Rate of conversion and recurrence after sotalol treatment in patients with direct current-refractory atrial fibrillation

BACKGROUND: A number of patients with persistent atrial fibrillation (AF) will not have sinus rhythm (SR) restored by direct current (DC) cardioversion. HYPOTHESIS: In patients with DC-refractory AF, oral pretreatment with sotalol increases the success rate at DC cardioversion. METHODS: Consecutive patients with persistent AF, refractory at a first DC cardioversion, were prospectively included. A comparative group of patients with AF not refractory at DC cardioversion was studied. Oral sotalol treatment was started after unsuccessful DC cardioversion and given at least 7 days before renewed cardioversion. Four weeks after cardioversion, an electrocardiogram was performed. RESULTS: In all, 53 patients were enrolled in the study. Forty-three (81%) in the sotalol group regained sinus rhythm (SR): 10 (19%) of these converted pharmacologically and 33 (62%) after a second DC cardioversion; SR was never restored in 10 patients (19%). After 4 weeks, SR was maintained in 29 patients (67%). The comparative group included 132 patients and differed significantly from the DC-refractory patients only with regard to weight. After 4 weeks, SR was maintained by 50 patients (37%) in this group. CONCLUSIONS: In patients with persistent AF refractory to DC cardioversion, oral pretreatment with sotalol results in a high rate of SR restoration, either pharmacologically or by DC cardioversion. Maintenance of SR at 4 weeks is of sufficient clinical relevance to consider this treatment option in patients with AF refractory to DC cardioversion.     

Conversion and maintenance of sinus rhythm by bepridil in patients with persistent atrial fibrillation.

BACKGROUND: Bepridil has multiple ion-channel blocking effects similar to amiodarone and is expected to have anti-arrhythmic effects that are useful for the management of atrial fibrillation (AF). The aim of this study was to clarify the conversion of persistent AF and maintenance of sinus rhythm (SR) by oral bepridil. METHODS AND RESULTS: Oral bepridil was administered to 112 patients (83 males, 29 females; age: 59.0+/-10.8 years) with persistent AF lasting an average of 5 months. The conversion effects and maintenance of SR after pharmacological or direct current (DC) cardioversion, as well as the incidence of adverse complications, were evaluated. In 65 of 112 (58%) patients, SR was restored within 6 months (average: 2.1 months) following bepridil administration. DC cardioversion was carried out for 21 of the remaining 47 patients with unsuccessful pharmacological conversion, and all had restoration of SR. Eventually, of the 86 patients in total who were restored to SR by either bepridil or DC cardioversion, 70 (81%) patients maintained SR after a mean follow-up of 18 months. No serious adverse complications were observed, except for marked QT prolongation in 2 cases. CONCLUSION: Bepridil showed favorable conversion effects in patients with persistent AF and was highly effective for maintaining SR after pharmacological or electrical cardioversion. However, careful follow-up is necessary for the prevention of torsade de pointes caused by QT prolongation.     

Reliability of Oscillometric Blood Pressure Monitoring in Atrial Fibrillation Patients Admitted for Electric Cardioversion

The reliability of automated oscillometric blood pressure (BP) monitors in atrial fibrillation (AF) has been poorly investigated, only comparing different patients with AF and sinus rhythm (SR), and is a method influenced by individual characteristics. This study compared the reliability of the oscillometric device A&D TM‐2430 (A&D Company, Tokyo, Japan) with that of a mercury sphygmomanometer in AF patients whose SR was restored after electric cardioversion (ECV). Three consecutive BP measurements were obtained on the day before and about 30 days after ECV in stable treatment conditions. Of the 100 patients studied, 63 reported an SR at follow‐up, with a significant increase in systolic BP and a significant decrease in diastolic BP according to both devices. There were no significant differences between the systolic and diastolic biases before and after ECV using Bland Altman analysis (P > .05 each). The oscillometric device analyzed, using three repeated measurements, is reliable in measuring BP in AF patients.     

Amiodarone after unsuccessful direct-current cardioversion of persistent atrial fibrillation

AIM: To assess the safety and efficacy of amiodarone used after unsuccessful direct current (DC) cardioversion of persistent atrial fibrillation (AF). METHODS: The study group comprised 67 patients (F/M 26/41; mean age 61.3+/-11.2 years) after unsuccessful DC cardioversion (DCC) of persistent AF (mean arrhythmia duration 212.6+/-135.2 days) in whom another attempt of DCC was intended. Repeat DC cardioversion was performed after loading with oral amiodarone, for a period necessary to achieve a cumulative dose of up to 12.0-16.0 g. Pretreatment was an outpatient procedure. After successful DC cardioversion all study subjects received a maintenance dose of amiodarone, 100-200 mg daily, aimed at preventing AF. The follow-up period was 12 months. RESULTS: Spontaneous conversion to sinus rhythm (SR) during amiodarone pretreatment was observed in 13 pts (19.2%). DCC was performed in 54 pts and SR was restored in 41 of the study pts (76%). Complications occurred in 3 pts, including 1 case of apparent hyperthyroidism and 2 cases of decreased TSH level, and required amiodarone withdrawal. After 12 months, 72.2% of pts maintained SR on low dose (179.2+/-42.1 mg/day) amiodarone. Spontaneous conversion to SR during amiodarone loading was significantly related to long-term SR maintenance after successful DC cardioversion (p<0.013; RR 2.01; 95% CI 1.34-3.03). CONCLUSION: Pretreatment with amiodarone and repeat DC cardioversion results in sinus rhythm restoration in about 80.6% of pts with persistent AF after an initial unsuccessful attempt. Direct-current cardioversion can be performed safely taking standard precautions for patients receiving amiodarone. At 12 months after successful repeated DC cardioversion, more than 72.2% of pts on low-dose amiodarone maintain SR.     

Blood pressure–lowering efficacy of indapamide SR/amlodipine combination in older patients with hypertension: A post hoc analysis of the NESTOR trial (Natrilix SR vs Enalapril in Hypertensive Type 2 Diabetics With Microalbuminuria)

To examine the antihypertensive efficacy and safety of indapamide sustained‐release (SR)/amlodipine compared with enalapril/amlodipine in patients 65 years and older with uncontrolled blood pressure (BP) on monotherapy, a post hoc analysis of the NESTOR trial (Natrilix SR vs Enalapril in Hypertensive Type 2 Diabetics With Microalbuminuria) was conducted. NESTOR randomized 570 patients (n=197, aged ≥65 years) with hypertension (systolic BP 140–180/diastolic BP <110 mm Hg) to indapamide SR 1.5 mg or enalapril 10 mg. If target BP (<140/85 mm Hg) was not achieved at 6 weeks, amlodipine 5 mg was added with uptitration to 10 mg if required. A total of 107 patients aged 65 years and older received dual therapy (53 indapamide SR/amlodipine and 54 enalapril/amlodipine). Amlodipine uptitration occurred in 22 and 24 patients, respectively. At 52 weeks, mean systolic BP (±SE) reduction was significantly greater with indapamide SR/amlodipine vs enalapril/amlodipine 6.2±2.7 mm Hg (P=.02). Indapamide SR/amlodipine was also associated with a greater BP response rate (88% vs 75%, respectively). Both regimens were well tolerated. Indapamide SR/amlodipine may be more effective than enalapril/amlodipine for lowering systolic BP in patients with hypertension aged 65 years and older.     

Burden and timing of premature atrial contractions after electrical cardioversion of persistent atrial fibrillation do not predict its recurrence

BACKGROUND: The heart is susceptible to recurrence of atrial fibrillation (AF) during the period immediately following conversion to sinus rhythm (SR). It is less clear whether various onset or trigger mechanisms can predict AF recurrence after direct current (DC) cardioversion of persistent AF. METHODS: In this study, 172 patients (117 men), mean age 69 +/- 11 y, and with persistent AF underwent elective electrical cardioversion. A detailed analysis was made of the heart rhythm and potential AF trigger mechanisms based on 5 min electrocardiogram (ECG) recordings after conversion. RESULTS: Of 151 patients discharged in SR, 45 (30%) had a recurrence of AF within 1 wk. Premature atrial contractions (PACs) were the most common potential trigger, occurring on an average of 3/min. They were equally frequent in patients with and without immediate and early reinitiation of AF, and in patients with and without AF recurrence at the 1-wk follow-up visit. Other trigger mechanisms were too infrequent to allow conclusions. CONCLUSION: Premature atrial contractions were the most common potential trigger mechanism occurring immediately after cardioversion in patients with persistent AF. However, they neither predicted immediate and/or early reinitiations, nor recurrences during the first wk after cardioversion.     

Safe and effective conversion of persistent atrial fibrillation to sinus rhythm by intravenous AZD7009

BACKGROUND: Acute drug conversion of persistent atrial fibrillation usually fails. OBJECTIVES: The purpose of this study was to test the proarrhythmic potential, safety, and efficacy of the novel antiarrhythmic agent AZD7009 in patients with persistent atrial fibrillation (AF) or atrial flutter (mean duration 43 days) scheduled for direct current (DC) cardioversion. METHODS: Patients were randomized to AZD7009 (3-hour intravenous infusion; n = 86) or placebo (n = 36). AZD7009 was given in doses intended to produce target pseudo-steady-state plasma levels of 0.25, 0.50, 0.75, 1.0, 1.5, 2.0, or 2.5 micromol/L after 30 minutes of infusion. DC cardioversion was performed if conversion to sinus rhythm (SR) did not occur within 2 hours of infusion. RESULTS: AZD7009 in a concentration-dependent manner increased the rate of conversion of AF to SR and shortened the time to conversion. At the three highest target concentrations of AZD7009, 45%, 64%, and 70% of AF patients converted after a mean time of 62, 55, and 26 minutes, respectively, whereas no placebo-treated patients converted. SR was maintained for 24 hours in 21 of 22 patients with drug-associated conversion. AZD7009 treatment was associated with QT-interval prolongation; the increase in QT corrected according to Fridericia typically ranged from 40 to 80 ms at targeted pseudo-steady-state plasma concentrations >or=0.75 micromol/L, but a number of outliers with QT corrected according to Fridericia >550 ms were seen in the higher concentration groups, particularly after conversion to SR and prolonged infusion. None of the patients exhibited torsades de pointes according to predefined criteria; however, one patient exhibited a nonsustained, polymorphic ventricular tachycardia of eight beats with torsades de pointes-like features after AZD7009 infusion (asymptomatic and discovered only upon retrospective Holter tape analysis). Clinical adverse events (primarily dizziness, bradycardia, hypotension, and nausea) were significantly more common in the highest target concentration AZD7009 group vs placebo (P <.001). CONCLUSION: AZD7009 exhibited dose-dependent effects in converting AF to SR in AF patients and appeared to be associated with a low risk of proarrhythmia despite continued administration during a period of heightened vulnerability.     

A Novel Echocardiographic Predictor of Atrial Fibrillation Recurrence: L‐Wave

Diastolic dysfunction leads to atrial fibrillation (AF) by increasing left atrial pressure and also increases recurrence rate after cardioversion. So, L‐wave, which is associated with severe diastolic dysfunction, could predict recurrent AF after cardioversion. The aim of this study was to investigate predictive value of L‐wave for AF recurrence at first month after electrical cardioversion. A total of 127 patients with persistent AF were evaluated for this study and finally 73 patients were included according to the study criteria. Echocardiographic examinations were performed for all patients before and at 24th hour after electrical cardioversion. Heart rates and rhythms were followed with electrocardiography monitor and 12‐lead ECG at first week and first month. Seventy patients achieved sinus rhythm (SR) after cardioversion and 3 patients who did not go into SR excluded from the study. Patients were divided into 2 groups according to having (group 1) or not having (group 2) L‐wave on echocardiography. Twenty‐two patients (6 men, 16 women) had L‐wave and 48 patients (19 men, 29 women) did not have L‐wave. Duration of AF was longer in group 1 as compared to group 2 (P = 0.03). Mean heart rate was lower in group 1 than in group 2 (P < 0.001). Duration of AF and presence of L‐wave were significant parameters for AF recurrence in univariate analysis, however, presence of L‐wave was the only significant parameter for AF recurrence in multivariate analysis. Ten patients in group 1 (45.5%) and 7 patients (14.6%) in group 2 (P = 0.005) had AF recurrence at the end of first month after cardioversion. L‐wave did predict AF recurrence with 59% sensitivity, 77% specificity, 45% positive predictive value, and 85% negative predictive value at 1 month. Echocardiographic L‐wave could predict the AF recurrence.     

A randomized controlled trial on the blood pressure–lowering effect of amlodipine and nifedipine‐GITS in sustained hypertension

In a multicenter, randomized trial, we investigated whether the long half‐time dihydropyridine calcium channel blocker amlodipine was more efficacious than the gastrointestinal therapeutic system (GITS) formulation of nifedipine in lowering ambulatory blood pressure (BP) in sustained hypertension (clinic systolic/diastolic BP 140‐179/90‐109 mm Hg and 24‐hour systolic/diastolic BP ≥ 130/80 mm Hg). Eligible patients were randomly assigned to amlodipine 5‐10 mg/day or nifedipine‐GITS 30‐60 mg/day. Ambulatory BP monitoring was performed for 24 hours at baseline and 4‐week treatment and for 48 hours at 8‐week treatment with a dose of medication missed on the second day. After 8‐week treatment, BP was similarly reduced in the amlodipine (n = 257) and nifedipine‐GITS groups (n = 248) for both clinic and ambulatory (24‐hour systolic/diastolic BP 10.3/6.5 vs 10.9/6.3 mm Hg, P ≥ 0.24) measurements. However, after missing a dose of medication, ambulatory BP reductions were greater in the amlodipine than nifedipine‐GITS group, with a significant (P ≤ 0.04) between‐group difference in 24‐hour (–1.2 mm Hg) and daytime diastolic BP (–1.5 mm Hg). In conclusion, amlodipine and nifedipine‐GITS were efficacious in reducing 24‐hour BP. When a dose of medication was missed, amlodipine became more efficacious than nifedipine‐GITS.     

Regression to the mean in home blood pressure: Analyses of the BP GUIDE study

The aim of our study was to estimate the size of regression to the mean with home blood pressure (BP) monitoring and compare with that for office BP. Office and home BP measures were obtained from the BP GUIDE (value of central Blood Pressure for GUIDing managEment for hypertension) study, in which 286 patients had BP measured every 3 months for 12 months. Patients were categorized by 10 mm Hg strata of baseline BP, and regression to the mean measures was calculated for home and office BP. High baseline home BP readings tended to be lower on long‐term follow‐up, and low baseline readings tended to be higher. For example, patients in the group with mean baseline home systolic BP ≥ 150 mm Hg had a mean baseline systolic BP of 156 mm Hg, which fell to 143 mm Hg at 12 months; and patients in the group with mean baseline home systolic BP < 120 mm Hg had a mean baseline systolic BP of 113 mm Hg which rose to 120 mm Hg at 12 months. Similar patterns were seen in intervention and control groups, and for diastolic BP. The regression dilution ratio for home systolic BP and diastolic BP was 0.52 and 0.64, respectively, compared to 0.40 and 0.55 for office systolic BP and diastolic BP, respectively. Home BP is subject to regression to the mean to a similar degree as office BP. These findings have implications for the diagnosis and management of hypertension using home BP.     

Long-term results of direct-current cardioversion after open commissurotomy for mitral stenosis

For a 7-year period, cardiac rhythm before and after surgery was determined in 106 patients with mitral stenosis presenting with atrial fibrillation (AF) who had undergone open mitral commissurotomy. Forty-three of the patients reverted to sinus rhythm (SR) after primary or secondary direct-current (DC) cardioversion after surgery and maintained it until discharge from hospital. Thirty patients maintained SR for 3 months to 7.2 years (mean 2.5 years) after surgery. The actuarial maintenance rate of SR was 50% 7 years after surgery in these 43 patients. The duration of AF, preoperative left atrial dimension by M-mode echocardiogram and pathologic classification of the mitral valve were factors supposedly influencing the maintenance of SR for a long period after DC cardioversion. In 30 patients who reverted back to SR and maintained SR late postoperatively, the preoperative duration of AF was up to 5 years, and 35% of the patients had had AF for more than 1 year. Also, in 40% of these 30 patients, the preoperative cardiothoracic ratio was more than 60%. It is concluded that if sinus rhythm is restored by DC cardioversion before discharge from hospital after open mitral commissurotomy, it has a 50% chance of being maintained for 7 years after surgery. Long duration of AF and large cardiothoracic ratio should probably not dissuade one from attempting secondary DC cardioversion in these patients.     

Management of persistent atrial fibrillation following balloon mitral valvotomy: safety and efficacy of low-dose amiodarone

BACKGROUND AND AIM OF THE STUDY: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia encountered in clinical practice. In developing countries, rheumatic mitral stenosis (MS) is the most frequent underlying condition in patients with AF. Sinus rhythm (SR) is difficult to achieve and maintain in these patients, but would be more easily achieved with reduction of left atrial pressure after successful balloon mitral valvotomy (BMV). METHODS: Eighty-five patients with persistent AF following BMV received amiodarone (600 mg once daily for two weeks, 200 mg daily thereafter). Electrical cardioversion was performed in those with persistent AF (at six and 12 weeks of drug therapy). RESULTS: Among patients, 33 (39%) converted with amiodarone alone. Of 52 patients who underwent cardioversion at six weeks, 41 (79%) converted to SR. Overall, 87% of patients converted to SR. None of the 11 patients with persistent AF could be converted to SR, despite a second attempt with direct current (DC) cardioversion at 12 weeks. Those who converted to SR had significantly shorter AF duration (AFD) (2.7+/-1.1 versus 3.2+/-0.7 years) and smaller left atrial (LA) size (50.0+/-7.7 versus 57.9+/-4.7 mm). Patient age, gender, NYHA class, ejection fraction and post-BMV variables were comparable between the two groups. Successful maintenance of SR was possible in 61/74 (82%) patients at a mean follow up of 30.6+/-7.1 months (range: 16-43 months). Again, mean AFD was shorter (1.8+/-0.6 versus 3.0+/-0.7 years) and LA size smaller (48.9+/-7.5 versus 54.7+/-6.9 mm) among those who maintained SR. However, even in patients with AFD > or =2 years, successful conversion and maintenance of SR was possible in 74% and 62% of patients, respectively. Among patients with LA size > or =60 mm (n = 16), the corresponding value were 84% and 77%, respectively. On multivariate analysis, only AFD was a predictor of acute and long-term success. The probability of SR remaining in those with AFD <2 years at 21, 30 and 43 months was 96%, 95% and 94.6%, respectively, while for those with AFD > or =2 years these values were 62%, 48% and 40%. CONCLUSION: Low-dose amiodarone was safe and effective in restoring and maintaining SR in patients with AF and rheumatic heart disease.     

Elevated Diastolic,But Not Systolic,Blood Pressure Measured in the Emergency Department Predicts Future Development of Hypertension in Normotensive Individuals

Elevated blood pressure (BP) is reported in many individuals without hypertension presenting to the emergency department (ED). Whether this condition represents a transient state or is predictive for the development of future hypertension is unknown. This observational prospective study investigated patients admitted to an ED without a diagnosis of hypertension in whom BP values were ≥140/90 mm Hg. The primary outcome was development of hypertension during follow‐up. Overall, 195 patients were recruited and at the end of follow‐up (average 30.14±15.96 months), 142 patients were diagnosed with hypertension (73%). The mean age (50±12.25 vs 48.31±13.9, P=.419) and sex distribution (78 men/64 women vs 24 men/20 women, respectively; P=.148) were similar in both groups. There were significant differences in systolic and diastolic BP between those who developed hypertension on follow‐up and those who did not (177.6 mm Hg±22.6/106.1 mm Hg±16.9 vs 168.6 mm Hg±18/95.2 mm Hg±12.2; P=.011 for systolic BP, P<.001 for diastolic BP). In multivariate analysis the only significant predictive factor for the development of hypertension was diastolic hypertension recorded in the ED (P=.03). Elevated diastolic, but not systolic, BP among patients presenting to the ED is associated with future development of hypertension in previously normotensive individuals.     

Role of oral amiodarone in patients with atrial fibrillation and congestive heart failure

Background

Amiodarone is recognized as the most effective therapy for maintaining sinus rhythm (SR) post cardioversion in patients with atrial fibrillation (AF). It is also recommended for controlling AF in patients with congestive heart failure (CHF). We retrospectively examined the efficacy and safety of oral amiodarone in patients with AF and CHF.

Methods

Forty-eight consecutive AF patients whose left ventricular ejection fraction (LVEF) was less than 50% and B-type natriuretic peptide (BNP) was higher than 100 pg/ml were investigated retrospectively, and divided into 3 groups: paroxysmal AF, 16 patients; persistent AF, 9 patients; and permanent AF, 23 patients.

Results

The permanent AF group had a longer history of AF, larger left ventricular end-diastolic diameter (LVDd) and left atrial diameter (LAD) than paroxysmal and persistent AF groups (p < 0.05). After median follow-up of 265 days, amiodarone suppressed paroxysms in 88% of paroxysmal AF patients, while SR was maintained in all persistent AF patients, and 35% of permanent AF patients. Of the 32 persistent and permanent AF patients, 12 (71%) out of 17 maintained SR after successful electrical cardioversion, and conversion to SR occurred spontaneously in 5 (33%) out of 15. The effective group had significantly smaller LVDd and LAD than the ineffective group. In the effective group, BNP decreased significantly from 723 ± 566 pg/ml to 248 ± 252 pg/ml, (p < 0.0005) and LVEF increased significantly from 33 ± 7% to 50 ± 13% (p < 0.0005) during follow up, while no changes were observed in the ineffective group. The patients with low LVEF (≤30%) benefited comparably from amiodarone to the patients with LVEF >30%. Complications occurred in 24 (50%) patients leading to discontinuation of amiodarone in 11 (23%).

Conclusions

Oral amiodarone helped restore SR in paroxysmal and persistent AF patients with CHF. The successful rhythm control by amiodarone resulted in the improvement of LV function and the decrease of BNP levels.     

Antecedent rest may not be necessary for automated office blood pressure at lower treatment targets

In SPRINT (Systolic Blood Pressure Intervention Trial), use of the Omron 907XL blood pressure (BP) monitor set at 5 minutes of antecedent rest to record BP produced an automated office BP value 7/6 mm Hg lower than awake ambulatory BP at 27 months. The authors studied the impact on automated office BP of setting the Omron 907XL to 0 minutes instead of 5 minutes of rest in patients with readings in the lower normal BP range, similar to on‐treatment BP in the SPRINT intensive therapy group. Patients (n = 100) in cardiac rehabilitation were randomized to three BP readings at 1‐minute intervals using an Omron 907XL BP device set for 5 or 0 minutes of antecedent rest. Mean (±standard deviation) automated office BP (mm Hg) after 5 minutes of rest (120.2 ± 14.6/66.9 ± 8.6 mm Hg) was lower (P < .001/P < .01) than without rest (124.2 ± 16.4/67.9 ± 9.1 mm Hg). When target BP is in the lower normal range, automated office BP recorded without antecedent rest using an Omron 907XL device should be higher and closer to the awake ambulatory BP, compared with readings taken after 5 minutes of rest.     

Similar Blood Pressure Values Across Racial and Economic Groups: Baseline Data from a Group Randomized Clinical Trial

This paper examines baseline characteristics from a prospective, cluster‐randomized trial in 32 primary care offices. Offices were first stratified by percentage of minorities and level of clinical pharmacy services and then randomized into 1 of 3 study groups. The only differences between randomized arms were for marital status (P=.03) and type of insurance coverage (P<.001). Blood pressures (BPs) were similar in Caucasians and minority patients, primarily blacks, who were hypertensive at baseline. On multivariate analyses, patients who were 65 years and older had higher systolic BP (152.4±14.3 mm Hg), but lower diastolic BP (77.3±11.8 mm Hg) compared with those younger than 65 years (147.4±15.0/88.6±10.6 mm Hg, P<.001 for both systolic and diastolic BP). Other factors significantly associated with higher systolic BP were a longer duration of hypertension (P=.04) and lower basal metabolic index (P=.011). Patients with diabetes or chronic kidney disease had a lower systolic BP than those without these conditions (P<.0001). BP was similar across racial and socioeconomic groups for patients with uncontrolled hypertension in primary care, suggesting that patients with uncontrolled hypertension and an established primary care relationship likely have different reasons for poor BP control than other patient populations.     

Temporal changes in atrial refractoriness following DC cardioversion of persistent atrial fibrillation in man.

AIMS: Studies have demonstrated shortening of the atrial effective refractory period (ERP) after episodes of atrial fibrillation (AF). This is termed atrial remodelling. It is unclear whether restoration of SR after persistent AF in patients with a clinical substrate results in reversal of this shortening and whether this is maintained long term. METHODS AND RESULTS: The ERP was determined at mid-lateral right atrial wall (MLRA) and right atrial appendage (RAA) at 600 ms and 400 ms drive cycle lengths and at basic sinus cycle length in 81 patients with persistent AF immediately, 24 h and 2 weeks following external DC cardioversion. All atrially active drugs were stopped for at least 5 half lives. (1) Prolongation of the ERP was observed at both atrial sites and all cycle lengths up to 24 h post cardioversion (p < 0.0001). (2) However, between 24 h and 2 weeks a subsequent shortening occurred in the ERP returning it to near post cardioversion levels. (3) The ERP was significantly longer at 24 h post cardioversion in patients who remained in SR for 2 weeks or longer compared with those who reverted to AF. CONCLUSION: Prolongation of the atrial ERP occurred following restoration of SR in persistent AF patients but was not maintained and displayed a biphasic pattern such that by 2 weeks the ERP had returned to baseline values. Despite this finding, a longer ERP at 24 h post cardioversion was associated with maintenance of SR in the medium-term.     

Daytime Systolic Ambulatory Blood Pressure With a Direct Switch Between Candesartan Monotherapy and the Fixed‐Dose Combination Olmesartan/Amlodipine in Patients With Uncontrolled Essential Hypertension (SEVICONTROL‐1)

A direct switch of candesartan to the fixed‐dose combination olmesartan/amlodipine in uncontrolled hypertension is a frequent clinical requirement but is not covered by current labeling. An open‐label, prospective, single‐arm phase IIIb study was performed in patients with 32 mg candesartan followed by olmesartan/amlodipine 40/10 mg. The primary endpoint was change in mean daytime systolic blood pressure (BP). Mean daytime systolic BP was reduced by 9.2±12.6 mm Hg (P<.0001) after substituting candesartan for olmesartan/amlodipine (baseline BP 140.2±9.7 mm Hg). The reduction in office BP was 9.4±18.4/4.0±9.6 mm Hg; P<.002). Overall, 61.3% of patients achieved a target BP <140/90 mm Hg using office BP and <135/85 mm Hg using ambulatory BP measurement. There were 8 adverse events with a possible relation to study drug and 1 unrelated serious adverse events. In conclusion, patients with uncontrolled moderate arterial hypertension being treated using candesartan monotherapy achieve a further reduction of BP when switched directly to a fixed‐dose combination of olmesartan 40 mg/amlodipine 10 mg.     

Acute Effects of an Oral Nitric Oxide Supplement on Blood Pressure,Endothelial Function,and Vascular Compliance in Hypertensive Patients

This blinded placebo‐controlled crossover study evaluated the acute effects of an orally disintegrating lozenge that generates nitric oxide (NO) in the oral cavity on blood pressure (BP) response, endothelial function, and vascular compliance in unmedicated hypertensive patients. Thirty patients with clinical hypertension were recruited and enrolled in a blinded placebo‐controlled clinical trial in an outpatient setting. Average baseline BP in 30 patients was 144±3/91±1 mm Hg. NO supplementation resulted in a significant decrease of 4 mm Hg in resting systolic BP (P<.003) and a significant decrease of 5 mm Hg in diastolic BP (P<.002) from baseline and placebo after 20 minutes. In addition, there was a further statistically significant reduction by 6 mm Hg in both systolic and diastolic pressure after 60 minutes (P<.0001 vs baseline). After a half hour of a single dose, there was a significant improvement in vascular compliance as measured by augmentation index and, after 4 hours, a statistically significant improvement in endothelial function as measured by the EndoPAT (Itamar Medical, Franklin, MA). A single administration of an oral active NO supplement appears to acutely lower BP, improve vascular compliance, and restore endothelial function in patients with hypertension.     

Use of bepridil in combination with Ic antiarrhythmic agent in converting persistent atrial fibrillation to sinus rhythm.

BACKGROUND: It has been reported that bepridil is as good as amiodarone in converting persistent atrial fibrillation (AF) to sinus rhythm (SR). The conversion effect of bepridil alone is not always satisfactory, however. The efficacy of pharmacological cardioversion by the combination of bepridil and a class Ic antiarrhythmic drug for persistent AF is studied. METHODS AND RESULTS: The participants comprised 37 consecutive patients in whom pharmacological cardioversion was conducted to treat persistent AF (duration 22.5+/-29.6 months). Each patient first received a class Ia or Ic antiarrhythmic drug, then bepridil alone, then a combined therapy of bepridil at 200 mg/day with a class Ic antiarrhythmic drug at a routine dose. Unaccompanied use of any of the antiarrhythmic drugs achieved pharmacological cardioversion in 14 (38%) of the 37 patients (single therapy group), whereas SR was restored by combination of bepridil and a class Ic antiarrhythmic drug in 22 (combined therapy group) of the remaining 23 patients. The duration of AF was significantly longer in the combined therapy group than in the single therapy group (28.3+/-31.0 vs 7.3+/-4.1 months). CONCLUSION: Combined therapy of bepridil and a class Ic antiarrhythmic drug is efficient for pharmacological cardioversion of refractory long-lasting persistent AF.