Short-term prevention of thromboembolic complications in patients with atrial fibrillation with aspirin plus clopidogrel: the Clopidogrel-Aspirin Atrial Fibrillation (CLAAF) pilot study

Background

We evaluated the short-term safety and efficacy of aspirin-plus-clopidogrel as antithrombotic therapy in nonvalvular atrial fibrillation (AF).

Methods and results

Thirty patients (11 women, 45 to 75 years of age) with non-high-risk permanent (n = 12) or persistent AF awaiting cardioversion (n = 18) underwent transesophageal echocardiography to exclude left heart thrombi and were then randomly assigned to receive warfarin (international normalized ratio, 2 to 3 for 3 weeks) or aspirin (100 mg/d alone for 1 week)-plus-clopidogrel (75 mg/d added to aspirin for 3 weeks). Bleeding time and serum thromboxane B2 were measured at entry and at 3 weeks. Bleeding time, not affected by warfarin, was prolonged by 71% by aspirin (P < .05) and further, by 144%, by adding clopidogrel (P < .01 vs aspirin alone; +319%, P < .01, vs baseline). Thromboxane B2, not affected by warfarin, was reduced by aspirin (−98%, P < .01) but not further by clopidogrel. No thrombi or dense spontaneous echo-contrast were found at the 3-week transesophageal echocardiography. Seven of 9 patients receiving warfarin and 7 of 9 patients receiving aspirin-plus-clopidogrel, undergoing electrical cardioversion, achieved sinus rhythm. No thromboembolic or hemorrhagic events occurred in both arms throughout the 3-week treatment and a further 3-month follow-up.

Conclusions

Aspirin-plus-clopidogrel and warfarin were equally safe and effective in preventing thromboembolism in this small group of patients with non-high-risk AF.     

A randomized trial comparing monophasic and biphasic waveform shocks for external cardioversion of atrial fibrillation

Background

We compared efficacy of and pain felt after biphasic truncated exponential (BTE) and monophasic damped sine (MDS) shocks in patients undergoing external cardioversion of atrial fibrillation (AF).

Methods

Patients with AF were randomized to BTE or MDS waveform cardioversion. Successive shocks were delivered at 70, 100, 200, and 360 J until successful cardioversion, with one 360 J attempt of the alternate waveform when all 4 shocks failed. Success was determined by blinded over-read of electrocardiograms. Peak current was calculated from energy and impedance. Patients rated their pain at 1 and 24 hours after cardioversion.

Results

Fourteen of 37 (38%) patients treated with MDS and 34 of 35 (97%) treated with BTE shocks were cardioverted at ≤200 J (P < .0001). Success rates of MDS versus BTE shocks were 5.4% versus 60% for 70 J, 19% versus 80% for ≤100 J, and 86% versus 97% for ≤360 J. BTE shocks cardioverted with less peak current (14.0 ± 4.3 vs 39.5 ± 11.2 A, P < .0001), less energy (97 ± 47 vs 278 ± 120 J, P < .0001), and less cumulative energy (146 ± 116 vs 546 ± 265 J, P < .0001). Patients felt less pain after BTE than MDS shocks at 1 hour (P < .0001) and 24 hours (P < .0001) after cardioversion.

Conclusion

This BTE waveform is superior to the MDS waveform for cardioversion of AF, requiring much less energy and current, and causing less postprocedural pain.     

Rapid loading of sotalol or amiodarone for management of recent onset symptomatic atrial fibrillation: a randomized, digoxin-controlled trial

Background

Amiodarone and sotalol are commonly used for the maintenance of sinus rhythm, but the efficacy of these agents administered as high-dose infusions for rapid conversion of atrial fibrillation is unknown. Use in this context would facilitate drug initiation in patients in whom ongoing prophylactic therapy is indicated.

Methods

We assessed the efficacy and safety of rapid high-dose intravenous infusions of amiodarone and sotalol for heart rate control and rapid reversion to sinus rhythm in patients who came to the emergency department with recent-onset symptomatic atrial fibrillation. Patients (n = 140) were randomized to receive 1.5mg/kg of sotalol infused in 10 minutes, 10mg/kg of amiodarone in 30 minutes, or 500 μg of digoxin in 20 minutes. Electrical cardioversion was attempted for patients not converting to sinus rhythm within 12 hours.

Results

The rapid infusion of sotalol or amiodarone resulted in more rapid rate control than digoxin. Each of the 3 trial strategies resulted in similar rates of pharmocological conversion to sinus rhythm (amiodarone, 51%; sotalol, 44%; digoxin, 50%; P = not significant). The overall rates of cardioversion after trial drug infusion and defibrillation were high for all groups (amiodarone, 94%; sotalol, 95%,; digoxin, 98%; P = not significant), but there was a trend toward a higher incidence of serious adverse reactions in the amiodarone group.

Conclusion

The rapid infusion of sotalol or amiodarone in patients with symptomatic recent-onset atrial fibrillation results in rapid control of ventricular rate. Even with high-dose rapid infusions, all 3 agents are associated with a poor overall reversion rate within 12 hours. Almost all patients were returned to sinus rhythm with a combination of pharmacological therapy and electrical cardioversion.     

Circadian variation of arrhythmia onset patterns in patients with persistent atrial fibrillation

Background

The circadian onset patterns and cycle lengths of atrial tachyarrhythmias (AT) were determined in a group of patients with persistent atrial fibrillation.

Methods

Fifteen patients, mean age 63 ± 14 years and 80% male, were implanted with the Jewel AF atrial defibrillator (Medtronic, Minneapolis, Minn) for persistent atrial fibrillation only. Onset times of AT and median onset atrial cycle lengths were determined from device memory.

Results

Over a follow-up period of 23.3 ± 7 months, 227 episodes of persistent AT were treated by patient-activated atrial defibrillation. The peak onset of persistent AT was nocturnal, with 74% of episodes initiating between 8 pm and 8 am. Eighty-seven percent of the patients experienced an additional 403 paroxysmal AT episodes. These episodes showed a “double-peaked” pattern with the least number of episodes occurring between midnight and 8 am. The mean onset atrial cycle length of persistent AT was significantly shorter than the paroxysmal AT episodes (200 ± 37 ms vs 240 ± 39 ms, P < .005). The atrial cycle lengths at arrhythmia onset of both paroxysmal and persistent AT episodes also demonstrated circadian variation.

Conclusion

There is a circadian distribution of onsets for persistent AT with predominance at night. Patients with persistent AF have >1 type of atrial arrhythmia with differences in the onset patterns and atrial cycle lengths, suggesting different triggers and onset mechanisms.     

Association of rate-controlled persistent atrial fibrillation with clinical outcome and ventricular remodelling in recipients of cardiac resynchronization therapy

Background

Whether patients with persistent atrial fibrillation (AF) obtain the same degree of benefit with cardiac resynchronization therapy (CRT) as those in sinus rhythm remains unclear.

Methods

We enrolled 93 patients undergoing CRT implantation, 20 (22%) of whom had rate-controlled persistent AF. The primary endpoint was CRT response defined as 1 class improvement in Specific Activity Scale and 15% reduction in left ventricular end-systolic volume (LVESV) during 12 months. Other endpoints included changes in 6-minute walk distance, quality of life, B-type natriuretic peptide, and survival.

Results

Baseline characteristics were similar in those with and without AF. Response to CRT was observed in 42% vs 54% of those with and without AF, respectively (P = 0.3). Both groups had significant improvements in 6-minute walk distance, quality of life, and LVESV, but the improvement in LVESV was smaller in those with AF (13.7% ± 14.9% vs 27.7% ± 23.7%; P = 0.02). During 2.8 ± 1.4 years of follow-up, AF was associated with a 2.2-fold increased risk of death or transplantation (95% confidence interval, 1.2-3.9; P = 0.01).

Conclusions

Compared with patients without rate-controlled persistent AF, those with rate-controlled persistent AF had similar rates of clinical improvement but less left ventricular reverse remodelling in the first year after CRT. AF was associated with a markedly higher risk of death or transplantation in long-term follow-up. Given these findings, randomized studies assessing CRT efficacy in those with AF are warranted.     

Safety of expedited anticoagulation in patients undergoing transesophageal echocardiographic-guided cardioversion

Background

In patients undergoing transesophageal echocardiography-guided cardioversion, we evaluated the use and safety of an expedited in-hospital anticoagulation regimen that incorporates shorter-than-standard durations of precardioversion intravenous unfractionated heparin and postcardioversion bridging therapy with a low-molecular-weight heparin.

Methods

Adult patients who underwent successful transesophageal echocardiography-guided cardioversion for atrial fibrillation or atrial flutter between May 2000 and August 2003 were classified into 2 groups by duration of intravenous unfractionated heparin therapy (<24 h or ≥24 h) before transesophageal echocardiography and cardioversion. Safety end points evaluated included all-cause death, stroke or other thromboembolic events, and major bleeding complications within 1 month after successful cardioversion.

Results

The study population of 386 patients included 199 (52%) who received expedited intravenous unfractionated heparin (<24 h; minimum duration, <4 h) and 193 patients (50%) who were discharged on low-molecular-weight heparin therapy. The adverse event rates at 1-month follow-up were not significantly different between the 2 unfractionated heparin patient groups, and the rate of stroke among patients dismissed on low-molecular-weight heparin was less than 1%. No adverse events occurred among patients who received intravenous unfractionated heparin for less than 12 hours and who were dismissed on low-molecular-weight heparin bridging therapy.

Conclusions

The use of an expedited heparin anticoagulation regimen in patients with atrial fibrillation or atrial flutter undergoing transesophageal echocardiography-guided cardioversion appears to be safe. Cardioversion can be performed as early as a few hours after initiation of intravenous unfractionated heparin, and bridging therapy with a low-molecular-weight heparin can be used after cardioversion until the international normalized ratio is therapeutic.     

Safety and efficacy of angiotensin-converting enzyme inhibitors in symptomatic severe aortic stenosis: Symptomatic Cardiac Obstruction-Pilot Study of Enalapril in Aortic Stenosis (SCOPE-AS)

Background

Animal models have demonstrated a benefit of angiotensin-converting enzyme inhibitors (ACEI) in experimental aortic stenosis (AS), and intravenous nitroprusside has shown hemodynamic improvements in AS with left ventricular (LV) dysfunction. Although routinely used in most heart failure situations, ACEI are avoided in AS because of the risk of hypotension. We aimed to determine the clinical tolerance and efficacy of the ACEI enalapril in the setting of symptomatic severe AS.

Methods

Patients with symptomatic severe AS were enrolled in a randomized, double-blinded, controlled trial to enalapril or placebo arms after initial stabilization. Standard antifailure medications were continued. Enalapril was started at 2.5 mg bid and increased to 10 mg bid. The primary end points were development of hypotension and improvements in Borg dyspnea index and 6-minute walk distance at 1 month. Secondary end points were minor ACEI intolerance, cough, presyncope, improvement in New York Heart Association class, and echocardiographic parameters.

Results

Fifty-six patients were enrolled (37 in the enalapril arm and 19 in the placebo arm). Enalapril was tolerated without hypotension or syncope when LV systolic function was preserved. Three of 5 patients with LV dysfunction and congestive heart failure had hypotension and were withdrawn. Patients who tolerated enalapril (n = 34) demonstrated significant improvement in NYHA class, Borg index (5.4 ± 1.2 vs 5.6 ± 1.7, P = .03), and 6-minute walk distance (402 ± 150 vs 376 ± 174, P = .003) compared with control subjects. Within the enalapril group, patients with associated regurgitant lesions improved the most.

Conclusions

ACEI are well tolerated in symptomatic patients with severe AS. Patients with congestive heart failure with LV dysfunction and low normal blood pressure are prone to have hypotension. Enalapril significantly improves effort tolerance and reduces dyspnea in symptomatic AS.     

Worldwide evaluation of a defibrillation lead with a small geometric electrode surface for high-impedance pacing

Background

Pacing leads with a small electrode surface for high-impedance stimulation have been shown to prolong pacemaker longevity, but no sufficient data is available on the safety and feasibility of a defibrillation lead with this novel design.

Methods

We evaluated the clinical performance of a tined, steroid-eluting defibrillation lead with a small electrode surface area (model 6944) in a prospective multicenter study. A total of 542 patients with conventional indications for an implantable cardioverter defibrillator were randomized 1:1 to receive either the model 6944 or a tined, steroid-eluting defibrillation lead with a conventional sized electrode surface area (model 6942). Device performance and electrical parameters were evaluated at implant and 1, 3, 6, and 12 months thereafter (mean follow-up 11.3 ± 5.6 months).

Results

Baseline characteristics, lead implant success rates, and defibrillation thresholds did not differ significantly between the 2 groups. While pacing thresholds did not differ significantly during follow-up, pacing impedance was approximately twice as high in the model 6944 as in the model 6942 lead (P < .0001). Mean R-wave amplitudes were smaller in patients with a 6944 (9.1 ± 3.1 mV vs 9.8 ± 3.6 mV for model 6942, P < .05), but remained stable within both groups throughout the observation period. The total number of ventricular lead-related adverse events and patient survival did not differ significantly between the 2 groups.

Conclusions

The use of a defibrillation lead with a small electrode surface for high-efficiency pacing is safe and feasible and increases pacing impedance without significantly compromising clinical performance.     

Serum amyloid a and C-reactive protein independently predict the recurrences of atrial fibrillation after cardioversion in patients with preserved left ventricular function

Background

Subclinical inflammation and atrial stretch have been recognized as important contributors to atrial fibrillation (AF) onset and perpetuation. The aim of the study was to compare the predictive role of serum inflammatory markers (serum amyloid A [SAA], and C-reactive protein [CRP]) and N-terminal pro brain natriuretic peptide (NT-proBNP) an indice of atrial strain in relation to subacute arrhythmic recurrence rate in patients with persistent AF and normal left ventricular ejection fraction (LVEF).

Methods

We studied 57 patients with a mean LVEF of 58.7 ± 6%. NT-proBNP, SAA and CRP levels were determined few hours before electrical cardioversion and 3 weeks after cardioversion.

Results

Subacute AF recurrences were documented in 19 (33 %) patients. Whereas NT-proBNP levels did not predict arrhythmic outcome, higher SAA (> 6.16-6.19 mg/L) and CRP levels (> 2.99-3.10 mg/L) were significantly associated with AF recurrences (odds ratio [OR], 5.39; 95% confidence interval [CI], 1.59-18.26; P = 0.007 and OR, 14.93; 95% CI, 3.90-57.19; P < 0.001). Both SAA (OR, 18.29; 95% CI, 2.07-161.46; P = 0.009) and high sensitivity CRP (OR, 42.03; 95% CI, 4.83-365.45; P = 0.001) through the multivariate logistic regression analysis show an independent role in predicting the AF recurrence with a sensitivity of 100% (38/38) and a specificity of 52.6% (10/19).

Conclusions

The present study demonstrates that in patients with persistent AF and preserved LVEF, SAA and CRP levels are independent predictors of AF subacute recurrence rate, whereas NT-proBNP, not associated with arrhythmic outcome, reflects the hemodynamic alterations secondary to arrhythmia presence. The simultaneous determination of SAA and high sensitivity CRP has a very high sensitivity (100%) in predicting the AF recurrence.     

Mechanisms of exercise training in patients with heart failure

Background

The reduction of exercise capacity because of fatigue and dyspnea in patients with heart failure can be improved with exercise training. We sought to examine the mechanisms of exercise training as an adjunctive treatment strategy for patients with heart failure.

Methods

We reviewed the published data on the possible mechanisms of effect of exercise training in heart failure.

Results

Symptoms of heart failure may be explained on the basis of abnormal skeletal muscle perfusion and structure and endothelial function. Exercise training has been shown to engender changes in muscle structure and biochemistry and vascular function, although effects on cardiac function have not been detected uniformly and may require longer training periods.

Conclusions

A suitable, long-term program of exercise training may reverse unfavorable interactions among the heart, vessels, and skeletal muscles. These improvements may be preserved with an ongoing maintenance program.     

Evaluation of resynchronization therapy for heart failure in patients with a QRS duration greater than 120 ms (GREATER-EARTH) trial: rationale, design, and baseline characteristics

Background

Heart failure is considered an epidemic of the modern era. In selected candidates on optimal medical therapy, cardiac resynchronization therapy (CRT) has emerged as a valuable adjunctive treatment. Despite its demonstrated salutary effects on clinical evolution, left ventricular (LV) function, and overall survival, at least 30% of patients fail to respond to CRT.

Methods

The Greater Evaluation of Resychronization Therapy for Heart Failure (GREATER-EARTH) (ClinicalTrials.gov Identifier NCT00901212) is a randomized, double-blind, multicentre study involving 11 centres across Canada and compares LV CRT with biventricular CRT in patients with severe LV dysfunction and a QRS duration > 120 ms.

Results

This article describes the rationale and design of the study and presents the baseline characteristics of all randomized patients. The primary outcome consists of the effects of CRT on submaximal exercise tolerance (treadmill test), and secondary outcomes explore mechanisms of asynchrony and effects of CRT on asynchrony and LV function.

Conclusion

The study was initiated in November 2003, with the last patient randomized on February 12, 2009. As expected, follow-up was in February 2010 and the results are presently being analyzed in March 2010.     

Real-time 3-dimensional echocardiography in assessing atrial and ventricular septal defects: an echocardiographic-surgical correlative study

Objective

The aim of this study is to explore the feasibility and the value of real-time 3-dimensional echocardiography (RT3DE) in quantitative evaluation of the size of atrial septal defect (ASD) and ventricular septal defect (VSD) and to correlate with the surgical findings.

Methods

Thirty eight patients with ASD and/or VSD were examined with RT3DE. Three-dimensional image data-base was post-processed using 3D work-station. The results were compared with the results measured by 2-dimensional echocardiography and surgical findings.

Results

RT3DE produced novel views of congenital septal defects and improved quantification of the size of the defect. The sizes obtained from 3DE have better correlation with surgical findings than diameter measured by 2-dimensional echocardiography (r = 0.69 vs r = 0.92).

Conclusions

RT3DE offers additional special information in congenital heart disease without extending examining time, permits quantitative recording of septal defect dynamics, and enhances the understanding of complex cardiac anatomy and elucidation of the disease mechanism. It is a potentially valuable clinical tool for diagnosing and managing patients with congenital heart disease.     

Transesophageal echocardiography before cardioversion of recurrent atrial fibrillation: does absence of previous atrial thrombi preclude the need of a repeat test?

Background

Atrial fibrillation (AF) is a recurrent problem that frequently requires repeat cardioversion. Transesophageal echocardiography (TEE) is indicated before cardioversion in patients who are underanticoagulated (warfarin therapy <3 weeks or international normalized ratio [INR] <2.0). It remains uncertain if TEE should be repeated in underanticoagulated patients who had no atrial thrombi detected by previous TEE.

Methods and results

From January 1996 to June 2001, 76 patients (43 men, 33 women; mean age, 68.8 ± 10.4 years) who were underanticoagulated and had no atrial thrombi in previous TEE underwent repeat TEE before cardioversion of recurrent AF. The duration of recurrent AF at the time of the second TEE was 5.1 ± 9.3 months (1 day to 4 years). The underlying diseases included coronary artery disease (n = 30), hypertension (n = 22), valvular heart diseases (n = 8), dilated cardiomyopathy (n = 4), hypertrophic cardiomyopathy (n = 2), and others (n = 10). Eight (10.5%) patients (2 men, 6 women; mean age, 68.6 ± 6.6 years) were found to have intra-atrial thrombi on the second TEE. Of these 8 patients, 3 had coronary artery disease, 1 had hypertension, 2 had dilated cardiomyopathy, 1 had hypertrophic cardiomyopathy, and 1 had AF of unknown cause. The duration of recurrent AF in patients with and without thrombi was not significantly different (3.6 ± 4.7 versus 5.3 ± 9.7 months, P = .22). Of the 8 patients with intra-atrial thrombi on the second TEE, 5 had been taking warfarin for 3 to 4 weeks but had subtherapeutic INR and 3 were taking aspirin only. Compared with patients without intra-atrial thrombi, patients with intra-atrial thrombi had lower ejection fraction (32.5% ± 18.1% versus 49.9% ± 14.1%, P = .015), slower left atrial appendage empty velocity (0.22 ± 0.08 versus 0.41 ± 0.17 m/s, P < .01), and higher prevalence of spontaneous echo contrast (87.5%) than in patients without intra-atrial thrombi (19.1%, P < .05) but similar left atrial size (49.5 ± 5.3 versus 47.3 ± 7.1 mm, P = .15). Cardioversion was cancelled in all patients with atrial thrombi.

Conclusions

In underanticoagulated patients, repeat TEE is necessary before cardioversion of recurrent AF even if the previous TEE showed no atrial thrombi.     

Predictors of Atrial Fibrillation Recurrence in Hyperthyroid and Euthyroid Patients

Background

Atrial fibrillation (AF) is the most common arrhythmia in adults, and is encountered in 10-15% of the patients with hyperthyroidism. Unless euthyroidism is restored, pharmacological or electrical cardioversion is controversial in patients with AF who remain hyperthyroid.

Objective

The aim of this study was to assess the efficacy of electrical cardioversion and predictors of AF recurrence in hyperthyroid and euthyroid patients.

Methods

The study included 33 hyperthyroid (21 males) and 48 euthyroid (17 males) patients with persistent AF. The patients were sedated with intravenous midazolam before undergoing electrical cardioversion delivered by synchronized biphasic shocks. Rates of AF recurrence were recorded.

Results

Mean follow-up was 23.63 ± 3.74 months in the hyperthyroid group and 22.78 ± 3.15 months in the euthyroid group (p = 0.51). AF recurred in 14 (43.8%) and 21 (44.7%) patients in each group, respectively (p = 0.93). Multivariate regression analysis in each group showed that AF duration was the only predictor of AF recurrence, with odds ratios of 1.38 (95% confidence interval [CI] = 1.05 - 1.82, p = 0.02) in the hyperthyroid group and 1.42 (95% CI = 1.05 - 1.91, p= 0.02) in the euthyroid group.

Conclusion

Rates of long-term AF recurrence were similar in successfully cardioverted hyperthyroid and euthyroid patients. The only predictor of AF recurrence in both groups was AF duration.     

Coronary ischemic events after first atrial fibrillation: risk and survival

Purpose

We aimed to determine the long-term, gender-specific incidence and mortality risk of coronary ischemic events after first atrial fibrillation (AF).

Methods

In this longitudinal cohort study, adult residents of Olmsted County, Minnesota, with an electrocardiogram-confirmed AF first documented in 1980 to 2000 and without prior coronary heart disease, were followed to 2004. The primary outcome was first coronary events (angina with angiographic confirmation, unstable angina, nonfatal myocardial infarction, or coronary death). Sex-specific incidence of coronary ischemic events and survival after development of such events were assessed using Cox proportional hazards modeling. Kaplan-Meier estimates of risks for coronary ischemic events were compared with those predicted by the Framingham equation.

Results

Of the 2768 subjects (mean age 71 years, 48% were men), 463 (17%) had a first coronary event during a follow-up of 6.0 ± 5.2 years. The unadjusted incidence was 31 per 1000 person-years, and there was no difference between men and women. The incidence was higher in men (hazard ratio 1.32, P = .004) after adjusting for age. The 10-year event estimates were 22% and 19% in men and women, respectively, by our Kaplan-Meier analyses, and 21% and 11%, respectively, by Framingham risk equation. The mortality risk after coronary events was higher in women (hazard ratio 2.99 vs 2.33; P = .044), even after multiple adjustment.

Conclusions

First AF marks a high risk for new coronary ischemic events in both men and women. AF conferred additional risk for coronary events beyond conventional risk prediction in women only. The excess mortality risk associated with the development of coronary events was significantly greater in women.     

Spatial characteristics of atrial fibrillation electrocardiograms

Background

The present study investigates spatial properties of atrial fibrillation (AF) by analyzing vectorcardiogram loops synthesized from 12-lead electrocardiograms (ECGs).

Methods

After atrial signal extraction, spatial properties are characterized through analysis of successive, fixed-length signal segments and expressed in loop orientation, that is, azimuth and elevation, as well as in loop morphology, that is, planarity and planar geometry. It is hypothesized that more organized AF, expressed by a lower AF frequency, is associated with decreased variability in loop morphology. Atrial fibrillation frequency is determined using spectral analysis.

Results

Twenty-six patients with chronic AF were analyzed using 60-second ECG recordings. Loop orientation was similar when determined from either entire 60- or 1-second segments. For 1-second segments, the correlation between AF frequency and the parameters planarity and planar geometry were 0.608 (P < .001) and 0.543 (P < .005), respectively.

Conclusions

Quantification of AF organization based on AF frequency and spatial characteristics from the ECG is possible. The results suggested a relatively weak coupling between loop morphology and AF frequency when determined from the surface ECG.     

The impact of rapid atrial pacing on ADMA and endothelial NOS

Background

The endothelial nitric oxide synthase (eNOS) inhibitor asymmetric dimethylarginine (ADMA) is a well-established risk factor for oxidative stress, vascular dysfunction, and congestive heart failure. The aim of the present study was to determine the impact of rapid atrial pacing (RAP) on ADMA levels and eNOS expression.

Methods and results

ADMA levels were studied in 60 age- and gender-matched patients. Thirty five patients had persistent atrial fibrillation (AF) ≥ 4 months. In AF-patients, parameters were studied before and 24 h after electrical cardioversion. Moreover, ADMA, eNOS expression, and calcium-handling proteins were studied in pigs subjected to RAP as well as in endothelial cell (EC) cultures. ADMA level was significantly higher in AF compared to sinus rhythm patients (p = 0.024). ADMA was highest in AF-patients, who also showed elevated troponin T (TnT) levels. Moreover, ADMA showed a significant linear correlation to TnT (r = 0.47; p < 0.01). After electrical cardioversion ADMA returned to normal within 24 h. In pigs, RAP for 7 h increased ADMA levels (p = 0.018) and TnI (p < 0.05), and reduced mRNA expression of ventricular and aortic eNOS (− 80%; p < 0.05) compared to sham-control. However, ADMA per se did not affect eNOS mRNA level in EC cultures.

Conclusion

The current study shows that acute and persistent episodes of atrial tachyarrhythmia are associated with elevated ADMA levels accompanied by increased ischemic myocardial markers. Moreover, RAP increases ADMA and down-regulates eNOS expression in an ADMA-independent manner. We conclude that the combination of these two separate and potentially synergistic mechanisms may contribute to long-term vascular injury during atrial tachyarrhythmia.     

Hypertension mega-trials with cardiovascular end points: effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers

Background

The renin-angiotensin-aldosterone system has a pivotal role in the short- and long-term regulation of blood pressure through its principal mediator, angiotensin II. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II-receptor blockers (ARBs) decrease the deleterious effects of angiotensin II on the vasculature and heart, but have different mechanisms of action. Although the blood pressure-lowering effect of ACE inhibitors and ARBs is equivalent to that of most other antihypertensive agents, emerging data suggest that these drug classes may have a greater effect on decreasing cardiovascular morbidity and mortality rates in specific patient populations.

Methods

We reviewed large (approximately ≥5000 patients) hypertension clinical trials using ACE inhibitors and ARBs and with cardiovascular morbidity/mortality end points.

Results

Six trials of ACE inhibitors and 5 trials of ARBs (3 completed, 2 ongoing) were selected for this analysis. Data from these hypertension mega-trials suggest that ACE inhibitors and ARBs may decrease cardiovascular morbidity and mortality rates, especially in patients with diabetes mellitus, renal dysfunction, and left ventricular hypertrophy. However, some trials showed important blood-pressure differences and are therefore partly inconclusive for particular drug effects.

Conclusions

Analysis of recently reported and ongoing mega-trials of renin-angiotensin-aldosterone system inhibitors may support the notion that their vasculoprotective properties confer greater benefit by virtue of their effects beyond blood-pressure reduction. Results from trials that will be completed in the next few years may provide further support of blocking the renin-angiotensin-system in cardiovascular protection in the management of hypertension.     

Improving physical fitness in adolescents through a school-based intervention: the EDUFIT study

Introduction and objectives

Physical fitness level is a marker of cardiovascular health in young people. The aim of this study was to analyze the effects of a school-based intervention program, focused on increasing the volume and intensity of physical education (PE) sessions, on adolescents’ physical fitness.

Methods

Sixty-seven adolescents (12-14 years old) from three secondary school classes participated in a 16-week intervention. The classes were randomly allocated to the control group, experimental group 1 (EG1) or experimental group 2 (EG2). The control group received standard PE (2 sessions/week), the EG1 received 4 standard PE sessions/week and the EG2 received four high-intensity PE sessions/week. Aerobic fitness, muscle strength, speed-agility and flexibility were assessed using previously validated field-based tests before and after the intervention.

Results

Doubling the number of PE sessions/week resulted in improvements in aerobic fitness and flexibility (P=.008 and P=.04, respectively). Further increases in the intensity of the sessions were related to improvements in speed-agility (P<.001). The maximal oxygen consumption increased by 3 and 5 mL/kg/min in the EG1 and EG2, respectively. No differences were observed for muscle strength.

Conclusions

The results suggest that doubling the frequency of PE sessions is a sufficient stimulus to improve physical fitness, particularly aerobic fitness, which has been shown to be a powerful indicator of cardiovascular health in children and adolescents. Future studies involving larger sample sizes should confirm or refute these findings.Full English text available from: www.revespcardiol.org     

Use of gadolinium as contrast agent in endoscopic retrograde cholangiopancreatography in patients with iodine allergy

Introduction

Radiologic contrasts are required during endoscopic retrograde cholangiopancreatography (ERCP). The most frequently used are iodine-based contrast media. Controversy still surrounds the optimal strategy in patients with previous adverse reactions to iodine contrasts that need to undergo an ERCP.

Objective

To evaluate the safety and efficacy of a gadolinium-derived contrast medium in patients with previous reactions to iodine-derived agents during ERCP.

Material and methods

Thirteen ERCP were performed in 11 patients with well-established adverse reactions to iodine compounds. ERCP was carried out with gadobutrol, a non-ionic gadolinium compound and without prophylaxis.

Results

In all patients, ERCP were satisfactorily completed. Thirteen cholangiograms and one pancreatogram were obtained. All procedures were technically successful, allowing diagnosis and endotherapy. The quality of the images was good, similar to those obtained with standard contrast media, and did not represent a limitation. No contrast-related adverse events were observed, and there were no post-ERCP complications.

Conclusions

Gadolinium-derived agents are a safe and effective alternative in iodine-allergic patients.