especially in atypical or multiple-form tachycardias. It was postulated that decremental conduction in the distal common pathway, which exists between the distal link of the reentry circuit and the H, is primarily responsible for this phenomenon.

Determinants of tachycardia recurrences after radiofrequency ablation of idiopathic ventricular tachycardia.

Clinical and electrophysiologic parameters were analyzed to define the factors potentially related to tachycardia recurrences in 79 patients undergoing successful radiofrequency ablation of idiopathic right or left ventricular tachycardia. It was found that the endocardial activation time at the successful ablation site was the only independent predictor of tachycardia recurrences.

Atypical atrioventricular nodal reentry tachycardia with atrioventricular block mimicking atrial tachycardia: electrophysiologic properties and radiofrequency ablation therapy.

INTRODUCTION: Fast-intermediate form AV nodal reentry tachycardia (AVNRT) sometimes may mimic atrial tachycardia or atrial flutter and render the diagnosis difficult when the tachycardia rate is fast and AV block occurs during tachycardia. METHODS AND RESULTS: A 45-year-old woman with paroxysmal supraventricular tachycardia was referred to this institution. Initially, the tachycardia was thought to be an atrial tachycardia because of: (1) a short cycle length of the tachycardia with 2:1 and Wenckebach AV block; (2) a difference in the atrial activation sequence during tachycardia and during ventricular pacing; and (3) failure of burst ventricular pacing to affect the atrial rate and the atrial activation sequence during tachycardia. An accurate diagnosis of fast-intermediate form AVNRT was subsequently made based on the finding that the tachycardia was induced following delivery of a third ventricular extrastimulus, which showed a sequence of V-A-H and a change on atrial activation sequence of the induced beat. Successful radiofrequency ablation was achieved only after accurate diagnosis of the tachycardia was made. CONCLUSION: Fast-intermediate form AVNRT sometimes may masquerade as atrial tachycardia. Accurate diagnosis is mandatory for successful ablation therapy.

Adenosine-sensitive ventricular tachycardia from the anterobasal left ventricle.

OBJECTIVES: This study demonstrates that exercise-provocable tachycardia resembling right ventricular outflow tract tachycardia may originate from the anterobasal left ventricle. BACKGROUND: Reentry is the operative mechanism of idiopathic left ventricular tachycardia, with a QRS complex of right bundle branch block and superior axis that is responsive to verapamil but not adenosine. Whether some mechanism other than reentry is operative in some idiopathic left ventricular tachycardias is unclear. METHODS: In 4 of 53 consecutive patients with idiopathic left ventricular tachycardia, the tachycardia was sensitive to adenosine. These four patients were women 63, 61, 61 and 31 years old and were the subjects of the present study. RESULTS: In all four patients, spontaneous tachycardia was related to exercise or emotional stress. The tachycardia displayed atypical left (one patient) or right (three patients) bundle branch block with an inferior axis and marked variation in cycle length. An intravenous bolus of adenosine triphosphate (10 to 20 mg) terminated tachycardia in all four patients. Tachycardia was terminated or prevented in three patients given intravenous or oral verapamil. Atrial or ventricular incremental or extrastimulus testing induced tachycardia in all four patients (three with, one without isoproterenol infusion). Electrically induced tachycardia also demonstrated marked variation in cycle length, which ranged from 230 to 390 ms. Entrainment was not demonstrable with overdrive pacing from multiple sites. Endocardial mapping during tachycardia revealed that the earliest activations were registered 25, 40, 35 and 50 ms before onset of the QRS complex, respectively, from the anterior aspect of the left ventricle just below the mitral annulus, adjacent to the left ventricular outflow tract. High frequency Purkinje spikes were not recorded at this site. Radiofrequency current delivered to this site successfully ablated the tachycardia in three of the four patients. CONCLUSIONS: Exercise-provocable, catecholamine-mediated, verapamil-responsive, adenosine-sensitive ventricular tachycardia may arise from the anterobasal left ventricle adjacent to the outflow tract.

Successful radiofrequency ablation of idiopathic left ventricular tachycardia at a site away from the tachycardia exit.

OBJECTIVES: This study sought to assess the possibility of ablating verapamil-responsive idiopathic left ventricular tachycardia at a site distant from the tachycardia exit and thus to define the tachycardia circuit. BACKGROUND: The nature of the reentry circuit in idiopathic left ventricular tachycardia is unclear. If the circuit is of considerable size, then it should be possible to ablate the tachycardia at a site distant from the exit site. METHODS: Electrophysiologic studies and radiofrequency ablation were performed in 27 consecutive patients with verapamil-responsive idiopathic left ventricular tachycardia. In all 27 patients, the tachycardia exit site was defined as the site where the earliest Purkinje potential was recorded > or = 25 ms before the onset of the QRS complex during the tachycardia and where the pace map QRS complex resembled that during the tachycardia. A potential ablation site other than the exit site was then sought around the midseptum, proximal to the exit site. At such sites the tachycardia could be terminated transiently by pressure applied to the catheter tip, without induction of ventricular ectopic beats. RESULTS: The potential ablation site, other than the tachycardia exit site, was identified in seven male patients (mean [+/-SD] age 31 +/- 12 years, range 13 to 52). Application of the radiofrequency current at this site resulted in termination of the tachycardia within 1 to 5 s (mean 2.9 +/- 1.6), and successful ablation of the tachycardia was achieved in all seven patients (success rate 100%, 95% exact confidence interval 0.5898 to 1). The mean distance between the ablation site and the tachycardia exit site was 3.1 +/- 0.7 cm (range 2.0 to 4.0). A presystolic Purkinje spike was recorded 14 +/- 5 ms (range 8 to 20) before the onset of the QRS complex during the tachycardia. During the follow-up period of 24 +/- 11 months (range 12 to 39), there was no recurrence of tachycardia in these seven patients. CONCLUSIONS: Successful ablation of idiopathic left ventricular tachycardia can be achieved at sites away from the tachycardia exit site in some patients. This finding suggests that the reentry circuit is likely to be of considerable size, encompassing the middle, inferior and lower aspects of the left interventricular septum.

Catheter-induced atrioventricular nodal block during radiofrequency ablation.

This study examined the incidence and significance of catheter-induced atrioventricular nodal block (AVNB) during a radiofrequency ablation procedure that uses stiff large-tip steerable ablation catheters. AVNB was noted in 10 (1.6%) of 613 consecutive patients undergoing radiofrequency ablation therapy for atrioventricular nodal (AVN) reentrant tachycardia (592 patients) or atrioventricular reentry tachycardia incorporating a midseptal accessory pathway (21 patients). Of these 10 patients, 9 underwent AVN modification for AVN reentrant tachycardia and 1 for ablation of a midseptal accessory pathway. One patient had two episodes of AVNB during two sessions undertaken because of recurrence of tachycardia. No patient had a preexisting conduction defect before the study. In all 10 patients, AVNB was transient, and it lasted for a mean of 9.1 +/- 19 minutes. It occurred during positioning of the ablation catheter in the junctional area before (8 patients) or after (2 patients) the start of radiofrequency current applications. Complete AVNB was noted on six occasions, second-degree AVNB on four occasions, and first-degree AVNB on one occasion. All blocks were associated with narrow QRS ventricular beats and with a site of block proximal to the His bundle. The mean ventricular heart rate during AVNB was 60 +/- 23 beats/min. Two patients had transient asystole, with one having loss of consciousness. No patient required special treatment for heart block. One-to-one conduction resumed after repositioning of the catheters, and the subsequent ablation procedure was successfully completed in 8 of the 10 patients. During a follow-up of 20 +/- 12 months, none of the patients had severe dizziness or syncope, and none required implantation of a permanent pacemaker. In conclusion, transient AVNB due to mechanical injury occurs during positioning of a stiff large-tip steerable ablation catheter in the junctional area. Delivery of radiofrequency current to the site that provokes catheter-induced AVNB should be avoided.

Radiofrequency ablation therapy of the posteroseptal accessory pathway.

Among 652 patients with Wolff-Parkinson-White syndrome who underwent radiofrequency ablation in this laboratory, 139 (21%) were found to have a total of 146 posteroseptal accessory pathways. Ablation was conducted by the regular transvenous or transaortic approach; ablation from cardiac venous structures was used only if regular approaches were unsuccessful. Of the 146 posteroseptal accessory pathways, 94 were successfully ablated from the left posteroseptal region and 45 from the right posteroseptal region. In 3, successful ablation of the accessory pathway required delivery of the current to the proximal coronary sinus, and in 1 it required delivery of the current to both the atrial and ventricular aspects of the tricuspid valve at the right posteroseptum. Thus, the accessory pathway was successfully ablated in 143 (98%) of 146 instances or in 136 (98%) patients. In 3 patients, ablation was unsuccessful despite delivery of current to the left posteroseptum, the right posteroseptum, the proximal coronary sinus, and the middle cardiac vein. Seventy-seven (57%) patients with an initial success, including 9 patients with resumed preexcitation or recurrence of paipitations, underwent a follow-up electro-physiologic study 90 +/- 72 days after ablation. Of these 9 patients, the initial successful ablation site was the right posteroseptum in 7 and the left posteroseptum in 2. The accessory pathways were ablated successfully by subsequent trials in 8 patients, whereas in 1 the accessory pathway was severely damaged. Thus radiofrequency ablation of posteroseptal accessory pathways can be achieved by the regular transvenous or transaortic approach; delivery of current to the coronary sinus or middle cardiac vein is unnecessary in most patients.

Apolipoprotein B 3' hypervariable repeat genotype: association with plasma lipid concentration, coronary artery disease, and other restriction fragment polymorphisms.

Apolipoprotein B gene 3' variable number tandem repeat (VNTR) and related regions were amplified by PCR and analyzed by agarose gel electrophoresis. Eighteen VNTR alleles (VNTR25, 26, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 58, 60) and 45 genotypes were observed in 477 Taiwanese subjects. The VNTR35 allele and genotype VNTR35/35 were observed most frequently in this population. The polymorphism information content was 0.62. Some minor alleles, such as VNTR25 and 60, were found only in coronary artery disease (CAD) and stroke patients in our sampling, and no statistically significant difference was observed in VNTR allelic frequency between control and CAD or stroke patients. Significant differences in allelic distribution of some VNTR alleles were observed between our normal Taiwanese population and a Caucasian group studied by others. VNTR43-47 and AluI+ (coding Ala591) restriction fragment length polymorphism (RFLP) as well as VNTR49-60 and EcoRI- (coding Lys4154) RFLP were found to be highly coinherited. No apparent association between the VNTR genotype and plasma lipid concentration was observed; however, for the same genotype, the CAD and stroke patients frequently showed higher lipoprotein(a) and lower HDL cholesterol concentrations than the control group.

Radiofrequency ablation for supraventricular and ventricular tachycardia in young patients.

Radiofrequency ablation therapy was conducted in 86 consecutive children and young patients with a mean age of 14 +/- 3 years (range = 3-18). Fifty-two patients had Wolff-Parkinson-White syndrome, one had re-entry tachycardia incorporating a nodoventricular fiber, 22 had atrioventricular node re-entry tachycardia, two had atrial tachycardia and nine had idiopathic ventricular tachycardia. Radiofrequency ablation was successful in 50 of the 52 patients (96%) with Wolff-Parkinson-White syndrome and the one with nodoventricular fiber. Radiofrequency modification of the atrioventricular node using the inferior approach was successful in eliminating atrioventricular node re-entry tachycardia in 20 of the 22 patients (91%). Radiofrequency ablation in the two patients with atrial tachycardia was unsuccessful. Of the nine patients with idiopathic ventricular tachycardia, eight from the left ventricle and one from the right ventricular outflow tract, eight were successfully ablated (88%). Follow-up over a period ranging from 1 to 46 months (21 +/- 13) revealed a recurrence of tachycardia in seven patients; a late electrophysiological study in 38 patients revealed the induction of tachycardia in 11 patients (seven with accessory pathway-mediated tachycardia, three with atrioventricular node re-entry tachycardia and one with idiopathic ventricular tachycardia). All 11 patients were successfully ablated by a second trial. In conclusion, radiofrequency ablation therapy is effective and safe in pediatric patients with supraventricular and ventricular tachycardia and should be considered as the therapy of choice in this group of patients.

Retrograde atrio-His bundle dissociation as a sign indicative of retrograde accessory pathway conduction.

Electrophysiologic study and radiofrequency ablation therapy were performed in a 36-year-old male with Wolff-Parkinson-White syndrome and Ebstein's anomaly. The study disclosed the presence of a posteroseptal accessory pathway and dual atrioventricular (AV) nodal pathways. Retrograde atrio-His bundle (A-H) dissociation was noted during rapid ventricular pacing, in which the atria were activated by retrograde impulse from the accessory pathway with a fixed ventriculo-atrial (VA) interval while the retrograde His bundle potential was visible during the diastolic isoelectric period due to the occurrence of Wenckebach periodicity within the His-Purkinje system. This phenomenon is a useful sign for rapid recognition of the accessory pathway conduction.