Effect of Patient's Symptom Interpretation on In-Hospital Mortality in Acute Coronary Syndrome.

BACKGROUND: The association between symptom interpretation and prognosis has not been investigated well among patients with acute coronary syndrome (ACS). As such, the present study evaluated the effect of heart disease awareness among patients with ACS on in-hospital mortality.Methods and Results: We performed a post hoc analysis of 1,979 consecutive patients with ASC with confirmed symptom interpretation on admission between 2014 and 2018, focusing on patient characteristics, recanalization time, and clinical outcomes. Upon admission, 1,264 patients interpreted their condition as cardiac disease, whereas 715 did not interpret their condition as cardiac disease. Although no significant difference was observed in door-to-balloon time between the 2 groups, onset-to-balloon time was significantly shorter among those who interpreted their condition as cardiac disease (254 vs. 345 min; P<0.001). Moreover, the hazard ratio (HR) for in-hospital mortality was significantly higher among those who did not interpret their condition as cardiac disease based on the Cox regression model adjusted for established risk factors (HR 1.73; 95% confidence interval 1.08-2.76; P=0.022). CONCLUSIONS: This study demonstrated that prehospital symptom interpretation was significantly associated with in-hospital clinical outcomes among patients with ACS. Moreover, the observed differences in clinical prognosis were not related to door-to-balloon time, but may be related to onset-to-balloon time.

Comparing In-Hospital Outcomes for Acute Myocardial Infarction Patients in High-Volume Hospitals Performing Primary Percutaneous Coronary Intervention vs. Regional General Hospitals.

BACKGROUND: It has been reported that patients with acute myocardial infarction (AMI) transferred to low-volume primary percutaneous coronary intervention (PCI) hospitals (<115/year) in low population density areas experience higher in-hospital mortality rates. This study compared in-hospital outcomes of patients admitted to high-volume primary PCI hospitals (≥115/year) with those for other regional general hospitals.Methods and Results: Retrospective analysis was conducted on data obtained from 2,453 patients with AMI admitted to hospitals in Iwate Prefecture (2014-2018). Multivariate analysis revealed that the in-hospital mortality rate of AMI among patients in regional general hospitals was significantly higher than among patients in high-volume hospitals. However, no significant difference in mortality rate was observed among patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI. Although no significant difference was found in the in-hospital mortality rate of patients with Killip class I STEMI, significantly lower in-hospital mortality rates were observed in patients admitted in high-volume hospitals for Killip classes II, III, and IV. CONCLUSIONS: Although in-hospital outcomes for patients with STEMI undergoing primary PCI were similar, patients with heart failure or cardiogenic shock exhibited better in-hospital outcomes in high-volume primary PCI hospitals than those in regional general hospitals.

Relationship between Impairment of the Vascular Endothelial Function and the CHA2DS2-VASc Score in Patients with Sinus Rhythm and Non-valvular Atrial Fibrillation.

Objective and methods There is little information concerning the influence of the heart rhythm on the vascular endothelial function in patients with non-valvular atrial fibrillation (AF) compared with studies concerning sinus rhythm (SR). The present study included paroxysmal (n=184) or chronic (n=53) AF patients without heart failure and control subjects with SR (n=79) matched for age, gender and the CHA2DS2-VASc score. Paroxysmal AF was defined as episodes that terminated spontaneously within 7 days, while chronic AF was defined as longstanding AF that was refractory to cardioversion for 12 months or longer. There were no significant differences in the numbers of patients receiving renin-angiotension-aldosterone system inhibitors or statins among the three groups. Results Among the 237 AF patients (155 men, mean age 64±9 years, mean CHA2DS2-VASc score 1.8±1.4), the flow-mediated dilatation (FMD) was 5.4%±2.6% in the paroxysmal AF group, 4.3%±2.1% in the chronic AF group and 6.5%±3.5% in the SR group. There were significant differences among the 3 groups (all, p<0.05). Nitroglycerin-induced dilatation (NMD) was noted in 14.6%±6.5% of the paroxysmal AF group, 16.5%±9.1% of the chronic AF group and 12.7%±5.9% of the SR group, with no significant differences among the 3 groups. There was a significant negative correlation between the CHA2DS2-VASc scores and the FMDs value in all 3 groups (paroxysmal AF group:r=-0.322, p<0.01; chronic AF group:r=-0.291, p<0.05; SR group:r=-0.326, p<0.01). Conclusion In comparison with SR, the frequency and duration of AF episodes appear to cause deterioration of the vascular endothelial function.

Comparison of the CHADS2, CHA2DS2-VASc and R2CHADS2 Scores in Japanese Patients with Non-valvular Paroxysmal Atrial Fibrillation Not Receiving Anticoagulation Therapy.

Objective It remains unclear whether the CHADS2, CHA2DS2-VASc, or R2CHADS2 score is the most useful for the risk stratification of ischemic stroke/systemic thromboembolism (IS/SE) in Japanese patients with paroxysmal non-valvular atrial fibrillation (PNVAF). Methods We investigated the incidence of IS/SE on the basis of the CHADS2, CHA2DS2-VASc, and R2CHADS2 scores in 332 consecutive PNVAF patients (224 men, mean age: 65±13 years) who had not been administered anticoagulation therapy but who were administered antiarrhythmic drug therapy to maintain sinus rhythm between August 1995 and July 2008 before the 2008 Japanese Circulation Society guideline was issued (mean follow-up period: 53±35 months). Results The annual rates of IS/SE without underlying antiarrhythmic drug therapy are shown in the table included in this article. Higher CHADS2, CHA2DS2-VASc, and R2CHADS2 scores were associated with greater annual rates of IS/SE (p<0.001). In a multivariate logistic regression analysis adjusted for potentially confounding variables, the CHADS2 scores [odds ratio (OR): 4.74, 95% confidence interval (CI): 2.80-8.00, p<0.001], CHA2DS2-VASc scores (OR: 4.15, 95% CI: 2.57-6.71, p<0.001), and R2CHADS2 scores (OR: 1.94, 95% CI: 1.48-2.53, p<0.001) were significant independent predictors of IS/SE. The area under the receiver-operator characteristic curve for predicting IS/SE was 0.89 for CHA2DS2-VASc scores, 0.87 for CHADS2 scores, and 0.85 for R2CHADS2 scores (all, p<0.001), with no significant difference among the three scores. Conclusion In Japanese patients with PNVAF, the CHADS2, CHA2DS2-VASc, and R2CHADS2 scores are all useful for the risk stratification of IS/SE cases.

Comparison of the effects of bepridil and aprindine for the prevention of atrial fibrillation after cardiac and aortic surgery: A prospective randomized study.

BACKGROUND: Approximately one-third of the patients undergoing cardiovascular surgery reportedly experience paroxysmal atrial fibrillation (AF) during the postoperative period. However, the usefulness of antiarrhythmic drugs for preventing postoperative AF recurrence in the Japanese population has not been extensively studied. METHODS: From a total of 118 patients who developed postoperative paroxysmal AF between April 2009 and March 2011, 72 patients (45 men, mean age 68±8 years) requiring treatment for postoperative AF due to symptoms lasting ≥30 min were enrolled to prospectively investigate the efficacy of oral bepridil (100 mg/day, n=37) or aprindine (40 mg/day, n=35). RESULT: The AF recurrence-free survival rates at 1, 3, 7, and 14 days were 100%, 94%, 57%, and 49%, respectively, in the aprindine group, and 100%, 97%, 86%, and 76%, respectively, in the bepridil group (P=0.028, aprindine vs. bepridil). CONCLUSION: Bepridil, at a fixed dose of 100 mg/day, was considered to be more effective than a routine dose of aprindine for the prevention of postoperative AF recurrence.

Comparison between CHADS2 and CHA2DS2-VASc score for risk stratification of ischemic stroke in Japanese patients with non-valvular paroxysmal atrial fibrillation not receiving anticoagulant therapy.

It remains unclear if the CHADS2 score or CHA2DS2-VASc score is more useful for the risk stratification of ischemic stroke/systemic thromboembolism in Japanese patients with non-valvular paroxysmal atrial fibrillation (NVPAF). We retrospectively investigated the incidence of ischemic stroke on the basis of CHADS2 and CHA2DS2-VASc scores in 332 NVPAF patients (224 men, mean age, 65 ± 13 years) who were not administered anticoagulation therapy before publication of the 2008 JCS guideline (mean follow-up period, 53 ± 35 months). Annual rates of ischemic stroke/ systemic thromboembolism underlying antiarrhythmic drug therapy were 0.2%/year for the 0-point group; 0.9%/year for the 1-point group; 2.8%/year for the 2-point group; 9.4 %/year for the 3-point group; and 10.9%/year for the ≥ 4-point group on the basis of the CHADS2 scores, and 0%/year for the 0-point group; 0.6%/year for the 1-point group; 1.0%/ year for the 2-point group; 2.0 %/year for the 3-point group; 5.5%/year for the 4-point group; 9.1%/year for the 5-point group; and 13.7%/year for the ≥ 6-point group on the basis of the CHA2DS2-VASc scores. Both higher CHADS2 and CHA2DS2-VASc scores were associated with greater annual rates of ischemic stroke/systemic thromboembolism (P < 0.001). In multivariate logistic regression analysis, the CHADS2 (odds ratio [OR]:4.74, 95% confidence interval [CI]:2.80-8.00, P < 0.001) and CHA2DS2-VASc scores (OR: 4.15, 95% CI:2.57-6.71, P < 0.001) were significant independent predictors for ischemic stroke/systemic thromboembolism. Area under the receiver-operator characteristic curves for predicting ischemic stroke/systemic thromboembolism were 0.89 in the CHA2DS2-VASc scores (P < 0.001) and 0.87 in the CHADS2 scores (P < 0.001). In Japanese patients with NVPAF, both the CHADS2 and CHA2DS2-VASc scores are useful parameters for the risk stratification of ischemic stroke/systemic thromboembolism.

Relationship between CHADS2 score and efficacy of antiarrhythmic drug therapy in patients with paroxysmal atrial fibrillation.

BACKGROUND: The Cardiac failure, Hypertension, Age, Diabetes, Stroke [Doubled] (CHADS(2)) score is a useful scheme for risk stratification of thromboembolism patients, but there is little information about its usefulness for the evaluation of antiarrhythmic drug (AAD) therapy. METHODS AND RESULTS: This study included 459 paroxysmal atrial fibrillation (AF) patients (309 men, mean age 66 ± 12 years, mean follow-up 50 ± 35 months) and prophylactic efficacy was analyzed on the basis of CHADS(2) score. (1) Survival rates free from AF recurrence at 1, 6, 12 and 24 months were, respectively, 89%, 74%, 63% and 47% in score-0 group (n=152); 92%, 68%, 59% and 48% in score-1 group (n=158); 86%, 64%, 56% and 46% in score-2 group (n=84); 81%, 65%, 51% and 35% in score-3 group (n=43); and 68%, 50%, 36% and 18% in ≥ score-4 group (n=22) (P<0.05; score-0, score-1 or score-2 vs. ≥ score-4 group). (2) Survival rates free from progression to chronic AF at 12, 36, 60 and 90 months were, respectively, 95%, 93%, 91% and 89% in score-0 group; 97%, 91%, 89% and 88% in score-1 group; 96%, 93%, 88% and 83% in score-2 group; 91%, 74%, 67% and 60% in score-3 group; and 91%, 82%, 68% and 55% in ≥ score-4 group (P<0.01; score-0, score-1 or score-2 vs. ≥ score-4 group). (3) In multivariate logistic regression analysis adjusted for potentially confounding variables, CHADS(2) score was associated with AF recurrence (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.16-1.81, P<0.001), and progression to chronic AF during AAD therapy (OR 1.64, 95% CI 1.04-2.69, P<0.001). CONCLUSIONS: When using a rhythm control strategy, the CHADS(2) score is a useful scheme for predicting the outcome of AAD treatment of patients with paroxysmal AF.

Relationship between CHA(2)DS(2)-VASc scores and ischemic stroke/cardiovascular events in Japanese patients with paroxysmal atrial fibrillation not receiving anticoagulant therapy.

BACKGROUND AND METHODS: The CHA(2)DS(2)-VASc score has been newly proposed for stratifying patients with nonvalvular atrial fibrillation (AF) according to the risk of ischemic stroke in the 2010 European Society of Cardiology guideline. However, there is little information about its usefulness for predicting long-term prognosis of cardiovascular events in Japanese patients with paroxysmal AF. This study retrospectively included 332 paroxysmal AF patients (224 men, mean age 65±13 years, mean follow-up period 53±35 months) without receiving anticoagulant therapy between June 1995 and August 2008 who were categorized into risk stratification on the basis of CHA(2)DS(2)-VASc score. RESULTS: The distribution of CHA(2)DS(2)-VASc scores was 0, 1, 2, 3, 4, 5, 6, and 7 points in 76 (23%), 60 (18%), 69 (21%), 69 (21%), 28 (8%), 23 (7%), 6 (2%), and 1 (0.3%) patients, respectively. The annual rates of symptomatic ischemic stroke were 0%, 0.60%, 0.95%, 1.96%, 5.45%, 9.06%, and 13.7% when the CHA(2)DS(2)-VASc score was 0, 1, 2, 3, 4, 5, and ≥6 points, respectively (p<0.001) and those of cardiovascular events including hospitalization for thromboembolism, heart failure and cardiovascular death were 0%, 1.43%, 1.50%, 2.52%, 10.14%, 12.85%, and 17.13% when the CHA(2)DS(2)-VASc score was 0, 1, 2, 3, 4, 5 and ≥6 points, respectively (p<0.001). Higher CHA(2)DS(2)-VASc scores were associated with greater annual rates of ischemic stroke and cardiovascular events. In a multivariate logistic regression analysis adjusted for the potentially confounding variables, the CHA(2)DS(2)-VASc score was associated with symptomatic ischemic stroke (odds ratio 7.051, 95% confidence interval 3.76-13.22, p<0.001) and cardiovascular events (odds ratio 3.448, 95% confidence interval 2.33-5.11, p<0.001). CONCLUSION: In Japanese patients with paroxysmal AF, the CHA(2)DS(2)-VASc score is a useful scheme for risk stratification of ischemic stroke and cardiovascular events.

Long-term efficacy of upstream therapy with lipophilic or hydrophilic statins on antiarrhythmic drugs in patients with paroxysmal atrial fibrillation: comparison between atorvastatin and pravastatin.

There is little information available on the benefits of selection of statins as upstream therapy for the prevention of paroxysmal atrial fibrillation (AF). We compared the efficacy and safety of atorvastatin (A-group, n = 43) and pravastatin (P-group, n = 41) as upstream therapy in patients with paroxysmal AF and dyslipidemia. A total of 84 patients (45 men, mean age, 66 ± 9 years, mean follow-up, 49 ± 32 months) were retrospectively assigned to receive atorvastatin (n = 41;10 mg/day) or pravastatin (n = 43 ; 10 mg/day). Survival rates free from AF recurrence at 1, 6, 12, and 24 months were 93%, 74%, 60%, and 53% in A-group, and 88%, 49%, 37%, and 29%, respectively, in P-group (P = 0.029, A-group versus P-group). Survival rates free from conversion to permanent AF at 12, 36, 60, and 90 months were 100%, 100%, 98%, and 95% in A-group, and 100%, 95%, 88%, and 83%, respectively, in P-group (P = 0.063, A-group versus P-group). Using a logistic regression model, atorvastatin was found to be associated with a significantly reduced risk of AF recurrence in comparison to pravastatin (unadjusted odds ratio [OR] = 0.27, 95% confidence interval 0.11-0.68, P = 0.005). This association remained significant after adjustment for potentially confounding variables (OR = 0.26, 95% CI 0.08-0.86, P = 0.027). Using a logistic regression model, atorvastatin was not associated with a significantly reduced risk of converting to permanent AF in comparison to pravastatin (unadjusted OR = 0.29, 95% CI 0.05-1.50, P = 0.138), but this association did show a significant difference after adjustment for potentially confounding variables in a multivariate model (OR = 0.08, 95% CI 0.06-0.96, P = 0.046). Adverse effects requiring discontinuation of statins were observed in 1 case (2%, myalgia) in A-group, and 1 case (2%, elevation in CPK level ≥ 500 IU/L) in P-group, respectively (P = NS, A-group versus P-group). Atorvastatin, a lipophilic statin, was considered to be more effective in preventing recurrence of paroxysmal AF and conversion to permanent AF than pravastatin, a hydrophilic statin.

Long-term efficacy of amiodarone therapy for the prevention of recurrence of paroxysmal atrial fibrillation. Analysis based on patient characteristics.

There is little information available on factors affecting the long-term prevention of paroxysmal atrial fibrillation (AF) in the Japanese population. A total of 71 patients (49 men, mean age, 68 ± 8 years) with paroxysmal AF refractory to ≥ 2 class I antiarrhythmic drugs received oral amiodarone (50-200 mg/day). All patients were observed for more than 12 months (mean follow-up period, 47 ± 26 months) and were analyzed on the basis of patient profiles. The percentage of patients with AF recurrence despite amiodarone therapy was 54% in all patients. In multivariate logistic regression analysis adjusted for age and sex, the following factors were associated with preventive efficacy for AF recurrence: left ventricular ejection fraction (LVEF) (relative risk [RR] 0.933, 95% confidence interval [CI] 0.877-0.993, P = 0.029), asymptomatic AF (RR 0.068, CI 0.005-0.870, P = 0.039), and AF occurring irrespective of circadian variation (RR 0.115, CI 0.013-0.988, P = 0.049). The percentage of patients with conversion to permanent AF despite amiodarone therapy was 31% in all patients. In multivariate logistic regression analysis adjusted for age and sex, asymptomatic AF (RR 0.085, CI 0.010-0.732, P = 0.025) was the only factor associated with preventive efficacy for conversion to permanent AF. Amiodarone appears to be effective in maintaining sinus rhythm, especially in patients with impaired left ventricular function. In contrast, amiodarone appears to be refractory in those with asymptomatic AF or AF occurring irrespective of circadian variation.

Prevalence and characteristics of asymptomatic excessive transmural injury after radiofrequency catheter ablation of atrial fibrillation.

BACKGROUND: Even with a low energy setting, radiofrequency energy applications on the left atrial (LA) posterior wall may cause excessive transmural injury (ETI) during catheter ablation of atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to clarify the prevalence and characteristics of ETI. METHODS: This study included 104 patients with AF who underwent extensive encircling pulmonary vein isolation (EEPVI) followed by an endoscopic examination (≤48 hours after EEPVI). EEPVI was performed under conscious sedation, and the ablation settings at the LA posterior wall were a maximum energy of 20 to 25 W and duration of ≤30 seconds. The ETI was defined as any injury that resulted from EEPVI, including esophageal damage or periesophageal nerve injury. RESULTS: ETIs were found in 10 (9.6%) patients and were all asymptomatic; esophageal damage in 4 patients and periesophageal nerve injury in the remaining 6. All patients with ETI were below normal weight (body mass index [BMI] < 24.9 kg/m(2)), and consisted of 17% of those below normal weight. The procedural parameters such as the type of energy source, total duration of energy applications to the LA posterior wall, additional LA linear ablation, and biochemical markers were not related to the ETI. In the logistic multiadjusted model, the BMI (per 1 kg/m(2)) was the only independent predictor of ETI (odds ratio = 0.76; 95% confidence interval = 0.59 to 0.97, P < .05). CONCLUSION: Asymptomatic ETIs were not rare even with a low energy setting in patients below normal weight. Tailored energy settings based on the patient's BMI may be required when performing EEPVI.

Clinical profiles, efficacy of antiarrhythmic drug therapy, and cardiovascular prognosis in patients with first detected paroxysmal atrial fibrillation.

Little information is available concerning clinical profiles and outcomes of treatment in Japanese patients with first detected atrial fibrillation (AF). In the present study, 459 patients with paroxysmal AF (309 males, mean age, 66 ± 12 years) were divided into a first detected AF group (group A, n = 143) and a non-first detected AF group (group B, n = 316). Clinical profiles, prophylactic efficacy of antiarrhythmic drug therapy (AAD), and cardiovascular prognosis during a mean follow-up period of 50 ± 35 months were compared between the two groups. The number of AF recurrences in the individual patients regardless of AAD were significantly lower in group A than in group B (0.8 ± 1.4 versus 1.7 ± 1.9)(P < 0.05). The percentages of patients free from conversion to chronic AF at 12, 36, 60, and 120 months were significantly higher in group A (98%, 96%, 93%, and 91%, respectively) than in group B (95%, 86%, 83%, and 79%, respectively)(P < 0.01). The annual rates of hospitalization for thromboembolism, heart failure, and cardiovascular death did not differ between group A (2.2%, 1.1% and 1.0%, respectively) and group B (2.2%, 1.9% and 1.1%, respectively). In multivariate logistic regression analysis, a CHADS2 score ≥ 2 points (odds ratio 13.1, 95% confidence interval 3.36-51.0, P = 0.001), nocturnal AF onset (OR 0.201, 95% CI 0.050-0.815, P = 0.025), left ventricular diastolic dimension (LVDd) ≥ 50 mm (OR 3.845, 95% CI 1.078-13.71, P = 0.038), and conversion to chronic AF (OR 3.547, 95% CI 1.002-13.64, P = 0.048) were associated with cardiovascular events in group A. Rhythm control therapy with antiarrhythmic drugs was shown to be more effective for patients in group A than in group B. It is particularly important to prevent cardiovascular events in first detected AF patients with a CHADS2 score ≥ 2 points, LVDd ≥ 50 mm, and conversion to chronic AF.

Concomitant chronic kidney disease increases the recurrence of atrial fibrillation after catheter ablation of atrial fibrillation: a mid-term follow-up.

BACKGROUND: Chronic kidney disease (CKD) is often associated with atrial fibrillation (AF). However, its impact on the results of radiofrequency catheter ablation for AF has not been fully examined. OBJECTIVE: The purpose of this study was to clarify the relationship between CKD and postcatheter ablation AF recurrence. METHODS: The study included 221 patients with AF who underwent successful catheter ablation. The prevalence and characteristics of AF recurrences were determined. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m(2). RESULTS: After mean follow-up of 31.9 ± 7.6 months, 87 (39%) patients had AF recurrences. Multivariate Cox regression analysis revealed that CKD (hazard ratio [HR] 2.089, 95% confidence interval [CI] 1.292-3.378, P <.01) and left atrial volume (HR 1.009, 95% CI 1.002-1.017, P <.05) were independent predictors of AF recurrences. Among the 221 patients, 54 (24.4%) had CKD. Patients with CKD had a higher incidence of AF recurrences (57.4%) compared to the non-CKD patients (33.5%, P <.01). Compared with patients without CKD, patients with CKD were older (64 ± 11 years vs 58 ± 10 years, P <.001) and had a higher prevalence of hypertension (72% vs 53%, P <.05), larger left atrial volume (74.7 ± 29.4 mL vs 62.0 ± 26.0 mL, P <.01), and higher plasma B-type natriuretic peptide levels (129.6 ± 209.3 pg/mL vs 68.8 ± 91.0 pg/mL, P <.01). CONCLUSION: The presence of CKD increased the risk of AF recurrences after catheter ablation. Multifactorial physiologic factors due to CKD may account for the higher prevalence of recurrent AF in patients with CKD than in those without.

Relationship between the long-term preventive effect of combined treatment with antiarrhythmic drugs plus angiotensin-converting enzyme inhibitors and circadian variation in the onset of paroxysmal atrial fibrillation.

We examined the relationship between the efficacy of combined treatment with antiarrhythmic drugs (AAD) plus enalapril for maintaining sinus rhythm and circadian variation in the onset of paroxysmal AF.Three hundred and forty-four patients with paroxysmal AF (239 men, mean age, 69 ± 11 years) who could be followed up ≥ 12 months were divided into 3 groups on the basis of circadian variation in the onset of AF: a diurnal group (7:00 AM-5:00 PM, n = 57), a nocturnal group (5:00 PM-7:00 AM, n = 108), and a mixed group (onset during both periods, n = 169). The maintenance rate of sinus rhythm during the follow-up period was compared between combined therapy (AAD plus enalapril) and AAD alone.In the diurnal group, the maintenance rates of sinus rhythm at 12, 36, 60, and 90 months were 100%, 100%, 100%, and 100%, respectively, for patients treated with AAD plus enalapril (n = 22) versus 97%, 91%, 89%, and 80% for patients treated with AAD alone (n = 35, P < 0.05). In the nocturnal group, the maintenance rates of sinus rhythm at 12, 36, 60, and 90 months were 96%, 96%, 96%, and 92%, respectively, in patients treated with AAD plus enalapril (n = 24) versus 100%, 100%, 100%, and 100% in patients treated with AAD alone (n = 84, P = NS). In the mixed group, maintenance rates of sinus rhythm at 12, 36, 60, and 90 months were 90%, 71%, 61%, and 57%, respectively, in patients treated with AAD plus enalapril (n = 49) versus 88%, 78%, 68%, and 61% in patients treated with AAD alone (n = 120, P = NS). Our findings suggest that the preventive efficacy of combined therapy with AAD plus enalapril is dependent on the timing of onset of paroxysmal AF, and this regimen seems to be most beneficial for the diurnal type of paroxysmal AF.

Prospective comparative study of intravenous cibenzoline and disopyramide therapy in the treatment of paroxysmal atrial fibrillation after cardiovascular surgery.

BACKGROUND: It has been reported that approximately one-third of patients undergoing cardiovascular surgery experience paroxysmal atrial fibrillation (AF) during the postoperative period. There is, however, little information on the selection of anti-arrhythmic drugs for terminating postoperative paroxysmal AF. METHODS AND RESULTS: Between April 2007 and March 2009, 118 patients (76 men, 42 women, mean age 68+/-10 years) who had postoperative paroxysmal AF lasting > or =30 min were randomly assigned to receive either iv cibenzoline (70 mg, n=60) or disopyramide (50 mg, n=58) for terminating postoperative paroxysmal AF. The success rate of iv cibenzoline therapy (47%) was significantly greater than that of iv disopyramide therapy (24%; P<0.05). To identify clinical factors to increase the termination efficacy of iv cibenzoline, multivariate logistic regression was used to adjust for several covariates and to generate adjusted odds ratios (OR). The significant variables for the termination of paroxysmal AF after iv cibenzoline therapy were pretreatment with oral beta-adrenergic blockers (OR =8.224, P=0.030) and smaller left atrial dimensions (OR =0.879, P=0.039). CONCLUSIONS: The efficacy of iv cibenzoline for the termination of postoperative paroxysmal AF was significantly better than that of disopyramide, especially in patients with pre-administration of oral beta-adrenergic blockers and those with smaller left atrium.

Efficacy of antiarrhythmic drug therapy in preventing recurrence of atrial fibrillation and long-term cardiovascular prognosis in patients with asymptomatic paroxysmal atrial fibrillation.

We evaluated the efficacy of antiarrhythmic drug therapy (AAD) and long-term cardiovascular prognosis in patients with asymptomatic paroxysmal atrial fibrillation (AF). This retrospective study included 334 patients (229 men and 105 women, mean age, 69 +/- 11 years, mean follow-up, 60 +/- 11 months) who were divided into two groups; patients with symptomatic AF (group I) and those with asymptomatic AF (group II) on the basis of subjective symptoms. (1) Actuarial rates of patients without AF recurrence, those with AF recurrence and with electrical/pharmacological cardioversion to restore sinus rhythm, and those with conversion to permanent AF despite AAD were 40%, 41%, and 19%, respectively, in group I, and 22%, 24%, and 54%, respectively, in group II at the end of the follow-up period. At 60 months, the percentage of patients with conversion to the permanent form of AF was significantly greater in group II than in group I (P < 0.05, group I versus group II). (2) Survival rates free from symptomatic thromboembolism at 36, 60, and 120 months were 96%, 93%, and 88%, in group I, and 82%, 76%, and 71%, respectively, in group II (P < 0.05, group I versus group II). In patients not undergoing anticoagulant therapy, the annual rate of symptomatic thromboembolism was significantly greater in group II (5.3%) than in group I (2.3%) (P < 0.05), while in patients undergoing anticoagulant therapy there was no significant difference in the annual rate of symptomatic thromboembolism between group I (0.9%) and group II (1.8%). The clinical course of asymptomatic paroxysmal AF is refractory to AAD when compared to symptomatic AF, meaning that anticoagulant therapy is required to prevent symptomatic thromboembolism in this group.

Long-term efficacy of upstream therapy using angiotensin-converting enzyme inhibitors and statins in combination with antiarrhythmic agents for the treatment of paroxysmal atrial fibrillation.

The long-term efficacy of upstream therapy to prevent occurrence of paroxysmal atrial fibrillation (AF) in Japanese patients remains unclear. We retrospectively assessed the long-term efficacy of combination therapy with pravastatin (10 mg/day) and enalapril (5 mg/day) in addition to antiarrhythmic drugs (AAD) for maintaining sinus rhythm in patients with AF. This study included 319 patients (221 men, 98 women, mean age, 68+/-10 years, mean follow-up period, 50+/-34 months) who were divided into 4 groups: group I (n=191) without combination therapy--namely pravastatin(-) and enalapril(-); group II (n=81) with combination therapy--pravastatin (-) and enalapril (+) (n=81); group III (n=29) with combination therapy--pravastatin (+) and enalapril (-); and group IV (n=18) with combination therapy--pravastatin (+) and enalapril (+). The percentages of patients free from conversion to permanent AF at 12, 36, 60, 90, and 120 months were as follows: group I 88, 83, 78, 75, and 73%, respectively; group II 96, 88, 79, 77, and 75%, respectively; group III 100, 97, 91, 91, and 86%, respectively; group IV 100, 100, 100, 94, and 94%, respectively. The actuarial rate free from conversion to permanent AF at 120 months was significantly higher in group IV than in group I (P<0.05). The results suggest that in patients with paroxysmal AF, the addition of both pravastatin and enalapril to AAD was more effective for maintaining sinus rhythm in terms of an upstream therapy.

A randomized study on the efficacy of intravenous cibenzoline and pilsicainide administered prior to electrical cardioversion in patients with lone paroxysmal and persistent atrial fibrillation.

METHODS AND RESULTS: This study included 68 patients (47 men, 21 women, mean age 69 years) in whom atrial fibrillation (AF) recurred immediately after electrical cardioversion (EC) was performed with no antiarrhythmic drugs. After administration of cibenzoline (Cib, 70 mg) or pilsicainide (Pil, 50 mg) on a randomized basis, all patients again underwent EC at the same energy as that prior to administration of antiarrhythmic drugs. We compared the efficacy of Cib (n = 35) and Pil (n = 33), and examined factors affecting successful cardioversion in patients treated with Cib. These patients were divided into a successful group (Group A) and an unsuccessful group (Group B). The success rate of EC at the same energy after intravenous Cib administration (77%) was significantly greater than that after intravenous Pil administration (42%) (p < 0.01). In patients treated with Cib, AF duration was significantly greater in Group B (55.8 ± 48.2 h) than in Group A (29.1 ± 17.0 h) (p < 0.05). Plasma concentrations of atrial natriuretic peptide (ANP) during AF and the ratio of ANP level during AF to that during sinus rhythm were also significantly greater in Group A (110.9 ± 69.7 pg/ml and 3.9 ± 2.8, respectively) than in Group B (58.2 ± 36.1 pg/ml and 1.8 ± 0.9, respectively) (both, p < 0.05). In patients treated with Pil, AF duration was also significantly greater in Group B (59.7 ± 44.6h) than in Group A (19.6 ± 21.7 h) (p < 0.05), and the ratio of ANP level during AF to that during sinus rhythm was significantly greater in Group A (3.5 ± 2.6) than in Group B (1.7 ± 0.9) (p < 0.05). CONCLUSIONS: In patients with AF previously refractory to conventional EC, intravenous Cib administration was more effective in restoring sinus rhythm with EC than intravenous Pil administration. The capacity of ANP secretion during AF tachycardia may be a predictive indicator for the prevention of AF recurrence in electrically remodeled atria.

Combination therapy with amiodarone and enalapril in patients with paroxysmal atrial fibrillation prevents the development of structural atrial remodeling.

The purpose of this study was to examine the relationship between long-term efficacy of amiodarone therapy (100-200 mg/day) combined with angiotensin converting enzyme inhibitor (ACEI; enalapril 5 mg/day) administration, and the development of structural atrial remodeling in patients with paroxysmal atrial fibrillation (AF). Fifty-eight patients (40 men, 18 women, mean age, 68 +/- 8 years, mean follow-up period, 43 +/- 18 months) with AF refractory to >or= two class I antiarrhythmic drugs were divided into two groups; those treated with enalapril on amiodarone (group A, n = 25) and those treated with amiodarone alone (group B, n = 33), to evaluate the efficacy of combination therapy. 1) At 12 and 24 months, the survival rates for patients free from AF recurrence were 80% and 64% in group A, and 45% and 30% in group B, respectively (P < 0.05, group A versus group B). The percentage of patients with conversion to permanent AF despite amiodarone therapy was 20% in group A and 48.5% in group B (P < 0.05, group A versus group B). 2) In group B, left atrial dimension (LAD) was significantly greater after amiodarone therapy (40.2 +/- 6.3 mm) than at baseline (35.2 +/- 6.6 mm) (P < 0.01), whereas there was no significant difference in LAD between baseline and after amiodarone therapy in group A (39.1 +/- 5.0 mm versus 41.0 +/- 5.0 mm, respectively). In patients with paroxysmal AF, ACE-I appears to enhance the efficacy of amiodarone therapy in maintaining sinus rhythm and preventing the development of structural remodeling in atria.

Efficacy of amiodarone for preventing the recurrence of symptomatic paroxysmal and persistent atrial fibrillation after cardioversion.

BACKGROUND: It has been previously reported that the efficacy of class I antiarrhythmics in preventing the recurrence of symptomatic paroxysmal and persistent atrial fibrillation (AF) is limited when AF lasts for 48 h or more. However, it is unclear whether the efficacy of amiodarone, a class III drug, is superior to class I antiarrhythmics in patients with long-lasting AF. METHOD AND RESULTS: The relationship between the duration of tachycardia and the efficacy of amiodarone in preventing recurrence of tachycardia was examined in 55 patients (37 men, 18 women, mean age 68+/-9 years) to whom amiodarone was administered after electrical or pharmacological cardioversion for paroxysmal and persistent AF. In 26 patients, paroxysmal and persistent AF ceased within 48 h after onset (Group A), and in the other 29 patients, it ceased after 48 h (Group B). Patient characteristics and actuarial recurrence-free rates were compared between the 2 groups. The mean follow-up period was 30+/-11 months. No statistically significant difference between the groups was found in patient characteristics. Actuarial recurrence-free rates in Group A and B at 1, 3, 6, 9, and 12 months were 100%, 81%, 69%, 62%, and 54%, and 93%, 79%, 66%, 52%, and 48%, respectively (p=NS at 12 months). The period of maintenance of sinus rhythm was 14.7+/-3.2 months in group A and 13.3+/-3.3 months in group B (mean+/-SE, p=NS). CONCLUSION: In the case of amiodarone, efficacy for maintaining sinus rhythm after cardioversion of AF was not biased by the duration of arrhythmia. This observation suggests amiodarone is effective in maintaining normal sinus rhythm after cardioversion, even in patients with long-lasting AF and electrical atrial remodeling.