Loss of FTO in adipose tissue decreases Angptl4 translation and alters triglyceride metabolism.

A common variant of the FTO (fat mass- and obesity-associated) gene is a risk factor for obesity. We found that mice with an adipocyte-specific deletion of FTO gained more weight than control mice on a high-fat diet. Analysis of mice lacking FTO in adipocytes fed a normal diet or adipocytes from these mice revealed alterations in triglyceride metabolism that would be expected to favor increased fatty acid storage by adipose tissue. Mice lacking FTO in adipocytes showed increased serum triglyceride breakdown and clearance, which was associated with lower serum triglyceride concentrations. In addition, lipolysis in response to ß-adrenergic stimulation was decreased in adipocytes and ex vivo adipose explants from the mutant mice. FTO is a nucleic acid demethylase that removes N(6)-methyladenosine (m(6)A) from mRNAs. We found that FTO bound to Angptl4, which encodes an adipokine that stimulates intracellular lipolysis in adipocytes. Unexpectedly, the adipose tissue of fasted or fed mice lacking FTO in adipocytes had greater Angptl4 mRNA abundance. However, after high-fat feeding, the mutant mice had less Angptl4 protein and more m(6)A-modified Angptl4 than control mice, suggesting that lack of FTO prevented the translation of Angptl4. Injection of Angptl4-encoding adenovirus into mice lacking FTO in adipocytes restored serum triglyceride concentrations and lipolysis to values similar to those in control mice and abolished excessive weight gain from a high-fat diet. These results reveal that FTO regulates fatty acid mobilization in adipocytes and thus body weight in part through posttranscriptional regulation of Angptl4.

Successful treatment of macroreentrant atrial tachycardia by radiofrequency ablation targeting channels with continuous activation.

BACKGROUND: Macroreentrant atrial tachycardia (MRAT) is frequently unresponsive to antiarrhythmic drugs. The application of three-dimensional (3D) mapping and entrainment pacing contributes to a high success rate for radiofrequency ablation, but programmed electrical pacing may either terminate or transform clinical tachyarrhythmias. On the basis of clinical experiences of the use of ventricular tachycardia ablation, channels with continuous activation are suitable for reentrant circuits, and ablation at these channels can lead to noninducibility of ventricular tachycardias. We reviewed patients referred for symptomatic MRAT with identified channels with continuous activation and evaluated the efficacy of MRAT ablation by targeting these channels. METHODS: Fifteen consecutive patients (10 men, 49 ± 14 years) with MRAT illustrated by endocardial activation maps using a 3D electroanatomical mapping system (CARTO™, Biosense Webster, Diamond Bar, CA, USA) were included in this study. Continuous activation was defined as double or continuous potentials without an isoelectric interval, and sites with continuous activation were tagged for measurements of channel properties. Radiofrequency ablation was performed at those targeted sites located within the reentrant circuit. RESULTS: Radiofrequency ablation successfully eliminated MRAT in all patients. The mean cycle length was 283 ± 60 ms, and the longest activation duration was 112 ± 38 ms. The minimal and maximal bipolar voltage amplitudes were 0.13 ± 0.1 mV and 0.7 ± 0.6 mV, respectively. The targeted ablation length and width were 28.9 ± 15.3 mm and 9.4 ± 3.3 mm, respectively. CONCLUSION: Radiofrequency ablation of MRAT targeting channels with continuous activation using a 3D electroanatomical mapping system yields a high success rate.

Dual protection therapy with staged coronary artery bypass surgery and stenting in patients with left main coronary artery stenosis: long-term results from a single center.

OBJECTIVE: We evaluated the efficacy and safety of dual protection therapy with staged coronary artery bypass grafting (CABG) and bare-metal stenting (BMS) in patients with left main coronary artery (LMCA) disease. BACKGROUND: CABG is currently the preferred therapy for complex LMCA disease; however, the long-term patency rates of these grafts are unsatisfactory, and stenting alone for LMCA may be associated with the potentially fatal consequences of stent thrombosis or restenosis. METHODS: Between January 1997 and October 2005, 42 patients underwent staged bypass surgery and BMS, with the latter procedure performed 2 weeks after the initial CABG. Of these patients, 40 received left internal mammary artery (LIMA) grafts, 34 saphenous vein grafts, 6 radial artery grafts, and 3 right IMA (RIMA) grafts. Minimally invasive bypass surgery was performed in 10 patients. RESULTS: There were no operative complications. Forty-two stents were implanted in 42 lesions without complications. During the follow-up period of 135 ± 55 months, 1 patient died of cancer, 2 of cardiac causes, and 5 patients (12%) experienced target lesion revascularization. The target vessel failure rate was 24%. Forty patients (95%) underwent a 6-month angiographic follow-up. Restenosis was noted in 7 patients (18%). Reocclusion was also noted in 5 LIMA grafts, 5 saphenous vein grafts, 1 radial artery graft, and 1 RIMA graft. Only 1 patient experienced both restenosis of LM stenting and total occlusion of the 2 bypass grafts. CONCLUSIONS: Dual protection therapy with staged CABG and stenting is not an appropriate therapeutic strategy because of unacceptable graft patency rate. A higher occlusive rate of the bypass grafts may result from decreased blood flow because of competing blood flow between the bypass graft and the native coronary vessel.

Piceatannol facilitates conduction block and ventricular fibrillation induction in ischemia-reperfused rabbit hearts with pacing-induced heart failure.

BACKGROUND: Piceatannol, a hydroxystilbene natural product, has been reported to exert antiarrhythmic action via INa inhibition and slow INa inactivation in ischemia-reperfused (IR) rat hearts. The present study aimed to clarify the proarrhythmic property of piceatannol during regional IR injury in failing rabbit hearts. METHODS: Heart failure (HF) was induced by rapid right ventricular pacing for 4 weeks. The IR model was created by coronary artery ligation for 30 min, followed by reperfusion for 15 min in vivo. Simultaneous voltage and intracellular Ca(2+) (Cai) optical mapping was then performed in isolated Langendorff-perfused hearts (n=11 in each HF and control group). Action potential duration (APD) restitution, arrhythmogenic alternans and VF inducibility were evaluated by a dynamic pacing protocol. Conduction velocity was measured along lines across the IR and non-IR zones during pacing. Piceatannol (10 µM) was administered after baseline studies. RESULTS: In the HF group, piceatannol decreased conduction velocity, induced rate-dependent regional inhomogeneity of conduction delay and wavelength shortening, slowed Cai decay, and facilitated arrhythmogenic alternans instead of APD prolongation to increase VF inducibility. In the control group, the proarrhythmic effects of piceatannol on APD restitution, arrhythmogenic alternans and conduction delay were offset by its antiarrhythmic effects (APD and wavelength prolongation), resulting in a neutral effect on VF inducibility. CONCLUSIONS: Piceatannol (10 µM) is proarrhythmic in failing rabbit hearts with regional IR injury. The increased VF inducibility by piceatannol in HF suggests that its undesirable effects are more pronounced than its benefits in failing hearts.

Remote past left ventricular function before chronic right ventricular pacing predicts responses to cardiac resynchronization therapy upgrade.

BACKGROUND: This study examined factors that could predict response to cardiac resynchronization therapy (CRT) upgrade in patients who developed heart failure (HF) after long-term right ventricular (RV) pacing. METHODS: Twenty-five consecutive patients who received CRT upgrade for long-term RV pacing (RVP) were enrolled in this study. None of these patients were eligible for CRT at the moment of starting RVP. After 5.7 ± 4.0 years chronic RVP, these 25 patients developed HF symptoms and received CRT upgrade. Echocardiography was conducted at the moment of CRT upgrade and 6 months after CRT. Remote past left ventricular ejection fraction (RP-LVEF) at the moment of starting RVP was retrospectively obtained from the echocardiographic and cardiac catherization reports. Responders were defined as a reduction in LV end-systolic volume (LVESV) ≥ 15%. Their clinical and echocardiographic parameters were analyzed and compared. RESULTS: Responders had significant higher RP-LVEF as compared to nonresponders (53.6 ± 16.5% vs 31.4 ± 11.6%, P = 0.002). RP-LVEF correlated with reduction in LVESV after CRT upgrade (P < 0.001). RP-LVEF ≥ 43.5% as a cutoff value predicted response to CRT upgrade with an area under the receiver-operating curve of 0.87, a sensitivity of 78%, and a specificity of 100%. Intrinsic QRS width, septal-posterior wall motion delay, or tissue Doppler-derived dyssynchrony indexes did not predict responses to CRT upgrade. CONCLUSION: In long-term RVP patients who developed HF and received CRT upgrade, RP-LVEF ≥ 43.5% predicts good response. Conventional dyssynchrony indexes do not predict responses to CRT upgrade in these patients.

Dantrolene suppresses ventricular ectopy and arrhythmogenicity with acute myocardial infarction in a langendorff-perfused pacing-induced heart failure rabbit model.

INTRODUCTION: Dantrolene prevents arrhythmogenic Ca(2+) release during heart failure (HF). However, direct evidence to support its antiarrhythmic effects in failing hearts with acute myocardial infarction (AMI) is lacking. METHODS AND RESULTS: HF was induced by right ventricular pacing (312 beats/min, 4 weeks) in 19 rabbits. AMI was induced by coronary artery ligation in rabbits surviving chronic pacing (n = 17). The hearts were quickly excised and Langendorff-perfused for simultaneous membrane potential and intracellular Ca(2+) (Cai ) optical mapping when ventricular fibrillation (VF) occurred or 4 hours after AMI. The VF inducibility was defined as the ability to provoke sustained VF (>2 minutes) by pacing. Dantrolene (10 µM) was administered after baseline studies. Spontaneous VF occurred in 5 rabbits (SVF group). The ventricular premature beat (VPB) burden was significantly higher in the SVF group than the non-SVF group (P < 0.05). Dantrolene suppressed VPB burden (P = 0.03) and prolonged action potential duration (APD; P < 0.05) to reduce VF inducibility (P < 0.05). However, dantrolene shortened immediate postshock APD50 even if VF storm was suppressed. CONCLUSION: In failing hearts with AMI, VPB burden plays a pivotal role in SVF occurrence. Dantrolene suppresses VPBs and/or prolongs repolarization to inhibit spontaneous VF and reduce VF inducibility.

Effects of SEA0400 on arrhythmogenicity in a Langendorff-perfused 1-month myocardial infarction rabbit model.

BACKGROUND: The effects of SEA0400, a Na(+) /Ca(2+) exchanger (NCX) blocker, on dynamic factors and arrhythmogenic alternans in 1-month myocardial infarction (MI) hearts remain unknown. METHODS: Simultaneous voltage and intracellular Ca(2+) (Cai ) optical mapping was performed in 12 rabbit hearts with MI for 1 month and six normal rabbit hearts as control. Western-blot studies were performed in both groups in an additional six hearts for each. Action potential duration (APD) restitution was constructed and arrhythmogenic alternans was induced by dynamic pacing. SEA0400 (0.03, 3 µM) was administered after baseline studies. RESULTS: SEA0400 suppressed pacing-induced ventricular premature beats in a concentration-dependent manner. SEA0400 at 0.03 µM steepened APD restitution slopes and enhanced spatially discordant alternans (SDA), which became insignificant at 3 µM. The VF inducibility was seven of nine at baseline, nine of nine at 0.03 µM SEA0400, and five of nine at 3 µM SEA0400 (P = NS). Significant upregulation of NCX in the remote but not periinfarct zone and less degree downregulation of DHP1α in the remote versus periinfarct zone may play a role in enhancing SDA induction by SEA0400 in 1-month MI hearts. CONCLUSIONS: In 1-month MI hearts, SEA0400 suppresses pacing-induced ventricular premature beats, but also is proarrhythmic by steepening APD restitution and enhancing SDA via NCX inhibition. Heterogeneous upregulation of NCX and downregulation of DHP1α may contribute to SDA augmentation by SEA0400 in this model. The insignificant effect of SEA0400 on VF inducibility suggests that suppression of both reentry and triggered activity is required to suppress VF induction in this model.

Risk factors of recurrence and complication in radiofrequency catheter ablation of atrioventricular reentrant tachycardia in children and adolescents.

BACKGROUND: To compare potential risk factors for complications and recurrence after radiofrequency catheter ablation in symptomatic atrioventricular reentrant tachycardia in children and adolescents. METHODS: We retrospectively reviewed the data of 213 consecutive patients with symptomatic atrioventricular reentrant tachycardia who underwent both electrophysiological study and radiofrequency catheter ablation, divided these patients into two groups, children (age < 12 years) and adolescents (12 < or = rage, 18 years), and compared the location of the accessory pathway, success rate, recurrence rate, complications, presence of congenital heart disease, presence of intermittent ventricular pre-excitation, and presence of Wolff­Parkinson­White syndrome in the two groups. RESULTS: The position of the accessory pathway was mostly right sided in children (61.3%) and left sided in adolescents (61.5%). Children had significantly more congenital heart disease than adolescents (6.4% versus 0.8%). Univariate analysis showed children or adolescents with right-sided accessory pathways to be 6.84 times and those with accessory pathways on both sides of the septum 25 times more likely to relapse than those with a single accessory pathway. Multivariate analysis indicated that children or adolescents with two accessory pathways were six times, and those with intermittent ventricular pre-excitation nine times more at risk of relapsing following radiofrequency ablation than those with single accessory pathways. All five complications occurred in children. CONCLUSIONS: The findings suggest that the position and number of accessory pathways and presence of intermittent ventricular pre-excitation are related to risks of recurrence of atrioventricular reentrant tachycardia in children and adolescents.

Blunted proarrhythmic effect of nicorandil in a Langendorff-perfused phase-2 myocardial infarction rabbit model.

BACKGROUND: Nicorandil (a K(ATP) opener) administration is reported to reduce ventricular arrhythmias 4.8 ± 2.2 hours after myocardial infarction (MI). The electrophysiological changes and the effects on dynamic factors and dynamically induced spatially discordant alternans by nicorandil during phase-2 MI are unclear. METHODS: Simultaneous voltage and intracellular Ca(2+) (Ca(i)) optical mapping was performed in nine Langendorff-perfused hearts 4-5 hours after coronary artery ligation and nine control hearts. Action potential duration (APD) restitution was constructed and arrhythmogenic alternans was induced by dynamic pacing. Western blot studies (Kir6.1 and Kir6.2) were performed in six more hearts for both groups. Nicorandil (100 µM) was administered after baseline studies. RESULTS: Phase-2 MI hearts showed longer APD, slower conduction velocity (CV), and higher ventricular fibrillation (VF) inducibility than the control hearts. Nicorandil shortened and restored APD without significant arrhythmogenic effects, and also increased the rate of Ca(i) reuptake and flattened CV restitution to suppress spatially discordant alternans, which might account for a tendency toward higher VF threshold with nicorandil infusion in phase-2 MI hearts. Immunoblotting studies showed significant down-regulation of K(ATP) protein expression, which was functionally correlated to the blunted APD shortening response to nicorandil. CONCLUSIONS: K(ATP) expression is down-regulated in phase-2 MI hearts. Nicorandil restores APD, increases the rate of Ca(i) reuptake, and flattens CV restitution to suppress spatially discordant alternans induction, which ameliorates its proarrhythmic effects during phase-2 MI.

Reversible left ventricular diastolic dysfunction on Doppler tissue imaging predicts a more favorable prognosis in chronic heart failure.

BACKGROUND: Early (e')/late (a') diastolic mitral annular velocity ratio is a powerful independent predictor of poor prognosis in patients with left ventricular (LV) dysfunction. Doppler tissue imaging, however, may change over time according to intervention and medical treatment. The aim of the present study was to prospectively evaluate whether, in clinically stable patients with chronic heart failure (CHF), the decrease of an initially high e'/a' ratio on long-term therapy predicts a more favorable outcome. METHODS AND RESULTS: One hundred and eighty-one adult patients with CHF and high e'/a' ratio (≥ 0.74) underwent repeat echocardiography 6 months after the initial examination, and were then followed up for a mean period of 20 months. After 6 months, e'/a' ratio did not change in 95 patients, whereas it was significantly decreased (<0.74) in the remaining 86 patients. During follow-up, 55 participants (30%) had cardiac events. According to multivariate Cox regression analysis, decrease in e'/a' ratio, initial New York Heart Association class III or IV, and change in LV mass index as well as in systolic mitral annular velocities emerged as independent predictors of survival. CONCLUSIONS: The decrease of an initially high e'/a' ratio on long-term therapy predicts a more favorable outcome in clinically stable patients with CHF.

A novel echocardiographic parameter for predicting the ischemic etiology of cardiomyopathy and its prognosis in patients with congestive heart failure.

BACKGROUND: Although previous studies have established the ability of mitral annular velocities and velocity dispersion indices to differentiate between ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy, prospective data are lacking on both the use of heterogeneity of mitral annular velocities to predict the ischemic etiology in patients with left ventricular dysfunction and further cardiovascular prognosis. METHODS: A total of 232 patients with left ventricular ejection fractions < 40% were admitted between 2008 and 2010. Doppler tissue imaging was performed on six mitral annular sites for three consecutive beats and then averaged for each site. Systolic (Vs') and early (Ve') and late (Va') diastolic mitral annular velocity dispersion indices among the six mitral annular sites were calculated. RESULTS: Ve' was a significant predictor (P < .01) of ICM in multivariate logistic regression models adjusted for clinical variables and conventional echocardiography. The optimal cutoff value for predicting ICM was Ve' ≥ 16.7 with an area under the receiver operating characteristic curve of 0.92. Its sensitivity and specificity were 87% and 85%, respectively. During follow-up (median, 32 months), 64 participants experienced cardiac mortality. The adjusted hazard ratio in Cox proportional-hazards analysis for death in the third tertile in comparison with the first tertile of Ve' was 2.92 (P = .02). CONCLUSIONS: A high degree of heterogeneity of e', expressed as Ve', provides incremental value over clinical variables and conventional echocardiography to predict the prevalence of low left ventricular ejection fractions patients with ICM. Furthermore, elevated Ve' could also identify patients at a high risk for cardiac mortality.

Epicardial ablation of rotors suppresses inducibility of acetylcholine-induced atrial fibrillation in left pulmonary vein-left atrium preparations in a beagle heart failure model.

OBJECTIVES: The purpose of this study was to provide direct evidences that rotor ablation suppresses atrial fibrillation (AF) inducibility. BACKGROUND: Micro-re-entrant wavefronts have been suggested to serve as sources of rapid activations during AF. Whether AF inducibility is suppressed by elimination of rotors remains unknown. METHODS: We used optical mapping to study Langendorff-perfused left pulmonary vein (PV)-left atrium (LA) preparations from 13 dogs with pacing-induced heart failure. Atrial arrhythmias were induced by pacing and mapped during acetylcholine infusion (1 µmol/l). Rotors were identified from optical recordings. Epicardial ablation was performed targeting the rotor anchoring sites in preparations with sustained (>10 min) or incessant spontaneous AF. Non-rotor ablation was performed in 4 preparations. Repeated pacing was performed to test the AF inducibility after ablation. RESULTS: Sustained AF (n = 12) and incessant spontaneous AF (n = 1) were induced after acetylcholine infusion. Pulmonary vein focal discharge was found in 9 preparations (9.2 ± 4.2 beats/s), and rotor anchoring was found at the left superior PV-LA junction in 13 preparations (9.1 ± 4.6 beats/s) and at the ligament of Marshall-PV-LA junction in 1 preparation. Epicardial rotor ablation successfully inhibited the inducibility of sustained AF in 12 of 13 preparations (p < 0.01), including 4 with the maximal dominant frequency sites located on the PV-LA junctional rotor zones (direct elimination of mother rotors). The longest AF duration was shortened significantly by rotor ablation (Wilcoxon Z = 3.60, p = 0.002, n = 13), but not by non-rotor ablation (Wilcoxon Z = 1.00, p = 0.317, n = 4). CONCLUSIONS: Epicardial ablation of the rotor anchoring sites suppresses AF inducibility. The arrhythmogenicity at the maximal dominant frequency sites is directly/indirectly suppressed by the rotor ablation.

Dynamic aortic pouch: a rare etiology of aortic regurgitation.

The causes of aortic regurgitation (AR) include rheumatic heart disease, infective endocarditis, and various congenital and degenerative defects. We report an unusual case of AR in a 72-year-old man due to an aortic root pouch. The diagnosis AR was made by cardiac echocardiography, and the cause was revealed by cardiac catheterization and 64-slice cardiac computed tomography. During aortic valve replacement, a saccular pouch between the noncoronary cusp and the right coronary cusp of the aortic valve was noted.

Metabolic syndrome and homocysteine level as predictors of the severity of coronary artery disease in patients with carotid stenosis.

BACKGROUND: Coronary artery disease (CAD) is the most important cause of mortality and morbidity in patients who have undergone carotid artery endovascular or surgical intervention. Metabolic syndrome (MetS) and hyperhomocysteinemia (HHCY) have been reported to be associated with CAD. However, no study has investigated the association between MetS or HHCY and the severity of CAD in patients with carotid stenosis. METHODS: Total of 148 consecutive patients with at least 1 side of the extracranial internal carotid artery were enrolled. Further, on the basis of the results of coronary angiography, the patients were divided into the CAD group (n = 85) and the non-CAD group (n = 63). RESULTS: Multiple regression analysis revealed that CAD was independently associated with HHCY (odds ratio: 4.07; 95% confidence interval: 1.93-8.57; P < 0.0001) and MetS (odds ratio: 3.38; 95% confidence interval: 1.56-7.29; P = 0.002). Furthermore, multivariate stepwise linear regression revealed that the MetS score and total plasma homocysteine level were significantly correlated with affected vessel number in CAD and the extent of coronary atherosclerosis. CONCLUSIONS: MetS and HHCY can predict the presence of CAD in patients with carotid stenosis. Furthermore, the MetS score and total plasma homocysteine level are significantly associated with the extent of coronary atherosclerosis.

Prognostic significance of diastolic dysfunction by tissue Doppler imaging in patients with chronic heart failure.

BACKGROUND: This study assesses the prognostic values of left ventricular (LV) filling patterns, as determined by tissue Doppler imaging (TDI), on cardiac events in patients with LV systolic dysfunction. Normally observed in patients with an advanced form of cardiac disease, an abnormal diastolic pattern by Doppler echocardiography reflects a poor prognosis. Recent studies using TDI have significantly contributed to efforts to evaluate diastolic function and demonstrate the prognostic importance of TDI-derived indices of the LV function. METHODS AND RESULTS: One hundred seventy-three consecutive adult patients, mean (standard deviation) age of 62.4 (14.3), with a diagnosis of dilated cardiomyopathy and LV ejection fraction <45% were enrolled. During a follow-up period of 321 +/- 100 days, 9 patients expired from cardiac complications and 29 underwent readmission for decompensated heart failure. In multivariate analysis, only the mean value of early (Em) and late (Am) diastolic velocities ratio assessed by TDI, and LV end-diastolic pressure were found to be independent predictors of a cardiac event. The optimal cutoff value for forecasting cardiac event was Em/Am > or = 0.74 with an area under the receiver operating characteristic curve of 0.82; sensitivity and specificity were 84% and 76%, respectively (P < 0.001; standard error = 0.046). CONCLUSIONS: Em/Am ratio is the important predictor of cardiac event, which allows normalization for other risk factors in patients with a clinical diagnosis of chronic heart failure with LV dysfunction comparing with conventional Doppler echocardiography.

Intracellular calcium dynamics and acetylcholine-induced triggered activity in the pulmonary veins of dogs with pacing-induced heart failure.

BACKGROUND: Heart failure increases autonomic nerve activities and changes intracellular calcium (Ca(i)) dynamics. OBJECTIVE: The purpose of this study was to investigate the hypothesis that abnormal Ca(i) dynamics are responsible for triggered activity in the pulmonary veins (PVs) during acetylcholine infusion in a canine model of heart failure. METHODS: Simultaneous optical mapping of Ca(i) and membrane potential was performed in isolated Langendorff-perfused PV-left atrial (LA) preparations from nine dogs with ventricular pacing-induced heart failure. Mapping was performed at baseline, during acetylcholine (1 micromol/L) infusion (N = 9), and during thapsigargin and ryanodine infusion (N = 6). RESULTS: Acetylcholine abbreviated the action potential. In four tissues, long pauses were followed by elevated diastolic Ca(i), late phase 3 early afterdepolarizations, and atrial fibrillation (AF). The incidence of PV focal discharges during AF was increased by acetylcholine from 2.4 +/- 0.6 beats/s (N = 4) to 6.5 +/- 2.2 beats/s (N = 8; P = .003). PV focal discharge and PV-LA microreentry coexisted in 6 of 9 preparations. The spatial distribution of dominant frequency demonstrated a focal source pattern, with the highest dominant frequency areas colocalized with PV focal discharge sites in 35 (95%) of 37 cholinergic AF episodes (N = 8). Thapsigargin and ryanodine infusion eliminated focal discharges in 6 of 6 preparations and suppressed the inducibility of AF in 4 of 6 preparations. PVs with focal discharge have higher densities of parasympathetic nerves than do PVs without focal discharges (P = .01), and periodic acid-Schiff (PAS)-positive cells were present at the focal discharge sites. CONCLUSION: Ca(i) dynamics are important in promoting triggered activity during acetylcholine infusion in PVs from pacing-induced heart failure. PV focal discharge sites have PAS-positive cells and high densities of parasympathetic nerves.

Implantable cardioverter defibrillator therapy: ten years experience in a medical center.

BACKGROUND: An implantable cardioverter defibrillator (ICD) is the therapy of choice for survivors of life-threatening ventricular tachyarrhythmias or sudden cardiac death. To date there is little data concerning the clinical features and outcome of ICD therapy among Taiwanese. This study identifies factors related to the outcome of ICD therapy over a ten-year period at this institution. METHODS: Forty-nine ICDs were implanted in 46 patients between August 1996 and January 2006. The mean follow-up duration was 32 +/- 21 months. Patient data, primary cardiac diagnosis, presenting cardiac arrhythmia, echocardiographic parameters, hemodynamic indexes, electrophysiologic findings, and follow-up observations were analyzed. The findings were compared to those of the Taiwan ICD Multicenter Registry (TIMR) Study and major secondary prevention ICD trials in the literature. RESULTS: The patients in this study were comparable to those of TIMR but were younger and had better left ventricular ejection fractions (LVEF) than those in Western countries. Furthermore, higher mortality on follow-up was observed in patients with any of the following: LVEF < 35%, New York Heart Association (NYHA) functional class III or IV, a left atrial dimension > or = 55 mm, a left ventricular end diastolic dimension > or = 75 mm, an end systolic dimension > or = 60 mm, triple vessel disease, a prior anterior myocardial infarction, and amiodarone or diuretic therapy. Patients with structural heart disease other than ischemic heart disease or dilated cardiomyopathy had higher event recurrence rates. CONCLUSION: Left ventricular function is a major determinant affecting the outcome in ICD recipients. Aggressive treatment for heart failure is warranted in these patients.

Electrocardiographic features of ventricular pacing lead in the middle cardiac vein vs. right ventricular apex in a patient with persistent left superior vena cava.

A 53-year-old woman with sinus node dysfunction underwent dual-chamber pacemaker implantation through a persistent left superior vena cava draining into the coronary sinus, which was detected at the time of implantation. We managed to fix the ventricular lead in the right ventricular (RV) apex by forming a clockwise loop in the right atrium. Inadvertently, the lead was placed in the middle cardiac vein resembling RV apical position under fluoroscopic guidance. The paced QRS complex showed a pattern of tall R in V(1) through V(3), RS in V(4) through V(5), and QS in V(6). The pacing lead was carefully manipulated back into the RV apex, with the paced QRS complex showing a pattern of right bundle branch block, rR' in V(1) through V(2), and QS in V(3) through V(6). Careful attention to the surface electrocardiogram helps in distinguishing the pacing site even in those patients showing a pseudo-right bundle branch block pattern with RV apical pacing.

Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts.

We hypothesize that remodelling of action potential and intracellular calcium (Ca(i)) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Ca(i) and membrane potential (V(m)) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Ca(i) prior to V(m) depolarization, suggesting reverse excitation-contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Ca(i) alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Ca(i). Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Ca(i) dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Ca(i) cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting.