Background Human minK protein is the β-subunit of IKs potassium channel and plays an important role in cardiac cellular electrophysiology. We investigated the association between human atrial fibrillation and the polymorphism of minK gene (38G or 38S) with a case-control study. Methods We included 108 patients with atrial fibrillation and 108 control subjects. The case patients and control subjects were matched regarding age, sex, presence of valvular heart disease, and presence of left ventricular dysfunction. The genotype of minK was determined with polymerase chain reaction and restriction fragment analysis. Results The results showed an association between the minK 38G allele and atrial fibrillation. The odds ratios for atrial fibrillation in patients with 1 and 2 minK 38G alleles were 2.16 (95% CI 0.81-5.74) and 3.58 (95% CI 1.38-9.27), respectively, when compared with patients without minK 38G allele. In a logistic regression model, the odds ratio for atrial fibrillation was 1.80 (95% CI 1.20-2.71, P <.0046) for patients with 1 more minK 38G allele. Conclusion We report the association between the minK 38G allele and clinical atrial fibrillation. Our findings suggest possible genetic control on the pathogenesis of atrial fibrillation. (Am Heart J 2002;144:485-90.)

OBJECTIVES The objective of this study was to assess the spatial distribution of atrial ectopic fod potentially triggering recurrent atrial tachyarrhythmias after electrical cardioversion of long-standing atrial fibrillation (AF).BACKGROUND It remains unknown whether targeted ablation of atrial ectopic foci concentrated in the pulmonary veins is feasible in patients with long-standing AF as it is in patients with paroxysmal AF.METHODS Two basket electrodes (32 bipoles on each eight splines) were positioned in the right and left atrium to identify the earliest endocardial activation sites of atrial ectopic foci emerging immediately after external electrical cardioversion of long-standing AF, before and after intravenous administration of dl-sotalol (16 patients) and propafenone (16 patients).RESULTS Before the use of antiarrhythmics, 91 distinct atrial ectopic foci were recognized after cardioversion. In 69 of the 91 foci, the earliest sites of presystolic atrial activation could be identified. Left atrial posterior (16 foci), left atrial anterior (11 loci) and right atrial posterior regions (13 foci) appeared to be prevalent. However, atrial ectopies from the remaining atrial regions (29 fed) were not uncommon. After adding dl-sotalol or propafenone, only 64 atrial ectopic foci were recognized after cardioversion; 50 of those were identifiable at the earliest activation sites. The scattered pattern of spatial distribution of the atrial ectopic foci was Virtually unchanged.CONCLUSIONS Atrial ectopic foci potentially triggering the recurrence of atrial tachyarrhythmias after successful electrical cardioversion of long-standing AF were scattered in spatial distribution at-id multiple in production, possibly rendering difficult the targeted ablation approach. (J Arm Coil Cardiol 2001;37:904-10) (C) 2001 by the American College of Cardiology.

OBJECTIVES This study was undertaken to assess the effects of sotalol on the transthoracic cardioversion energy requirement for chronic atrial fibrillation (AF) and on the atrial electrograms during AF recorded by two basket electrodes.BACKGROUND The effects of sotalol infusion on transthoracic electrical cardioversion for chronic atrial fibrillation in humans have not been well investigated.METHODS We included 18 patients with persistent AF for more than three months. Atrial electrograms were recorded by two basket electrodes positioned in each atrium respectively Transthoracic cardioversion was performed before and after sotalol 1.5 mg/kg IV infusion.RESULTS In the 14 patients whose AF could be terminated by cardioversion before sotalol infusion, the atrial defibrillation energy was significantly reduced after sotalol infusion (236 +/- 74 jules UI vs. 186 +/- 77 J; p < 0.01). Atrial fibrillation was refractory to cardioversion in four patients at baseline and was converted to sinus rhythm by cardioversion after sotalol. infusion in two of them. We further divided the patients into two groups. Group A consisted of 10 patients in whom the energy requirement was decreased by sotalol while group B consisted of eight patients in whom the energy requirement was not decreased. The mean A-A (atrial local electrogram) intervals during AF were significantly increased after sotatol infusion in both groups, but the increment of A-A interval was significantly larger in group A than it was in group B patients (36 +/- 13 ms vs. 22 +/- 8 ms for the right atrium; 19 +/- 7 ms vs. 9 +/- 7 ms for the left atrium; both p < 0.05). The spatial and temporal dispersions of A-A intervals were not significantly changed after sotalol infusion in both atria in both groups.CONCLUSIONS Sotalol decreases the atrial defibrillation energy requirement by increasing atrial refractoriness but not by decreasing the dispersion of refractoriness. (C) 2000 by the American College of Cardiology.

Objective-To search for a reliable anatomical landmark within Koch's triangle to predict the risk of atrioventricular (AV) block during radiofrequency slow pathway catheter ablation of AV nodal re-entrant tachycardia (AVNRT).Patients and methods-To test the hypothesis that the distal end of the AV nodal artery represents the anatomical location of the AV node, and thus could be a useful landmark for predicting the risk of AV block, 128 consecutive patients with AVNRT receiving slow pathway catheter ablation were prospectively studied in two phases. In phase I (77 patients), angiographic demonstration of the AV nodal artery and its ending was performed at the end of the ablation procedure, whereas in the subsequent phase II study (51 patients), the angiography was performed immediately before catheter ablation to assess the value of identifying this new landmark in reducing the risk of AV block. Multiple electrophysiologic and anatomical parameters were analysed. The former included the atrial activation sequence between the His bundle recording site (HBE) and the coronary sinus orifice or the catheter ablation site, either during AVNRT or during sinus rhythm. The latter included the spatial distances between the distal end of the AV nodal artery and the HBE and the final catheter ablation site, and the distance between the HBE and the tricuspid border at the coronary sinus orifice floor.Results-In phase I, nine of the 77 patients had complications of transient (seven patients) or permanent (two patients) complete AV block during stepwise, anatomy guided slow pathway catheter ablation. These nine patients had a wider distance between the HBE and the distal end of the AV nodal artery, and a closer approximation of the catheter ablation site to the distal end of the AV nodal artery, which independently predicted the risk of AV block. In contrast, none of the available electrophysiologic parameters were shown to be reliable. When the distance between the distal end of the AV nodal artery and the ablation target site was more than 2 mm, the complication of AV block virtually never occurred. In phase II, all 51 patients had successful elimination of the slow pathways without complication when the ablation procedure was guided by preceding angiography with identification of the distal end of the AV nodal artery.Conclusions-The distal end of the AV nodal artery shown by angiography serves as a useful landmark for the prediction of the risk of AV block during slow pathway catheter ablation of AVNRT.

Objective-To investigate the electrophysiological determinant underlying the electrical induction of counterclockwise and clockwise isthmus dependent atrial butter.Patients and methods-The isthmus bordered by the inferior vena caval orifice-tricuspid annulus-coronary sinus ostium (IVCO-TA-CSO) has been assumed to be the site of both slow conduction and unidirectional block critical to the initiation of atrial flutter. Trans-isthmus and the global atrial conduction were studied in 25 patients with isthmus dependent atrial flutter (group A) and in 21 patients without atrial flutter (group B), by pacing at the coronary sinus ostium and the low lateral right atrium (LLRA) and mapping with a 20 pole Halo catheter in the right atrium.Results-Mean (SD) fluoroscopic isthmus length between the coronary sinus ostium and LLRA sites was 28.1 (4.0) mm in. group A and 28.0 (3.09) mm in group B (p = 0.95), but the trans-isthmus conduction velocity of both directions at various pacing cycle lengths was nearly halved in group A compared with group B (mean 0.39-0.46 mis v 0.83-0.89 m/s, p < 0.0001). Pacing at coronary sinus ostium directly induced counterclockwise atrial flutter in 14 patients and pacing at LLRA induced clockwise atrial flutter in 11 patients, following abrupt unidirectional transisthmus block. Transient atrial tachyarrhythmias preceded the onset of atrial flutter in 10 counterclockwise and six clockwise cases of atrial flutter. None of the group B patients had inducible atrial flutter even in the presence of transisthmus block. The intra- and interatrial conduction times, as well as the conduction velocities at the right atrial free wall and the septum, were similar and largely within the normal range in both groups.Conclusions-Critical slowing of the trans-IVCO-TA-CSO isthmus conduction, but not the unidirectional block or the global atrial performance, is the electrophysiological determinant of the induction of counterclockwise and clockwise isthmus dependent atrial flutter in man.

Aims: To evaluate the correlation of the flow patterns of the four pulmonary veins as assessed by transesophageal echocardiography and the influence of significant mitral regurgitation on this correlation. Methods and Results: Eighty-eight patients with normal sinus rhythm and variable underlying cardiovascular diseases underwent transthoracic and transesophageal echocardiographic studies. Doppler flow of the four pulmonary veins could not be adequately interpreted in 19 patients (22%). The left atrial dimension of these patients was significantly larger than that of the patients with complete study of the flow in the four pulmonary veins (49 ± 6 vs. 43 ± 7 mm; p < 0.05). Of the 69 patients with complete evaluation of the four pulmonary veins, 48 patients without significant mitral regurgitation were analyzed as group A, and the remaining 21 patients as group B. The peak systolic and diastolic forward flow velocities of the four pulmonary veins were measured and the ratio of peak systolic (S) to diastolic (D) flow velocity was calculated. Group A had a significantly larger S/D ratio in all four pulmonary veins than group B (p < 0.05 in each pulmonary vein measurement). There was good correlation of the flow pattern represented as S/D ratio between left upper and lower pulmonary veins (r = 0.90) and between right upper and lower pulmonary veins (r = 0.89) in group A. The correlation of the flow pattern among the four pulmonary veins deteriorated in group B. Conclusion: Pulmonary veins on the same side share rather similar flow patterns in comparison with pulmonary veins on the opposite sides. The correlation of flow patterns among the four pulmonary veins is good in subjects without significant mitral regurgitation, but it worsens in patients with significant mitral regurgitation. Therefore, cautious interpretation of flow patterns of the four pulmonary veins in patients with significant regurgitation is indicated for grading the severity of mitral regurgitation.

OBJECTIVES We investigated the gene expression of calcium-handling genes including L-type calcium channel, sarcoplasmic reticular calcium adenosine triphosphatase (Ca2+-ATPase), ryanodine receptor, calsequestrin and phospholamban in human atrial fibrillation.BACKGROUND Recent studies have demonstrated that atrial electrical remodeling in atrial fibrillation is associated with intracellular calcium overload. However, the changes of calcium-handling proteins remain unclear.METHODS A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The messenger ribonucleic acid (mRNA) amount of the genes was measured by reverse transcription-polymerase chain reaction and normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase.RESULTS The mRNA of L-type calcium channel and of Ca2+-ATPase was significantly decreased in patients with persistent atrial fibrillation for more than 3 months (0.36 +/- 0.26 vs. 0.90 +/- 0.88 for L-type calcium channel; 0.69 +/- 0.42 vs. 1.21 +/- 0.68 for Ca2+-ATPase; both p < 0.05, all data in arbitrary unit). We further demonstrated that there nas no spatial dispersion of the gene expression among the four atrial tissue sampling sites. Age, gender and underlying cardiac disease had no significant effects on the gene expression. In contrast, the mRNA levels of ryanodine receptor, calsequestrin and phospholamban showed no significant change in atrial fibrillation.CONCLUSIONS L-type calcium channel and the sarcoplasmic reticular Ca2+-ATPase gene were downregulated in atrial fibrillation. These changes may be a consequence of, as well as a contributory factor for, atrial fibrillation. (C) 1999 by the American College of Cardiology.

General anesthesia is sometimes required during radiofrequency catheter ablation (RFCA) of various tachyarrhythmias because of an anticipated prolonged procedure and the need to ensure stability during critical ablation. In this study, we examine the feasibility of using propofol anesthesia for RFCA procedure. There were 150 patients (78 male, 72 female; mean age 30 years, range 4-96 years) in the study. Electrophysiologic study was performed before and during propofol infusion in the initial 20 patients and was performed only during propofol infusion in the remaining 130 patients. In the initial 20 patients, propofol infusion increased the sinus rate and facilitated AV nodal conduction. The accessory pathway effective refractory period, as well as the sinus node recovery time, atrial effective refractory period, and ventricular effective refractory period were not significantly changed. There were 152 tachyarrhythmias in 150 patients (24 atrial flutter, 31 AV nodal reentrant tachycardia, 68 AV reciprocating tachycardia, 12 ventricular tachycardia, and 17 atrial tachycardia). Most (148/152) tachycardias remained inducible after anesthesia and RFCA was performed uneventfully. However, in four of the seven pediatric patients with ectopic atrial tachycardia, the tachycardia terminated after propofol infusion and could not be induced by isoproterenol infusion. Consequently, RFCA could not be performed. Intravenous propofol anesthesia is feasible during RFCA for most tachyarrhythmias except for ectopic atrial tachycardia in children.

A case is reported of an extrauterine pelvic arteriovenous malformation involving branches of the internal iliac arteries. Cardiomegaly and a rough cardiac murmur were the clinical presentations mimicking a structural heart disease. A continuous bruit could only be detected by the diaphragm of the stethoscope applied firmly to the left lower abdomen. Multiple blood samplings from inferior vena cava, and iliac and femoral veins for determination of oxygen saturation may be necessary for suspected cases. However, selective arteriography remains the best method for diagnosing the presence, extent, and multiplicity of the lesions before surgery or percutaneous arterial embolization.

Introduction: The funny current (I-f)contributes to phase IV spontaneous depolarization in cardiac pacemaker tissue. Enhanced I-f activity in myocardial tissue may lead to increased automaticity and therefore tachyarrhythmia. We measured the amount of I-f activity in the messenger ribonucleic acid (mRNA) in human atrial tissue and correlated the mRNA amount to left atrial filling pressure and atrial fibrillation (AF).Methods and Results: A total of 34 patients undergoing open heart surgery were included (15 men and 19 women, aged 55 +/- 10 years). Atrial tissue was obtained from the right atrial free wall, the right atrial appendage, the left atrial free wall, and the left atrial appendage, respectively. The mRNA amount of the I-f channel was measured by reverse transcription polymerase chain reaction and was normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase. We found that the I-f channel mRNA was present at all the atrial sampling sites. A higher left atrial filling pressure, an indicator of congestive heart failure, was associated with a higher I-f mRNA level (r(2) = 0.446, P < 0.01 by linear regression). We also found that the mRNA amount was significantly higher in patients with AF than in patients without AF (1.68 +/- 0.49 vs 1.27 +/- 0.43; P < 0.05). Age, sex, right atrial filling pressure, left atrial dimension, and left ventricular ejection fraction had no significant effect on the mRNA level.Conclusion: The mRNA of the I-f channel is present in the free-wall area and appendage area from both atria. Increased left atrial filling pressure and clinical AF are associated with increased I-f mRNA level.

Background p-Blocker therapy is believed to modulate the detrimental effect of overcompensating neurohormonal activation in chronic heart failure. However, clinical doubts remain, particularly the physiologic sympathovagal balance.Methods To respond to clinical concern about worsening autonomic nervous perturbation in P blocker therapy of advanced congestive heart failure, 15 consecutive patients were longitudinally studied to elucidate the evolution of cardiac function versus 24-hour heart rate variability (HRV) before and after 1, 3, and 6 to 9 months of atenolol-combined therapy.Results Two patients died prematurely within 1 month. All 13 surviving patients showed improvement in New York Heart Association functional class, with decrease in left ventricular end-systolic and end-diastolic dimensions and increase in fraction shortening and election fraction by echocardiography after at least 3 months of atenolol use. The retarded therapeutic effect was accompanied by a general rise of total, very low, low-, and high-frequency components (9.0 +/- 0.5, 8.8 +/- 0.5, 6.2 +/- 0.6, and 6.1 +/- 0.5 vs 10.9 +/- 0.3, 10.7 +/- 0.4, 8.6 +/- 0.3, and 7.8 +/- 0.3; all P < .02) of daily HRV. This implied recovery of parasympathetic and baroreceptor function. Return of sympathovagal interaction was further supported by the suppression of Cheyne-Stokes type HRV as detected by Wigner-Ville distribution.Conclusions Long-term P-blocker therapy for advanced congestive heart failure upwardly regulates the autonomic nervous interaction in synchrony with the evolution of cardiac function performance.

Introduction: We measured mRNA levels of delayed rectifier potassium channels in human atrial tissue to investigate the mechanism of the shortening of the atrial effective refractory period and the loss of rate-adaptive shortening of the atrial effective refractory period in human atrial fibrillation. Methods and Results: A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The mRNA amounts of KVLQT1 (IKs), minK (β-subunit of IKs), HERG (IKr), and KV1.5 (IKur) were measured by reverse transcription-polymerase chain reaction and normalized to the mRNA amount of GAPDH. We found that the mRNA levels of KV1.5, HERG and KVLQT1 were all significantly decreased in patients with persistent atrial fibrillation for more than 3 months. In contrast, the mRNA level of minK was significantly increased in patients with persistent atrial fibrillation for more than 3 months. We further showed that these changes were independent of the underlying cardiac disease, atrial filling pressure, gender and age. We also found that there was no spatial dispersion of mRNA levels among the four atrial sampling sites. Conclusions: Because the decrease in potassium currents results in a prolonged action potential, the shortening of the atrial effective refractory period in atrial fibrillation should be attributed to other factors. However, the decrease in IKs might contribute, at least in part, to the loss of rate-adaptive shortening of the atrial refractory period.

OBJECTIVE:To develop new electrocardiographic (ECG) criteria for the differentiation between counterclockwise and clockwise atrial flutters.BACKGROUND:Traditionally, the ECG differentiation between counterclockwise and clockwise atrial flutters is based on the flutter wave polarity in the inferior leads. However, determination of flutter wave polarity is subjective and sometimes difficult, especially in flutter waves of undulating pattern.PATIENTS:The study comprised 37 consecutive patients with drug resistant atrial flutter; 30 had counterclockwise and 17 had clockwise atrial flutter (10 had both forms of atrial flutter). The isthmus dependence was confirmed by entrainment study and catheter ablation. The ECG patterns of both types of atrial flutter were compared and the flutter wave polarity in the inferior leads was determined by four independent cardiologists.RESULTS:The flutter wave polarity in the inferior leads appeared negative in 24, positive in one, and equivocal in five of the counterclockwise atrial flutters; polarity appeared negative in one, positive in 10, and equivocal in six of the clockwise atrial flutters. However, the aVF/lead I flutter wave amplitude ratio was > 2.5 in all counterclockwise but < 2.5 in all clockwise atrial flutters. The flutter wave nadirs in the inferior leads corresponded to the upstrokes in V1 in all counterclockwise atrial flutters, but corresponded to the downstrokes in V1 in all clockwise atrial flutters.CONCLUSIONS:The flutter wave polarity in the inferior leads does not correlate well with the flutter wave rotating direction. However, counterclockwise and clockwise atrial flutters can be differentiated by new ECG criteria with high accuracy.

We investigated the clinical characteristics and coronary risk factors of Chinese patients with suspected coronary artery disease (CAD) having low serum concentrations of both low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Of 1,450 patients with suspected CAD (age range, 30-92 years; 948 men and 502 women), 760 had established CAD. The patients were divided into three groups according to lipid profile patterns. Group 1 patients (n = 138) had low LDL-C concentrations (< 100 mg/dL) and low TC concentrations (< 160 mg/dL). They were characterized by lower triglyceride concentrations, lower frequencies of high TC/high-density lipoprotein cholesterol (HDL-C) ratios (> 5) and LDL-C/HDL-C ratios (> 5), and lower frequencies of a family history of CAD and obesity. Group 3 patients (n = 610) had LDL-C concentrations of 130 mg/dL or above and TC concentrations of 200 mg/dL or above, much higher than in group 1. The prevalence of CAD was 41.3% (57/138) in group 1. 46.7% (328/702) in group 2, and 61.5% (375/610) in group 3. Groups with higher TC and LDL-C concentrations had a higher CAD prevalence. Coronary risk factors of group 1 patients appeared to be low HDL-C concentration, high TC/HDL-C ratio, advanced age, cigarette smoking, hypertension, and diabetes mellitus. Among these risk factors, HDL-C and hypertension were independent predictors of CAD. Unlike in the other two groups, hypertension was the only independent nonlipid risk factor. We conclude that in therapy or prevention of CAD, the goals should be to reduce LDL-C concentration to below 100 mg/dL and the TC concentration to below 160 mg/dL. However, other risk factors should also be considered.

Atrial dissociation with segmental atrial arrhythmia is an interesting electrophysiological phenomenon. It was rarely reported before to be caused by anatomical exit block after cardiac surgery. We report the case of a 28‐year‐old patient who developed atrial dissociation after a surgical method for correcting atrial fibrillation—atrial compartment operation. The segmental atrial flutter was first found by Doppler echocardiography and proved later by detailed intracardiac mapping.

The purpose of this study was to investigate the atrioventricular AV nodal physiology and the inducibility of AV nodal reentrant tachycardia (AVNRT) under pharmacological autonomic blockade (AB). Seventeen consecutive patients (6 men and 11 women, mean age 39 ± 17 years) with clinical recurrent slow‐fast AVNRT received electrophysiological study before and after pharmacological AB with atropine (0.04 mg/kg) and propranolol (0.2 mg/kg). In baseline, all 17 patients could be induced with AVNRT, 5 were isoproterenol‐dependent. After pharmacological AB, 12 (71 %) of 17 patients still demonstrated AV nodal duality. AVNRT became noninducible in 7 of 12 nonisoproterenol dependent patients and remained noninducible in all 5 isoproterenol dependent patients. The sinus cycle length (801 ± 105 ms vs 630 ± 80 ms, P < 0.005) and AV blocking cycle length (365 ± 64 ms vs 338 ± 61 ms, P < 0.005) became shorter after AB. The antegrade effective refractory period and functional refractory period of the fast pathway (369 ± 67 ms vs 305 ± 73 ms, P < 0.005; 408 ± 56 ms vs 350 ± 62 ms, P < 0.005) and the slow pathway (271 ± 30 ms vs 258 ± 27 ms, P < 0.01; 344 ± 60 ms vs 295 ± 50 ms, P < 0.005) likewise became significantly shortened. However, the ventriculoatrial blocking cycle length (349 ± 94 ms vs 326 ± 89 ms, NS) and effective refractory period of retrograde fast pathway (228 ± 38 ms vs 240 ± 80 ms, NS) remained unchanged after autonomic blockade. Pharmacological AB unveiling the intrinsic AV nodal physiology could result in the masking of AV nodal duality and the decreased inducibility of clinical AVNRT.