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1.  A Case of Long QT Syndrome Type 3 Aggravated by Beta-Blockers and Alleviated by Mexiletine: The Role of Epinephrine Provocation Test 
Yonsei Medical Journal  2013;54(2):529-533.
Long QT syndrome (LQTs) is an uncommon genetic disease causing sudden cardiac death with Torsade de Pointes (TdP). The first line drug treatment has been known to be β-blocker. We encountered a 15-year-old female student with LQTs who had prolonged QTc and multiple episodes of syncope or agonal respiration during sleep. Although her T wave morphology in surface electrocardiography resembled LQTs type 1, her clinical presentation was unusual. During the epinephrine test, TdP was aggravated during β-blocker medication, but alleviated by sodium channel blocker (mexiletine). Therefore, she underwent implantable cardioverter defibrillator implantation.
PMCID: PMC3575977  PMID: 23364992
Long QT syndrome type 3; torsade de pointes; β-blocker; mexiletine; SCN5A
2.  Electroanatomical Characteristics of Idiopathic Left Ventricular Tachycardia and Optimal Ablation Target during Sinus Rhythm: Significance of Preferential Conduction through Purkinje Fibers 
Yonsei Medical Journal  2012;53(2):279-288.
We hypothesized that Purkinje potential and their preferential conduction to the left ventricle (LV) posteroseptum during sinus rhythm (SR) are part of reentrant circuits of idiopathic left ventricular tachycardia (ILVT) and reentry anchors to papillary muscle.
Materials and Methods
In 14 patients with ILVT (11 men, mean age 31.5±11.1 years), we compared Purkinje potential and preferential conduction during SR with VT by non-contact mapping (NCM). If clear Purkinje potential(SR) was observed in the LV posteroseptum and the earliest activation site (EA) of preferential conduction at SR (EASR) was well matched with that of VT (EAVT), EASR was targeted for radiofrequency catheter ablation (RFCA). Also, the anatomical locations of successful ablation sites were evaluated by echocardiography in five additional patients.
1) All induced VTs exhibited clear Purkinje potential(VT) and preferential conduction in the LV posteroseptum. The Purkinje potential(VT) and EAVT was within 5.8±8.2 mm of EASR. However, the breakout sites of VT were separated by 30.2±12.6 mm from EAVT to the apical side. 2) Purkinje potential(SR) demonstrated a reversed polarity to Purkinje potential(VT), and the interval of Purkinje potential(SR)-QRS was longer than the interval of Purkinje potential(VT)-QRS (p<0.02) 3) RFCA targeting EASR eliminated VT in all patients without recurrence within 23.3±7.5 months, and the successful ablation site was discovered at the base of papillary muscle in the five additional (100%) patients.
NCM-guided localization of EASR with Purkinje potential(SR) matches well with EAVT with Purkinje potential(VT) and provides an effective target for RFCA, potentially at the base of papillary muscle in patients with ILVT.
PMCID: PMC3282975  PMID: 22318814
Idiopathic left ventricular tachycardia; catheter ablation; non-contact map; Purkinje
3.  Does additional linear ablation after circumferential pulmonary vein isolation improve clinical outcome in patients with paroxysmal atrial fibrillation? Prospective randomised study 
Heart  2012;98(6):480-484.
Circumferential pulmonary vein isolation (CPVI) has been considered the cornerstone of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). However, it is unclear whether linear ablation in addition to CPVI improves clinical outcome.
Prospective randomised study to compare the efficacy of CPVI and CPVI with additional linear ablation in patients with paroxysmal AF (PAF).
University hospital.
This study enrolled 156 patients (male 76.3%, 55.8±11.5 years old (mean±SD)) who underwent RFCA for PAF.
CPVI (n=52), CPVI+roof line (CPVI+RL; n=52) and CPVI+RL+posterior inferior line (CPVI+PostBox; n=52).
Main outcome measures
Procedure time, ablation time and clinical outcome.
(1) The CPVI group showed shorter total procedure time (180.4±39.5 min vs 189.6±29.0 min and 201.7±51.7 min, respectively (mean±SD); p=0.035) and ablation time (4085.5±1384.1 s vs 5253.5±1010.9 s and 5495.0±1316.0 s, respectively; p<0.001) than the CPVI+RL and CPVI+PostBox groups. (2) During 15.6±5.0 months of follow-up, the recurrence rates 3 months after RFCA were 11.5% in CPVI, 21.2% in CPVI+RL and 19.2% in CPVI+PostBox (p=0.440). (3) The achievement rate of CPVI was 100.0%, and bidirectional block rate was 80.8% in CPVI+RL and 59.6% in CPVI+PostBox. The clinical recurrence rates with or without achieving bidirectional block were not significantly different from each other (p=0.386).
In patients with PAF, linear ablation in addition to CPVI did not improve clinical outcome, regardless of bidirectional block achievement, while it prolonged the total procedure and ablation time.
PMCID: PMC3285139  PMID: 22285969
Paroxysmal atrial fibrillation; catheter ablation; circumferential pulmonary vein isolation; linear ablation; recurrence; arrhythmias
4.  Early Experience Using a Left Atrial Appendage Occlusion Device in Patients with Atrial Fibrillation 
Yonsei Medical Journal  2011;53(1):83-90.
Atrial fibrillation (AF) is one of the major risk factors for ischemic stroke, and 90% of thromboembolisms in these patients arise from the left atrial appendage (LAA). Recently, it has been documented that an LAA occlusion device (OD) is not inferior to warfarin therapy, and that it reduces mortality and risk of stroke in patients with AF.
Materials and Methods
We implanted LAA-ODs in 5 Korean patients (all male, 59.8±7.3 years old) with long-standing persistent AF or permanent AF via a percutaneous trans-septal approach.
1) The major reasons for LAA-OD implantation were high risk of recurrent stroke (80%), labile international neutralizing ratio with hemorrhage (60%), and 3/5 (60%) patients had a past history of failed cardioversion for rhythm control. 2) The mean LA size was 51.3±5.0 mm and LAA size was 25.1×30.1 mm. We implanted the LAA-OD (28.8±3.4 mm device) successfully in all 5 patients with no complications. 3) After eight weeks of anticoagulation, all patients switched from warfarin to anti-platelet agent after confirmation of successful LAA occlusion by trans-esophageal echocardiography.
We report on our early experience with LAA-OD deployment in patients with 1) persistent or permanent AF who cannot tolerate anticoagulation despite significant risk of ischemic stroke, or 2) recurrent stroke in patients who are unable to maintain sinus rhythm.
PMCID: PMC3250321  PMID: 22187236
Atrial fibrillation; left atrial appendage; occlusion device; thromboembolism
5.  Mid-Septal Hypertrophy and Apical Ballooning; Potential Mechanism of Ventricular Tachycardia Storm in Patients with Hypertrophic Cardiomyopathy 
Yonsei Medical Journal  2011;53(1):221-223.
Medically refractory ventricular tachycardia (VT) storm can be controlled with radiofrequency catheter ablation (RFCA), however, it may be difficult to control in some patients with hemodynamic overload. We experienced a patient with intractable VT storm controlled by hemodynamic unloading. The patient had mid-septal hypertrophic cardiomyopathy with an implantable cardioverter defibrillator (ICD) back-up. Because of the severe mid-septal hypertrophy, his left ventricle (LV) had an hourglass-like morphology and showed apical ballooning; the focus of VT was at the border of apical ballooning. Although we performed VT ablation because of electrical storm with multiple ICD shocks, VT recurred 1 hour after procedure. As the post-RFCA monomorphic VT was refractory to anti-tachycardia pacing or ICD shock, we reduced the hemodynamic overload of LV with β-blockade, hydration, and sedation. VT spontaneously stopped 1.5 hours later and the patient has remained free of VT for 24 months with β-blockade alone. In patients with VT storm refractory to antiarrhythmic drugs or RFCA, the mechanism of mechano-electrical feedback should be considered and hemodynamic unloading may be an essential component of treatment.
PMCID: PMC3250344  PMID: 22187256
Catheter ablation; radiofrequency; electrical storm; ventricular tachycardia; hypertrophic cardiomyopathy
7.  Serological Predictors for the Recurrence of Atrial Fibrillation After Electrical Cardioversion 
Korean Circulation Journal  2010;40(4):185-190.
Background and Objectives
Although electrical cardioversion (CV) is effective in restoring sinus rhythm (SR) in patients with atrial fibrillation (AF), AF frequently recurs in spite of antiarrhythmic medications. We investigated the predictors of failed CV and AF recurrence after successful CV.
Subjects and Methods
In 81 patients (M:F=63:18, 59.1±10.5 years old) with AF who underwent CV, clinical findings and pre-CV serologic markers were evaluated.
During 13.1±10.6 months of follow-up, 8.6% (7/81) showed failed CV, 27.16% (22/81) showed early recurrence atrial fibrillation (ERAF; ≤2 weeks), 32.1% (26/81) had late recurrence atrial fibrillation (LRAF; >2 weeks), and 32.1% (26/81) remained in SR and had no recurrence (NR). Plasma levels of transforming growth factor beta (TGF)-β were significantly higher in patients with failed CV than in those with successful CV (p=0.0260). Patients in whom AF recurred were older (60.4±9.0 years old vs. 55.3±12.5 years old, p=0.0220), and had lower plasma levels of stromal cell derived factor (SDF)-1α (p=0.0105). However, there were no significant differences in these parameters between ERAF patients and LRAF patients.
Post-CV recurrence commonly occurs in patients aged >60 years and who have low plasma levels of SDF-1α. High plasma levels of TGF-β predict failure of electrical CV.
PMCID: PMC2859336  PMID: 20421959
Atrial fibrillation; Electric countershock; Recurrence
8.  Early Repolarization and Myocardial Scar Predict Poorest Prognosis in Patients with Coronary Artery Disease 
Yonsei Medical Journal  2014;55(4):928-936.
Recent studies show positive association of early repolarization (ER) with the risk of life-threatening arrhythmias in patients with coronary artery disease (CAD). This study was to investigate the relationships of ER with myocardial scarring and prognosis in patients with CAD.
Materials and Methods
Of 570 consecutive CAD patients, patients with and without ER were assigned to ER group (n=139) and no ER group (n=431), respectively. Myocardial scar was evaluated using cardiac single-photon emission computed tomography.
ER group had previous history of myocardial infarction (33% vs. 15%, p<0.001) and lower left ventricular ejection fraction (57±13% vs. 62±13%, p<0.001) more frequently than no-ER group. While 74 (53%) patients in ER group had myocardial scar, only 121 (28%) patients had in no-ER group (p<0.001). During follow up, 9 (7%) and 4 (0.9%) patients had cardiac events in ER and no-ER group, respectively (p=0.001). All patients with cardiac events had ER in inferior leads and horizontal/descending ST-segment. Patients with both ER in inferior leads and horizontal/descending ST variant and scar had an increased adjusted hazard ratio of cardiac events (hazard ratio 16.0; 95% confidence interval: 4.1 to 55.8; p<0.001).
ER in inferior leads with a horizontal/descending ST variant was associated with increased risk of cardiac events. These findings suggest that ER in patients with CAD may be related to myocardial scar rather than pure ion channel problem.
PMCID: PMC4075396  PMID: 24954320
Electrocardiography; coronary artery disease; sudden cardiac death; cardiac arrhythmia
9.  Atrial Tachycardia Originating from the Aortomitral Junction 
Yonsei Medical Journal  2014;55(2):530-534.
Atrial tachycardia (AT) originating from the aortomitral junction is a very rare and challenging disease. Its arrhythmic characteristics have not been described in detail compared with the descriptions of the arrhythmic characteristics of AT originating from the other locations. Only a few case reports have documented successful ablation of this type of AT using transaortic or transseptal approaches. We describe a case with AT that was resistant to right-sided ablation near the His bundle failed and transaortic ablation at the aortomitral junction successfully eliminated.
PMCID: PMC3936642  PMID: 24532528
Atrial tachycardia; electrophysiological study; radiofrequency catheter ablation
10.  Transvenous Pacemaker Lead Removal in Pacemaker Lead Endocarditis with Large Vegetations: A Report of Two Cases 
Korean Circulation Journal  2014;44(2):118-121.
Pacemaker lead endocarditis is treated with total removal of the infected device and proper antibiotics. The outcomes of patients undergoing percutaneous lead extraction for large vegetations (>2 cm) have not yet been shown. In this case report, we present two patients with pacemaker lead endocarditis with large vegetations of maximum diameter 2.4 cm and 3.2 cm. The first patient had multiple vegetations attached to the tricuspid and mitral valves and developed septic emboli to the brain, lung, and liver. The second patient had a large, persistent vegetation on the tricuspid valve, even two weeks after complete removal of the leads. Both patients were successfully treated with transvenous pacemaker lead removal and antibiotics.
PMCID: PMC3958606  PMID: 24653742
Cardiac pacemaker, artificial; Endocarditis
11.  Abnormal Response of Superior Sinoatrial Node to Sympathetic Stimulation Is a Characteristic Finding in Patients With Atrial Fibrillation and Symptomatic Bradycardia 
We hypothesize that unresponsiveness of superior sinoatrial node (SAN) to sympathetic stimulation is strongly associated with the development of symptomatic bradycardia in patients with atrial fibrillation (AF).
Methods and Results
We performed 3-dimensional endocardial mapping in healthy control (Group 1, n=10) and in patients with AF without (Group 2, n=57) or with (Group 3, n=15) symptomatic bradycardia at baseline and during isoproterenol infusion. Corrected SAN recovery time was abnormal in 0%, 11% and 36% of groups 1, 2 and 3, respectively (p=0.02). At baseline, 90%, 26% and 7% (p<0.001) of the patients had multicentric SAN activation patterns. For groups 1, 2 and 3, respectively, the median distance from the superior vena cava-right atrial junction to the most cranial earliest activation site (EAS) was 5.0 (25–75 percentile range, 3.5–21.3) mm, 10.0 (4–20) mm and 17.5 (12–34) mm at baseline (p=0.01), and was 4.0 (0–5) mm, 5.0 (1–10) mm and 15.0 (5.4–33.3) mm during isoproterenol infusion (p=0.01), suggesting upward shift of EAS during isoproterenol infusion. However, while the EAS during isoproterenol infusion was at the upper 1/3 of crista terminalis in 100% of Group 1 and 78% of Group 2 patients, only 20% of the groups 3 patients moved EAS to that region (p < 0.001).
Superior SAN serves as the EAS during sympathetic stimulation in normal patients and in most patients with AF without symptomatic bradycardia. In contrast, unresponsiveness of superior SAN to sympathetic stimulation is a characteristic finding in patients with AF and symptomatic bradycardia.
PMCID: PMC3247651  PMID: 22007035
sinoatrial node; nervous system; sympathetic; atrial fibrillation; sick sinus syndrome; pacemakers
12.  Male Pseudohermaphroditism Presented with Sudden Cardiac Arrest 
Yonsei Medical Journal  2012;53(3):658-661.
Torsades de Pointes is a life-threatening arrhythmia associated with a number of causes, but is very rare among endocrinologic disorders. We report a case of male pseudohermaphroditism with hyperaldosteronism due to a 17α-hydroxylase deficiency presented with sudden cardiac arrest.
PMCID: PMC3343435  PMID: 22477014
Torsades de Pointes; pseudohermaphroditism; 17α-hydroxylase deficiency
13.  Fever-Induced QTc Prolongation and Ventricular Fibrillation in a Healthy Young Man 
Yonsei Medical Journal  2011;52(6):1025-1027.
Long QT syndrome is associated with lethal tachyarrhythmia that can lead to syncope, seizure, and sudden death. Congenital long QT syndrome is a genetic disorder, characterized by delayed cardiac repolarization and prolongation of the QT interval on the electrocardiogram (ECG). Type 2 congenital long QT is linked to mutations in the human ether a go-go-related gene (HERG). There are environmental triggers of adverse cardiac events such as emotional and acoustic stimuli, but fever can also be a potential trigger of life-threatening arrhythmias in long QT syndrome type 2 patients. Herein, we report a healthy young man who experienced fever-induced polymorphic ventricular tachycardia and QT interval prolongation.
PMCID: PMC3220263  PMID: 22028170
Sudden cardiac death; long QT syndrome; fever
14.  Heart Rate Acceleration of a Subsidiary Pacemaker by β-Adrenergic Stimulation 
Korean Circulation Journal  2011;41(11):658-665.
Background and Objectives
Recent evidence indicates that the membrane voltage and Ca2+ clocks jointly regulate sinoatrial node (SAN) automaticity. However, the mechanism of heart rhythm acceleration of the subsidiary pacemaker (SP) during β-adrenergic stimulation is still unknown. Here we tested the hypothesis that the heart rate acceleration of the SP by β-adrenergic stimulation involves synergistic interactions between both clock mechanisms.
Subjects and Methods
We performed optical mapping and pharmacological interventions in 15 isolated Langendorff-perfused canine right atriums (RA). The SP model was produced by ligation of the SAN artery at the mid portion of the sulcus terminalis.
In the 6 RAs with an intact SAN, 1 µmol/L isoproterenol infusion increased the heart rate from 82±9 to 166±18 bpm (102%) with late diastolic Cai elevation (LDCAE) at the superior SAN. However, in the 6 SP models, the heart rate increased from 55±10 bpm to 106±11 bpm (92%, p=0.005) without LDCAE at the earliest activation site. The isoproterenol induced heart rate increase was reversed to 74±5 bpm (33% from baseline) by administering an infusion of the funny current blocker ZD 7288 (3 µmol/L, n=3), whereas, it was suppressed to 69±7 bpm (24% from baseline) by sarcoplasmic reticulum (SR) Ca2+ emptying with administering ryanodine (10 µmol/L) plus thapsigargin (200 nmol/L, n=3). The isoproterenol induced heart rate increase was completely abolished by combined treatment with funny current blocker and SR Ca2+ emptying (n=3).
Acceleration of the Ca2+ clock in the SP plays an important role in the heart rate acceleration during β-adrenergic stimulation, and this interacts synergistically with the voltage clock to increase the heart rate.
PMCID: PMC3242021  PMID: 22194761
Calcium channel; Sympathetic nervous system; Sinoatrial node
15.  Implantable Cardioverter-Defibrillator Lead Extraction by Conventional Traction and Counter-Traction Technique 
Korean Circulation Journal  2011;41(3):164-166.
A 46-year-old man presented to our institution with inappropriate implantable cardioverter-defibrillator (ICD) shock delivery. The ICD (single chamber, dual shock coils) was implanted for sustained monomorphic ventricular tachycardia with unstable hemodynamics and underlying systolic left ventricular dysfunction. ICD interrogation revealed recurrent episodes of ICD shock due to noise sensing and increased impedance of right ventricular-lead. With the impression of lead fracture, ICD lead extraction was performed. The fractured ICD lead was completely removed by traction of locking stylet and counter-traction of polypropylene dilator sheath. A new lead was inserted and the patient was discharged without complications after 2 days. To our knowledge, this is the first report on ICD lead extraction by conventional traction and counter-traction technique in Korea.
PMCID: PMC3079139  PMID: 21519518
Implantable cardioverter defibrillators; Medical device failure; Device removal
16.  Long-Term Outcome of Single-Chamber Atrial Pacing Compared with Dual-Chamber Pacing in Patients with Sinus-Node Dysfunction and Intact Atrioventricular Node Conduction 
Yonsei Medical Journal  2010;51(6):832-837.
The optimal pacing mode with either single chamber atrial pacemaker (AAI or AAIR) or dual chamber pacemaker (DDD or DDDR) is still not clear in sinus-node dysfunction (SND) and intact atrioventricular (AV) conduction.
Materials and Methods
Patients who were implanted with permanent pacemaker using AAI(R) (n = 73) or DDD(R) (n = 113) were compared.
The baseline characteristics were comparable between the two groups, with a mean follow-up duration of 69 months. The incidence of death did not show statistical difference. However, the incidence of hospitalization for congestive heart failure (CHF) was significantly lower in the AAI(R) group (0%) than the DDD(R) group (8.8%, p = 0.03). Also, atrial fibrillation (AF) was found in 2.8% in the AAI(R) group, which was statistically different from 15.2% of patients in the DDD(R) group (p = 0.01). Four patients (5.5%) with AAI(R) developed AV block, and subsequently switched to DDD(R) pacing. The risk of AF was lower in the patients implanted with AAI(R) than those with DDD(R) [hazard ratio (HR), 0.84; 95% confidence interval, 0.72 to 0.97, p = 0.02].
In patients with SND and intact AV conduction, AAI(R) pacing can achieve a better clinical outcome in terms of occurrence of CHF and AF than DDD(R) pacing. These findings support AAI(R) pacing as the preferred pacing mode in patients with SND and intact AV conduction.
PMCID: PMC2995980  PMID: 20879047
Sinus node dysfunction; intact AV conduction
17.  Implantable Cardioverter-Defibrillator Lead Extraction by Conventional Traction and Counter-Traction Technique 
Korean Circulation Journal  2010;40(8):418-420.
A 46-year-old man presented to our institution with inappropriate implantable cardioverter-defibrillator (ICD) shock delivery. The ICD (single chamber, dual shock coils) was implanted for sustained monomorphic ventricular tachycardia with unstable hemodynamics and underlying systolic left ventricular dysfunction. ICD interrogation revealed recurrent episodes of ICD shock due to noise sensing and increased impedance of right ventricular (RV)-lead. With the impression of lead fracture, ICD lead extraction was performed. The fractured ICD lead was completely removed by traction of locking stylet and counter-traction of polypropylene dilator sheath. A new lead was inserted and the patient was discharged without complications after 2 days. To our knowledge, this is the first report on ICD lead extraction by conventional traction and counter-traction technique in Korea.
PMCID: PMC2933469  PMID: 20830258
Device failure, Implantable cardioverter defibrillator; Device removal
18.  Coexisting Sustained Tachyarrthymia in Patients With Atrial Fibrillation Undergoing Catheter Ablation 
Korean Circulation Journal  2010;40(5):235-238.
Background and Objectives
During the index procedure of catheter ablation (CA) for atrial fibrillation (AF), it is important to assess whether other atrial or ventricular tachyarrhythmia coexist. Their symptoms are often attributed to residual tachycardia after successful elimination of AF by CA. This tachycardia could also be non-pulmonary vein (PV) foci initiated AF. This study examined the coexistence of other sustained tachyarrhythmia of patients who underwent radiofrequency CA (RFCA) for AF.
Subjects and Methods
Four hundred fifty-nine consecutive patients (375 males, aged 53.4±11.4 years) who underwent RFCA for AF were investigated. Atrial and ventricular programmed stimulation (PS) with or without isoproterenol infusion were performed, and spontaneously developed tachycardias were analyzed.
Fifteen patients (3.3% of total) were diagnosed to have other sustained arrhythmias that included slow-fast type atrioventricular nodal reentrant tachycardia (AVNRT, n=6), atrioventricular reentrant tachycardia (AVRT, n=5) that utilized left posteroseptal (n=4) and parahisian bypass tract (n=1), atrial tachycardia (AT, n=2) originating from the foramen ovale (n=1) and the ostium of coronary sinus (n=1), sustained ventricular tachycardia (VT, n=2) involving one from the apical posterolateral wall of left ventricule in a normal heart and one from an anterolateral wall in an underlying myocardial infarction (MI). These sustained tachycardias were neither clinically documented nor had structural heart diseases, with the exception of one patient with MI associated VT. Two patients had the triple tachycardia; one involved AVNRT, AVRT, and AF, and the other involved VT, AT, and AF. All associated tachycardias were successfully eliminated by RFCA.
Fifteen (3.3%) patients with AF had coexisting sustained tachycardia. RFCA was successful in these patients. Identification of tachycardia by PS before RFCA for AF should be done to maximize the efficacy of the first ablation session.
PMCID: PMC2877788  PMID: 20514334
Atrial fibrillation; Tachycardia supraventricular; Catheter ablation
19.  Effects of simvastatin on cardiac neural and electrophysiologic remodeling in rabbits with hypercholesterolemia 
Significant cardiac neural and electrophysiologic remodeling occurs with hypercholesterolemia (HC). Whether simvastatin can reverse HC-induced remodeling is unclear.
The purpose of this study was to determine the mechanisms underlying the antiarrhythmic effects of statins.
Rabbits (N = 38) were fed HC chow (HC), standard chow (Control), HC chow followed by standard chow (Withdrawal), or HC chow and simvastatin (Statin) for 8 weeks. The hearts then were Langendorff-perfused for electrophysiologic studies. Nerves were identified by immunostaining of growth-associated protein-43 (GAP43) and tyrosine hydroxylase (TH). Action potential duration (APD) restitution in normal hearts with (N = 5) and without (N = 5) simvastatin therapy also was studied.
Serum cholesterol levels (mg/dL) were 1,855 ± 533 in HC, 50 ± 21 in Control, 570 ± 115 in Withdrawal, and 873 ± 112 in Statin groups (P <.001). Compared with HC (16,700 ± 5,342; 12,200 ± 3,878 µm2/mm2), the Statin group had significantly reduced GAP43-positive (10,289 ± 3,393 µm2/mm2, P = .03) and TH-positive (7,685 ± 2,959 µm2/mm2, P = .04) nerve density, respectively. APD was longer in HC rabbits than in controls (192 ± 20 ms vs 174 ± 17 ms; P <.03). Withdrawal and Statin groups had less APD prolongation than HC group. Statin group has less repolarization heterogeneity than HC group (P <.01). Statin therapy flattened the slope of APD restitution in normal hearts. Ventricular fibrillation was either induced or occurred spontaneously in 79% of hearts in HC, 20% in Control, and 66% in Withdrawal groups. However, there was no VF in hearts of Statin group (P <.001).
Simvastatin significantly reduced vulnerability to ventricular fibrillation via the mechanism of reduction of HC-induced neural and electrophysiologic remodeling.
PMCID: PMC2757294  PMID: 19121803
Arrhythmia; Statin; Lipids; Nervous system; Pathology
20.  The Relationship among Complex Fractionated Electrograms, Wavebreak, Phase Singularity, and Local Dominant Frequency in Fibrillation Wave-Dynamics: a Modeling Comparison Study 
Journal of Korean Medical Science  2014;29(3):370-377.
Although complex fractionated electrogram (CFE) is known to be a target for catheter ablation of fibrillation, its physiological meaning in fibrillation wave-dynamics remains to be clarified. We evaluated the spatiotemporal relationships among the parameters of fibrillation wave-dynamics by simulation modeling. We generated maps of CFE-cycle length (CFE-CL), local dominant frequency (LDF), wave break (WB), and phase singularity (PS) of fibrillation in 2-dimensional homogeneous bidomain cardiac modeling (1,000 × 1,000 cells ten Tusscher model). We compared spatiotemporal correlations by dichotomizing each maps into 10 × 10 lattice zones. In spatial distribution, WB and PS showed excellent correlation (R = 0.963, P < 0.001). CFE-CL had weak correlations with WB (R = 0.288, P < 0.001), PS (R = 0.313, P < 0.001), and LDF (R = -0.411, P < 0.001). However, LDF did not show correlation with PS or WB. PSs were mostly distributed at the periphery of low CFE-CL area. Virtual ablation (5% of critical mass) of CFE-CL < 100 ms terminated fibrillation at 14.3 sec, and high LDF ablation (5% of critical mass) changed fibrillation to organized tachycardia, respectively. In homogeneous 2D fibrillation modeling, CFE-CL was weakly correlated with WB, PS, and LDF, spatiotemporally. PSs are mostly positioned at the periphery of low CFE-CL areas, and virtual ablation targeting low CFE-CL regions terminated fibrillation successfully.
Graphical Abstract
PMCID: PMC3945132  PMID: 24616586
Fibrillation; Complex Fractionated Electrogram; Simulation Modeling

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