Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial / 中华心血管病杂志

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.

Efficacy of Radiofrequency Ablation of Atrial Tachycardia Originating From the Non-coronary Aortic Cusp Guided by Three-dimensional Mapping in 11 Patients / 中国循环杂志

Objectives: To analyze the electrophysiological mapping characteristic and evaluate the effect of radiofrequency ablation in atrial tachycardia (AT) originating from the non-coronary aortic cusp (NCC). Methods: Data from 11 patients with AT originated from NCC and underwent electrophysiological mapping and radiofrequency ablation under the guidance of three-dimensional mapping system were analyzed. The electrical anatomical model of right atrium, His bundle and the root of the aorta was constructed during the procedure to measure the distance between the earliest atrial activation and His bundle. Ablation was performed at the earliest atrial activation site. Results: Cardiac electrophysiological examination evidenced the focal originating of AT in all 11 cases, right atrial activation mapping showed that all the earliest activation site was located in the left or left upper posterior of His bundle, activation time was (21.0 ± 7.9) ms prior to coronary sinus proximal reference wave A, the distance between the earliest activation site and the His bundle was (6.9 ± 3.4) mm. Aortic root mapping showed that the earliest activation sites were all located in the NCC, activation time was (35.0 ± 8.6) ms prior to coronary sinus proximal reference wave A, the distance between the earliest activation site and His bundle was (7.3 ± 4.6) mm. AT in all 11 patients were terminated after ablation, Post ablation, AT could no longer be induced by repeated stimulations. No atrioventricular conduction block occurred during and after operation. No AT recurrences were observed in all 11 patients during the 6 months follow-up. Conclusions: The success rate and safety of three-dimensional mapping guided ablation of AT originated from NCC are high. The main point of the mapping, which is crucial for the successful ablation, is that if the earliest atrial activation site of AT is located at left or left upper posterior of His bundle, it is mandatory to perform aortic root mapping and to routinely determine whether NCC is the earliest activation site of AT.

Prevalence and risk factors of atrial fibrillation in hospitalized patients with chronic kidney disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>Atrial fibrillation (AF) is the most common sustained tachyarrhythmia in the general population. AF and Chronic Kidney Disease (CKD) share several common risk factors. We investigated the association between chronic kidney disease and risk of atrial fibrillation in hospitalized patients with CKD.</p><p><b>METHODS</b>One thousand one hundred and sixty-eight patients [(63.3 ± 14.2) years, 54.5% males] hospitalized CKD patients were included. AF was determined by electrocardiogram or medical history. The prevalence of atrial fibrillation was compared in CKD patients with various age, sex and glomerular filtration rate (eGFR). Binary logistic regression analysis was used to determine the risk factors of AF.</p><p><b>RESULT</b>The mean eGFR was (22.2 ± 19.7) ml · min(-1) · 1.73 m(-2); eGFR was ≤ 45 ml · min(-1) · 1.73 m(-2) in 84.2% patients and 38.5% patients received hemodialysis. AF was present in 14.2% of the study population and 17.2% in patients ≥ 60 years old. Prevalence of AF was significantly higher in patients with eGFR ≤ 45 ml · min(-1) · 1.73 m(-2) compared patients with eGFR > 45 ml · min(-1) · 1.73 m(-2) (15.8% vs. 5.4%, P < 0.001). Binary logistic regression analysis showed that age, body mass index (BMI), heart failure (HF), left atrial diameter (LAD), eGFR and dialysis were independent risk factors for AF.</p><p><b>CONCLUSIONS</b>AF is much more frequent in CKD patients than in the general population. Age, BMI, HF, LAD, eGFR and dialysis are risk factors for AF in hospitalized patients with CKD.</p>

Efficacy of rate and rhythm control strategy in patients with atrial fibrillation: meta-analysis / 中华心血管病杂志

<p><b>OBJECTIVE</b>The efficacy of rate and rhythm control strategies for treating atrial fibrillation (AF) patients was analyzed in this meta-analysis.</p><p><b>METHODS</b>Eligible trials were searched in MEDLINE, the Cochrane Library, the Clinical Trials, the Chinese VIP database up to May 31, 2010. Ten prospective randomized control trials with 7876 patients (rate control n = 3932, rhythm control n = 3944) were included for final analysis.</p><p><b>RESULTS</b>All cause mortality (5.3% vs. 5.0%; OR: 1.03; 95%CI: 0.84 - 1.26; I(2) < 25%) and incidence of worsening heart failure (3.81% vs. 3.61%; OR: 1.04; 95%CI: 0.80 - 1.36; I(2) < 50%) were similar between the two groups. Subgroup analysis showed that all cause mortality (3.6% vs.1.9%; OR: 1.89; 95%CI: 1.01 - 3.53; I(2) < 25%) and rate of worsening heart failure (2.3% vs. 0.3%; OR: 5.6; 95%CI: 1.44 - 21.69; I(2) < 25%) were significantly higher in rate control group than in rhythm control group in patients with age < 65 years. Thromboembolic events (1.49% vs. 1.46%; OR: 1.02, 95%CI: 0.71 - 1.48) and bleeding events (1.78% vs. 1.73%; OR: 1.02, 95%CI: 0.70 - 1.49) were similar between rhythm control and rate control groups while rehospitalization rate was significantly lower in rate control group than in rhythm control group (17.56% vs. 22.98%; OR: 0.37, 95%CI: 0.19 - 0.71).</p><p><b>CONCLUSION</b>This meta-analysis shows that rhythm control strategy is superior to rate control strategy for AF patients with age < 65 years in terms of reducing all cause mortality and incidence of worsening heart failure.</p>

Predict value of clinical risk score, thrombolysis in myocardial infarction flow grade and combined clinical risk score plus TIMI flow on outcome evaluation of patients with acute coronary syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the prognostic value of clinical risk score and thrombolysis in myocardial infarction (TIMI) flow grade alone or combined on outcome of acute coronary syndrome (ACS).</p><p><b>METHODS</b>A total of 206 eligible patients [135 males, mean age (67.57 +/- 9.88) years] were enrolled. The primary endpoints included cardiac death and non-cardiac death. The secondary endpoints included non-fatal stroke, reinfarction, heart failure and recurrent angina. Receiver operating characteristic curve (ROC) established by using different endpoints and clinical risk score, TIMI flow grade or combined risk scores. The prognostic value for different endpoint expressed as the area under the curve (AUC).</p><p><b>RESULTS</b>Eleven patients lost during the (11.41 +/- 5.33) months follow up and data were available for 195 patients, 8 patients reached the primary endpoints, and 17 patients reached the secondary end-points at the end of follow up. The AUC was 0.67 (95% CI = 0.557 approximately 0.786), P = 0.006; 0.68 (95% CI = 0.557 approximately 0.786), P = 0.004 and 0.730 (95% CI = 0.691 approximately 0.815), P < 0.001, respectively for clinical risk score, TIMI flow grade and the combined risk score respectively. There were no significant differences among clinical risk score, TIMI flow grade and combined risk score (all P > 0.05) for AUC and for primary end point and the secondary end point.</p><p><b>CONCLUSION</b>The result from this study suggests that the efficacy of predicting the total events based on clinical risk score, TIMI flow grade and combined risk score was similar.</p>

Renin-angiotensin system blocking agents reverse the myocardial hypertrophy in experimental hyperthyroid cardiomyopathy via altering intracellular calcium handling / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the mechanisms of myocardial hypertrophy induced by Levothyroxine (L-Thy).</p><p><b>METHODS</b>A rabbit model of hyperthyroidism was established by daily intraperitoneal injections of L-Thy (45 microg/kg per day) for 28 days. New Zealand rabbits were randomly divided into four groups (n = 10 each): control group, L-Thy group (L-Thy alone), imidapril group (L-Thy + 0.5 mg/kg imidapril), and valsartan group (L-Thy + 8 mg/kg valsartan). All rabbits were treated for 4 weeks. At the end of the treatments, all rabbits underwent echocardiography and IVS, LV and LVPW thickness were measured. Ventricular tissues were then collected.Cardiac hypertrophy index, cardiomyocyte diameter, structural and ultrastructural changes were obtained. Ventricular myocytes were isolated by enzymatic digestion method and intracellular Ca2+ concentration was determined with the fluorescent Ca2+ indicator Fluo3/AM and laser scanning confocal microscopy. Activity of Sarco/Endoplasmic reticulum Ca2+ ATPase (SERCA) was evaluated with P-NPP method.mRNA expression of L-type Ca2+ channel (LCC), ryanodine receptor (RyR), and SERCA was semi-quantified with RT-PCR. Protein of IP3R was localized by immunostaining and semi-quantified with pathological image analytic system.</p><p><b>RESULTS</b>Compared with control group, rabbits treated with L-Thy displayed remarkable myocardial hypertrophy and morphological changes in both structure and ultrastructure levels. Increased intracellular Ca2+ concentration [(576.2 +/- 41.7) nmol/L vs. (314.6 +/- 35.6) nmol/L, P < 0.01] and decreased SERCA activity [(0.062 +/- 0.013) micromol x min(-1)xg(-1) vs. (0.133 +/- 0.022) micromol x min(-1)xg(-1), P < 0.01] were detected in L-Thy treated rabbits. RT-PCR analysis and (or) immunohistochemistry revealed decreased mRNA expression of LCC mRNA (0.48 +/- 0.11 vs. 0.75 +/- 0.16, P < 0.01) and increased RyR mRNA (1.19 +/- 0.21 vs. 0.73 +/- 0.15, P < 0.01), SERCA mRNA (1.01 +/- 0.08 vs. 0.76 +/- 0.09, P < 0.01) and IP3R protein (65.3 +/- 13.7 vs. 47.9 +/- 10.2, P < 0.01) expression in L-Thy treated rabbits. Both imidapril and valsartan could significantly attenuate cardiomyocyte hypertrophy and structural remodeling induced by L-Thy. Compared with L-Thy group, decreased intracellular Ca(2+) concentration [(376.4 +/- 32.5) nmol/L vs. (576.2 +/- 41.7) nmol/L, P < 0.01 and (392.6 +/- 41.2) nmol/L vs. (576.2 +/- 41.7) nmol/L, P < 0.01, respectively], and increased LCC mRNA (0.68 +/- 0.14 vs. 0.48 +/- 0.11, P < 0.01; 0.64 +/- 0.13 vs. 0.48 +/- 0.11, P < 0.01, respectively) and SERCA activity [(0.115 +/- 0.019) micromol x min(-1)xg(-1) vs. (0.062 +/- 0.013) micromol x min(-1)xg(-1), P < 0.01; (0.109 +/- 0.015) micromol x min(-1)xg(-1) vs. (0.062 +/- 0.013) micromol x min(-1)xg(-1), P < 0.01, respectively] were found in both imidapril and valsartan treated rabbits, but expression of RyR, SERCA and IP3R remained unchanged.</p><p><b>CONCLUSION</b>Intracellular Ca(2+) overload may play important roles in myocardial hypertrophy induced by L-Thy. Imidapril and valsartan may exert beneficial effects on hyperthyroid myocardial hypertrophy via altering intracellular calcium handling.</p>

Relationship between body mass index, waist circumference and blood pressure among 5246 residents in Chongqing area / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the relationship between body mass index, waist circumference and blood pressure among residents in Chongqing area.</p><p><b>METHODS</b>A total of 5246 residents aged 15 and over in Chongqing area were enrolled in this study by use of stratified sampling and cluster sampling methods. Data on blood pressure (SBP, DBP), pulse, height, body weight, waist and hip circumferences as well as questionnaire survey were analyzed.</p><p><b>RESULTS</b>The level of SBP and DBP and hypertension prevalence rate were significantly positively correlated with BMI (all P < 0.01). SBP, DBP levels and hypertension prevalence rate were significantly higher in people with abdomen obesity than people with normal waist circumference (all P < 0.01). BMI, waist circumference in hypertensive residents were significantly higher than non-hypertensive residents (all P < 0.01).</p><p><b>CONCLUSION</b>Blood pressure level and hypertension prevalence rate were closely related with BMI and waist circumference among residents in Chongqing area.</p>

Chronic effects on the prevention of atrial fibrillation recurrence in patients with lone paroxysmal atrial fibrillation treated with amiodarone, segmental pulmonary vein ablation, or amiodarone plus losartan: a prospective cohort study / 中华心血管病杂志

<p><b>OBJECTIVE</b>This study was designed to compare clinical efficacy of segmental pulmonary vein ablation (SPVI), amiodarone or amiodarone plus losartan on sinus rhythm maintenance in patients with lone paroxysmal atrial fibrillation (PAF).</p><p><b>METHODS</b>Patients with lone PAF were treated with amiodarone alone (A, n = 52), segmental pulmonary vein isolation (SPVI, n = 51), or amiodarone plus losartan (AL, n = 51). The primary endpoint of this study was the incidence of symptomatic atrial tachyarrhythmia (> 30 s) documented by 12 lead ECG or Holter during 12 months follow-up period.</p><p><b>RESULTS</b>During follow-up, AF was documented in 24 patients (46.2%) in A group, 11 patients (21.6%) in SPVI group and 12 (23.5%) in AL group (P < 0.05 vs. A group). The Kaplan-Meier survival analysis demonstrated a significant equally reduction in AF recurrence in SPVI and AL groups (P = 0.009, log-rank test and P = 0.018, log-rank test, respectively) compared with A group. The hazard ratio for AF recurrence in patients treated with SPVI and amiodarone plus losartan was 0.41 (95% CI 0.200 to 0.848, P = 0.016) and 0.46 (95% CI 0.225 to 0.953, P = 0.036), respectively. Incidences of major adverse cardiac events were similar among the groups (9.6% in A, 3.9% in SPVI and 7.8% in AL group, P > 0.05).</p><p><b>CONCLUSION</b>The results of this study suggest that the segmental pulmonary vein isolation and amiodarone plus losartan are superior to amiodarone alone for preventing AF recurrence in patients with lone PAF.</p>

Long-term clinical efficacy of losartan or perindopril combination therapy with low-dose amiodarone in patients with paroxysmal atrial fibrillation / 中华心血管病杂志

<p><b>OBJECTIVE</b>The purpose of the present study was to evaluate the clinical efficacy of perindopril or losartan in combination with low-dose amiodarone on maintenance of sinus rhythm in patients with idiopathic paroxysmal atrial fibrillation (PAF).</p><p><b>METHODS</b>One hundred and eighty-one patients with idiopathic PAF were included in the study and randomly divided into three groups: group 1 (amiodarone group, n = 61) was treated with amiodarone alone, group 2 (amiodarone plus losartan, n = 59) was treated with amiodarone and perindopril in combination, and group 3 (amiodarone plus perindopril group, n = 61) was treated with amiodarone and perindopril in combination. The left atrial diameter (LAD) was measured with transthoracic echocardiogram at before and after 6, 12, 18 and 24-month of treatment. The duration of observation was up to two years and the primary end point of the study was the first recurrence of AF.</p><p><b>RESULTS</b>During the 6 month following up, there was no difference in LAD among the three groups. After 12 months, LAD in group 1 was significantly larger than group 2 and group 3 (P < 0.05). At 7th-month, the sinus rhythm maintenance of group 1 was lower significantly than group 2 and group 3. At the end of the study, the maintenance of sinus rhythm in group 2 and group 3 was higher significantly than in group 1 (83.05% and 80.33% vs 59.01%, P < 0.05), nevertheless, there was no significant difference between group 2 and group 3.</p><p><b>CONCLUSIONS</b>The results of this study suggest that the combination of amiodarone with angiotensin converting enzyme inhibitor perindopril or with angiotensin II receptor antagonist losartan are more effective than amiodarone alone in sinus rhythm maintenance for idiopathic PAF. ACEI and ARB can inhibit the enlargement of left atrium and reduce recurrence rate in patients with idiopathic PAF.</p>