BACKGROUNDRenin-angiotensin-aldosterone system has been demonstrated to be associated with both congestive heart failure (CHF) and atrial fibrillation (AF). This study investigated the effects of spironolactone, a kind of aldosterone antagonist, on atrial electrical remodeling and fibrosis in CHF dogs induced by chronic rapid ventricular pacing.

METHODSTwenty one dogs were randomly divided into sham-operated group, control group, and spironolactone group. In control group and spironolactone group, dogs were ventricular paced at 220 beats per minute for 6 weeks. Additionally, spironolactone at 15 mg x kg(-1) x d(-1) was given to dogs 1 week before rapid ventricular pacing until pacing stopped. Transthoracic and transoesophageal echocardiographic examinations were performed to detect structural and functional changes of the atrium. Swan2 Ganz floating catheters were used to measure hemadynamics variances. Atrial effective refractory period (AERP), AERP dispersion (AERPd), intra- and inter-atrium conduction time (CT) and intra-atrium conduction velocity (CV) were determined. The inducibility and duration of AF were also measured in all groups. Finally, atrial fibrosis was quantified with Masson staining.

RESULTSAERP did not change significantly after dogs were ventricular paced for 6 weeks. However, AERPd, intra- and inter-atrium CT increased significantly, and CV decreased apparently, which was negatively correlated to the atrial fibrosis (r = -0.74, P < 0.05). Simultaneously, left atriums were enlarged and cardiac hemadynamics worsened in pacing dogs. Although spironolactone could not affect cardiac hemadynamics effectively, it can obviously improve left atrial ejection fraction (P < 0.05). Spironolactone treatment did not alter AERP duration, but this medicine dramatically decreased AERPd (P < 0.05), shortened intra- and inter-atrium conduction time (P < 0.05), and increased atrium CV. Moreover, spironolactone decreased the inducibility and duration of AF (P < 0.05), as well as atrial fibrosis (P < 0.01) induced by chronic rapid ventricular pacing.

CONCLUSIONSpironolactone contributes to AF prevention in congestive heart failure dogs induced by chronic rapid ventricular pacing, which is related to atrial fibrosis reduction and independent of hemadynamics.

Animals ; Atrial Fibrillation ; prevention & control ; Cardiac Volume ; Collagen ; analysis ; Dogs ; Heart Atria ; drug effects ; pathology ; physiopathology ; Heart Failure ; drug therapy ; pathology ; physiopathology ; Hemodynamics ; drug effects ; Spironolactone ; therapeutic use

BACKGROUNDAtrial electrical remodeling (AER) contributes to the maintainance of atrial fibrillation (AF). This study was to compare the effects of Losartan with those of Diltiazem on tachycardia-induced acute AER in rabbits.

METHODSTwenty-one rabbits paced with maximal atrial capture rate for 3 hours in the right atrium (RA) were randomly divided into saline group, Diltiazem group and Losartan group. After autonomic blockage, we measured atrial effective refractory period (AERP), AERP rate adapting feature, AERP dispersion and RA conduction time at basic cycle lengths (BCLs) of 200 ms and 150 ms at baseline, 0.5 hour, 1 hour, 2 and 3 hours after rapid atrial pacing.

RESULTSIn the saline group, there was a prompt decrease in AERP as a result of rapid atrial pacing, and AERP200 and AERP150 were shortened sharply within 0.5 hour of pacing (30.2 +/- 10.5 ms and 24.1 +/- 9.1 ms, respectively). The AERP did not change dramatically in the Diltiazem and Losartan groups. In the saline group, the value of (AERP200-AERP150)/50 ms in high RA was 0.17 +/- 0.08 at baseline and became significantly smaller at 0.5 hour (0.08 +/- 0.06), 1 hour (0.09 +/- 0.06), 2 hours (0.08 +/- 0.04) and 3 hours (0.09 +/- 0.05) (all P < 0.05), suggesting a reduction of rate adaptation of AERP. The value of (AERP200-AERP150)/50 ms in high RA did not change during the 3 hours of pacing in both Diltiazem and Losartan groups. In the saline group, AERP dispersion increased significantly at 2 and 3 hours (P < 0.05). However, Diltiazem could not prevent the increase of AERP dispersion at 3 hours (P < 0.05). During Losartan infusion, the AERP dispersion was no longer increased after rapid atrial pacing. There was no significant difference in RA conduction time among the three groups.

CONCLUSIONLike calcium antagonist Diltiazem, Losartan could prevent AERP shortening and preserve rate adaptation of AERP after rapid atrial pacing. Losartan is more effective than Diltiazem in inhibiting the increase of AERP dispersion.

Animals ; Atrial Fibrillation ; drug therapy ; physiopathology ; Calcium ; metabolism ; Cardiac Pacing, Artificial ; Diltiazem ; pharmacology ; Heart Conduction System ; drug effects ; physiopathology ; Losartan ; pharmacology ; Rabbits ; Refractory Period, Electrophysiological ; drug effects

PURPOSE: Comparisons of rhythm and rate control strategies for stroke prevention in patients with atrial fibrillation (AF) are still inconclusive. We compared differences in clinical outcomes between the rhythm and rate control strategies. MATERIALS AND METHODS: The COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry prospectively enrolled 6000 patients who were treated for AF using real-world guideline adherence at multiple referral centers. In total, 2508 (41.8%) patients were clinically followed up for over six months. Of these, 1134 (45.2 %) patients treated by rhythm control and 1374 (54.8 %) patients treated by rate control were analyzed for clinical outcomes, including stroke and cardiovascular outcomes. RESULTS: Among all patients (age, 68±10 years; male, 62.4%), those treated with the rhythm control strategy were significantly younger, had more symptomatic paroxysmal AF, and a shorter AF duration, and were less likely to have diabetes, renal dysfunction, and heart failure, compared to those treated with the rate control strategy (CHA₂DS₂-VASc score 2.4±1.5 vs. 3.1±1.7, p < 0.001). Even though oral anticoagulation was similarly prescribed in both groups, occurrence of stroke was less likely to occur in the rhythm control strategy group (0.0% vs. 0.7%, p=0.015). Multivariate Cox hazard regression showed that only age, especially more than 75 years old, were significantly correlated with the occurrence of stroke, regardless of the strategy used for treatment. CONCLUSION: In this prospective AF cohort, compared with the rate control strategy, the rhythm control strategy was associated with fewer cardiovascular events and strokes in a short-term period.
Administration, Oral ; Aged ; Antithrombins/administration & dosage/therapeutic use ; Atrial Fibrillation/drug therapy/*physiopathology ; Female ; Heart Rate/*physiology ; Humans ; Kaplan-Meier Estimate ; Male ; Proportional Hazards Models ; Prospective Studies ; Stroke/drug therapy/*etiology/*physiopathology ; Treatment Outcome

BACKGROUNDLong-term maintenance of sinus rhythm after successful conversion of chronic atrial fibrillation (CAF), often ameliorates patients' symptoms, reduces the risk of ischemic stroke and improves cardiovascular hemodynamics. This prospective study aims to evaluate the long-term efficacy and safety of very low-dose amiodarone (100 mg daily) for the maintenance of sinus rhythm after successful direct-current (DC) cardioversion in patients with CAF and rheumatic heart disease (RHD) post intervention.

METHODSThis study was a randomized prospective trial. One day after successful DC cardioversion (remained normal sinus rhythm) in patients with CAF and RHD post intervention for more than six months and adequate anticoagulation, all were randomly administered either amiodarone 200 mg daily in group A or amiodarone 100 mg daily in group B.

RESULTSA total of 76 patients (40 men and 36 women) were examined from February 1998 to December 1999. The mean age of the patients was (66 +/- 10) years, and the mean follow-up was (67 +/- 8) months (range 61 to 84 months). Actuarial rates of the maintenance of sinus rhythm were similar in the two groups after 5 years of follow-up. Four patients (11%) in group A but none in group B experienced significant adverse effects that necessitated withdrawal of amiodarone. No death occurred during the study period.

CONCLUSIONA very low dose of amiodarone results in adequate long-term efficacy and is safe for maintaining sinus rhythm in patients with CAF and RHD post intervention after successful DC cardioversion.

Aged ; Amiodarone ; administration & dosage ; adverse effects ; Anti-Arrhythmia Agents ; administration & dosage ; Arrhythmia, Sinus ; drug therapy ; Atrial Fibrillation ; drug therapy ; physiopathology ; Chronic Disease ; Cohort Studies ; Electric Countershock ; methods ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies

OBJECTIVETo investigate the effect of cilazapril on endothelial cell function and fibrinolysis system in the canine atrial fibrillation (AF) models.

METHODSAll canines were divided into three groups: (1) Control group, without atrial pacing; (2) Atrial pacing group, in which atrial fibrillation was established by rapid atrial pacing at 400 bpm for 6 weeks; (3) Atrial pacing together with cilazapril group, in which cilazapril was given before and after atrial pacing. Nitric oxide (NO) of atrial endocardium was measured with NO-specific microelectrode. The expression of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) protein in atrium was determined by Western Blot analysis and immunohistochemical staining. Plasma levels of von Willebrand Factor (vWF), PAI-1 and tPA were analyzed by enzyme-linked immunoadsorbent assay.

RESULTSNO production from atrial endocardium was significantly increased in atrial pacing together with cilazapril group than atrial pacing group [(42.6 +/- 9.9) nmol/L vs (23.4 +/- 5.8) nmol/L, P < 0.05], whereas the plasma levels of vWF were decreased [(75.4 +/- 12.8)% vs (125.9 +/- 20.6)%, P < 0.05]. Compared to controls, the expression of atrium tPA protein in atrial pacing together with cilazapril group was significantly upregulated (4052 +/- 857 vs 1936 +/- 421, P < 0.05) and PAI-1 protein was downregulated (2487 +/- 542 vs 3164 +/- 827, P < 0.05). Cilazapril also significantly increased tPA antigen and decreased PAI-1 antigen in plasma.

CONCLUSIONCilazapril can favorably improve endothelial function and resume the balance of fibrinolysis system in AF, which might be of beneficial to hypercoagulated state in AF.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Atrial Fibrillation ; blood ; drug therapy ; physiopathology ; Cilazapril ; pharmacology ; Disease Models, Animal ; Dogs ; Endothelial Cells ; drug effects ; physiology ; Female ; Fibrinolysis ; drug effects ; Immunohistochemistry ; Male ; Plasminogen Activator Inhibitor 1 ; analysis ; Tissue Plasminogen Activator ; analysis

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Atrial Fibrillation ; blood ; drug therapy ; physiopathology ; Cilazapril ; pharmacology ; Dogs ; Echocardiography ; Endothelial Cells ; drug effects ; physiology ; Fibrinolysis ; drug effects ; Nitric Oxide ; biosynthesis ; Plasminogen Activator Inhibitor 1 ; analysis ; Tissue Plasminogen Activator ; analysis

BACKGROUNDWarfarin is the most common oral anticoagulant to decrease the stroke risk associated with atrial fibrillation (AF). There are very few prospective studies that have explored whether warfarin has an association with damage on renal function in Chinese patients with nonvalvular AF (NVAF). The aim of this study was to evaluate the effects of warfarin on renal function and study the factors associated with kidney dysfunction in Chinese adult NVAF patients without dialysis therapy.

METHODSFrom January 2011 to December 2013, a total of 951 NVAF patients from 18 hospitals were enrolled. The estimated glomerular filtration rate (eGFR) was calculated from baseline and follow-up serum creatinine levels. Kaplan-Meier survival curves compared the survival of a ≥25% decline in eGFR (hereafter, endpoint), while Cox models estimated hazard ratios (HR s) and 95% confidence intervals for this event after adjustment for age, gender, and selected potential risk factors for renal dysfunction. Cox regression analysis of the various clinical potential variables was performed to identify the predictors of a ≥25% decline in eGFR.

RESULTSAfter a 58-month follow-up, 951 NVAF patients were divided by observation into warfarin (n = 655) and no anticoagulation groups (n = 296) and 120 (12.6%) patients experienced renal endpoint. Kaplan-Meier survival curves showed that the survival period was not different in the two groups (χ2 = 0.178, log-rank P= 0.67), but patients with systolic blood pressure (SBP) <140 mmHg have significant difference with patients with SBP ≥140 mmHg (χ2 = 4.903, log-rank P= 0.03). Multivariate Cox regression analysis revealed baseline eGFR and SBP as independent predictors of the endpoint, with HR s of 1.00, and 1.02, respectively.

CONCLUSIONIn patients with NVAF, eGFR and SBP are associated with the deterioration of kidney function while Warfarin is not the risk factor of the ≥25% decline in eGFR.

TRIAL REGISTRATIONChinese Clinical Trial Registry (No. ChiCTR-OCH-13003729); http://www.chictr.org.cn/showproj.aspx?proj = 5831.

Aged ; Anticoagulants ; adverse effects ; therapeutic use ; Atrial Fibrillation ; drug therapy ; physiopathology ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Kaplan-Meier Estimate ; Kidney ; drug effects ; Male ; Middle Aged ; Prospective Studies ; Warfarin ; adverse effects ; therapeutic use

An evidence-based practice method according to literature retrieval through PICO (Patients, Intervention, Comparison, Outcome) questions and complementary and alternative medicine (CAM) topics, which can obtain helpful evidence for guiding clinical practice, was introduced with a practical example in this paper. The knowledge of diseases and Western medicine treatment can be acquired by literature retrieval through PICO question, while searching by CAM topics may provide evidence for Chinese medicine (CM). Thus the author held that literature retrieval through both PICO question and CAM topics was an ideal evidence-based practice method for integrative Chinese and Western medicine (ICWM). However, since the standard in CM evidence hierarchy is still under study, the value of the CAM thematic retrieval method remains very limited. In the future, studies on the definition and hierarchy of CM evidences and the herb-drug interaction between Western and Chinese medicine during a combination therapy should be strengthened to improve the status of ICWM evidence-based practice.
Atrial Fibrillation ; physiopathology ; therapy ; Complementary Therapies ; methods ; Evidence-Based Medicine ; methods ; Heart Rate ; physiology ; Herb-Drug Interactions ; Humans ; Integrative Medicine ; methods ; Internet ; Medicine, Chinese Traditional ; methods ; Surveys and Questionnaires ; Treatment Outcome

BACKGROUND/AIMS: Amiodarone is one of the most widely used antiarrhythmic agents; however, amiodarone-induced pulmonary toxicity (APT) can be irreversible and sometimes fatal. The aim of this study was to evaluate the feasibility of chest computed tomography (CT) as a diagnostic tool for APT and to assess the utility of the CT APT score as an index for predicting the severity of APT. METHODS: Patients underwent amiodarone treatment for various reasons, most often atrial fibrillation, for more than 2 years, and those that received a cumulative dose > 100 g were enrolled. A total of 34 patients who underwent chest CT between December 2011 and June 2012 were enrolled, whether or not they had clinical symptoms. The APT CT score was defined as the number of involved regions in the lung, which was divided into 18 regions (right and left, upper, middle, and lower, and central, middle, and peripheral). The CT findings were evaluated according to the total dose and duration of amiodarone treatment and the results of a pulmonary function test. Clinical symptoms and outcomes were also evaluated according to APT CT scores. RESULTS: Seven patients had positive APT CT scores (interstitial fibrosis in five, organizing pneumonia in one, and mixed interstitial fibrosis and organizing pneumonia in one), and these patients exhibited significantly lower diffusion capacity for carbon monoxide in the lungs compared with patients without an increased APT CT score (70.2% +/- 6.9% vs. 89.7% +/- 19.4%; p = 0.011). Three of the seven patients experienced overt APT that required hospital admission. CONCLUSIONS: Chest CT is a useful diagnostic tool for APT, and the APT CT score might be a useful index for assessing the severity of APT.
Aged ; Amiodarone/*adverse effects ; Anti-Arrhythmia Agents/*adverse effects ; Atrial Fibrillation/diagnosis/*drug therapy ; Cross-Sectional Studies ; Cryptogenic Organizing Pneumonia/chemically induced/physiopathology/*radiography/therapy ; Feasibility Studies ; Female ; Forced Expiratory Volume ; Hospitalization ; Humans ; Lung/drug effects/physiopathology/*radiography ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Pulmonary Diffusing Capacity ; Pulmonary Fibrosis/chemically induced/physiopathology/*radiography/therapy ; Respiratory Function Tests ; Risk Factors ; Time Factors ; *Tomography, X-Ray Computed ; Vital Capacity