Interferon related pericarditis: Review.

AIM: To conduct a review of "interferon related pericarditis". METHODS: We searched MEDLINE, EMBASE, Cinahl, and the Cochrane Database from the earliest available date through September 2016. A search strategy using the Medical Subject Headings and text keywords "interferon" and "pericarditis" were used. RESULTS: Nine case reports were eligible for the present study. Six of 8 cases were women and the mean age was 43.8 ± 13.8 years with chronic hepatitis C in 6 cases, malignant melanoma in 2 cases and chronic myelogenous leukemia in 1 case. The patients complained of chest pain in 6 cases, dyspnea in 5 cases and edema in 2 cases. Pericardial friction rub was heard in 3 of 9 cases. Congestive heart failure occurred in 3 of 9 cases. Two mechanisms for pericarditis were demonstrated, one is autoimmune included lupus like syndrome in 2 cases and the other is cardio toxicity in 4 cases. Treatment of interferon related pericarditis is discontinuation of Interferon treatment. Four of 9 cases were treated with prednisone and 4 with nonsteroidal anti-inflammatory drugs. CONCLUSION: Interferon related pericarditis still remains uncertain. Treatment of interferon related pericarditis rests mainly on early recognition and drug discontinuation. Interferon related pericarditis was treated with steroid and/or nonsteroidal anti-inflammatory drugs.

Clinical implication of monitoring rivaroxaban and apixaban by using anti-factor Xa assay in patients with non-valvular atrial fibrillation.

BACKGROUND: Although patients taking non-vitamin K antagonist oral anticoagulants (NOACs) do not require routine coagulation monitoring, high-risk patients require monitoring to assess pharmacodynamics. METHODS: We measured (1) anti-factor Xa activity (AXA), using chromogenic assay with the HemosIL Liquid Heparin kit, (2) prothrombin time (PT), and (3) activated partial thromboplastin time (aPTT) in 188 blood samples from 70 patients with non-valvular atrial fibrillation, of whom 36 received rivaroxaban once daily and 34 received apixaban twice daily. RESULTS: After the rivaroxaban therapy, AXA ranged from 0 to 3.65 IU/mL; PT, from 9.6 to 44.5 s; and APTT, from 19.3 to 69.7 s. After the apixaban therapy, AXA ranged from 0.02 to 3.18 IU/mL; PT, from 10.2 to 20.8 s; and APTT, from 21.8 to 59.8 s. At peak time, the AXA of patients who received rivaroxaban and apixaban were almost the same (2.08±0.91 IU/mL vs. 1.71±0.57 IU/mL), but the PT and APTT of patients who received rivaroxaban were more prolonged than those of patients who received apixaban (18.1±5.6 s vs. 13.8±0.9 s, p<0.001 and 40.9±7.3 s vs. 35.5±7.5 s, p<0.01, respectively). At trough time, the AXA and PT of patients who received rivaroxaban were respectively lower and shorter than those of patients who received apixaban (0.28±0.31 IU/mL vs. 1.04±0.72 IU/mL, p<0.001 and 11.9±2.0 s vs. 13.7±2.4 s, p<0.01, respectively), but the APTT of patients who received rivaroxaban and apixaban did not significantly differ (32.3±4.3 s vs. 34.3±3.8 s). CONCLUSIONS: Measurement of AXA might be useful to assess the pharmacodynamics of high-risk patients, such as high age, low body weight, and/or low renal function, and to assess the intensity of anticoagulation by using different methods of administration, such as crushed tablet via the nasogastric tube.

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.

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.

Angiotensin-converting enzyme and bradykinin gene polymorphisms and cough: A meta-analysis.

AIM: To evaluate the association between genetic polymorphisms and angiotensin converting enzyme inhibitor (ACEI)-related cough, and the race- or ethnicity-related difference in the prevalence of cough attributed to ACEI therapy. METHODS: We conducted a search in PubMed, EMBASE, Cinahl, and the Cochrane Database without language limitation. A database of 11 studies on ACEI-related cough, with detailed information regarding ACE I/D or bradykinin B(2) receptor polymorphisms, was created. Eligible studies were synthesized using meta-analysis methods, including cumulative meta-analysis. A subgroup analysis was also performed using ethnicity. RESULTS: Six studies were included on ACE I/D polymorphism (398 Caucasians, 723 East Asians), and three studies were included on bradykinin B(2) receptor polymorphism (300 East Asians). The distribution of ACE genotypes showed significant differences in the entire population (P = 0.004) and in East Asians (P = 0.005) but not in Caucasians (P = 0.23). Allelic frequencies of ACE showed significant differences in East Asians [odds ratio (OR) = 1.49 (1.11-2.02)]. The meta-analysis with a random effects model showed a significant association between ACE allele I/D and ACEI-related cough [random effects (RE) OR = 1.49 (1.11-2.02), P = 0.009] in East Asians, but not in Caucasians [RE OR = 0.90 (0.60-1.35)]. The allelic frequencies of the bradykinin B(2) receptor gene were significantly different [OR = 2.25 (1.42-3.57)]. The distributions of the T/C genotypes of the bradykinin B(2) receptor gene were significantly different (χ(2) = 8.366, P = 0.015). The meta-analyses revealed that there was a significant association between the bradykinin B(2) receptor allele and ACEI-related cough in East Asians [RE OR = 2.29 (1.42-3.69), P = 0.001]. CONCLUSION: ACE I/D and Bradykinin B(2) receptor polymorphisms contributed to the risk of ACEI-related cough in East Asians, but a negative association between ACE I/D polymorphism and ACEI-related cough was observed in Caucasians.

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.

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.

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.

Relationship between CHADS2 score and ischemic stroke during rhythm control therapy for paroxysmal atrial fibrillation.

The CHADS2 score has been proposed for stratifying patients with nonvalvular atrial fibrillation (NVAF) according to the risk of thromboembolism in the AHA/ACC/ESC guidelines. However, there is little information about its usefulness for predicting the long-term risk of ischemic stroke in Japanese patients with paroxysmal AF. We retrospectively evaluated the incidence of ischemic stroke and the efficacy of anticoagulant therapy in paroxysmal AF patients on rhythm control therapy who were stratified by their CHADS2 score. The subjects were 334 NVAF atients (229 men and 105 women, mean age, 68 +/- 12 years, mean follow-up period, 60 +/- 35 months) who were categorized into low risk (score 0), moderate risk (1 or 2), and high risk (3 or more) groups for thromboembolism. The low, moderate, and high risk groups accounted for 34%, 50%, and 16% of the patients, respectively. Among 257 patients without warfarin therapy, the annual rate of symptomatic ischemic stroke was 0.6% in the score 0 group, 0.5% in the score 1 group, 3.1% in the score 2 group, and 9.6% in the score 3 or more group. Among 77 patients treated with warfarin (target PT-INR: 1.6-3.0), the stroke rate was 0% in the score 0 group, 0% in the score 1 group, 1.4% in the score 2 group, and 6.6% in the score 3 or more group. The annual rate of ischemic stroke was 0.88% in patients treated with warfarin versus 2.67% in those without warfarin, or a decrease in risk of 68% with warfarin (P < 0.01). In Japanese patients with paroxysmal AF, the CHADS2 score is useful for predicting the risk of ischemic stroke. Anticoagulant therapy is needed to prevent ischemic stroke in patients with paroxysmal AF, especially those who have a CHADS2 score of 2 or more.

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.

Randomized crossover study of the long-term effects of pilsicainide and cibenzoline in preventing recurrence of symptomatic paroxysmal atrial fibrillation: influence of the duration of arrhythmia before therapy.

BACKGROUND: There is little information on the selection of antiarrhythmic agents for long-term prevention of paroxysmal atrial fibrillation (PAF). In the present study the preventive effects of pilsicainide (Pil) and cibenzoline (Cib) were compared in patients with PAF that was defibrillated at <48 h or >or=48 h after onset. METHODS AND RESULTS: A total of 60 patients (45 men, 15 women, mean age 66+/-10 years) were divided into 2 groups: Group I consisted of 22 patients in whom atrial fibrillation (AF) lasted for <48 h before cardioversion and Group II consisted of 38 patients in whom AF lasted for >or=48 h. A randomized, crossover protocol of treatment with Pil (150 mg/day) and Cib (300 mg/day) was used. Mean follow-up was 35+/-18 months. In Group I, the mean duration of maintenance of sinus rhythm was 12.3+/-2.9 months in patients treated with Pil, compared with 12.9+/-2.5 months in those givem Cib (p=NS between 2 groups). Actuarial event-free rates at 1, 3, 6, 12 months were 82%, 68%, 59% and 41%, respectively, in patients treated with Pil, and 91%, 77%, 68% and 50%, respectively, in those givenh Cib (p=NS between 2 groups). In Group II, the mean duration of maintenance of sinus rhythm was 1.6+/-0.5 months in patients treated with Pil, compared with 5.9+/-1.7 months in those given Cib (p<0.01). Actuarial event-free rates at 1, 3, 6, 12 months were 45%, 18%, 8% and 3%, respectively, in patients treated with Pil, and 63%, 45%, 29% and 16%, respectively, in those given Cib (p<0.05, at 12 months). CONCLUSIONS: Prolonged tachycardia (>or=48 h) in patients with PAF seems to cause electrical remodeling. Cib, a multichannel blocker, is considered to be more effective in preventing the recurrence of PAF in the electrically remodeled atria than Pil, a pure sodium-channel blocker.

Factors affecting the blood concentration of ionized magnesium in patients in the acute phase of myocardial infarction.

Magnesium is physiologically active in its free state (Mg2+). In the present study, we attempted to clarify factors affecting blood concentrations of Mg2+ in the acute phase of myocardial infarction (AMI). Subjects were 84 consecutive patients with AMI. Blood samples were collected at the time of admission, 24h after admission, and 1 week after admission, to measure blood concentration of Mg2+ and noradrenaline (NA). Furthermore, to assess daily Mg intake the hardness of local drinking water was determined, and a survey was conducted regarding dietary preferences and habits. Based on the results of this survey, the patients were defined as having a low Mg intake (L Group) or not. In addition, based on chronological shifts in blood Mg2+ concentrations, subjects were divided into the following four groups: Normal group, blood concentration of Mg2+ within normal range at all measurement points; Early recovery group, low at time of admission, but normalized on the next day; Delayed recovery group, low at time of admission, but normalized 1 week after admission; and Unrecovered group, below normal range at all measurement points. The mean blood Mg2+ concentration on admission was 0.52 +/- 0.06 mmol/l, significantly lower than the normal range (P < 0.05). A negative correlation between blood Mg2+ and NA concentrations on admission was observed (r = 0.49, P < 0.005). As a result, blood Mg2+ concentrations were normalized in 94% of subjects by 1 week after admission. Mean blood Mg2+ concentration on admission in the L Group was 0.47 +/- 0.05 mmol/l, significantly lower than that found in other subjects (0.52 +/- 0.05 mmol/l, P < 0.01). Eighty percent of the patients classified into the Unrecovered group belonged to the L Group. These findings suggest that lower blood concentrations of Mg2+ and higher plasma NA levels may be a result of serious AMI. However, chronic Mg intake deficiency may play a partial role in patients whose blood concentrations of Mg2+ remain low for long periods of time.