Changes in arrhythmogenic properties and five-year prognosis after carbon-ion radiotherapy in patients with mediastinum cancer.

INTRODUCTION: Carbon-ion irradiation of rabbit hearts has improved left ventricular conduction abnormalities through upregulation of gap junctions. However, to date, there has been no investigation on the effect of carbon-ion irradiation on electrophysiological properties in human. We investigated this effect in patients with mediastinum extra-cardiac cancer treated with carbon-ion radiotherapy that included irradiating the heart. METHODS AND RESULTS: In April-December 2009, eight patients were prospectively enrolled (including two male, aged 72.5 ± 13.0 years). They were treated with 44-72 Gray equivalent (GyE), with their hearts exposed to 1.3-19.1 GyE. High-resolution ambulatory electrocardiography was performed before and after radiotherapy to investigate arrhythmic events, late potentials (LPs), and heart rate variability. Five patients had pre-existing premature ventricular contraction (PVC)/atrial contraction (PAC) or paroxysmal atrial fibrillation (PAF)/AF; after irradiation, this improved in four patients with PVC/PAF/AF and did not deteriorate in one patient with PAC. Ventricular LP findings did not deteriorate and improved in one patient. In eight cases with available atrial LP findings, there was no deterioration, and two patients showed improvements. The low frequency/high frequency ratio of heart rate variability improved or did not deteriorate in the six patients who received radiation exposure to the bilateral stellate ganglions. During the five-year follow-up for the prognosis, six of the eight patients died because of cancer; there was no history of hospitalization for cardiac events. CONCLUSION: Although this preliminary study has several limitations, carbon-ion beam irradiation to the heart is not immediately cardiotoxic and demonstrates consistent signals of arrhythmia reduction.

Incidence of Positive Ventricular Late Potentials Differs in Postural Changes among Supine, Left, and Right Lateral Decubitus, and Prone and Sitting Positions in Brugada Syndrome.

BACKGROUND: High-risk patients with Brugada syndrome (BrS) have inherent late potential (LP) fluctuations that might be explained by autonomic activity, electrolyte abnormality, and body temperature changes. However, the correlation between postural changes and LP determinates remains unknown. METHODS: Forty patients with BrS (38 men, 43.9 ± 13.5 years) and 15 controls (15 men, 42.4 ± 11.2 years) were enrolled. LP variations were investigated at five body positions using high-resolution ambulatory monitoring electrocardiography (HR-ambulatory ECG). The HR-ambulatory ECG was recorded for 3 hours and LP parameters (fQRSd, LAS40, and RMS40) were obtained for at least 15 minutes in each at the supine, left and right lateral decubitus, and prone and sitting positions. RESULTS: Determinate LP in the BrS group was significantly abnormal in all positions. Among the five body positions, positive LP were much more frequent in the supine and left and right lateral decubitus positions than in the prone and sitting positions and normalized in the last two positions in patients with BrS. RMS40 variance by postural change was significantly larger in the coved group than in the saddle back group. Determinate LP improved in the sitting position compared to the supine position in the coved group. CONCLUSIONS: Positive LP findings normalized in the sitting position in patients in the coved BrS group with a resuscitation history, suggesting that depolarization instability might be related to the risk of fatal ventricular arrhythmia. Posture-induced LP variance should be examined using HR-ambulatory ECG analysis in patients with BrS.

Usefulness of Continuous 24-hour Ventricular Late Potential to Predict Prognosis in Patients with Heart Failure.

OBJECTIVES: An estimated 50,000 patients have heart failure (HF) in Japan, and the left ventricular ejection fraction (LVEF) is the typical predictor of prognosis. The identification of a noninvasive marker to predict most high-risk patients is urgently needed. This study aimed to log the continuous ventricular late potential (LP) by using high-resolution ambulatory monitoring in patients with HF with non-sustained ventricular tachycardia, and determine the association between the LP variation and prognosis. METHODS: The 90 hospitalized patients were classified into cardiogenic death (n = 10) and non-death (n = 80) groups. The LVEF, LP, and coefficient of variation (CV) of the filtered QRS (fQRS), and low-amplitude signal < 40 µV for the terminal QRS portion of (LAS40) of both groups were evaluated. The maximum fQRS over 24 h was defined as the maximum fQRS (Max-fQRS). RESULTS: The results were as follows: (1) cardiogenic death occurred in 32% (10/31 patients) with an LVEF ≤ 45% and a Max-fQRS ≤ 114 ms; (2) cardiogenic death occurred in 38% (10/26 patients) with a LAS40-CV ≥ 0.09; and (3) using LVEF, Max-fQRS, and LAS40-CV as the three predictors, the specificity and accuracy were 83% and 82%, respectively, with an odds ratio of 12.3. CONCLUSIONS: LAS40 variations and increases might be new risk indicators of prognosis.

Identification of high-risk Brugada syndrome patients by combined analysis of late potential and T-wave amplitude variability on ambulatory electrocardiograms.

BACKGROUND: Risk stratification is important in the management of Brugada syndrome (BrS). Late potentials (LPs) and T-wave amplitude variability (TAV) in high-resolution ambulatory electrocardiography (ECG) were retrospectively investigated. METHODS AND RESULTS: One hundred and twenty-seven patients diagnosed with BrS on 12-lead ECG were classified into 3 groups: documented ventricular fibrillation (VF)/asystole (n=19), episodes of syncope alone (n=30), and asymptomatic (n=78). Healthy volunteers were enrolled as controls (n=25). In the BrS patients, LPs showed appreciable circadian periodicity; filtered QRS duration (fQRS) and duration of the terminal low-amplitude signal <40 µV (LAS40) increased, whereas root mean square voltage of the terminal 40 ms of the fQRS (RMS40) decreased at night compared with the day. TAV did not have such a circadian periodicity. LP-positive incidence (night-time) and peak TAV were as follows: VF/asystole>syncope/asymptomatic>control (P<0.001). VF/asystole was discriminated from control at a ratio of 81-84% by night-time LPs (fQRS >116 ms, LAS40 >35 ms, RMS40 <25 µV) or peak TAV (>54 µV); VF/asystole was discriminated from syncope/asymptomatic at a ratio of 60-69%, by night-time LPs (fQRS >122 ms, LAS40 >42 ms, RMS40 <18µV) or peak TAV (>58 µV). Combined analysis of LPs and peak TAV increased the discriminant ratio up to 93% and 77%, respectively. CONCLUSIONS: Analysis of both LPs and TAV (taking circadian periodicity into account) is useful in identification of high-risk BrS patients.

Potential difficulty for accurate categorization of drug-eluting stent thrombosis without coronary angiography: unignorable involvement of the cases with new onset acute myocardial infarction occurred in target vessels.

Very late stent thrombosis (VLST) is a major unresolved problem of drug-eluting stent (DES) implants. However, its actual incidence with respect to the distribution of DES-target vessel and accuracy of adjudicating stent thrombosis according to the ARC definition has not been yet adequately evaluated. We studied 720 patients who had completed over 1 year from elective DES implantation. In this cohort, we extracted patients who present acute coronary syndrome (ACS) (n = 3, 0.4%). The timing of ACS events was 17, 19, and 24 months after DES implantation. At the time of presentation, VLST was strongly suspected as the initial diagnosis, however, coronary angiography (CAG) confirmed the different culprit lesion from DES and clearly no thrombus within the DES. According to ARC definition, three probable stent thromboses in this cohort before CAG, however, no stent thrombosis was confirmed after the CAG. Thus, no stent thrombosis was confirmed among this study population. In the very late phase after DES implantation, new onset ACS is not at all extraordinary occurrence in the target vessels of previous DES implantation. However, stent thrombosis is often assumed without angiographic confirmation. The clinical possibility that non-stent thrombosis is incidentally diagnosed with stent thrombosis without angiographic confirmation should be considered within the current accepted definition of stent thrombosis.

Angiographic evaluation of right upper-limb arterial anomalies: implications for transradial coronary interventions.

OBJECTIVES: Upper-limb arterial anomalies are sometimes encountered during transradial coronary procedures. These anomalies may contribute to procedural failure or to vascular complications, and are a major reason why many operators tend to avoid transradial procedures. We investigated the frequency of right upperlimb arterial anomalies using antegrade arteriography in patients undergoing transbrachial coronary angiography or intervention, and discuss the potential impact of these anomalies on the transradial procedure. METHODS: We prospectively studied 163 consecutive patients who underwent right transbrachial coronary angiography or intervention for the first time during the period from May 2007 to December 2007. Following the transbrachial procedure, we performed antegrade transbrachial arteriography of right upper-limb arteries in these patients and investigated the frequency and anatomy of arterial anomalies. RESULTS: A total of 40 upper-limb arterial anomalies were observed in 38 patients (23.3%). These included 8 abnormal origins (4.9%), 2 radio-ulnar loops (1.2%), 25 tortuosities (15.3%), 4 stenoses (2.5%) and 1 loop (0.6%). In patients with congenital lesions (8 patients; 4.9%), abnormal origin of the radial artery was the most common anomaly encountered, and in the acquired group (25 patients; 15.3%), tortuosity was the most common abnormality. CONCLUSION: Even with a 23.3% incidence of right upper-limb arterial abnormalities, 98.8% of patients were acceptable for transradial coronary intervention except for 1.2% of radio-ulnar loops.

Analysis of right radial artery for transradial catheterization by quantitative angiography--anatomical consideration of optimal radial puncture point.

OBJECTIVES: To determine the optimal radial puncture point, we analyzed the anatomy and luminal diameter of the right radial artery (RA) by quantitative angiography. BACKGROUND: Difficulty of radial puncture has impeded the establishment of the transradial approach as the standard procedure for cardiac catheterization. METHODS: Antegrade angiography was performed from the right brachial artery in 135 patients who underwent coronary angiography. Presence and location of a bifurcation in the area of the RA puncture were analyzed. Furthermore, inner luminal diameter of the RA was quantitatively measured. We used the line between the styloid process and the ulnar styloid process (R-U line) as an anatomical reference point. RESULTS: Radial arterial bifurcation with a superficial palmar branch was angiographically observed in 66 patients (48.9%). The inner luminal diameter was significantly larger at the proximal point to the point of bifurcation. The bifurcation level was located at a median of -3.33 mm (interquartile range: -5.60 to 4.69 mm) below the R-U line. Radial puncture at 10 mm proximal to the R-U line could avoid bifurcation in 91.9% of all cases. Mean radial, ulnar and brachial arterial inner diameters were 2.94 +/- 0.52 mm, 2.51 +/- 0.49 mm and 4.53 +/- 0.62 mm. The RA size within 10-60 mm above the R-U line was nearly invariable throughout the range. CONCLUSION The radial puncture level should be proximal to the radial bifurcation because of its lumen size. The ideal puncture point was found to be at least 10 mm proximal to the R-U line.

Comparative study of nifekalant versus amiodarone for shock-resistant ventricular fibrillation in out-of-hospital cardiopulmonary arrest patients.

BACKGROUND: In Japan, intravenous nifekalant (NIF) was often used for direct current cardioversion-resistant ventricular fibrillation (VF), until the use of intravenous amiodarone (AMD) was approved in 2007. The defibrillatory efficacy of NIF and AMD has thus far not been compared for resuscitation. METHODS AND RESULTS: Between August 2007 and April 2009, 403 consecutive out-of-hospital patients with cardiopulmonary arrest were transferred to the Emergency Medical Service of Tokai University. Of these, 30 patients with first defibrillation failure or VF recurrence were enrolled for this NIF/AMD study. The final defibrillation success (and hospital survival rate) was 67% (10/15) in the AMD and 47% (7/15) in the NIF group. The discharge survival rate was 53% (8/15) in the AMD and 21% (4/15) in the NIF group (P = 0.06). Notably, all 4 survivors in the NIF group could take up normal daily life again, whereas this was restricted to only 2 patients from the 11 survivors in the AMD group. The difference is probably partly attributable to longer time from AMD administration to defibrillation success compared with NIF. In the cases of defibrillation failure, VF continued in 4/8 by NIF, however, asystole or pulseless electrical activity occurred in 4/5 patients by AMD. CONCLUSIONS: AMD may be borderline superior over NIF to facilitate defibrillation in out-of-hospital patients with cardiopulmonary arrest. However, from the view point of preservation of brain function, NIF is not inferior to AMD for CPR.

Atrial fibrillation induced by applying acetylcholine to subadventitial layer of pulmonary vein in normal canine heart.

OBJECTIVES: We determined whether acetylcholine (Ach) application to the pulmonary vein (PV) wall could induce AF and clarified its mechanisms, and determined whether circumferential PV radiofrequency ablation (CPVA) could prevent Ach-induced AF in canine hearts. METHODS: Thirty seven beagle dogs were used for the study. Ach was injected into the subadventitial layer of the left superior PV (LSPV), at different distance from the LSPV-left atrium junction (LSPV-LA-J) to locate AF initiation. When AF was not induced by Ach alone, programmed electrical stimulation (S1-S2 method) was added to elicit AF. Atropine was injected at the same site of Ach injection to determine whether muscarine-receptor blockade suppressed AF, and CPVA at the LSPV-LA-J was performed using a newly devised basket electrode-catheter. RESULTS: AF was reproducibly induced by Ach injection in 19 of the 26 dogs (73%). S1-S2 method after Ach initiated AF in 5 of the remaining 7 dogs. Ach into the subadventitial layer of the LSPV, especially the distal portion, could elicit AF, which was preceded by pause (sinus arrest) ≥ 2.0 sec (37%) (pause-AF group), sinus bradycardia (32%) (brady-AF group) and sinus tachycardia (32%) (tachy-AF group). The time from Ach injection to AF initiation and AF duration were not significantly different between pause-AF, brady-AF and tachy-AF groups. AF was not initiated by injecting Ach after atropine pretreatment. To eliminate AF, 1-6 (average 4.1 ﾂｱ 1.2) CPVAs at the LSPV-LA-J were required. CONCLUSIONS: Our observations suggest that local Ach application can initiate AF in PVs, preceded by a variety of modes such as pause, bradycardia or tachycardia, and an increase in vagal tone at the LSPV plays a critical role in eliciting AF in structurally normal heart.

Longitudinal analysis of the depressive effects of intravenous amiodarone on depolarization and repolarization: a case report.

Intravenous amiodarone (AMD) induces multiple antiarrhythmic effects via blocking of Na(+), Ca(2+), and IKr channels, and beta receptors. A patient on chronic dialysis was administered AMD for nonsustained ventricular tachycardia after successful cardiopulmonary resuscitation. QT prolongation occurred 5 h after AMD administration. AMD was withdrawn at 24 h because of prolonged QTc interval (716 ms), which persisted for a further 48 h (661 ms). Ventricular premature contraction (VPC) was significantly decreased at 7h; however, VPC increased again after discontinuing AMD. Depolarization changes induced by the Na(+)-channel blocking action of AMD were analyzed. There was increasing filtered QRS-duration and duration of low-amplitude signals at voltage <40 µV, and decreasing root-mean-square voltage of signals in the last 40 ms of ventricular late potentials (LPs) within 7 h. However after stopping AMD, LPs were reversed. The blood concentration of AMD reached the effective level within 10 min but decreased immediately to an ineffective level. Onset and disappearance of the VPC-inhibiting effect corresponded to the depressive effect on depolarization but not with the increase in the prolonged repolarization effect and blood concentration. Even if the QT interval is sufficiently prolonged, the Na(+)-channel blocking action is required for AMD to induce the antiarrhythmic effect.