Conversion to partial isthmus-dependent flutter during cavotricuspid isthmus ablation: The utility of Advisor HD grid in identifying local fragment electrograms.

Complete block creation by radiofrequency (RF) ablation at the cavotricuspid isthmus (CTI) is a highly successful procedure for the treatment of typical atrial flutter (AFL). Occasionally, a rare type of AFL, such as lower or upper loop reentry, or partial isthmus-dependent flutter, can coexist with typical right AFL. A 73-year-old man underwent CTI ablation for a clockwise CTI-dependent typical atrial flutter. During the ablation procedure, the morphology of the flutter wave changed in the surface electrocardiogram and endocardial atrial activation sequence, suggesting that the typical AFL had converted to another AFL (AFL2). High-density mapping using the HD grid catheter could not reveal the reentrant circuit of AFL2 but detected a critical conduction gap at the boundary between the inferior vena cava and CTI. There was also an impulse collision in the remaining CTI. The RF application at the gap terminated the AFL2 and completed the block line of the CTI. Based on these findings, AFL2 was comparable with partial isthmus-dependent flutter. The present case demonstrates the utility of high-density mapping with a HD grid for the identification of small amplitude high-frequency electrograms at critical sites of the arrhythmia. Learning objective: A rare type of atrial flutter (AFL) can coexist with typical AFL. In such cases, a high-density mapping is useful to identify the critical portion of the reentrant circuit. The Advisor HD grid multipolar catheter (Abbott, St Paul, MN, USA) is unique in that it allows bipolar recording perpendicular and parallel to the splines via 16 electrodes. In this case report, high density mapping using HD grid catheter identified small amplitude high-frequency electrograms at critical sites of the arrhythmia.

Paradoxical delayed capture proved the dual-loop tachycardia mechanism of a cavotricuspid isthmus-dependent atrial flutter.

A 37-year-old man underwent catheter ablation for a cavotricuspid isthmus-dependent atrial flutter. Two 20-pole deflectable electrode catheters were placed in a parallel position on the tricuspid annulus and right atrial lateral wall. The dual-loop tachycardia mechanism of the atrial flutter was suggested by paradoxical delayed capture of the lateral wall of the right atrium during entrainment pacing from the lateral tricuspid annulus.

Differences in the Slope of the QT-RR Relation Based on 24-Hour Holter ECG Recordings between Cardioembolic and Atherosclerotic Stroke.

Objective Detecting paroxysmal atrial fibrillation in patients with ischemic stroke presenting in sinus rhythm is difficult because such episodes are often short, and they are also frequently asymptomatic. It is possible that the ventricular repolarization dynamics may reflect atrial vulnerability and cardioembolic stroke. Hence, we compared the QT-RR relation between cardioembolic stroke and atherosclerotic stroke during sinus rhythm. Methods The subjects comprised 62 consecutive ischemic stroke patients including 31 with cardioembolic strokes (71.8±12.7 years, 17 men) and 31 with atherosclerotic strokes (74.8±10.8 years, 23 men). The QT and RR intervals were measured from ECG waves based on a 15-sec averaged ECG during 24-hour Holter recording using an automatic QT analyzing system. The QT interval dependence on the RR interval was analyzed using a linear regression line for each subject ([QT]=A[RR]+B; where A is the slope and B is the y-intercept). Results The mean slope of the QT-RR relation was significantly greater in cardioembolic stroke than in atherosclerotic stroke (0.187±0.044 vs. 0.142±0.045, p<0.001). The mean QT, RR, or QTc during 24-hour Holter recordings did not differ between them. An increased slope (≥0.14) of the QT-RR regression line could predict cardioembolic stroke with 97% sensitivity, 55% specificity and a positive predictive value of 64%. Conclusion The increased slope of the QT-RR linear regression line based on 24-hour Holter ECG in patients with ischemic stroke presenting in sinus rhythm may therefore be a simple and useful marker for cardioembolic stroke.

Usefulness of entrainment mapping using the activation sequence of the last captured excitation in complex dual-loop atrial tachycardia.

BACKGROUND: Electroanatomical mapping is useful for locating the atrial reentrant circuit, but analysis of the dynamic relation of the reentrant circuit is sometimes difficult. This article describes three cases of complex dual-loop reentrant atrial tachycardia analyzed by entrainment mapping using not only the postpacing interval (PPI) but also the activation sequence of the last captured beats. METHODS: Case 1 was dual-loop reentry consisting of the tricuspid annulus (TA) and a localized atrial reentry at the coronary sinus (CS) ostium with different exit sites to the right and the left atrium that was cured by catheter ablation at the CS ostium showing fractionated potential. Case 2 was dual-loop reentry around the TA and the superior trans-septal incision line. Case 3 was dual-loop reentry around the TA and longitudinal dissociation along the cavo-tricuspid isthmus. RESULTS: In Cases 1 and 2, entrainment with a shorter pacing cycle length demonstrated antidromic penetration to the circuit and changed the activation sequence of the last captured beat depending on the anatomical relation of the reentrant circuit. In Cases 1-3 with dual-loop reentry, the excitation wavefront induced by stimulation entered one circuit after going around the other; thus, the penetration to the other reentry circuit became the second beat after the stimulus (one lap behind). CONCLUSIONS: The PPI is obtained from the pacing site only, but the last captured beat could be obtained from all electrodes. It is advantageous to use the information from all available electrode recordings to determine the dynamic relation between complex dual-loop reentrant circuits.

Bepridil enhances aprindine-induced prolongation of atrial effective refractory period in a canine atrial rapid pacing model.

BACKGROUND: Bepridil in combination with aprindine could restore sinus rhythm in patients with persistent atrial fibrillation (AF). The present study aimed to investigate the electrophysiological mechanisms of the combined effects of bepridil and aprindine. METHODS: Subjects consisted of 6 dogs without and 6 dogs with atrial rapid pacing (ARP) carried out at 400 bpm for 2 weeks. Bepridil was administered for 1 week in both groups (ARP dogs were administered bepridil in the second week). The electrophysiological effects of the intravenous administration of aprindine (1mg/kg) were evaluated before and after the administration of bepridil. RESULTS: In non-paced dogs, the atrial effective refractory period (AERP) became longer after the administration of bepridil (from 151±10 ms to 170±7 ms, p<0.05); however, no additional AERP prolongation was observed after the acute administration of aprindine. In ARP dogs, the AERP shortened with ARP for a week, and tended to lengthen after the administration of bepridil (from 93±5 ms to 118±9 ms, p=0.08). In these dogs, the acute aprindine administration did not prolong the AERP before the administration of bepridil, although it did after the administration of bepridil (from 118±9 ms to 142±8 ms, p<0.01). AF duration did not change after the administration of bepridil, although it shortened significantly after the additional administration of aprindine (from 2.2±0.3s to 1.4±0.8s, p<0.05). CONCLUSIONS: Bepridil enhances the effect of aprindine for the prevention of AF by reversing atrial electrical remodeling.

Evaluation of repolarization dynamics using the QT-RR regression line slope and intercept relationship during 24-h Holter ECG.

QT-RR linear regression consists of two parameters, slope and intercept, and the aim of this study was to evaluate repolarization dynamics using the QT-RR linear regression slope and intercept relationship during 24-h Holter ECG. This study included 466 healthy subjects (54.6 ± 14.6 years; 200 men and 266 women) and 17 patients with ventricular arrhythmias, consisted of 10 patients with idiopathic ventricular fibrillation (IVF) and 7 patients with torsades de pointes (TDP). QT and RR intervals were measured from ECG waves based on a 15-s averaged ECG during 24-h Holter recording using an automatic QT analyzing system. The QT interval dependence on the RR interval was analyzed using a linear regression line for each subject ([QT] = A[RR] + B; where A is the slope and B is the y-intercept). The slope of the QT-RR regression line in healthy subjects was significantly greater in women than in men (0.185 ± 0.036 vs. 0.161 ± 0.033, p < 0.001) and the intercept was significantly smaller in women than in men (0.229 ± 0.028 vs. 0.240 ± 0.027, p < 0.001). A scatter diagram of the QT-RR regression line slope and intercept among healthy subjects demonstrated a statistically significant negative correlation (B = -0.62A + 0.34, r = -0.79). Distribution of both scatter diagrams of the slope and the intercept of the QT-RR regression line in patients with IVF and TDP was different from healthy subjects (left corner for IVF and upward shift for TDP). The slope and intercept relationship of the QT-RR linear regression line based on 24-h Holter ECG may become a simple useful marker for abnormality of ventricular repolarization dynamics.

Electrophysiological and anatomical differences of the slow pathway between the fast-slow form and slow-slow form of atrioventricular nodal reentrant tachycardia.

AIMS: This study aimed to clarify whether electrophysiological and anatomical properties of the slow pathway (SP) could be different between the fast-slow form (F/S) and the slow-slow form (S/S) atrioventricular nodal reentrant tachycardia (AVNRT). METHODS AND RESULTS: Nine patients with F/S and 15 patients with S/S of atypical AVNRT were studied. The patients with S/S were divided into two groups; those with the anterograde SP being eliminated (S/S aSP-E) or preserved (S/S aSP-P) during catheter ablation. HA (CS-His) was determined as the difference of the shortest HA interval between the His bundle region and the coronary sinus (CS) region. The ratio of the amplitudes of atrial and ventricular potential (A/V ratio) of the successful ablation site of the SP was also evaluated. Effective refractory period of the retrograde SP was shorter and HA intervals during both tachycardia and ventricular pacing were longer in F/S than in S/S. HA (CS-His) did not differ between F/S and S/S (-4.3 ± 20.2 vs.-4.4 ± 18.4 ms, NS). The A/V ratio was significantly greater in the S/S aSP-P group compared with the both groups of F/S and S/S aSP-E (0.83 ± 0.29 vs. 0.38 ± 0.09 and 0.26 ± 0.15 ms, P < 0.01). CONCLUSION: Properties of the retrograde SP differ between F/S and S/S of AVNRT. Fast-slow form may utilize the same pathway for the retrograde conduction as the anterograde SP in S/S.

High prevalence of cyclical variation in heart rate before nocturnal episodes of paroxysmal atrial fibrillation.

OBJECTIVE: Nighttime onset of atrial fibrillation (AF) is sometimes associated with obstructive sleep apnea accompanied by a characteristic heart rate (HR) pattern known as cyclical variation of HR. The aim of this study was to evaluate whether cyclical variation of HR is prevalent in patients with nocturnal AF. METHODS: The subjects consisted of 34 patients (68±12 years) with paroxysmal AF, including 14 patients with daytime AF and 20 patients with nighttime AF. Holter electrocardiogram (ECGs) were examined for the presence of cyclical variation in HR and to quantify the HR variability within the 40-minute period preceding each AF episode using a fast Fourier transform (FFT) methods. RESULTS: Cyclical variation in HR was observed in 12 of 20 (60%) nighttime episodes and in only two of 14 (14%) daytime episodes. The prevalence of cyclical variation in HR was significantly greater in the nighttime AF episodes than in the daytime AF episodes (Chi=5.34, p<0.05). The mean frequency of cyclical variation in HR was 0.015±0.003 Hz. The mean power of the VLF (very low frequency) component (0.008-0.04 Hz) before the onset of AF was significantly greater in the nighttime AF episodes than in the daytime AF episodes. Among the nighttime AF episodes, the power of the HF (high frequency), LF (low frequency) and very low frequency (VLF) components increased significantly just before the onset of AF compared with that observed 40 minutes before onset. CONCLUSION: The high prevalence of cyclical variation in HR observed before nocturnal AF episodes suggests that sleep apnea may play a role in the onset of nighttime AF.

Tranilast prevents atrial remodeling and development of atrial fibrillation in a canine model of atrial tachycardia and left ventricular dysfunction.

OBJECTIVES: This study sought to assess the effects of tranilast on atrial remodeling in a canine atrial fibrillation (AF) model. BACKGROUND: Tranilast inhibits transforming growth factor (TGF)-ß1 and prevents fibrosis in many pathophysiological settings. However, the effects of tranilast on atrial remodeling remain unclear. METHODS: Beagles were subjected to atrial tachypacing (400 beats/min) for 4 weeks while treated with placebo (control dogs, n = 8) or tranilast (tranilast dogs, n = 10). Sham dogs (n = 6) did not receive atrial tachypacing. Atrioventricular conduction was preserved. Ventricular dysfunction developed in the control and tranilast dogs due to rapid ventricular responses. RESULTS: Atrial fibrillation duration (211 ± 57 s) increased, and AF cycle length and atrial effective refractory period shortened in controls, but these changes were suppressed in tranilast dogs (AF duration, 18 ± 10 s, p < 0.01 vs. control). The L-type calcium channel α1c (Cav1.2) micro ribonucleic acid expression decreased in control dogs (sham 1.38 ± 0.24 vs. control 0.65 ± 0.12, p < 0.01), but not in tranilast dogs (0.97 ± 0.14, p = not significant vs. sham). Prominent atrial fibrosis (fibrous tissue area, sham 0.8 ± 0.1 vs. control 9.3 ± 1.3%, p < 0.01) and increased expression of tissue inhibitor of metalloproteinase protein 1 were observed in control dogs but not in tranilast dogs (fibrous tissue area, 1.4 ± 0.2%, p < 0.01 vs. control). The TGF-ß1 (sham 1.00 ± 0.07 vs. control 3.06 ± 0.87, p < 0.05) and Rac1 proteins were overexpressed in control dogs, but their overexpression was inhibited in tranilast dogs (TGF-ß1, 1.28 ± 0.20, p < 0.05 vs. control). CONCLUSIONS: Tranilast prevented atrial remodeling and suppressed AF development in a canine model. Its inhibition of TGF-ß1 and Rac1 overexpression may contribute to its antiremodeling effects.

Sick sinus syndrome induced by interferon and ribavirin therapy in a patient with chronic hepatitis C.

The therapeutic effect of interferon (IFN) on chronic hepatitis C and its adverse effects have been well documented. Although the incidence of IFN-related cardiotoxicity is low, careful observation is necessary because of its possible fatal outcome. We describe a 45-year-old woman who suffered from sinus node dysfunction after the combination therapy of pegylated IFN-alpha and ribavirin for chronic hepatitis C. Despite the cessation of IFN therapy, sinus node dysfunction was not reversible, and led her to the implantation of permanent pacemaker. Physicians should therefore be aware of the possibility of sinus node dysfunction in patients receiving IFN therapy. .

Xanthine oxidase inhibition prevents atrial fibrillation in a canine model of atrial pacing-induced left ventricular dysfunction.

AIMS: Oxidative stress could be a possible mechanism and a therapeutic target of atrial fibrillation (AF). Xanthine oxidase (XO) inhibition reduces oxidative stress, but the effects of XO inhibitor on AF have not been evaluated. Hence, we assessed the effects of XO inhibitor, allopurinol, on progression of atrial vulnerability in dogs associated with tachycardia-induced cardiomyopathy. METHODS AND RESULTS: The dogs were subjected to atrial tachypacing (ATP, 400 bpm) without atrioventricular block for 4 weeks. The dynamics of atrial-tachycardia remodeling were evaluated in allopurinol-treated dogs (ALO, n = 5), placebo-treated controls (CTL, n = 6), and sham-operated dogs (n = 6). In CTL dogs, 4 weeks of ATP significantly increased AF duration (DAF; from 0.2 ± 0.2 seconds to 173 ± 67 seconds, P < 0.05) and decreased atrial effective refractory period (ERP; from 152 ± 9 milliseconds to 80 ± 4 milliseconds at a cycle length of 350 milliseconds, P < 0.01). Allopurinol attenuated the ATP effects on ERP (118 ± 6 milliseconds, P < 0.01) or DAF (0.6 ± 0.3 seconds, P < 0.05). In CTL dogs, ATP-induced rapid ventricular responses decreased left ventricular ejection fraction (LVEF; from 58.6 ± 0.1 to 23.5 ± 2.4%, P < 0.01), and increased left atrial diameter (LAD; from 17 ± 1 mm to 24 ± 1 mm, P < 0.01). ATP increased atrial fibrosis when compared with sham-operated dogs (CTL 10.7 ± 0.8% vs Sham 1.1 ± 0.3%, P < 0.01). Allopurinol suppressed atrial fibrosis (2.3 ± 0.6%, P < 0.01 vs CTL) and eNOS reduction without affecting LVEF (20.6 ± 2.2%, ns) and LAD (23 ± 1 mm, ns). CONCLUSION: Allopurinol suppresses AF promotion by preventing both electrical and structural remodeling. These results suggest that XO may play an important role in enhancement of atrial vulnerability, and might be a novel target of AF therapy.

Anticoagulation control quality affects the D-dimer levels of atrial fibrillation patients.

BACKGROUND: Anticoagulation control quality affects the incidence of thromboembolic events in atrial fibrillation (AF) patients. However, the effects of anticoagulation control quality on the prothrombotic state of AF patients are unclear. METHODS AND RESULTS: Ninety-five AF patients who had been treated with warfarin were prospectively followed-up for 449 ± 92 days. We analyzed whether time in the therapeutic range (TTR) of the international normalized ratio (INR) of prothrombin time, percentage of INR values in the range (%INR), and coefficient of variation of INR values (CV-INR) were related to D-dimer levels. The mean values of TTR, %INR, and CV-INR were 62%, 59%, and 0.19, respectively, and their median values were 67%, 63%, and 0.19, respectively. TTR was significantly correlated with %INR (R(2) = 0.917, P<0.01), but not with CV-INR (R(2) = 0.050, P = 0.26). The mean and median D-dimer levels were 0.79 and 0.60 µg/ml, respectively. Low TTR, low %INR, and high CV-INR were found to contribute to high D-dimer levels (P = 0.02, 0.03, and 0.02, respectively). CONCLUSIONS: In AF patients treated with warfarin, not only the duration outside the target INR range, but also the fluctuation in INR level may influence the prothrombotic state.

Early repolarization in Wolff-Parkinson-White syndrome: prevalence and clinical significance.

AIMS: Idiopathic ventricular fibrillation (IVF) with early repolarization (ER) has recently been reported; however, ER is a common finding in healthy subjects and is also found sporadically in patients with Wolff-Parkinson-White (WPW) syndrome. The present study was designed to evaluate the prevalence and clinical significance of ER in patients with WPW syndrome. METHODS AND RESULTS: One hundred and eleven patients with WPW syndrome were studied retrospectively. Early repolarization was defined as QRS slurring or notching with J-point elevation ≥ 1 mm. The prevalence of ER was determined before and after successful catheter ablation. Before ablation, ER was found in 35 of 75 patients with a left free wall, 6 of 23 with a right free wall, and 7 of 13 with a septal accessory pathway (48 of 111, 43% as a whole). Early repolarization was always observed in leads with positive deflection of the initial part of the delta wave. After successful ablation of accessory pathways, ER was preserved in 28 (25%), disappeared in 20 (18%), and newly developed in 8 (7%) patients. In the remaining 55 (50%) patients, ER was not observed either before or after ablation. In patients with persistent ER, the amplitude and width of ER were significantly decreased 3-7 days after the ablation (1.7 ± 0.7 vs. 1.4 ± 0.6 mm, P < 0.005 and 42 ± 11 vs. 34 ± 9 ms, P < 0.001, respectively). CONCLUSION: In patients with WPW syndrome, ER could be partly related to early depolarization through the accessory pathway. However, persistent ER and new ER appearing after the ablation were frequently found. Therefore, in these patients, mechanisms other than early depolarization may be involved in the genesis of ER.

QT/RR relation during atrial fibrillation based on a single beat analysis in 24-h Holter ECG: the role of the second and further preceding RR intervals in QT modification.

BACKGROUND: During atrial fibrillation (AF) irregularity of RR intervals may modify QT/RR relation differently from sinus rhythm. The purpose of this study was to compare QT/RR relation based on a single-beat analysis using the first preceding RR interval with the modified RR interval reflecting not only the first preceding but also the second and further preceding RR intervals during AF. METHODS: QT and RR intervals were measured using an automatic QT analyzing system in 32 patients who had both AF and sinus rhythm on the same 24-h Holter ECG recording. In 12 patients antiarrhythmic drugs (AADs) were administered. To reflect irregularity of the preceding RR intervals during AF, a modified RR (mRR) using a weighted average of five successive RR intervals: (5RR(1)+2RR(2)+RR(3)+RR(4)+RR(5))/10 was adopted. Linear regression analyses between QT and RR intervals were performed using the preceding RR(1) (QT/RR) and the modified RR (QT/mRR) during AF. RESULTS: During AF the slope of QT/RR was lower than that of QT/mRR and was also lower than that of QT/RR during sinus rhythm in patients with and without AAD. Slopes of regression line in QT/RR during sinus rhythm, QT/RR and QT/mRR during AF were steeper in patients with AAD than those in patients without. Slopes of QT/RR during sinus rhythm correlated with those of QT/mRR (r=0.79, p<0.01) better than those of QT/RR (r=0.64, p<0.05) during AF. QT interval at an RR interval of 1.20s or 1.00 s obtained from QT/RR during AF was significantly smaller than that during sinus rhythm in patients with and without AAD. CONCLUSIONS: The slope of QT/mRR during AF became closer to that of QT/RR during sinus rhythm compared with that of QT/RR during AF. QT interval during sinus rhythm could be estimated better using QT/mRR than using QT/RR during AF.

Identification of a novel TPM1 mutation in a family with left ventricular noncompaction and sudden death.

Left ventricular noncompaction (LVNC) is a cardiomyopathy morphologically characterized by 2-layered myocardium, numerous prominent trabeculations, and deep intertrabecular recesses communicating with the left ventricular cavity. The purpose of this study was to investigate patients with LVNC for possible disease causing mutations. We screened 4 genes (TAZ, LDB3, DTNA and TPM1) in 51 patients with LVNC for mutations by polymerase chain reaction and direct DNA sequencing. A novel missense substitution in exon 1 of TPM1 (c.109A>G: p.Lys37Glu) was identified in three affected members of a family with isolated LVNC. The substitution brings about a change in amino acid charge at a highly conserved residue and could result in aberrant mRNA splicing. This variant was not identified in 200 normal control samples. Pathologic analysis of a right ventricular myocardial specimen from the proband's maternal aunt revealed endocardial and subendocardial fibrosis with prominent elastin deposition, as well as the presence of adipose tissue between muscle layers, pathologic changes that are distinct from those seen in patients with HCM or DCM. Screening of the proband and her mother for variants in other sarcomeric protein-encoding candidate genes, MYH7, MYBPC3, TNNT2, TNNI3, ACTC, MYL2, and MYL3, did not identify any other non-synonymous variants or variants in splice donor-acceptor sequences that were potentially disease causing. We conclude TPM1 is a potential candidate disease-causing gene for isolated LVNC, especially in patients experiencing sudden death.

Torsades de pointes induced by garenoxacin in association with pacing failure in an elderly woman with VDD pacemaker.

An 86-year-old woman was admitted to the hospital for syncope and convulsion 4 days after starting antibiotic therapy for pneumonia with oral garenoxacin 400 mg/day. She had a VDD pacemaker for complete atrioventricular (AV) block. Her electrocardiogram showed marked QT prolongation and during pacemaker interrogation pacing failure probably due to battery depletion induced torsades de pointes. After cessation of garenoxacin, QTc returned to normal range subsequently and a new pacemaker was implanted. In patients with risks of QT prolongation, garenoxacin should be used cautiously with QT interval monitoring.