Prospective evaluation of corrected QT intervals and arrhythmias after exposure to epirubicin, cyclophosphamide, and 5-fluorouracil in women with breast cancer.

BACKGROUND: Corrected QT (QTc) interval prolongation can induce fatal arrhythmias such as torsade de pointes. PATIENTS AND METHODS: To assess the characteristics of QTc intervals and arrhythmias in women with early breast cancer who received FEC100 adjuvant chemotherapy, electrocardiograms (ECGs) were recorded before and after each chemotherapy. Associations between QTc interval prolongation and single nucleotide polymorphisms (SNPs) of potassium channel genes were also investigated. RESULTS: A total of 131 ECG records were obtained in 34 patients who received 153 cycles of FEC100. QTc intervals could be measured in 127 records. There was a significant trend toward QTc interval prolongation after each treatment, persisting through four cycles of chemotherapy (P < 0.001). Median QTc interval prolongations were 13, 11, 18, and 14 ms in the first through fourth cycles of chemotherapy, respectively. QTc intervals differed significantly between cycles 1 and 4 before treatment as well as after treatment (P < 0.05). A single supraventricular premature contraction was noted in 3 (2.3%) of the 131 cycles in 2 (5.9%) of the 34 patients. There was no significant association between QTc interval prolongation and SNPs of potassium channel genes. CONCLUSION: This prospective study confirmed that FEC100 is associated with significant QTc interval prolongation in women with early breast cancer.

Ventricular activation and recovery measured in electrocardiographic limb leads correlate with measurements from specific areas in body surface mapping.

AIMS: Dispersion of ventricular depolarization-repolarization in 12-lead electrocardiograms (ECGs) has been reported to provide noninvasive information on arrhythmogenicity. However, there are two methods to calculate the dispersion from ECGs including and excluding limb leads. The aim of this study was to examine whether temporal parameters from limb leads represent activation and repolarization of a particular part of the body surface. METHODS AND RESULTS: We compared the temporal parameters of activation time (AT), activation-recovery interval (ARI), and recovery time (RT) from limb leads of ECGs with those from an 87-lead body surface maps. The study population consisted of 50 normal subjects (25 men and 25 women, 19.4 +/- 1.6 years). The temporal parameters in leads I, II, and III were highly (r > 0.9) correlated with those in unipolar leads over the left lateral, left lower, and right lower chest, respectively. The temporal parameters in leads aVR, aVL, and aVF showed a significant correlation (r > 0.8) with those in unipolar leads over the right upper, left upper, and lower anterior chest, respectively. The mean AT, ARI, and RT from each limb lead of ECG were almost the same as those of unipolar leads over the corresponding areas of the body surface. CONCLUSIONS: These findings suggest that ATs, ARIs, and RTs from limb leads may represent those from unipolar leads of particular areas over the body surface in normal subjects. The temporal parameters from limb leads of ECGs may provide information on activation and repolarization as well as the precordial leads of ECGs.

Prolongation of activation-recovery interval over a preexcited region before and after catheter ablation in patients with Wolff-Parkinson-White syndrome.

INTRODUCTION: Preexisting changes in repolarization properties play an important role in T wave abnormalities (cardiac memory) after ablation in patients with Wolff-Parkinson-White (WPW) syndrome. However, no report has provided direct evidence for prolongation of action potential duration (APD) over a preexcited region before and after ablation. METHODS AND RESULTS: We studied 10 patients with ventricular preexcitation due to a left-sided accessory pathway (AP) (group M) and 12 patients with concealed left-sided AP (group C) to clarify prolongation of APD using activation-recovery intervals (ARIs) from epicardial and endocardial unipolar electrograms in patients with WPW syndrome. ARI was calculated from unipolar electrograms at the His bundle and the coronary sinus adjacent to the AP during atrial pacing (100 beats/min) before and 30 minutes after ablation. Before ablation, ARIs at the AP site were significantly longer in group M than in group C (255+/-21 msec vs 211+/-24 msec; P < 0.01), whereas ARIs at the His bundle did not differ between the two groups (255+/-20 msec vs 245+/-27 msec; P = NS). After ablation, group M showed no significant changes in ARIs at the AP and His bundle (256+/-19 msec and 253+/-15 msec) compared with before ablation. CONCLUSION: We found by direct analysis of ARIs from the epicardium that APD prolongation over the preexcited region was present before catheter ablation and persisted after catheter ablation. The gradual changes in repolarization properties, including APD prolongation after discontinuation of AP, may be one mechanism of cardiac memory after catheter ablation in patients with WPW syndrome.

Activation-recovery intervals of 12-lead electrocardiograms before and after catheter ablation in patients with Wolff-Parkinson-White syndrome.

Preexcitation in Wolff-Parkinson-White syndrome (WPW) has been reported to induce long-lasting changes in ventricular recovery properties. However, there has not been a report concerning changes in the activation-recovery interval (ARI) in 12-lead ECGs before and after catheter ablation (CA) in patients with WPW syndrome. The present study compared changes in ARIs from 12-lead ECGs with those from body surface unipolar leads before and after CA to examine whether ARIs from limb leads of 12-lead ECGs provide useful information on changes in recovery properties in addition to the ARIs from precordial leads. The study population consisted of 27 manifest WPW patients with a left- (n=18, group A) or right-sided accessory pathway (n=9, group B). ARIs in leads I, II, and III were strongly correlated with those in unipolar leads over the left lateral, left lower, and right lower chest, respectively. ARIs in leads aVR, aVL, and aVF showed a significant correlation with those in unipolar leads over the right upper, left upper, and lower anterior chest, respectively. These correlations were maintained before and after CA. Furthermore, in group A, ARIs in lead V1 tended to increase on day 7 post CA compared with before CA and on day 1. In group B, ARIs in lead III significantly decreased on day 7 compared with before CA and on day 1. These findings suggest that ARIs from the limb leads of 12-lead ECGs may represent those from unipolar leads of a particular area over the body surface, and that ARIs from 12-lead ECGs may provide useful quantitative information on changes in recovery properties before and after CA in patients with manifest WPW syndrome.

Comparison of vectorcardiographic and 12-lead electrocardiographic detections of abnormalities in repolarization properties due to preexcitation in patients with Wolff-Parkinson-White syndrome: proposal of a novel concept of a "remodeling gradient".

Repolarization abnormalities after radiofrequency ablation in patients with manifest Wolff-Parkinson-White syndrome (WPW) have been attributed to cardiac memory of pre-existing changes in repolarization properties. We compared spatial ventricular gradient (VG) from vectorcardiograms with QRST values of 12-lead ECG in 41 patients with WPW (group A, manifest WPW due to left-sided accessory pathway (n = 20); group B, manifest WPW due to right-sided accessory pathway (n = 12); group C, concealed WPW (n = 9)) before and after ablation. Group N (n = 607) served as control. In groups A and B, the abnormalities of spatial VG and QRST values of 12-lead ECG that existed before and 1 day after ablation significantly decreased 1 week after ablation. In group C, spatial VG and QRST values of 12-lead ECG showed no significant changes. The diagnostic ability of spatial VG is almost equivalent to that of the QRST value of ECG in detecting repolarization abnormalities in patients with WPW before and after ablation. We propose a new concept of a "remodeling gradient" directing from the preexcited area to the opposite side of the ventricle as a result of preexcitation-induced electrical remodeling.

Antiarrhythmic efficacy of dipyridamole in treatment of reperfusion arrhythmias : evidence for cAMP-mediated triggered activity as a mechanism responsible for reperfusion arrhythmias.

BACKGROUND: Intracellular calcium overload is believed to play an important role in development of reperfusion arrhythmias. Dipyridamole, an inhibitor of cellular uptake of adenosine, may prevent or terminate reperfusion arrhythmias by reducing intracellular calcium overload. METHODS AND RESULTS: First, we tested for a preventive effect of dipyridamole. Sixty-one patients who underwent primary PTCA for treatment of acute anterior wall myocardial infarction were enrolled in this prospective study. Patients were divided into dipyridamole (DP) and nondipyridamole (non-DP) groups. The 2 groups had similar baseline characteristics. In the DP group, dipyridamole 0.5 mg/kg was infused intravenously for 3 minutes immediately before reperfusion during primary PTCA. Arrhythmias after reperfusion were analyzed from continuous ECG recordings. None of the patients in the DP group (n=23) had accelerated idioventricular rhythms (AIVR) or ventricular tachycardia (VT). In contrast, 7 (18.4%) had AIVR and 3 (7.9%) had VT in the non-DP group (n=38; P<0.01). Second, we tested for a termination effect of dipyridamole. Dipyridamole 0.5 mg/kg was infused intravenously while continuous ECG recordings were obtained in 9 patients who had either sustained AIVR (n=7) or sustained VT (n=2) after reperfusion of occluded coronary artery. Arrhythmias were terminated in all patients. CONCLUSIONS: These results indicate that administration of dipyridamole can prevent and terminate reperfusion arrhythmias such as AIVR and VT. cAMP-mediated triggered activity may, at least in part, be responsible for reperfusion-induced AIVR and VT.

Inverse relation of body-surface activation-recovery interval and recovery time to activation time in normal subjects: stronger correlation and more heterogeneous distribution in activation-recovery interval than in recovery time.

The activation-recovery interval (ARI), measured directly from the myocardium, has shown a good correlation with the action potential duration (APD) in experiments. APD has been reported to be inversely related to the activation time (AT). However, no studies have examined the correlation between the body-surface ARI and AT in normal subjects. Fifty normal subjects (25 men and 25 women) were studied to elucidate the relationship between the body-surface ARI and AT. The body-surface AT was defined as the duration between the QRS onset and the minimum dV/dt of the QRS wave, and ARI as the interval between the minimum dV/dt of the QRS wave and the maximum dV/dt of the T wave in each lead of an 87 unipolar lead system. We also measured the recovery time (RT) defined as the duration between the QRS onset and the maximum dV/dt of the T wave. ARI was inversely correlated with AT (r = -0.73). RT was also inversely correlated with AT (r = -0.61), however, RT had a less heterogeneous distribution than ARI (148 ms vs 159 ms). There were no differences between male and female subjects in the relation between ARI and RT or in the body-surface distribution of ARI and RT. These findings suggest that the body-surface ARI may reflect recovery properties over the cardiac surface and that APD may distribute inhomogeneously over the human cardiac surface with a longer RT over an area with a shorter AT. ARI calculated from body-surface ECG may be a useful noninvasive and repeatedly measurable estimate of APD.

Localization of precise origin of idiopathic ventricular tachycardia from the right ventricular outflow tract by a 12-lead ECG: a study of pace mapping using a multielectrode "basket" catheter.

Radiofrequency catheter ablation guided by pace-mapping techniques has proven effective in eliminating idiopathic ventricular tachycardia (VT) originating from the right ventricular outflow tract (RVOT). A method for rapidly identifying the origin of VT from 12-lead electrocardiogram (ECG) findings would be helpful for the catheter ablation procedure. The purpose of this study is to precisely localize the origin of idiopathic VT from the RVOT by a 12-lead ECG from a study of multipoint pace mapping. In one patient with premature ventricular complex (PVC) and 3 with VT, a "basket" catheter was deployed in the RVOT for bipolar pacing from 56 sites in the endocardium of RVOT. Under fluoroscopy the pacing sites were classified into the septum and free wall. We investigated the QRS morphology in leads, I, II, and III; the depth of the QS wave in leads aVR and aVL; and the height of the initial r wave in leads V1 and V2. Pacing was captured in 30-47 of 56 sites (54%-84%). As the pacing sites changed from the anterior to posterior of the septum, the QS notch (-) type in lead I shifted through rs to R, while a shift from R type to rR' or Rr' was noted in leads II and III. As the pacing sites changed from the anterior to posterior of the free wall, lead I showed a shift from the QS notch (+) type to R, while a shift from rR' to Rr' (or rR' unchanged) was found in leads II and III. The depth of the QS wave in leads aVR and aVL showed a tendency for aVR to be deeper than aVL toward the posterolateral attachment of both the septum and free wall, whereas aVL tended to be deeper than aVR toward the anterior attachment. The initial r waves in V1 and V2 became greater as the pacing site was positioned at a higher or more posterior location. These findings may provide more precise and clinically useful diagnostic information on the site of the origin of idiopathic VT originating from the RVOT by a 12-lead ECG.

Relationship between Joint National Committee-VI classification of hypertension and ambulatory blood pressure in patients with hypertension diagnosed by casual blood pressure.

BACKGROUND: White-coat hypertension has been diagnosed arbitrarily based on different criteria. In 1997, the Joint National Committee-VI (JNC-VI) reported a new classification of hypertension and strongly emphasized the importance of ambulatory blood pressure (ABP) monitoring. The report pronounced normal ABP values for the first time. HYPOTHESIS: The study's aim was to clarify the relationship between casual blood pressure (BP) and ABP of patients with essential hypertension in each stage of JNC-VI classification, and the prevalence of white-coat hypertension diagnosed by using JNC-VI normal ABP criteria. METHODS: Ambulatory blood pressure was monitored non-invasively in 232 patients with essential hypertension whose casual BP was > or = 140/90 mmHg. The patients were classified according to JNC-VI classification, and their casual BP was compared with ABP. The criterion of white-coat hypertension was defined as casual BP > or = 140/90 mmHg with normal ABP according to JNC-VI criteria (< 135/85 during daytime and < 120/75 during nighttime). RESULTS: Mean ABP increased as the stage advanced, and the differences between casual BP and ABP also increased. There were considerable overlaps in the distribution of ABP among stages. The prevalence of white-coat hypertension was 13% overall: 30% of the patients with isolated systolic hypertension, 19% of those in stage 1, 10% in stage 2, and 4% in stage 3. CONCLUSIONS: Classification of hypertension based on casual BP may not always correspond in severity to that based on ABP. Ambulatory blood pressure monitoring recommended by JNC-VI is very useful for the evaluation of hypertension to differentiate white-coat hypertension from true hypertension.

Body-surface distribution of changes in activation-recovery intervals before and after catheter ablation in patients with Wolff-Parkinson-White syndrome: clinical evidence for ventricular 'electrical remodeling' with prolongation of action-potential duration over a preexcited area.

BACKGROUND: T-wave abnormalities after catheter ablation in patients with manifest Wolff-Parkinson-White (WPW) syndrome have been attributed to a continuation of repolarization abnormalities induced by preexcitation (cardiac memory). METHODS AND RESULTS: To clarify changes in repolarization properties, we analyzed the activation-recovery interval (ARI) obtained from body-surface maps and the relationship between the activation time (AT) and ARI in 30 patients with WPW syndrome (group A, 18 patients with manifest left-sided accessory pathway; group B, 7 patients with manifest right-sided accessory pathway; and group C, 5 patients with concealed left-sided accessory pathway) before, 1 day after, and 1 week after ablation. The ARI significantly decreased 1 week after ablation compared with before and 1 day after ablation over the preexcited area in groups A and B. Correlation coefficients between the AT and ARI showed a significantly (P<.01) stronger inverse relationship before (r=-.58) and 1 week after (r=-.64) ablation than 1 day after ablation (r=-.46) in groups A and B. In group C, the ARI and correlation coefficients between the AT and ARI showed no significant changes. CONCLUSIONS: These findings suggest a prolongation of the action-potential duration over the preexcited area before and just after ablation as ventricular "electrical remodeling," a decrease in the inverse relationship between the AT and action-potential duration 1 day after ablation, and a gradual recovery of the action-potential duration over the preexcited area and inverse relationship 1 week after ablation.

Body surface distribution of significant changes in QRST time-integral values after radiofrequency catheter ablation in patients with Wolff-Parkinson-White syndrome.

We analyzed 87-lead body surface QRST time-integral values (QRST values) in 29 patients with Wolff-Parkinson-White syndrome (group A, 17 patients with manifest left-sided accessory pathway; group B, 6 patients with manifest right-sided accessory pathway; and group C, 6 patients with concealed left-sided accessory pathway), before, 1 day after, and 1 week after radiofrequency catheter ablation (RCA). The number of leads with abnormal QRST values was significantly lower 1 week after RCA compared with those before RCA and 1 day after RCA in groups A and B (p < 0.05); there was no significant difference in QRST values before and 1 day after RCA in groups A and B. The QRST values over areas with preexisting repolarization abnormalities were significantly altered 1 week after RCA compared with before and 1 day after RCA in groups A and B (p < 0.01). However, there was no significant difference in the QRST values over areas without preexisting abnormalities before RCA. In group C, there were no significant differences in the QRST values or the number of leads with abnormal QRST values before, 1 day and 1 week after RCA. In conclusion, RCA did not significantly influence repolarization properties over areas without preexisting abnormalities, but gradually reduced preexisting repolarization abnormalities, which were closely related to the location of the accessory pathway in patients with manifest Wolff-Parkinson-White syndrome. Our results suggest that body surface QRST values are useful for assessment of repolarization abnormalities during the periablation period.

QRST time integral values in 12-lead electrocardiograms before and after radiofrequency catheter ablation in patients with Wolff-Parkinson-White syndrome.

OBJECTIVES: We investigated the usefulness of QRST values obtained from 12-lead electrocardiograms (ECGs) for identification of repolarization abnormalities before and after radiofrequency ablation in patients with Wolff-Parkinson-White syndrome. BACKGROUND: Marked T wave abnormalities often appear after ablation and have been attributed to a continuation of repolarization abnormalities present before ablation (cardiac memory). However, to our knowledge repolarization properties before and after ablation have not been assessed quantitatively. METHODS: We calculated the ECG QRST values from 53 patients with Wolff-Parkinson-White syndrome and compared these values before, immediately after and 1 day and 1 week after successful ablation in 25 patients. RESULTS: QRST values were abnormally high in lead V1 in 7 of 28 patients with a left-sided accessory pathway and abnormally low in leads III and aVF and high in lead aVL in 12, 9 and 10 of 20 patients, respectively, with a right-sided accessory pathway. Preexisting QRST abnormalities were still present immediately and 1 day after ablation but were usually absent by 1 week after ablation. QRST values before, immediately after and 1 day after ablation were not significantly different in any lead. In 14 patients with ablation of a left-sided accessory pathway, QRST values before, immediately after and 1 day after ablation in lead V1 and immediately after ablation in leads I, aVR and V2 were significantly different from QRST values in those leads 1 week after ablation. In six patients with ablation of a right-sided accessory pathway, QRST values before, immediately after and 1 day after ablation in leads III, aVL and aVF and immediately after ablation in lead II were significantly different from QRST values in those leads 1 week after ablation. CONCLUSIONS: Electrocardiographic QRST values may provide useful quantitative information with respect to repolarization properties before and after ablation in patients with Wolff-Parkinson-White syndrome that is otherwise difficult to obtain by conventional ECG analysis.

Body surface distribution of abnormally low QRST areas in patients with Wolff-Parkinson-White syndrome. Evidence for continuation of repolarization abnormalities before and after catheter ablation.

BACKGROUND: Whether the Wolff-Parkinson-White syndrome (WPW) is associated with repolarization abnormalities is controversial. The QRST isointegral map (I-map) is theoretically independent of the activation sequence and dependent on repolarization properties. There have been no reports concerning the effects of radiofrequency (RF) catheter ablation of accessory pathway (AP) on repolarization properties analyzed by I-mapping. METHODS AND RESULTS: I-maps were constructed from data recorded in 38 patients with WPW to investigate repolarization properties and their body surface distribution in a physiological state, without pharmacological influences, and in 13 ablated patients to elucidate the effects of RF ablation on repolarization properties. Patients were divided into three groups: group A, 15 patients with type A WPW (left-sided AP); group B, 10 patients with type B (right-sided AP); and group C, 13 patients who were successfully ablated. Group C consisted of three subgroups: subgroup CA, 7 patients with type A WPW; subgroup CB, 3 patients with type B WPW; and subgroup CC, 3 patients with concealed WPW. Controls consisted of 608 normals. Although I-maps of WPW were highly (r = .87) correlated with the mean normal I-map, the location of the minimum in groups A and B differed significantly from that in normals. The minimum was located over the upper right anterior chest in normal subjects, over the back in 82% of 22 patients with type A WPW including ablated patients (groups A+CA), and over the mid to lower right anterior chest in 62% of 13 patients with type B WPW including ablated patients (groups B+CB). Groups A+CA and B+CB had an abnormally low QRST area ("-2SD area") over the back and right anterior chest, respectively. The abnormally located minimum and the "-2SD area" were present in 7 of 10 ablated patients with manifest WPW (groups CA+CB). After RF ablation, the distribution of the minimum, initially abnormal, became normal over a period of days or weeks, and the "-2SD area" disappeared over 1 week in all 7 patients. Correlation coefficients between I-maps and the mean normal I-map increased after RF ablation. CONCLUSIONS: (1) WPW is often associated with abnormalities in repolarization properties. (2) Repolarization abnormalities were located over the back in type A WPW and over the right mid to lower chest in type B WPW: (3) The abnormalities remain immediately after RF ablation and gradually normalize. These findings support the concept that ST-T abnormalities in 12-lead ECGs following RF ablation are attributable to "cardiac memory."

[A carcinoma of the right breast arising after a mastectomy in primary malignant lymphoma of the left breast].

In 1987, a 51-year-old woman visited our hospital, having noticed a painless 1.5 x 1.5 cm tumor of the left breast. On biopsy, it was pathologically diagnosed as being a primary malignant lymphoma of the breast. Thus we performed a modified radical mastectomy (Patey's method), in combination with chemotherapy (Cyclophosphamide, Vincristine, Prednisolone). Two years after the operation, a tumor of the right breast, 1.0 x 1.0 cm in size, was noticed. At this time, since an excised specimen was pathologically determined as being a scirrhous carcinoma, we performed a modified radical mastectomy (Auchincloss' method), followed by chemotherapy (Tegafur).