The presence of late potentials after percutaneous coronary intervention for the treatment of acute coronary syndrome as a predictor for future significant cardiac events resulting in re-hospitalization.

INTRODUCTION: We previously reported that LP positive patients after percutaneous coronary intervention (PCI) had higher rate of re-hospitalization in the small-scale study (135 patients). In this study, we evaluated correlation between LP and later cardiac events leading to re-hospitalization more extensively in greater population. METHODS AND RESULTS: A 24-h high-resolution (HR) ambulatory electrocardiogram (ECG) was performed in 421 patients that received PCI for the treatment of acute coronary syndrome (ACS) within 30 days. Various baseline characteristics and post-PCI ECG parameters including LP were examined for correlation with later re-hospitalization. LP was evaluated based on 3 different conditions, i.e., the worst, mean and best values, from 24-h signal-averaged QRS wave data. During the post-PCI follow-up period (611 ±â€¯489.0 days), 90 patients were re-hospitalized due to cardiac events. Multivariate analysis identified only positive LP based on the worst value as an independent predictor for re-hospitalization with OR 2.26. Most of re-hospitalization cases (>75%) were predominantly attributed to ischemic events. LP positive population had significantly higher incidences of ischemic events as well as overall re-hospitalization compared to LP negative population. The predictive power of LP was decreased when it was combined with other variables. The receiver operating characteristic analysis determined the LP cut-off values consistent with the LP positive criteria previously reported and standardized. CONCLUSION: The presence of LP in the 24-h HR ambulatory ECG post-PCI was an independent predictor for a risk of re-hospitalization due to ischemic cardiac events in ACS patients.

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.

Inducibility of Ventricular Arrhythmia 1 Year Following Treatment with Heavy Ion Irradiation in Dogs with Myocardial Infarction.

BACKGROUND: Targeted external heavy ion irradiation (THIR) of rabbit hearts 2 weeks after myocardial infarction (MI) reduced the vulnerability of fatal ventricular tachyarrhythmias (VT/VF) in association with the increased connexin43 (Cx43). Increased Cx43 was maintained for at least 1 year in normal rabbits, but the long-term antiarrhythmic effects in the MI model are unknown. We investigated the propensity for late potentials and VT/VF inducibility. METHODS: Intracoronary injection of microspheres was performed to induce nontransmural MI in anesthetized eight beagles. Four beagles were treated with THIR (12 C6+ , 15 Gy) 2 weeks later (MI + THIR group), and four without THIR served as controls (MI group). Signal-averaged electrocardiography, programmed electrical stimulation, immunohistochemical analysis, and echocardiograms were performed at 1 year. RESULTS: Filtered QRS duration was exacerbated after MI and remained unchanged for 1 year in the MI group (118 ± 1.4 ms), but significantly returned toward baseline in the MI + THIR group (109 ± 6.9 ms). Similarly, root mean square voltage of the last 40 ms was exacerbated after MI, but recovered after THIR. VT/VF inducibility decreased to 25% in the MI + THIR group compared with 100% in the MI group. Immunostaining Cx43 expression in cardiac tissues significantly increased by 24-45% in the MI + THIR group. Left ventricular ejection fractions remained within the normal range in both groups. CONCLUSION: A single exposure of the dog heart to 12 C irradiation attenuated vulnerability to ventricular arrhythmia after the induction of MI for at least 1 year through the modulation of Cx43 expression.

Late Potential as a Predictor of re-Hospitalization after Percutaneous Coronary Intervention for Acute Coronary Syndrome.

OBJECTIVE: The aim of this study was to investigate the significance of late potential (LP) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS). METHOD: We enrolled 135 consecutive patients with ACS admitted to Tokai University Hospital from February to December 2012. Twenty-four hour high-resolution ambulatory electrocardiogram was performed between post-PCI procedure and hospital discharge. The patients were divided into the LP-positive (33 patients) and LP-negative (102 patients) groups, and the relationship between LP and re-hospitalization was prospectively investigated. RESULTS: The body mass index, serum creatinine, and creatine phosphokinase-MB were higher in the LP-positive group than in the LP-negative group (p < 0.05). The re-hospitalization rate was higher in the LP-positive group. (9 patients, 27.3% vs. 10 patients, 9.8%; p = 0.03). There were no significant differences in the occurrence of ventricular tachycardia or cardiac death between the groups. According to Kaplan-Maier analysis, proportion of re-hospitalization was significantly lower in the LP-positive group than in the LP-negative group (p = 0.01; average follow-up, 451.4 ± 25.9 days). The odds ratio of LP presence was 3.45 (highest among all variables; 95% confidence interval, 1.3-9.4; p < 0.01). CONCLUSION: Positive LP in patients with ACS after PCI may predict re-hospitalization.

Arrhythmogenic Substrates in Sleep-Disordered Breathing with Arterial Hypertension.

BACKGROUND: Sleep-disordered breathing (SDB) is highly associated with arterial hypertension (HT). Sympathetic hypertonia increases the risk of sudden cardiac death in patients with sleep apnea. This study aims to noninvasively investigate the electrophysiological features in SDB patients with and without arterial HT. METHODS: Fifty-three patients with SDB were classified into two groups: SDB group and SDB + HT group. Twenty subjects with arterial HT were enrolled as controls (HT group). To assess arrhythmogenic vulnerability, high-resolution 24-hour ambulatory electrocardiograms were obtained for analyzing continuous late potential (LP), T-wave amplitude variability (TAV), and heart rate variability (HRV). RESULTS: A higher incidence of positive LP was observed in the SDB + HT (85%) group than that observed in the SDB (50%) and HT (20%) groups (P < 0.01). TAV was highest in the SDB + HT group (78 µV) compared with the SDB (61 µV) and HT groups (42 µV; P < 0.01). Positive LP and TAV values were observed at night in the SDB + HT and SDB groups. The low-frequency/high-frequency of the HRV analysis was highest in the SDB + HT (4.7) group compared with that in the SDB (2.9) and HT (2.9) groups (P = 0.01). CONCLUSION: Nocturnal LP, TAV, and HRV examinations were useful to investigate arrhythmogenesis. SDB patients with arterial HT showed a high prevalence of depolarization and repolarization abnormalities and relative sympathetic hyperactivity. This suggests that an electrophysiological instability is more prevalent in SDB patients with arterial HT.

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.

Sudden cardiac arrest recorded during Holter monitoring: prevalence, antecedent electrical events, and outcomes.

BACKGROUND: Causative arrhythmias of sudden cardiac arrest (SCA) are changing in this age of improved coronary care. OBJECTIVE: The purpose of this study was to examine the frequency of terminal arrhythmias and the electrical events prior to SCA. METHODS: We analyzed 24-hour Holter recordings of 132 patients enrolled from 41 institutions who either died (n = 88) or had an aborted death (n = 44). The Holter recordings were obtained for diagnosing and evaluating diseases and arrhythmias in those without any episodes suggestive of SCA. RESULTS: In 97 patients (73%), SCA was associated with ventricular tachyarrhythmias and in 35 (27%) with bradyarrhythmias. The bradyarrhythmia-related SCA patients were older than those with a tachyarrhythmia-related SCA (70 ± 13 years vs. 58 ± 19 years, P < .001). The most common arrhythmia for a tachyarrhythmia-related SCA was ventricular tachycardia degenerating to ventricular fibrillation (45%). The bradyarrhythmia-related SCA was caused by asystole (74%) or AV block (26%). Spontaneous conversion was observed in 37 patients (38%) with ventricular tachyarrhythmias. Of those, 62% of the patients experienced symptoms including syncope, chest pain, or convulsion. Multivariate logistic analysis revealed that independent predictors of mortality for tachyarrhythmia-related SCAs were advanced age (odds ratio 1.04, 95% confidence interval 1.02-1.08) and ST elevation within the hour before SCA (odds ratio 3.54, 95% confidence interval 1.07-13.5). In contrast, the presence of preceding torsades de pointes was associated with spontaneous conversion (odds ratio 0.20, 95% confidence interval 0.05-0.66). CONCLUSION: The most frequent cause of SCA remains ventricular tachyarrhythmias. Advanced age and ST elevation before SCA are risk factors for mortality in tachyarrhythmia-related SCAs.

Effects of a combination of losartan and hydrochlorothiazide in patients with hypertension and a history of heart failure.

OBJECTIVES: To evaluate the switching from an angiotensin receptor blocker (ARB) to a drug combination containing an ARB and a diuretic drug in terms of effects on hypertension, cardiac load, and cardiac function. METHODS: In a study conducted on 82 patients with a history of heart failure and hypertension who had been treated with an ARB but failed to reach the target blood pressure, ongoing oral ARB treatment was switched to a drug combination of losartan and hydrochlorothiazide (HCTZ). Using ambulatory blood pressure monitoring (ABPM), the variations in blood pressure and the effects on cardiac load and cardiac function were evaluated before and after treatment. RESULTS: Comparison of the ABPM findings before and after switching treatment showed significant improvements in mean systolic and diastolic blood pressure, improvements in systolic and diastolic blood pressure 1 hour before getting out of bed, and improvements in the plasma levels of human brain natriuretic peptide as an indicator of cardiac load. CONCLUSION: The drug combination of losartan and hydrochlorothiazide showed a stronger antihypertensive effect than that of the conventional ARB and improved heart function.

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.

Intravascular ultrasound criteria for determination of optimal longitudinal positioning of sirolimus-eluting stents.

BACKGROUND: Several studies have indicated that the clinical outcomes of sirolimus-eluting stents (SES) are significantly associated with longitudinal positioning of the stent relative to the underlying plaque distribution. METHODS AND RESULTS: Optimal SES landing was determined using unique stepwise intravascular ultrasound (IVUS) criteria, mainly targeting the sites with plaque burden <50% (plaque area/external elastic membrane area x100). To verify the criteria, (1) achievability and (2) actual impact on clinical and angiographic outcomes were assessed. A total of 162 consecutive patients with 180 lesions were enrolled and treated according to the IVUS criteria. Plaque burden at the proximal and distal margins was 41.4+/-13.6% (n=144) and 34.9+/-15.6% (n=170), respectively (within 3 mm of stent ends). The target was achieved in 72.3% of the proximal and 84.1% of the distal margin for the criteria. A strikingly low angiographic margin re-stenosis rate (2.7% of proximal and 1.4% of distal margin) and low target lesion revascularization rate (2.2%) were achieved. Receiver operator characteristic curve indicated that plaque burden was the strongest predictor of margin re-stenosis and its threshold (51.6%) was almost identical to that of the criteria. CONCLUSIONS: The proposed stepwise IVUS criteria mainly targeting plaque burden <50% are feasible and useful in the real-world practice of SES implantation.

Analysis of peripheral arterial bends that interfere with coronary catheterization.

OBJECTIVES: The aim of this study was to analyze the characteristics of peripheral arterial bends that interfere with coronary catheterization. BACKGROUND: Complex aortic and peripheral arterial bends are important factors in unsuccessful coronary catheterization. Methods.We classified peripheral arterial bends based on the difficulty of coronary catheterization: no bend, type A: easy; type B1: difficult but possible; type B2: difficult but possible with assistance of a device such as a long sheath; type C: impossible. We analyzed 1,626 consecutive cardiac catheterizations. RESULTS: Reproducibility (+/- 1 grade) was 98.9% in 256 patients undergoing multiple procedures from the same approach site. Peripheral arterial bend class distribution was as follows: no bend: 76.4%, type A: 12.5%, type B1: 5.0%, type B2: 5.5%, and type C: 0.6%. Fluoroscopy time and contrast volume were significantly greater in type B2/C (9.6 +/- 6.26 min versus 13.8 +/- 8.9 min, p < 0.0001 and 142.0 +/- 38.8 ml versus 168.4 +/- 53.6 ml, p < 0.0001, respectively). There were no differences in the distribution of types B and C by approach site; femoral approach, 6.4%% right upper limb approach, 6.1%; and left upper limb approach, 5.0%. Furthermore, in the patients who underwent multiple catheterizations from different approach sites, the arterial bend classes were similar. Predictors of a type B2/C arterial bend were mainly atherosclerotic risk factors, suggesting that longitudinal arterial elongation is the major cause of arterial bends. CONCLUSIONS: Peripheral arterial bends are a feature of the individual patient, not of the approach site.

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.

Year-long upregulation of connexin43 in rabbit hearts by heavy ion irradiation.

A previous study from our laboratory has shown that a single targeted heavy ion irradiation (THIR; 15 Gy) to rabbit hearts increases connexin43 (Cx43) expression for 2 wk in association with an improvement of conduction, a decrease of the spatial inhomogeneity of repolarization, and a reduction of vulnerability to ventricular arrhythmias after myocardial infarction. This study investigated the time- and dose-dependent effects of THIR (5-15 Gy) on Cx43 expression in normal rabbit hearts (n = 45). Five rabbits without THIR were used as controls. A significant upregulation of Cx43 protein and mRNA in the ventricular myocardium was recognized by immunohistochemistry, Western blotting, and real-time PCR from 2 wk up to 1 yr after a single THIR at 15 Gy. THIR > or =10 Gy caused a significant dose-dependent increase of Cx43 protein and mRNA 2 wk after THIR. Anterior, lateral, and posterior free wall of the left ventricle, interventricular septum, and right ventricular free wall were affected similarly by THIR in terms of Cx43 upregulation. The radiation-induced increase of immunolabeled Cx43 was observed not only at the intercalated disk region but also at the lateral surface of ventricular myocytes. The increase of immunoreactive Cx43 protein was predominant in the membrane fraction insoluble in Triton X-100, that is the Cx43 in the sarcolemma. In vivo examinations of the rabbits 1 yr after THIR (15 Gy) revealed no significant changes in ECGs and echocardiograms (left ventricular dimensions, contractility, and diastolic function), indicating no apparent late radiation injury. A single application of THIR causes upregulation and altered cellular distribution of Cx43 in the ventricles lasting for at least 1 yr. This long-lasting remodeling effect on gap junctions may open the pathway to novel therapy against life threatening ventricular arrhythmias in structural heart disease.

Serial angiographic and endovascular documentation of peri-stent contrast stains after sirolimus-eluting stent implantation: Multiple cavity formations between entirely covered stent struts.

A 72-year-old woman with a history of treatment with a single sirolimus-eluting stent (SES) for right coronary artery stenosis 21 months previously, was hospitalized to undertake invasive coronary evaluation due to recurrence of symptoms of effort angina. At the time of 9 months of angiographic follow-up, no in-stent restenosis was detected, however, several contrast filled "dimples" were noticed outside the stent border. At this time, further increments in the numbers of dimple formation were documented, in addition to progression of stenosis at the distal non-stented portion. Intravascular ultrasound demonstrated multiple cavity formations between the stent struts, due to positive remodeling occurring at the previously relatively disease-free side of the vessel wall. Surprisingly, optical coherence tomography demonstrated all the stent struts, including those located adjacent to cavities, were exclusively covered with neointima or other tissue components, completely attaching to the vessel wall throughout the stented segment. No evident thrombus formation was detected in these cavities. Despite no exposed stent struts, a hypothetical concern remains because such cul-de-sac formations may produce local blood flow turbulence within stents, which may be potentially associated with activation of local platelet aggregation. Careful long-term follow-up may be necessary for these patients.

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.