Effects of Acupuncture on Cardiac Remodeling in Patients with Persistent Atrial Fibrillation: Results of a Randomized, Placebo-Controlled, Patient- and Assessor-Blinded Pilot Trial and Its Implications for Future Research.

Background and Objectives: In this study, we attempted to determine the effects of acupuncture on cardiac remodeling and atrial fibrillation (AF) recurrence rates in patients with AF after electrical cardioversion (EC). Materials and Methods: We randomly assigned 44 patients with persistent AF to an acupuncture group or a sham acupuncture group. An electroacupuncture treatment session was administered once weekly for 12 weeks at four acupuncture points (left PC5, PC6, ST36, and ST37). Results: Among the 44 recruited participants, 16 (treatment group) and 15 (control group) completed the trial. The three-month AF recurrence rate (primary outcome) was not significantly different between the two groups. Following the completion of treatment, patients who had been treated with acupuncture had a significant reduction in left atrial volume index (42.2 ± 13.9 to 36.1 ± 9.7 mL/m2; p = 0.028), whereas no change in atrial size was observed in the sham acupuncture group. No serious adverse events were observed. The AF recurrence rate and cardiac function did not differ significantly between the two groups. At three months, the acupuncture treatment group showed more favorable atrial structural remodeling compared to the sham acupuncture group. Conclusion: In future research on acupuncture in AF management, it is recommended that the inclusion criteria be amended to include only symptomatic AF, that an appropriate control group is designed, and that the acupuncture treatment frequency is increased to several times per week.

The Electrical Isolation of the Left Atrial Posterior Wall in Catheter Ablation of Persistent Atrial Fibrillation.

OBJECTIVES: This study explored whether complete electrical isolation of the left atrial (LA) posterior wall improves the rhythm outcome of catheter ablation of persistent atrial fibrillation (AF). BACKGROUND: Although the STAR AF2 (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) proved no additional benefit of empirical extra-pulmonary vein (PV) LA ablation, the long-term recurrence rate after circumferential PV isolation (CPVI) alone remains high. METHODS: We randomly assigned 217 patients with persistent AF (83.1% men, age 58.7 ± 10.8 years, 73.3% long-standing persistent AF) to ablation with CPVI alone (CPVI group) or CPVI with a POsterior wall Box Isolation (POBI group). The endpoint of the POBI group was the elimination of the posterior atrial potentials by roof and posterior inferior lines and touch-up focal ablation. RESULTS: After a mean follow-up of 16.2 ± 8.8 months, the clinical recurrence rate did not significantly differ between the 2 groups (23.8% vs. 26.5%; p = 0.779) in the CPVI and POBI groups. The recurrence rate for atrial tachycardias (16.0% vs. 11.1%; p = 0.913) and cardioversion rates (6.7% vs. 13.7%; p = 0.093) to control clinical recurrences also did not significantly differ between the 2 groups. At the final follow-up, sinus rhythm was maintained without antiarrhythmic drug in 50.5% and 55.9% in the CPVI and POBI groups, respectively (p = 0.522). No significant difference was found in the major complication rates between the 2 groups, but the total ablation time was significantly longer in the POBI group (4,289 ± 1,837 s vs. 5,365 ± 2,358 s; p < 0.001). CONCLUSIONS: In patients with persistent AF, an empirical complete POBI did not improve the rhythm outcome of catheter ablation or influence the type of recurrent atrial arrhythmia. (Comparison of Circumferential Pulmonary Vein Isolation Alone Versus Linear Ablation in Addition to Circumferential Pulmonary Vein Isolation for Catheter Ablation in Persistent Atrial Fibrillation: Prospective Randomized Controlled Trial; NCT02721121).

Label Adherence for Non-Vitamin K Antagonist Oral Anticoagulants in a Prospective Cohort of Asian Patients with Atrial Fibrillation.

PURPOSE: Label adherence for non-vitamin K antagonist oral anticoagulants (NOACs) has not been well evaluated in Asian patients with non-valvular atrial fibrillation (AF). The present study aimed to assess label adherence for NOACs in a Korean AF population and to determine risk factors of off-label prescriptions of NOACs. MATERIALS AND METHODS: In this COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, patients with AF who were prescribed NOACs between June 2016 and May 2017 were included. Four NOAC doses were categorized as on- or off-label use according to Korea Food and Drug Regulations. RESULTS: We evaluated 3080 AF patients treated with NOACs (dabigatran 27.2%, rivaroxaban 23.9%, apixaban 36.9%, and edoxaban 12.0%). The mean age was 70.5±9.2 years; 56.0% were men; and the mean CHA2DS2-VASc score was 3.3±1.4. Only one-third of the patients (32.7%) was prescribed a standard dose of NOAC. More than one-third of the study population (n=1122, 36.4%) was prescribed an off-label reduced dose of NOAC. Compared to those with an on-label standard dosing, patients with an off-label reduced dose of NOAC were older (≥75 years), women, and had a lower body weight (≤60 kg), renal dysfunction (creatinine clearance ≤50 mL/min), previous stroke, previous bleeding, hypertension, concomitant dronedarone use, and anti-platelet use. CONCLUSION: In real-world practice, more than one-third of patients with NOAC prescriptions received an off-label reduced dose, which could result in an increased risk of stroke. Considering the high risk of stroke in these patients, on-label use of NOAC is recommended.

Electroacupuncture prevents endothelial dysfunction induced by ischemia-reperfusion injury via a cyclooxygenase-2-dependent mechanism: A randomized controlled crossover trial.

OBJECTIVE: Exploring clinically effective methods to reduce ischemia-reperfusion (IR) injury in humans is critical. Several drugs have shown protective effects, but studies using other interventions have been rare. Electroacupuncture (EA) has induced similar protection in several animal studies but no study has investigated how the effects could be translated and reproduced in humans. This study aimed to explore the potential effect and mechanisms of EA in IR-induced endothelial dysfunction in humans. METHODS: This is a prospective, randomized, crossover, sham-controlled trial consisting of two protocols. Protocol 1 was a crossover study to investigate the effect of EA on IR-induced endothelial dysfunction. Twenty healthy volunteers were randomly assigned to EA or sham EA (sham). Flow mediated dilation (FMD) of the brachial artery (BA), nitroglycerin-mediated endothelial independent dilation, blood pressure before and after IR were measured. In protocol 2, seven volunteers were administered COX-2 inhibitor celecoxib (200 mg orally twice daily) for five days. After consumption, volunteers underwent FMD before and after IR identical to protocol 1. RESULTS: In protocol 1, baseline BA diameter, Pre-IR BA diameter and FMD were similar between the two groups (p = NS). After IR, sham group showed significantly blunted FMD (Pre-IR: 11.41 ± 3.10%, Post-IR: 4.49 ± 2.04%, p < 0.001). However, EA protected this blunted FMD (Pre-IR: 10.96 ± 5.30%, Post-IR: 9.47 ± 5.23%, p = NS, p < 0.05 compared with sham EA after IR). In protocol 2, this protective effect was completely abolished by pre-treatment with celecoxib (Pre-IR: 11.05 ± 3.27%; Post-IR: 4.20 ± 1.68%, p = 0.001). CONCLUSION: EA may prevent IR-induced endothelial dysfunction via a COX-2 dependent mechanism.

Close look at the experiences of patients enrolled in a clinical trial of acupuncture treatment for atrial fibrillation in Korea: a qualitative study nested within a randomised controlled trial.

OBJECTIVE: To explore the experiences of patients with atrial fibrillation (AF) in the context of a prospective, two-parallel-armed, participant-blinded and assessor-blinded sham-controlled randomised trial. DESIGN: A nested qualitative study within an ongoing randomised controlled trial to explore acupuncture's antiarrhythmic effects on drug refractory acupuncture in persistent atrial fibrillation (AF) (ACU-AF trial). PARTICIPANTS: Participants were recruited using purposeful sampling and a maximum variation strategy with regard to treatment allocation (treatment or control) and protocol completion (completion or non-completion). SETTING: This was a single-centre in-depth interview qualitative study conducted at a tertiary-level university hospital in Seoul, Republic of Korea. RESULTS: Data saturation was reached after 8 participants. Thematic analysis identified that most patients were not aware of their condition until medical check-up; physician referral was the main reason for trial participation, and patients had high expectations regardless of previous acupuncture experiences. Patients tended to depend on their physicians' opinions because they felt helpless of their condition. No one questioned their assigned treatment groups and generally believed acupuncture treatment was different for cardiovascular diseases. A few patients expressed disappointment in the strict and rigid protocols, in which most practitioners refrained from explaining their acupuncture procedures. CONCLUSIONS: For cardiovascular patients their physician's advice was one of the biggest reasons for enrolling in the acupuncture trial therefore relying on standard recruitment methods may not be effective. Fortunately both real and sham acupuncture groups in our sample were receiving treatment as intended, but in the future, designing a more pragmatic trial (better reflecting clinical settings, expanding the inclusion criteria and using more treatment points) will allow researchers to better explore the comprehensive effects of acupuncture. The findings of this study will allow researchers to improve the currently ongoing ACU-AF trial and to further help interpretation of main trial outcomes once the trial is completed. TRIAL REGISTRATION NUMBER: NCT02110537.

Effect of Coffee Added to a Polyethylene glycol plus Ascorbic acid Solution for Bowel Preparation prior to Colonoscopy.

BACKGROUND AND AIMS: Conventional bowel cleansers for colonoscopy have an unpleasant taste and a large volume of solution must be ingested. Coffee increases bowel motility and has an intense flavor. The addition of coffee to a polyethylene glycol+ascorbic acid solution reduces the volume of the solution to be consumed without reducing efficacy, improves the taste of the solution and enhances patient comfort. METHODS: Outpatients with clinical indication or people who wanted screening for cancer were considered eligible. Control group (PEGAS group) consumed a 1-L solution of polyethylene glycol+ascorbic acid twice. Study group (COF group) consumed 750 mL of coffee+polyethylene glycol+ascorbic acid twice. Bowel cleansing was rated using the Aronchick, Ottawa scale, polyp detection rate and colonoscopic insertion time. Tolerability, acceptability, preference, and adverse events were investigated by questionnaires. RESULTS: The COF group had non-inferiority in efficacy (non-inferiority margin, -15%; lower limit of 95% confidence interval for difference between success rates, -4.7% and -8.4% from both scales, respectively). Polyp detection rates were 0.48 and 0.60, respectively (P=0.067). Colonoscopic insertion times were 323.6+/-166.8 s and 330.7+/-243.6 s, respectively (P=0.831). Significant improvement was observed with respect to ease of drinking (P=0.012), taste (P=0.026) and preference (P=0.046) in the COF group. Adverse events occurred in 52.4% and 60.4% in the two groups, respectively (P = 0.251). CONCLUSION: The addition of coffee to polyethylene glycol+ascorbic acid solution reduces the required volume for bowel preparation without reduced efficacy and enhances patient comfort in coffee-drinkers.

Effects of electroacupuncture on endothelial function and circulating endothelial progenitor cells in patients with cerebral infarction.

This study evaluated the effects of electroacupuncture (EA) on endothelial function and endothelial progenitor cells (EPC) in patients with cerebral infarction. In a randomized, placebo-controlled, crossover study, 20 patients with cerebral infarction were randomized into two treatment groups: EA or placebo. Before and after each intervention, pulse amplitude tonometry (PAT) was used to assess endothelial function and peripheral blood was analyzed for the number of EPCs. Circulating EPCs were quantified by flow cytometry as CD45(low) CD34(+) KDR2(+) cells. Plasma vascular endothelial growth factor (VEGF) and interleukin (IL)-10 levels were measured. Seven days later, crossover was performed on each group, with each group receiving the other treatment using the same protocol. The PAT hyperemia ratio ranged from 1.57 ± 0.41 to 2.04 ± 0.51 after EA, representing a significant improvement (P = 0.002); however, there was no improvement in the placebo group (P = 0.48). Circulating EPCs, as measured by flow cytometry, increased to 110.6 ± 74.3/100 µL in the EA group (P = 0.001) but did not change in the placebo group (45.9 ± 35.3/100 µL, P = 0.08). The increases in the number of EPCs and the PAT ratio after treatment were correlated (r = 0.78, P < 0.001). Plasma VEGF levels increased with EA compared to baseline (261.2 ± 34.0 vs 334.9 ± 80.5 pg/mL, P = 0.003). The number of circulating EPCs was positively correlated with plasma levels of VEGF (r = 0.50, P = 0.02). In conclusion, EA induced improvement of EPC levels and the PAT ratio in patients with cerebral infarction.

Acupuncture antiarrhythmic effects on drug refractory persistent atrial fibrillation: study protocol for a randomized, controlled trial.

Background. Atrial fibrillation (AF) is the most common form of arrhythmia. Several trials have suggested that acupuncture may prevent AF. However, the efficacy of acupuncture for AF prevention has not been well investigated. Therefore, we designed a prospective, two-parallel-armed, participant and assessor blinded, randomized, sham-controlled clinical trial to investigate acupuncture in persistent AF (ACU-AF). Methods. A total of 80 participants will be randomly assigned to active acupuncture or sham acupuncture groups in a 1 : 1 ratio. Both groups will take the same antiarrhythmic medication during the study period. Patients will receive 10 sessions of acupuncture treatment once a week for 10 weeks. The primary endpoint is AF recurrence rate. Secondary endpoints are left atrium (LA) and left atrial appendage (LAA) changes in function and volume, and inflammatory biomarker changes. Ethics. This study protocol was approved by the institutional review boards (IRBs) of Kyung Hee University Hospital (number 1335-04). This trial is registered with clinicaltrials.gov NCT02110537.

Additional Effects of Back-Shu Electroacupuncture and Moxibustion in Cardioprotection of Rat Ischemia-Reperfusion Injury.

Many preclinical studies show that electroacupuncture (EA) on PC6 and ST36 can reduce infarct size after ischemia-reperfusion (IR) injury. Yet studies to enhance the treatment effect size are limited. The purpose of this study was to explore whether EA has additional myocardial protective effects on an ischemia-reperfusion (IR) injury rat model when back-shu EA and moxibustion are added. SD rats were divided into several groups and treated with either EA only, EA + back-shu EA (B), or EA + B + moxibustion (M) for 5 consecutive days. Transthoracic echocardiography and molecular and immunohistochemical evaluations were performed. It was found that although myocardial infarct areas were significantly lower and cardiac function was also significantly preserved in the three treatment groups compared to the placebo group, there were no additional differences between the three treatment groups. In addition, HSP20 and HSP27 were expressed significantly more in the treatment groups. The results suggest that adding several treatments does not necessarily increase protection. Our study corroborates previous findings that more treatment, such as prolonging EA duration or increasing EA intensity, does not always lead to better results. Other methods of increasing treatment effect size should be explored.