Single center experience of transcatheter aortic valve replacement with a simplified operative protocol / 中华心血管病杂志

Objective: To summarize the single center experience of transcatheter aortic valve replacement (TAVR) with a simplified operative protocol. Methods: Consecutive patients who underwent transfemoral TAVR (TF-TAVR) from July 2020 to December 2020 in Fuwai Hospital were retrospectively analyzed. We compared the baseline characteristic, procedure information, 30-day follow-up outcomes of the patients who underwent TF-TAVR without the simplified operative protocol (routine group) or with the simplified operative protocol (simplified protocol group). Results: 93 patients were collected, 42 patients belonging to routine group, 51 patients belonging to simplified protocol group. In simplified protocol group, there were 51 patients planned to use ultrasound-guided femoral access puncture, procedure was successful in all 51 patients (100%). There were 49 patients planned to use the radial artery as the secondary access, procedure was successful in 45 patients (92%). There were 48 patients planned to use the strategy of avoidance of urinary catheter, this strategy was achieved in 35 patients (73%). There were 12 patients planned to use the left ventricular guidewire to pace, procedure was successful in 11 patients (92%). There were no differences in baseline characteristics, major clinical endpoints and 30-day follow-up outcomes between the two groups. Meanwhile, the procedure time ((62.5±17.9)min vs. (78.3±16.7)min, P<0.001), operation room time ((133.7±25.1)min vs. (159.2±42.6)min, P<0.001), X-ray exposure time ((17.2±6.5)min vs. (20.2±7.7)min, P=0.027) were significantly shorten in simplified protocol group compared with the routine group. Conclusion: Our study results indicate that the simplified operative protocol of TF-TAVR is as effective and safe as the routine operative protocol, meanwhile using the simplified operative protocol can significantly increase the operative efficiency of TF-TAVR.

Left ventricular guidewire pacing during transcatheter aortic valve replacement / 中华心血管病杂志

Objective: To investigate the safety and efficacy of left ventricular guidewire pacing during transcatheter aortic valve replacement (TAVR). Methods: This is a retrospective study. Thirteen patients, who underwent TAVR with left ventricular guidewire pacing from October 2019 to December 2019 in Fuwai Hospital, were included. Clinical data and operational procedure data of the patients were collected. Changes in blood pressure and electrocardiogram were observed during operations. Ascending aorta angiography was performed to evaluate the regurgitation of aortic valve after valve implantion. The incidence of major adverse cardiac events during hospitalization and at 3-months after discharge was recorded. Results: There were 7 male and 6 female patients in this cohort,and age was (73.8±8.3) years old. Among the 13 patients, 9 were tricuspid aortic valves, 3 were bicuspid aortic valves, and 1 was degenerated bioprosthetic surgical aortic valve. TAVR were successfully performed in all of the 13 cases using pacing through the left ventricular guidewire. During balloon dilation, the blood pressure decreased to below 60 mmHg (1 mmHg=0.133 kPa) after 180 beats/min pacing, and the valve release process was smooth and the position was stable. The results of aortography showed that there was no regurgitation in 7 cases, mild regurgitation in 5 cases and moderate regurgitation in 1 case. Three patients required temporary pacing during the procedure due to complete heart block, among whom 1 patient was implanted with permanent pacemaker during hospitalization, and the other 2 patients recovered within 24 hours after operation. In another case, there was no significant change of electrocardiogram during the operation, and complete heart block occurred 10 days after the operation, and treated with permanent pacemaker. The other 10 patients began to carry out bedside activities and rehabilitation training 24 hours after operation. There was no death, myocardial infarction, stroke and other major adverse cardiac events during hospitalization and at 3-month follow-up after discharge. Conclusion: Left ventricular guidewire pacing is a safe and effective strategy for TAVR.

Feasibility of single-stage stent implantation following rotational atherectomy combined with TAVR / 中华心血管病杂志

Objective: To explore the feasibility of the single-stage stent implantation following rotational atherectomy combined with transcatheter aortic valve replacement (TAVR) in treating patients with severe aortic stenosis(AS) and severe calcified coronary artery stenosis. Methods: Three patients who received single-stage stent implantation following rotational atherectomy combined with TAVR in Fuwai hospital from April to October 2019 were included in this retrospective analysis. Clinical and anatomical features (including echocardiography and aortic CT) of the patients were collected, efficacy and safety of this operation strategy were observed and 6 months follow up results were summarized. Results: Three patients (2 females, 66-80 years old) were included. The mean Society of Thoracic Surgeons (STS) risk score was 7.8%. The mean maximum velocity of aortic valve was 4.4 m/s, the mean transvalvular pressure gradient was 53.2 mmHg (1 mmHg=0.133 kPa), mean left ventricular ejection fraction (LVEF) was 48.6%. All three patients had severe calcified coronary artery stenosis: left anterior descending artery (LAD, n=2) and left main coronary artery (LM, n=1), requiring rotary grinding. The mean SYNTAX score was 20. All the procedures were performed through transfemoral access. After aortic valve crossing, all coronary lesions were successfully treated with stent implantation following rotational atherectomy, transfemoral TAVR was then immediately performed with a self-expandable Venus-A valve. One patient underwent"valve-in-valve"implantation due to the high-implantation position of the first valve. The procedures were completed without complications in all the three patients. The immediate effect was satisfactory. Echocardiography results showed that the mean maximum velocity of aortic valve was 2.1 m/s, mean gradient was 9.3 mmHg, and mean LVEF was 59% after the procedure. There was no death and revascularization during the 6 months follow-up. Conclusion: In patients with severe calcified coronary artery and severe AS with high risk of cardiac surgery, the single-stage stent implantation following rotational atherectomy combined with TAVR is feasible and results are satisfactory in this patient cohort.

Safety and feasibility of carotid artery stenting in patients with coexisting carotid and coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the safety and feasibility of carotid artery stenting (CAS) for treating patients with coexisting carotid and coronary artery disease.</p><p><b>METHODS</b>The clinical data of 237 consecutive patients [(66.1 ± 7.7) years old, 79.7% male] with coexisting carotid and coronary artery disease undergoing CAS in Fuwai hospital from January 2005 to June 2010. The patients were analyzed retrospectively.Indication for CAS was defined as carotid artery diameter reduction of > 60% (symptomatic) or > 80% (asymptomatic) with suitable carotid artery anatomy for stenting. Thirty-day rates of stroke, death and myocardial infarction after CAS were assessed.</p><p><b>RESULTS</b>All patients suffered from coronary artery disease, of whom 87(36.7%) had unstable angina pectoris and 82(34.6%) had recent myocardial infarction (< 30 days). The procedural success rate of CAS was 99.2 % (235/237). Cerebral protection devices were used in 234 patients (99.6%). Among them, 36(15.2%) patients received simultaneous bilateral CAS and 79(33.3%) patients underwent simultaneous percutaneous intervention of other non-coronary arteries.Within 30 days after CAS, 127(53.6%) patients underwent coronary revascularization, including 118(49.6%) coronary artery bypass grafting and 9 (3.8%) percutaneous coronary intervention. The rate of major stroke, minor stroke, death and myocardial infarction from time of CAS to 30 days was 2.1% (5/237), 3.0% (7/237),0.4% (1/237) and 0.4% (1/237) respectively.</p><p><b>CONCLUSION</b>Data from this study indicate that CAS is safe and feasible for treating patients with coexisting carotid and coronary artery disease with a low incidence of periprocedural complication rate.</p>

Clinical analysis of simultaneous bilateral carotid stenting for treating patients with bilateral atherosclerotic carotid stenosis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the safety and feasibility of simultaneous bilateral carotid stenting for treating patients with bilateral atherosclerotic carotid stenosis.</p><p><b>METHODS</b>The clinical data of 39 consecutive patients with bilateral atherosclerotic carotid stenosis undergoing simultaneous bilateral carotid artery stenting in Fuwai hospital from January 2005 to December 2009 were collected and analyzed retrospectively. The reduction of the angiographic diameter stenosis after stenting and clinical outcomes of 30 days after stenting including hyperperfusion syndrome, hemodynamic depression, stroke, myocardial infarction and death were assessed.</p><p><b>RESULTS</b>The patients were 43 - 78 (65.9 ± 8.5) years old, and there were 25 (64.1%) male. Carotid stenting procedure success rate was 100%. Distal embolic protection devices were used in all patients, and 20 (51.3%) out of 39 patients underwent coronary artery bypass surgery after carotid stenting. The angiographic diameter stenosis reduced from (87.0 ± 5.8)% to (10.2 ± 5.6)% after stenting (P < 0.01). Up to 30 days after carotid artery stenting, the incidence of hyperperfusion syndrome, hemodynamic depression, minor stroke, major stroke, myocardial infarction and death was 2.6% (1/39), 28.2% (11/39), 5.1% (2/29), 0, 2.6% (1/39), 2.6% (1/39), respectively.</p><p><b>CONCLUSION</b>The data show that simultaneous bilateral carotid stenting is a technically feasible and safe alternative for patients with severe bilateral atherosclerotic carotid stenosis.</p>

Clinical and angiographic correlates of left ventricular dysfunction in patients with three vessel coronary disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Among patients with advanced multivessel coronary disease, left ventricular (LV) function is widely variable, and clinical and angiographic correlates of ventricular dysfunction remain to be defined.</p><p><b>METHODS</b>Among 73 339 patients undergoing diagnostic cardiac catheterization at a single center in China, patients with left ventriculographic assessment were identified with three-vessel coronary disease with or without left main involvement. Clinical and angiographic characteristics were examined among patients with normal or varying extent of LV dysfunction, and predictors of LV impairment (ejection fraction (EF): < 25%, 25% - 40% or > 40%) were determined.</p><p><b>RESULTS</b>Among 11 950 patients identified with three-vessel coronary disease, the sample distribution of LVEF was > 40%, n = 10 776; 25% - 40%, n = 948; < 25%, n = 226. Patients with reduced LV function (< 40%) more commonly were male and had a history of myocardial infarction (MI), diabetes or unstable angina. Hypertension was more frequent in those with LVEF ≥ 40%. In a multivariate Logistic regression analysis, prior MI (odds ratio (OR), 3.37; 95% confidence interval (CI), 2.96 - 3.84) was most predictive of LVEF < 40%, followed by male gender, diabetes, and presentation with unstable angina. For LVEF < 25%, only prior MI was identified as a significant correlate of severe LV dysfunction (OR 4.06, 95%CI 3.06 - 5.39). Following exclusion of patients with previous MI (n = 7416), male gender and diabetes were predictive of LVEF < 40%, yet presentation with unstable angina was the only factor significantly associated with LVEF < 25%.</p><p><b>CONCLUSION</b>Among individuals identified with three-vessel coronary disease with or without left main involvement, previous MI was the most significant risk factor of LV dysfunction.</p>

Readthrough of nonsense mutation W822X in the SCN5A gene can effectively restore expression of cardiac Na+ channels W822X / 中华心血管病杂志

<p><b>OBJECTIVE</b>In this study we investigated the functional restoration of nonsense mutations in the SCN5A gene.</p><p><b>METHODS</b>The readthrough-enhancing reagents were introduced to HEK293 cells to suppress one nonsense mutation W822X in the SCN5A gene. Patch-clamp was used to record the whole-cell current and dynamics. Western blot and immunofluorescence staining were used to certify the expression and the location of the sodium channel.</p><p><b>RESULTS</b>In transfected HEK293 cells, the nonsense mutation in SCN5A inhibited the expression level of full-length protein, and the sodium currents from the mutant channels were less than 3% of the wild-type level. Readthrough enhancement by decreasing translation termination efficiency with a siRNA targeting eukaryotic release factor eRF3a (a GTPase that binds eRF1), the sodium current from the mutant cDNAs was restored to as much as 30% of the wild-type. After the treatment by the readthrough-enhancing reagents, the channels from cDNA carrying W822X remained the features of wild-type phenotype, and Western blot and immunochemical staining also showed the expression of full-length channel proteins.</p><p><b>CONCLUSION</b>Readthrough-enhancing reagents could effectively suppress nonsense mutations in SCN5A and partially restore the function of sodium channel and the expression of full-length channels.</p>

The Val606Met mutation of human beta myosin heavy chain in a Chinese familial hypertrophic cardiomyopathy family / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the disease-causing gene mutation in Chinese families with hypertrophic cardiomyopathy (HCM) and to analyze the correlation between the genotype and phenotype.</p><p><b>METHODS</b>Samples of peripheral blood were collected from three Chinese families with HCM (at least two HCM patients existed/family). The exons in the functional regions of the beta myosin heavy chain gene (MYH7) were amplified with PCR and the products were sequenced.</p><p><b>RESULTS</b>A Val606Met missen mutation was identified in the exon 16 of MYH7 gene in a Chinese family and this mutation was identified in all HCM patients (n = 4) and there was also a 15-years-old young mutation carrier who was not HCM patient now (penetrance of 80%). This mutation was not identified in other healthy family members in this family, in other 2 Chinese familiar HCM families and in 120 non-HCM control patients.</p><p><b>CONCLUSION</b>The Val606Met missen mutation is closely associated with familiar HCM in a Chinese family which is associated with clinical phenotype with a penetrance of 80%.</p>

Electrocardiogram analysis in high risk population of unexplained sudden death in Yunnan province / 中华心血管病杂志

<p><b>OBJECTIVE</b>The purpose of this study was to analyze the electrocardiographic features of the people living in the area with high incidence of unexplained sudden deaths in Yunnan province.</p><p><b>METHOD</b>The electrocardiograms of 338 residents from three villages (Dayao, Ninglang, Heqing) with high incidence of unexplained sudden deaths and one control village (Dali) were analyzed [averaged age was (33.4 +/- 11.7) years, 175 men and 163 women].</p><p><b>RESULTS</b>The incidence of cardiac arrhythmias was similar low in all groups. The left ventricular hypertrophy was observed in 34.6% of residents from Dayao. QTc significantly prolonged in the residents from all 3 high incidence areas compare the control area of Dali [control (386.8 +/- 27.22) ms, Ninglang (428.92 +/- 25.71) ms, Heqing (440.67 +/- 28.03) ms, Dayao (417.7 +/- 24.00) ms, P < 0.05 vs. control]. Incidence of U wave was significantly higher in Heqing village than that in control village (P < 0.05). The QUc of these 3 villages was: (613.67 +/- 37.34) ms, (597.19 +/- 46.47) ms, (608.59 +/- 39.59) ms respectively, and also significantly longer than the control village of Dali (589.33 +/- 41.27) ms (P < 0.05). The typical pattern of U wave presents as enlarged U wave and apparent T-U complex. In the 7 residents who have the family history of unexplained sudden death, 6 residents have U wave, and 4 of them present typical U wave pattern.</p><p><b>CONCLUSION</b>The significant ECG changes in villages with high incidence of unexplained sudden death in Yunnan province were prolonged QTc, enlarged U wave and apparent T-U complex and these ECG features suggested the repolarization abnormalities of the heart in these subjects.</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>

Electrophysiological characterization of long QT syndrome associated mutations V630A and N633S / 中华心血管病杂志

<p><b>OBJECTIVE</b>To identify the electrophysiological properties of long-QT syndrome (LQTS) associated missense mutations in the outer mouth of the HERG potassium channel in vitro.</p><p><b>METHODS</b>Mutations V630A and N633S were constructed by Megaprimer PCR method and cRNA were produced by T7 RNA polymerase. The electrophysiological properties of the mutation were investigated in the Xenopus oocyte heterologous expression system.</p><p><b>RESULTS</b>Coexpression of mutant and wild-type HERG subunits caused a dominant-negative effect, and the currents were significantly decreased. Compared with wild-type HERG channels, V630A and N633S mutations were related to decreased time constants for inactivation for V630A/WT and N633S/WT at all potentials, reduced slope conductance and the voltage dependence of steady-state inactivation was shifted to negative potentials for V630A/WT and N633S/WT.</p><p><b>CONCLUSION</b>Present study shows that LQTS associated missense mutations located in the outer mouth of HERG cause a dominant-negative effect and alterations in steady-state voltage dependence of channel gating of heteromultimeric channels suggesting a reduction in expressional current might be one of the pathophysiologic mechanisms of LQTS.</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>

The association of single nucleotide polymorphism of slow delayed rectifier K+ channel genes with atrial fibrillation in Han nationality Chinese / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between atrial fibrillation and the single nucleotide polymorphism (SNP) of slow delayed rectifier K(+) channel (I(Ks)) genes in Han nationality Chinese.</p><p><b>METHODS</b>Three hundred and eighty of Han nationality Chinese (142 atrial fibrillation, 120 in-hospital and 118 out-hospital control) were enrolled in this study. Asian specific non-synonymous SNPs of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N were genotyped by restriction fragment length polymorphism analysis. A newly cloned KCNE4 gene was also screened for any possible SNP.</p><p><b>RESULTS</b>The minor allele frequency of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N in out-hospital subjects was 0.079, 0, 0.042, 0.317 and 0.004, respectively. None of these SNPs was relationed with any atrial fibrillation phenotype. A KCNE4 E145D was discovered and proven statistically to relation significantly to atrial fibrillation by logistic regression analysis (OR = 1.66, P = 0.044). The minor allele frequency of KCNE4 E145D was as high as 0.271 in out-hospital subjects.</p><p><b>CONCLUSIONS</b>None of the SNPs of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N was associated with atrial fibrillation phenotype, but KCNE4 E145D may relation to atrial fibrillation. The effect of KCNE4 E145D variation on the function of I(Ks) channel is to be determined.</p>