Variants of Brugada Syndrome and Early Repolarization Syndrome: An Expanded Concept of J-Wave Syndrome.

BACKGROUND: The role of J-waves in the pathogenesis of ventricular fibrillation (VF) occurring in structurally normal hearts is important. METHODS: We evaluated 127 patients who received an implantable cardioverter-defibrillator (ICD) for Brugada syndrome (BS, n = 53), early repolarization syndrome (ERS, n = 24), and patients with unknown or deferred diagnosis (n = 50). Electrocardiography (ECG), clinical characteristics, and ICD data were analyzed. RESULTS: J-waves were found in 27/50 patients with VF of unknown/deferred diagnosis. The J-waves were reminiscent of those seen in BS or ERS, and this subgroup of patients was termed variants of ERS and BS (VEB). In 12 VEB patients, the J/ST/T-wave morphology was coved, although amplitudes were <0.2 mV. In 15 patients, noncoved-type J/ST/T-waves were present in the right precordial leads. In the remaining 23 patients, no J-waves were identified. VEB patients exhibited clinical characteristics similar to those of BS and ERS patients. Phenotypic transition and overlap were observed among patients with BS, ERS, and VEB. Twelve patients with BS had background inferolateral ER, while five ERS patients showed prominent right precordial J-waves. Patients with this transient phenotype overlap showed a significantly lower shock-free survival than the rest of the study patients. CONCLUSIONS: VEB patients demonstrate ECG phenotype similar to but distinct from those of BS and ERS. The spectral nature of J-wave morphology/distribution and phenotypic transition/overlap suggest a common pathophysiologic background in patients with VEB, BS, and ERS. Prognostic implication of these ECG variations requires further investigation.

Long-term outcomes of abandoned leads of cardiac implantable electronic devices.

BACKGROUND: Evidence of the long-term outcomes of abandoned leads (ALs) in patients with cardiac implantable electronic devices (CIEDs) is scarce. OBJECTIVE: This study aimed to investigate the long-term outcomes of ALs. METHODS: This retrospective cohort study reviewed a single-center CIED registry of 2962 procedures performed from 1984-2018 and identified 130 patients with AL (AL group). We matched 2 controls without AL (by age, sex, device type, and device revision/removal date) to each patient with AL (n = 260) and compared CIED-related infection, venous thrombosis/stenosis, and all-cause mortality between groups using a Cox proportional hazard model analysis. RESULTS: For a mean follow-up period of 11.2 ± 8.2 years, 14 (3.6%), 7 (1.8%), and 143 (36.7%) patients had a CIED-related infection, venous thrombosis/stenosis, or experienced all-cause mortality, respectively. The AL group had more comorbidities than the control group. Lead malfunction was the most common cause of abandonment (64.6%). After adjustment for covariates, no significant intergroup differences were noted in the risks of infection, venous thrombosis/stenosis, or all-cause mortality (adjusted hazard ratio [aHR] 2.52; 95% confidence interval [CI] 0.77-8.25; aHR 1.18; 95% CI 0.25-5.64; aHR 1.26; 95% CI 0.89-1.80, respectively). Patients with multiple ALs had increased risks of infection and all-cause mortality vs controls (aHR 8.61; 95% CI 2.13-34.84; aHR 2.42; 95% CI 1.17-5.00, respectively). CONCLUSION: Patients with a single AL showed similar risks of CIED-related infections, venous thrombosis/stenosis, and all-cause mortality as those without ALs, whereas those with multiple ALs showed increased risks of infection and all-cause mortality.

Circadian and seasonal variations of ventricular tachyarrhythmias in patients with early repolarization syndrome and Brugada syndrome: analysis of patients with implantable cardioverter defibrillator.

INTRODUCTION: The circadian and seasonal patterns of ventricular tachyarrhythmia (VTA) in patients with early repolarization syndrome (ERS) have not been determined. We compared the timing of VTAs in patients with ERS and Brugada syndrome (BS). METHODS AND RESULTS: We enrolled patients with ERS (n = 14) and BS (n = 53) who underwent implantable cardioverter defibrillator (ICD) implantation. The timing of VTAs, including cardiac arrest and appropriate shocks, was determined. During follow up of 6.4 ± 3.6 years in the ERS group and 5.0 ± 3.3 years in the BS group, 5 of 14 (36%) ERS and 10 of 53 (19%) BS patients experienced appropriate shocks (P = 0.37). Cardiac arrest showed a trend of nocturnal distribution peaking from midnight to early morning (P = 0.14 in ERS, P = 0.16 in BS). Circadian distribution of appropriate shocks showed a significant nocturnal peak in patients with ERS (P < 0.0001) but a trend toward a nocturnal peak in patients with BS (P = 0.08). There were no seasonal differences in cardiac arrest in patients with ERS and BS. However, patients with ERS showed a seasonal peak in appropriate shocks from spring to summer (P < 0.0001). There was no significant seasonal peak in patients with BS. The timing of VTAs (cardiac arrest plus appropriate shock) showed significant nocturnal distributions in patients with ERS and BS (P < 0.01, respectively). A significant clustering of VTAs was noted from spring to summer (P < 0.01) in patients with ERS, but not in patients with BS (P = 0.42). CONCLUSIONS: Incidence of VTAs showed marked circadian variations with night-time peaks in patients with ERS and BS.

Complex fractionated electrograms and AF nests in vagally mediated atrial fibrillation.

BACKGROUND: Catheter ablation targeting of complex fractionated atrial electrograms (CFAEs) is one of the techniques used for atrial fibrillation (AF) ablation. The ablation of sites showing a high-frequency spectral component (HFC) during sinus rhythm, known as AF nests, has been introduced as an adjunct to conventional ablation. Known locations of some AF nests are similar to CFAE sites. However, it has not been systematically evaluated whether these two targets represent the same foci. The purpose of this study was to compare the anatomical locations of these sites using an animal model of vagally mediated AF. METHODS: Five anesthetized open-chest dogs were evaluated. Atrial electrograms were obtained epicardially. AF was induced by burst atrial pacing with 20 Hz during vagal stimulation. A total of 15 sites (eight sites in right atrium and seven sites in left atrium) were evaluated in each animal. The CFAE was determined during AF according to the electrogram patterns. After sinus conversion, real-time spectrum analysis was used for AF nest assessment at the same location. RESULTS: The CFAE was observed at the high and mid sulcus terminalis areas, pulmonary vein antrum, and mid portion of the coronary sinus. Among them, only 60% of the CFAE sites showed HFC during sinus rhythm. In addition, some of the non-CFAE sites (22%) showed HFC during sinus rhythm. CONCLUSION: The CFAE sites were not the same as the AF nests in this animal model of vagally mediated AF. Therefore, these two types of ablation methods appear to target different substrates of AF.

Characteristics of P wave in patients with sinus rhythm after maze operation.

Maze operation could alter P wave morphology in electrocardiogram (ECG), which might prevent exact diagnosis of the cardiac rhythm of patients. However, characteristics of P wave in patients with sinus rhythm after the operation have not been elucidated systematically. Consecutive patients who underwent the modified Cox Maze operation from January to December 2007 were enrolled. The standard 12-lead ECG and echocardiography were evaluated in patients who had sinus rhythm at 6 months after the operation. The average axis of P wave was 65+/-30 degrees. The average amplitude of P wave was less than 0.1 mV in all 12-leads, with highest amplitude in V(1). The most common morphology of P wave was monophasic with positive polarity (49%), except aVR lead, which was different from those in patients with enlarged left atrium, characterized by large P-terminal force in the lead V(1). There were no significant differences in P-wave characteristics and echocardiographic parameters between patients with LA activity (30.6%) versus without LA activity (69.4%) at 6 months after the operation. In conclusion, the morphology of P wave in patients after Maze operation shows loss of typical ECG pattern of P mitrale: P wave morphology is small in amplitude, monophasic and with positive polarity.

Long-term prognosis of left ventricular lead.

Transvenous left ventricular (LV) lead implantation is on the increase due to cardiac resynchronization therapy (CRT). However, there has been paucity of data on the prognosis of LV lead. Consecutive 32 patients with LV lead for CRT (n=22) or pacemaker (n=10) were subjected. Serial changes in pacing threshold and impedance along with lead-related complications were evaluated. Over 2 yr follow-up, there was no significant change in relative threshold voltage to the initial value (100%, 110%, 89.6%, and 79.6% at baseline, 1, 6, and 24 months respectively, P=0.62) as well as lead impedance (816±272, 650±178, 647±191, and 590±185 ohm at baseline, 1, 6, and 24 months respectively, P=0.80). The threshold change was not affected by lead position, lead polarity, and indication of lead implantation. The cumulative rates of lead revision were 6.3% (n=2) and 9.4% (n=3) in 6 month and 2 yr follow-up, respectively. One case of phrenic nerve capture at left lateral decubitus position was detected 1 month after the implantation. However, there were no serious complications over 2 yr period. In conclusion, transvenous LV lead implantation showed favorable long-term prognosis. Pacing parameters remained stable without significant changes over 2 yr follow-up.

N-acetylcysteine versus AScorbic acid for preventing contrast-Induced nephropathy in patients with renal insufficiency undergoing coronary angiography NASPI study-a prospective randomized controlled trial.

BACKGROUND: Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired renal failure and affects mortality and morbidity. There has been no study comparing the efficacy of N-acetylcysteine (NAC) and ascorbic acid that have potential for CIN prevention in patients with renal insufficiency. METHODS: We conducted a prospective randomized controlled trial. A total of 212 patients who had pre-existing renal impairment with basal creatinine clearance < or =60 mL/min and/or serum creatinine (SCr) level of > or =1.1 mg/dL, were randomized to have either high-dose NAC (1,200 mg orally twice a day before and on the day of coronary catheterization, n = 106) or ascorbic acid (3 g and 2 g orally before, and 2 g twice after coronary catheterization with a 12-hour interval, n = 106). The primary end point was the maximum increase of SCr level, and the secondary end point was the incidence of CIN. RESULTS: The maximum increase of SCr level was significantly lower in NAC group than in ascorbic acid group as follows: -0.03 +/- 0.18 mg/dL versus 0.04 +/- 0.20 mg/mL, respectively (P = .026). Patients with diabetes or who had received a high dose of contrast media experienced significantly less rise of SCr level with NAC than ascorbic acid; in diabetic subgroup, -0.05 +/- 0.22 mg/dL versus 0.09 +/- 0.29 mg/mL, respectively (P = .020); in patients with high dose of dye, -0.03 +/- 0.17 mg/dL versus 0.04 +/- 0.21 mg/mL, respectively (P = .032). The incidence of CIN, the secondary end point, tended to be in favor of NAC rather than ascorbic acid, 1.2% versus 4.4%, respectively (P = .370). Notably, among the diabetes patients, the NAC significantly lowered CIN rate than ascorbic acid, 0% (0/38) versus 12.5% (4/32), respectively (P = .039). CONCLUSION: High-dose NAC seems more beneficial than ascorbic acid in preventing contrast-induced renal function deterioration in patients, especially diabetic patients, with renal insufficiency undergoing coronary angiography.

Prevention of radiocontrast medium-induced nephropathy using short-term high-dose simvastatin in patients with renal insufficiency undergoing coronary angiography (PROMISS) trial--a randomized controlled study.

BACKGROUND: Contrast media cause oxidative stress, which has been suggested as one possible mechanism responsible for contrast-induced nephropathy. Statins appear to have pleiotropic effects, including antioxidant properties. We investigated to determine whether simvastatin pretreatment reduces the risk of contrast-induced nephropathy in a high-risk population of patients with renal insufficiency undergoing coronary angiography. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled, 2-center trial, involving 247 consecutive patients with chronic renal insufficiency (calculated creatinine clearance < or = 60 mL/min and/or serum creatinine > or = 1.1 mg/dL) undergoing coronary angiography. Patients were randomized to simvastatin (n = 124; 160 mg total, 40 mg orally every 12 hours starting the evening before and ending the morning after the procedure) or placebo (n = 123). All patients received pre - and postprocedure hydration. The iso-osmolar contrast agent iodixanol was used for coronary angiography in all patients. RESULTS: There was no difference between simvastatin and placebo in mean peak increase in serum creatinine measured within 48 hours after coronary angiography, the primary study end point (0.002 +/- 0.164 vs 0.017 +/- 0.230 mg/mL respectively, P = .559). The incidence of contrast-induced nephropathy, a secondary end point defined as increase of either > or = 25% or > or = 0.5 mg/dL in serum creatinine, was 2.5% in simvastatin-treated patients (3/118) and 3.4% in placebo-treated patients (4/118), a nonsignificant difference (P = 1.00). There were also no differences between the 2 groups in length of hospital stay or 1- and 6-month clinical outcomes. CONCLUSIONS: Simvastatin pretreatment for short-term at high dose do not prevent renal function deterioration after administration of contrast medium in patients with baseline renal insufficiency undergoing coronary angiography.

Echocardiographic and hemodynamic findings in patients with mitral stenosis undergoing percutaneous mitral commissurotomy comparing those with chronic atrial fibrillation versus those with normal sinus rhythm.

Chronic atrial fibrillation (AF) is common in patients with mitral stenosis (MS). Because AF induces electrical and mechanical remodeling of the left atrium, left atrial (LA) compliance is likely to be changed in its presence. This study was performed to investigate the influence of AF on LA compliance in patients with moderate to severe MS. Data were analyzed for 356 patients (282 women; mean age 40 +/- 11 years; range 17 to approximately 71) who were registered in the percutaneous mitral commissurotomy database. Mean LA pressure was lower (21 +/- 7 vs 26 +/- 8 mm Hg; p <0.001), but LA volume was higher in the AF than sinus-rhythm group (126 +/- 62 vs 74 +/- 27 ml; p <0.001), indicating higher LA compliance, which was further confirmed by lower LA v wave at catheterization in the AF group (27 +/- 9 for AF vs 32 +/- 10 mm Hg for sinus rhythm; p <0.001). In conclusion, the presence of AF has a significant influence on LA compliance in patients with moderate to severe MS.

Typical atrioventricular nodal reentrant tachycardia in a patient with fasciculoventricular pathway.

We report a 34-year-old female patient with preexcitation electrocardiogram and recurrent paroxysmal palpitations. Standard 12-lead electrocardiogram showed minimal preexcitation with normal PR interval and normal frontal QRS axis. The electrophysiologic study showed normal AH intervals, short HV intervals, and no change in the degree of preexcitation by rapid atrial pacing. These findings were compatible with the fasciculoventricular pathway. Typical atrioventricular nodal reentrant tachycardia with narrow QRS complex and normal HV interval was induced reproducibly by programmed electrical stimulation. Slow pathway was ablated successfully with radiofrequency catheter ablation, and then the patient remained asymptomatic during a follow-up of 12 months. Although the fasciculoventricular pathway is rare and supraventricular tachycardia in a patient with fasciculoventricular pathway may mimic Wolff-Parkinson-White syndrome, possibility of typical atrioventricular nodal reentrant tachycardia with fasciculoventricular pathway should be considered as a mechanism of supraventricular tachycardia in a patient showing preexcitation electrocardiogram.

Impact of the maze operation combined with left-sided valve surgery on the change in tricuspid regurgitation over time.

BACKGROUND: Atrial fibrillation (AF) has been reported to be a predisposing factor for the progression of TR in patients with previous mitral or combined mitral/aortic valve surgery. We hypothesized that the maze operation (MAZE) can prevent the progression of tricuspid regurgitation (TR) in these patients. METHODS AND RESULTS: We analyzed 170 patients (age, 45.5+/-10.9 years) who had undergone mitral or combined mitral/aortic valve surgery. On the basis of preoperative rhythm, patients were divided into 3 groups; GrI was composed of 44 patients with sinus rhythm, GrII of 48 who had undergone MAZE, and GrIII of 78 with AF who had not undergone MAZE. Echocardiographic examinations were performed before, immediately after, and 92.2+/-17.2 (range, 50 to 131) months after surgery. Preoperative and immediate postoperative clinical and echocardiographic parameters were similar among the groups. Insignificant TR at the immediate postoperative examination worsened with time in 7.3% of GrI (3 of 41), 12.8% of GrII (6 of 47), and 38.8% of GrIII (26 of 67) patients at the final examination (P=0.63 for GrI versus GrII, P=0.001 for GrI versus GrIII, P=0.005 for GrII versus GrIII). The incidence of significant TR at the final echocardiographic examination was higher in GrIII (39.7%) compared with GrI (9.1%) and GrII (14.6%) (P=0.001 for GrI versus GrIII, P=0.005 for GrII versus GrIII), whereas GrI and GrII did not show any difference (P=0.63). By multivariate analysis, the only factor identified to prevent TR progression was the group factor (GrI and GrII versus GrIII, P=0.002 and P=0.005, respectively). In a subgroup analysis of GrII according to the presence or absence of atrial mechanical activity, the absence of atrial mechanical activity was identified as an independent parameter for the progression of TR (P=0.001). CONCLUSIONS: AF predisposes patients undergoing mitral valve surgery to the progression of TR, which can be prevented by MAZE. This additional benefit of MAZE is largely dependent on the restoration and maintenance of atrial mechanical function.

Physiologic assessment of jailed side branch lesions using fractional flow reserve.

OBJECTIVES: This study was performed to evaluate the feasibility of the physiologic assessment of jailed side branches using fractional flow reserve (FFR) and to compare the measured FFR with the stenosis severity assessed by quantitative coronary angiography (QCA). BACKGROUND: It is not well-known which side branches should be treated after stent implantation at main branches and how to assess the functional significance of these lesions. METHODS: Ninety-seven jailed side branch lesions (vessel size > 2.0 mm, percent stenosis > 50% by visual estimation) after stent implantation at main branches were consecutively enrolled. The FFR was measured using a pressure wire at 5 mm distal and proximal to the ostial lesion of the jailed side branch. RESULTS: The FFR measurement was successful in 94 lesions. Mean FFRs were 0.94 +/- 0.04 and 0.85 +/- 0.11 at the main branches and jailed side branches, respectively. There was a negative correlation between the percent stenosis and FFR (r = -0.41, p < 0.001). However, no lesion with < 75% stenosis had FFR < 0.75. Among 73 lesions with > or = 75% stenosis, only 20 lesions were functionally significant. CONCLUSIONS: The FFR measurement in jailed side branch lesions is both safe and feasible. Quantitative coronary angiography is unreliable in the assessment of the functional severity of jailed side branch lesions, and measurement of FFR suggests that most of these lesions do not have functional significance.

Prediction of outcome in patients undergoing surgery for severe tricuspid regurgitation following mitral valve surgery and role of tricuspid annular systolic velocity.

This study was performed to identify echocardiographic parameters related to postoperative clinical outcome in patients who undergo surgery for severe tricuspid regurgitation after mitral valve surgery. Eighteen patients (2 men, 16 women; mean age 58 years) were prospectively enrolled. Echocardiographic examinations were performed before and 15 +/- 7 months after surgery. Favorable postoperative clinical outcome was defined as an improvement of > or = 1 in New York Heart Association functional class or a > 25% increase in respiratory variation of inferior vena cava diameter. Operative mortality was 11% (2 of 18). Of the 16 survivors, 9 (56%) achieved favorable postoperative clinical outcomes. Only systolic tricuspid annulus velocity (S'T) was found to be associated with postoperative clinical outcome (favorable vs unfavorable postoperative clinical outcome 12.9 +/- 2.1 vs 9.7+/- 1.7 cm/s, p < 0.05). For S'T < 9.5 cm/s, the sensitivity, specificity, and positive and negative predictive values for predicting an unfavorable postoperative clinical outcome were 67%, 100%, 100%, and 75%, respectively. In conclusion, S(T') can predict postoperative clinical outcomes in these patients.

Determinants of the severity of functional tricuspid regurgitation.

We performed a prospective study of patients with chronic right ventricular (RV) dilation to determine the factors associated with the degree of functional tricuspid regurgitation (FTR). We prospectively enrolled 64 patients with chronic RV dilation and measured right atrial (RA) area, RV area and its fractional area change (RVFAC), tricuspid annular diameter and contraction, tricuspid valve (TV) tethering area, and systolic pulmonary artery pressure. We also measured the RV eccentricity index and the RV sphericity index for simple presentation of RV geometry. Regurgitant orifice area of FTR was obtained for the quantification of FTR. End-systolic RV eccentricity index (r=0.73), end-diastolic RV eccentricity index (r=0.56), RA area (r=0.49), TV tethering area (r=0.37), age (r=0.31), end-systolic (r=0.42) and end-diastolic (r=0.30) tricuspid annular diameters, and left ventricular ejection fraction (r=-0.37) were significantly related to the regurgitant orifice area of FTR in univariate analysis. However, RV area, RVFAC, and systolic pulmonary artery pressure were not. In multivariate analysis, the end-systolic RV eccentricity index (p<0.001), TV tethering area (p=0.003), and end-diastolic tricuspid annulus diameter (p=0.007) showed the independent associations with regurgitant orifice area of FTR. The sensitivities and specificities for predicting more than mild FTR were found to be 79% and 82% with an end-systolic RV eccentricity index>2.0, 69% and 73% with an end-systolic tethering area>1.0 cm2, and 64% and 59% for an end-systolic tricuspid annulus diameter>3.9 cm, respectively. FTR severity was found to show the best correlation with the end-systolic RV eccentricity index. In conclusion, these findings underscore the importance of eccentric RV dilation for determining FTR severity and should lead to the development of more rational surgical approaches to FTR beyond TV annuloplasty.

Regulation of endothelial cell and endothelial progenitor cell survival and vasculogenesis by integrin-linked kinase.

OBJECTIVE: New vessel formation is a dynamic process of attachment, detachment, and reattachment of endothelial cells (ECs) and endothelial progenitor cells (EPCs) with each other and with the extracellular matrix (ECM). Integrin-linked kinase (ILK) plays a pivotal role in ECM-mediated signaling. Therefore, we investigated the role of ILK in ECs and EPCs during neovascularization. METHODS AND RESULTS: In human umbilical cord vein ECs and EPCs, endogenous ILK expression, along with subsequent cell survival signals phospho-Akt and phospho-glycogen synthase kinase 3beta, was reduced after anchorage or nutrient deprivation. Even brief anchorage deprivation resulted in retarded capillary tube formation by ECs. Adenoviral ILK gene transfer in ECs and EPCs reversed the decrease in cell survival signals after anchorage or nutrient deprivation, leading to enhanced survival, reduced apoptosis, and significantly accelerated the functional recovery after reattachment. And ILK overexpressing EPCs significantly improved blood flow recovery and prevented limb loss in nude mice hindlimb ischemia model. Furthermore, the efficacy of systemic delivery was equivalent to local injection of ILK-EPCs. CONCLUSIONS: ILK overexpression protects ECs and EPCs from anchorage- or nutrient-deprived stress and enhances neovascularization, suggesting that ILK is an optimal target gene for genetically modified cell-based therapy. Neovascularization is a dynamic process of detachment and reattachment of ECs and EPCs. Endogenous ILK expression was decreased in various stress conditions, and the gene transfer of ILK protected ECs and EPCs from temporary anchorage or nutrient deprivation. Furthermore, ILK gene transfer in EPCs significantly enhanced neovascularization in vivo.

Mobilized endothelial progenitor cells by granulocyte-macrophage colony-stimulating factor accelerate reendothelialization and reduce vascular inflammation after intravascular radiation.

BACKGROUND: Endothelial progenitor cells (EPCs) play a pivotal role in repair and regeneration of damaged vessels. We investigated the role of mobilized EPCs in the healing process after intravascular radiation therapy. METHODS AND RESULTS: One iliac artery of hypercholesterolemic rabbits was subjected to balloon injury and intravascular radiation with a Re-188 balloon and the contralateral iliac artery to balloon injury only. Rabbits received granulocyte-macrophage colony-stimulating factor (recombinant human GM-CSF) (60 microg/d subcutaneously) daily for 1 week, either 7 days before the angioplasty or at the time of angioplasty. Control rabbits received human albumin. GM-CSF significantly increased the double-positive (CD31+ and KDR+) fraction in peripheral blood monocytes and showed a higher number of EPCs than albumin after culture and, furthermore, enhanced migration and incorporation of EPCs. In the albumin group, intravascular radiation therapy reduced neointimal hyperplasia but delayed reendothelialization and aggravated monocyte infiltration. GM-CSF treatment significantly accelerated the reendothelialization and inhibited monocyte infiltration (reendothelialization index, 81+/-13% in the GM-CSF radiation [n=7] versus 30+/-11% in the control radiation [n=9] at 2 weeks, P<0.01). GM-CSF treatment produced an additional significant reduction in neointimal formation at 14 and 28 days after injury in the intravascular radiation groups (intima to media ratio, 0.14+/-0.11 in the GM-CSF radiation [n=5] versus 0.36+/-0.07 in the control radiation [n=5] at 4 weeks, P<0.01). CONCLUSIONS: GM-CSF treatment mobilizes EPCs, accelerates reendothelialization, and reduces monocytes infiltration after intravascular radiation therapy, suggesting that stem cell mobilization is a promising strategy for enhancing the vascular healing process after cytotoxic angioplasty.

Clinical validity of measuring time difference between onset of mitral inflow and onset of early diastolic mitral annulus velocity in the evaluation of left ventricular diastolic function.

OBJECTIVES: This study was performed to validate the clinical usefulness of measuring the time difference between onset of mitral inflow and onset of early diastolic mitral annulus velocity (T(E'-E)) for the evaluation of left ventricular (LV) diastolic function. BACKGROUND: In recent studies, T(E'-E) correlated well with the time constant of LV pressure decay (tau), and the ratio of IVRT/T(E'-E), where IVRT is isovolumic relaxation time, was useful in the prediction of elevated LV filling pressure. METHODS: Simultaneous left heart catheterization and Doppler echocardiography were performed in 40 patients. RESULTS: The T(E'-E) was evaluated in the same cardiac cycle and in the same hemodynamic status in 31 patients. Despite the wide range of tau (31 to 70 ms), there was no delay in the onset of mitral annulus velocity compared with the onset of mitral inflow (T(E'-E) = 0) in 27 patients and, therefore, T(E'-E) did not correlate with tau. Only three patients showed prolongation in T(E'-E), and all three showed tau >or=50 ms and pre-A-wave pressure >or=18 mm Hg. In one patient, mitral annulus velocity began earlier than the onset of mitral inflow. Because T(E'-E) was 0 in the majority of patients, the LV filling pressure could not be predicted by the previously suggested index of IVRT/T(E'-E.) CONCLUSIONS: In contrast to previous studies, T(E'-E) did not correlate with tau, and IVRT/ T(E'-E) could not be applied in the prediction of filling pressure, because of the limitation of a zero denominator. However, prolongation of T(E'-E) might suggest an elevated filling pressure in the setting of prolonged tau.

Absence of postprandial surge in coronary blood flow distal to significant stenosis: a possible mechanism of postprandial angina.

OBJECTIVES: This study was designed to investigate a possible mechanism of postprandial angina. BACKGROUND: Postprandial angina has been recognized for more than two centuries; however, its mechanism is still controversial. The most widely accepted mechanism involves increased myocardial oxygen demand after food intake. Recently, the redistribution in coronary blood flow (CBF) was suggested as a possible mechanism. METHODS: Twenty young, healthy volunteer controls and 20 patients with significant stenosis in the left anterior descending (LAD) or left main coronary artery were enrolled in the study. Coronary blood flow was evaluated in the distal LAD by using transthoracic Doppler echocardiography before and 15, 30, 45, and 60 min after food intake. In the CBF curve, the time velocity integral of diastolic flow (Dtvi) and the product of Dtvi and heart rate (HR) were measured. In six patients, these measurements were repeated after successful coronary intervention. RESULTS: In the healthy volunteer controls, Dtvi and Dtvi x HR increased after food intake with a peak value at 15 min, which indicates the presence of postprandial surge in the CBF. Fasting values and peak values at 15 min were significantly different (Dtvi: 15.1 +/- 4.9 cm/s vs. 18.9 +/- 5.9 cm/s, p = 0.04, Dtvi x HR: 862.2 +/- 261.5 cm/min vs. 1,174.2 +/- 307.5, p = 0.002). In contrast with the controls, despite postprandial increase in double product (HR x blood pressure), Dtvi and Dtvi x HR in the patient group decreased after food intake, with a nadir value at 45 min. Fasting values and nadir values at 45 min were significantly different (Dtvi: 24.0 +/- 19.6 cm/s vs. 19.3 +/- 17.1 cm/s, p < 0.001, Dtvi x HR: 1,449.6 +/- 1,044.0 cm/min vs. 1,273.4 +/- 1,000.9 cm/min, p = 0.002). In six patients, the CBF pattern resumed the normal pattern of postprandial surge in the CBF after successful coronary intervention. CONCLUSIONS: Results of our study suggest that "steal phenomenon" may play a role in the mechanism of postprandial angina.

Constitutively active glycogen synthase kinase-3beta gene transfer sustains apoptosis, inhibits proliferation of vascular smooth muscle cells, and reduces neointima formation after balloon injury in rats.

OBJECTIVE: Glycogen synthase kinase (GSK)-3beta is a crucial factor in many cellular signaling pathways and may play an important role in smooth muscle proliferation and apoptosis after angioplasty. METHODS AND RESULTS: To investigate the effect of GSK-3beta modulation on neointima formation, smooth muscle proliferation, and apoptosis after balloon injury in vivo, we delivered adenoviral vectors expressing the constitutively active form of GSK-3beta (GSK-S9A: 9th serine switched to alanine) or a control gene into rat carotid arterial segments after balloon injury with a 2F Fogarty catheter. Viral infusion mixtures (5x108 pfu) were incubated in the arterial lumen for 20 minutes, and the effects of gene delivery were evaluated 3 days and 2 weeks after gene delivery with morphometry and immunohistochemical staining for proliferating and apoptotic cells. There were no significant differences in intimal, medial, and lumen areas at 3 days after the procedure. However, 2 weeks after gene delivery, the active GSK-3beta gene transfer resulted in a significantly lower intima to media ratio (0.29+/-0.06 versus 0.86+/-0.09, P<0.01) and a greater lumen area (0.41+/-0.02 versus 0.31+/-0.01 mm2, P<0.01) compared with the control gene transfected group. This was attributable to a significant reduction in intimal area (0.05+/-0.01 versus 0.15+/-0.02 mm2, P<0.01), whereas the medial area was similar (0.17+/-0.01 versus 0.18+/-0.01 mm2, P=0.21). Proliferation index was significantly reduced both at 3 days and 2 weeks in the active GSK-3beta gene transferred group (2.97+/-0.29% versus 5.71+/-0.50%, P<0.01). In addition, apoptotic index, which was not significantly different between the 2 groups at 3 days, was significantly higher in the active GSK-3beta gene transferred group at 2 weeks (3.14+/-0.68% versus 22.7+/-1.63%, n=10, P<0.01, for control versus active GSK-3beta gene transfer). CONCLUSIONS: In vivo delivery of the active GSK-3beta gene inhibits smooth muscle proliferation, sustains apoptosis, and reduces neointima formation after balloon injury in rats and may be a future therapeutic target to limit neointima hyperplasia after angioplasty.

Aortoduodenal fistula complicated by acupuncture.

Recently, acupuncture has become a common therapeutic procedure for pain control worldwide. Although it has been repeatedly reported that acupuncture is effective and safe, several serious complications were also reported. In this article, we present a case of 68-year-old man who died of massive hematemesis resulting from aortoduodenal fistula (ADF), a rare complication of acupuncture therapy.