Clinical study of 39 Chinese patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are few studies on the clinical profile of Chinese patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). The purpose of this study was to describe the clinical characteristics of ARVD/C patients from China, particularly to define the features of electrocardiograph and treatment outcomes.</p><p><b>METHODS</b>Thirty-nine patients hospitalized in Fu Wai Cardiovascular Hospital from 1998 to 2006 were included. The data were obtained from the medical archive and the follow-up records.</p><p><b>RESULTS</b>Of these patients 33 were male and 6 female (age at the first presentation was (34.9 +/- 9.8) years). The most common symptoms were palpitation (62%) and syncope (44%). Right precordial QRSd >or= 110 ms was detected in 69% of the patients, epsilon wave in 59%, and a ratio of QRSd in V(1) + V(2) + V(3)/V(4) + V(5) + V(6) >or= 1.2 in 82%. The most frequent features of electrocardiogram in patients without right bundle-branch block were T-wave inversions and S-wave upstroke in V(1)-V(3) >or= 55 ms (96% and 90% of 28 patients, respectively). Radiofrequency catheter ablation (RFCA) for ventricular tachycardia (VT) was successful in 15 (68%) of 22 patients. The recurrence rate of VT was 46% (7/15) during the follow-up of (16.7 +/- 11.2) months. Seven patients had cardioverter/defibrillator (ICD) implanted plus drug therapy and 17 patients took antiarrhythmic drugs alone. During the follow-up of (35.6 +/- 19.0) months, all patients with ICD implanted received at least one appropriate ICD shock. One patient died of ventricular fibrillation suddenly and one patient underwent heart transplantation for progressive biventricular heart failure during the drug therapy alone.</p><p><b>CONCLUSIONS</b>This study demonstrated the clinical and ECG features of the 39 ARVD/C Chinese patients. ICD provided life-saving protection by effectively terminating malignant arrhythmias, and the high recurrence of VT was the major problem of RFCA therapy.</p>

Clinical and ECG features of arrhythmogenic right ventricular cardiomyopathy: a retrospective analysis of 31 cases / 中华心血管病杂志

<p><b>OBJECTIVE</b>To retrospectively analyze the clinical and electrocardiographic features of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC).</p><p><b>METHODS</b>The clinical, electrocardiographic features and the efficacy of various therapies were analyzed in 31 patients (27 males) diagnosed as ARVC according to the criteria established by European Society of Cardiology.</p><p><b>RESULTS</b>The averaged age when the ARVC was first diagnosed was (34.7 +/- 9.4) years (19 - 58 years), palpitation was present in 28 patients (90.3%) and syncope in 13 patients (41.9%), a family history of sudden death was present in 1 patient. Dilatated right ventricle was documented in 29 patients by echocardiography and (or) magnetic resonance imaging (MRI), 2 of them with dilated left ventricles. ECG changes included: T wave inversion, mostly seen in precordial leads (100%); epsilon (epsilon) wave (54.8%); QRS duration >or= 110 ms in V(1) to V(3) (83.9%); reduced extremity amplitude (41.9%); the first degree of AV block (22.6%); sustained VT (100%) including 15 monomorphic VT (48.4%) and 16 polymorphic VT (51.6%). The mean values of QRS duration in leads of V(1 - 3) [(120.8 +/- 13.7) ms] was significantly longer than that in V(4 - 6) [(99.4 +/- 13.7) ms, P < 0.05]. Fourteen patients underwent radiofrequency catheter ablation (RFCA) with an immediate success rate of 78.6% (11/14). During follow up (18.3 +/- 10.2) months, VT reoccurred in 6 patients (54.5%). The remaining 17 patients were treated with conventional medications, 7 of them were medicated under implanted cardioverter defibrillator (ICD). During the follow-up (35.6 +/- 19.0) months, VT reoccurred in 11 patients (64.7%) and one patient died suddenly.</p><p><b>CONCLUSIONS</b>ARVC patients developed symptoms at mid-30s with significant ECG changes including appearance of an epsilon wave, T wave inversion and QRS duration >or= 110 ms in leads of V(1 - 3). The long term therapy efficacy was not satisfactory both for RFCA and conventional medications and ICD implantation should be recommended to patients with ARVC.</p>

Modulation of KCNQ1 current by atrial fibrillation-associated KCNE4 (145E/D) gene polymorphism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Atrial fibrillation is a common arrhythmia with multi-factorial pathogenesis. Recently, a single nucleotide polymorphism (G/T) at position 1057 in the KCNE4 gene, resulting in a glutamic acid (Glu, E)/aspartic acid (Asp, D) substitution at position 145 of the KCNE4 peptide, was found in our laboratory to be associated with idiopathic atrial fibrillation (atrial fibrillation more frequent with KCNE4 145D). However, the functional effect of the KCNE4 145E/D polymorphism is still unknown.</p><p><b>METHODS</b>We constructed KCNE4 (145E/D) expression plasmids and transiently co-transfected them with the KCNQ1 gene into Chinese hamster ovary-K1 cells and performed whole-cell patch-clamping recording to identify the possible functional consequences of the single nucleotide polymorphism. Quantitative data were analyzed by Student;s t test. Probability values less than 0.05 were considered statistically significant.</p><p><b>RESULTS</b>A slowly activating, non-inactivating voltage-dependent current ((24.0 +/- 2.9) pA/pF, at +60 mV)) could be recorded in the cells transfected with KCNQ1 alone. Co-expression of wild type KCNE4 inhibited the KCNQ1 current ((7.3 +/- 1.1) pA/pF)). By contrast, co-expression of KCNE4 (145D) augment the KCNQ1 current ((42.9 +/- 7) pA/pF)). The V(1/2) of activation for the KCNQ1/KCNE4 (145D) current was shifted significantly towards the depolarizing potential compared to that for the KCNQ1 current ((-2.3 +/- 0.2) mv vs (-13.0 +/- 1.5) mv, P < 0.01)) without changing the slope factorkappa. Furthermore, KCNE4 (145D) also affected the activation and deactivation kinetics of KCNQ1 channels.</p><p><b>CONCLUSION</b>We provide experimental evidence that the KCNE4 (145E/D) polymorphism exerts the effect of "gain of function" on the KCNQ1 channel. It may underlie the genetic mechanism of atrial fibrillation. Further studies on the functional association between I(Ks) and KCNE4 (145D) polymorphism in cardiac myocytes are suggested.</p>

Effects of Chinese herbs on multiple ion channels in isolated ventricular myocytes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Shensong Yangxin (SSYX) is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current (I(Na)), L-type calcium current (I(Ca, L)), transient outward potassium current (I(to)), delayed rectifier current (I(K)), and inward rectifier potassium currents (I(K1)) in isolated ventricular myocytes.</p><p><b>METHODS</b>Whole cell patch-clamp technique was used to study ion channel currents in enzymatically isolated guinea pig or rat ventricular myocytes.</p><p><b>RESULTS</b>SSYX decreased peak I(Na) by (44.84 +/- 7.65)% from 27.21 +/- 5.35 to 14.88 +/- 2.75 pA/pF (n = 5, P < 0.05). The medicine significantly inhibited the I(Ca, L). At concentrations of 0.25, 0.50, and 1.00 g/100 ml, the peak I(Ca, L) was reduced by (19.22 +/- 1.10)%, (44.82 +/- 6.50)% and (50.69 +/- 5.64)%, respectively (n = 5, all P < 0.05). SSYX lifted the I - V curve of both I(Na) and I(Ca, L) without changing the threshold, peak and reversal potentials. At the concentration of 0.5%, the drug blocked the transient component of I(to) by 50.60% at membrane voltage of 60 mV and negatively shifted the inactive curve and delayed the recovery from channel inactivation. The tail current density of I(K) was decreased by (30.77 +/- 1.11)% (n = 5, P < 0.05) at membrane voltage of 50 mV after exposure to the medicine and the time-dependent activity of I(K) was also inhibited. Similar to the effect on I(K), the SSYX inhibited I(K1) by 33.10% at the test potential of -100 mV with little effect on reversal potential and the rectification property.</p><p><b>CONCLUSIONS</b>The experiments revealed that SSYX could block multiple ion channels such as I(Na) I(Ca, L), I(k), I(to) and I(K1), which may change the action potential duration and contribute to some of its antiarrhythmic effects.</p>

Observation of functional remodeling of Ca2+-activated Cl- channel in pacing-induced canine failing heart / 中华心血管病杂志

<p><b>OBJECTIVE</b>To study whether Ca(2+)-activated Cl(-) current (I(to2)) contributes to the functional remodeling of the failing heart.</p><p><b>METHODS</b>The cardiac myocytes were isolated enzymatically from rapidly pacing-induced failing canine hearts (HF) at room temperature. Patch-Clamp whole cell recording technique was employed to record the I(to2). The Cl(-) transport blocker 4, 4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS, 200 micromol) was used to isolated the I(to2). The relations of I(to2) to L-type Ca(2+) current (I(Ca-L)) and to the membrane voltage under the constant intracellular [Ca(2+)]i were evaluated in HF and the normal hearts.</p><p><b>RESULTS</b>We found that the current density of I(to2) was significantly decreased in HF cells compared with the controls. At membrane voltage of 20 mV, for example, the I(to2) density was (3.02 +/- 0.54) pA/pF in control cells (n = 7) vs. (1.31 +/- 0.25) pA/pF in HF (n = 8) cells, P < 0.05. While the averaged I(Ca-L) density did not show difference between two groups. The time constant of current decay of I(to2) was similar in both types of cells. However, in intracellular Ca(2+) clamped mode with 100 micromol [Ca(2+)]i, I(to2) density was increased significantly in HF cells at membrane voltage of +30 mV or higher.</p><p><b>CONCLUSIONS</b>Our results suggest that the decrease of I(to2) density may contribute to the prolongation of the action potential in failing heart. I(to2) density abnormality may cause cardiac arrhythmia and a delayed after-depolarization. Impaired Ca(2+) handing in HF cells rather than reduced CLCA function itself may result in this abnormality.</p>