Central sympathetic inhibition to reduce postablation atrial fibrillation recurrences in hypertensive patients: a randomized, controlled study.

BACKGROUND: The autonomic system is an important determinant of atrial arrhythmogenesis. Current evidence indicates that a combined sympathovagal drive is most commonly responsible for eliciting atrial fibrillation (AF) episodes. The purpose of this study was to test whether moxonidine, a centrally acting sympathoinhibitory agent, can lead to a reduction in postablation AF recurrence. METHODS AND RESULTS: This was a prospective, double-blinded, randomized study of 291 hypertensive patients with symptomatic paroxysmal AF who were scheduled to undergo pulmonary vein isolation. Patients were randomly assigned to receive either moxonidine (0.2-0.4 mg daily) or placebo, along with standard antihypertensive treatment. No significant differences in blood pressure levels were observed between the 2 groups. In the primary outcome analysis, mean recurrence-free survival was 467 days (95% CI, 445-489 days) in the moxonidine group as compared with 409 days (95% CI, 381-437 days) in control subjects (log rank test, P=0.006). The calculated 12-month recurrence rate estimates were 36.9% in the control group and 20.0% in the moxonidine group (P=0.007). Moxonidine treatment was associated with lower recurrence risk after adjustment for age, body mass index, number of AF episodes in the previous year, and left atrial diameter (adjusted hazard ratio, 0.35 [95% CI, 0.22-0.55]; P<0.001). CONCLUSIONS: Treatment with moxonidine is associated with less AF recurrences after ablation treatment for drug-refractory AF in patients with hypertension. The observed effect does not appear to depend on the antihypertensive action of this agent. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01791699.

Relation of ventricular tachycardia/fibrillation to beta-blocker dose maximization guided by pacing mode analysis in nonpacemaker-dependent patients with implantable cardioverter-defibrillator.

We hypothesized that uptitration of ß blockade and adjustment of pacing parameters to achieve a prevalence of single chamber atrial inhibited rate-responsive (AAIR) pacing in patients with dual-chamber implantable cardioverter--defibrillators (ICDs) would result in maximization of ß-blocker dosage and thus decrease appropriate ICD therapies. We included patients with ischemic or dilated cardiomyopathy and implanted ICDs without contraindications to ß blockers and atrioventricular conduction disturbances. Two 6-month periods were compared: clinically guided phase (pacing function set at back-up dual-chamber rate-responsive pacing mode at a lower rate of about 40 beats/min) and pacing-guided phase, during which ß-blocker dosage was titrated with a target of achieving >90% AAIR pacing (lower rate 60 beats/min). Sixty-one patients (64.2 ± 8.3 years old) were included. During the pacing-guided phase the target of ≥90% AAIR pacing was achieved in 80.3% of patients. Mean metoprolol dose during the clinically guided phase was 96.7 ± 29.4 versus 127.0 ± 39.6 mg/day in the pacing-guided phase (p <0.001). Appropriate ICD therapies were recorded in 35 patients (57.4%) during the clinically guided phase versus 20 (32.8%) during the pacing-guided phase (p <0.001; 1.15 and 0.48 appropriate ICD therapies per patient, respectively, p <0.001). In multivariate analysis, AAIR pacing and ß-blocker dose were inversely related to appropriate ICD therapies. In conclusion, a pacing-guided approach for maximizing ß-blocker doses guided by maximizing AAIR pacing in patients with ICDs may be beneficial compared to the conventional strategy. This pacing-guided approach led to higher daily ß-blocker doses, which were correlated to fewer appropriate ICD therapies.

Estimation of atrial fibrillation recency of onset and safety of cardioversion using NTproBNP levels in patients with unknown time of onset.

OBJECTIVE: As shown previously in patients with new-onset atrial fibrillation (AF) without symptoms or signs of heart failure, N-terminal pro-brain natriuretic peptide (NTproBNP) increases rapidly, reaching a maximum within 24-36 h, and then decreases even if AF persists. A study was undertaken to use NTproBNP measurements in patients with AF of unknown time of onset to identify patients with presumed recent onset of the arrhythmia. DESIGN: Two-group open cross-sectional study. SETTING: Hospitalised patients in cardiology departments of four hospitals. PATIENTS: Patients presenting with AF of unknown onset and no signs or symptoms of heart failure were separated into two groups: group A with NTproBNP above the cut-off level and group B with a low NTproBNP level. INTERVENTIONS: No therapeutic intervention. All patients underwent transoesophageal echocardiography (TEE). MAIN OUTCOME MEASURES: Presence of left atrial thrombus on TEE. RESULTS: In group A (N=43) only two patients (4.7%) were found to have an atrial thrombus on TEE (negative predictive value of raised NTproBNP levels 95.3%) compared with 13 of 43 patients in group B (30.2%; p=0.002). Patients with a higher CHA(2)DS(2)VASc score (p=0.002) and a larger left atrium (p<0.001) were more likely to have an atrial thrombus. In the multivariate analysis, NTproBNP below the cut-off level was the most powerful predictor of the presence of thrombus (OR 25.0; p=0.016). CONCLUSION: The reported strong correlation between raised NTproBNP levels and the absence of atrial thrombi on TEE suggests that the short-term increase in NTproBNP levels after AF onset might be used to assess the age of the arrhythmia and thus the safety of cardioversion in patients with AF of unknown onset and no heart failure.

Cardioprotective role of remote ischemic periconditioning in primary percutaneous coronary intervention: enhancement by opioid action.

OBJECTIVES: We sought to determine the potential of remote ischemic periconditioning (RIPC), and its combination with morphine, to reduce reperfusion injury in primary percutaneous coronary interventions. BACKGROUND: Remote ischemic post-conditioning is implemented by applying cycles of ischemia and reperfusion on a remote organ, which result in release of circulating factors inducing the effects of post-conditioning on the myocardium. METHODS: A total of 96 patients (59 men) were enrolled. The patients were randomized to groups as follows: 33 to each treatment group (Group A: RIPC; Group B: RIPC and morphine) and 30 to the control group (Group C). Measures of efficacy were achievement of full ST-segment resolution (primary), and reduction of ST-segment deviation score and peak troponin I during hospitalization. RESULTS: A higher proportion of patients in Groups A (73%) and B (82%) achieved full ST-segment resolution after percutaneous coronary intervention, compared with control patients (53%) (p = 0.045). Peak troponin I was lowest in Group B, 103.3 +/- 13.3 ng/ml, in comparison to peak levels in Group A, 166.0 +/- 28.0 ng/ml, and the control group, 255.5 +/- 35.5 ng/ml (p = 0.0006). ST-segment deviation resolution was 87.3 +/- 2.7% in Group B, compared with 69.9 +/- 5.1% in Group A and 53.2 +/- 6.4% in the control group (p = 0.00002). In paired comparisons between groups, Group B did better than the control group in terms of both ST-segment reduction (p = 0.0001) and peak troponin I (p = 0.004), whereas Group A differences from the control group did not achieve statistical significance (p = 0.054 and p = 0.062, respectively). CONCLUSIONS: These findings demonstrate a cardioprotective effect of RIPC and morphine during primary percutaneous coronary intervention for the prevention of reperfusion injury. This is in agreement with observations that the beneficial effect of RIPC is inhibited by the opioid receptor blocker naloxone.

Effect of quinapril on in-stent restenosis and relation to plasma apoptosis signaling molecules.

Angiotensin-converting enzyme inhibitors have been reported to inhibit in-stent restenosis. To assess the effect of angiotensin-converting enzyme inhibition on in-stent restenosis and its relation to apoptosis, 86 patients with chronic coronary artery disease who required stent implantation in the left anterior descending coronary artery or a major diagonal branch were studied. Patients were randomized to receive quinapril 40 mg/day orally (n = 43) or a placebo (n = 43). Drug therapy was initiated 1 week before initial stenting and continued for 6 months. Plasma levels of the apoptotic signaling molecules soluble Fas and soluble Fas ligand obtained from blood drawn from the left anterior descending coronary artery were measured just before initial stenting and 6 months later, at the time of repeat coronary angiography. In-stent restenosis was present in 9.3% of patients in the quinapril group and 25.6% of patients in the placebo group (p = 0.047). Mean late luminal loss was 0.56 +/- 0.51 mm in the quinapril group and 0.95 +/- 0.95 mm in the placebo group (p = 0.003). There were no significant differences in plasma soluble Fas or soluble Fas ligand levels at baseline. At 6 months, the change in plasma soluble Fas level was significantly higher in the quinapril group (0.72 +/- 1.24 ng/ml) than in the placebo group (0.28 +/- 0.72 ng/ml) (p = 0.024). The change in plasma soluble Fas ligand levels at 6 months was significantly higher in the quinapril group (7.43 +/- 12.2 pg/ml) than in the placebo group (0.06 +/- 6.8 pg/ml) (p = 0.002). In conclusion, the angiotensin-converting enzyme inhibitor quinapril inhibits in-stent restenosis by stimulating apoptosis after percutaneous intervention.

Comparison of muscle functional electrical stimulation to conventional bicycle exercise on endothelium and functional status indices in patients with heart failure.

The aim of this prospective, open-label, cohort study was to compare the effect of muscle functional electrical stimulation (FES) on endothelial function to that of conventional bicycle training. Eligible patients were those with New York Heart Association class II or III heart failure symptoms and ejection fractions ≤ 0.35. Two physical conditioning programs were delivered: FES of the muscles of the lower limbs and bicycle training, each lasting for 6 weeks, with a 6-week washout period between them. Brachial artery flow-mediated dilation (FMD) and other parameters were assessed before and after FES and the bicycle training program. FES resulted in a significant improvement in FMD, which increased from 5.9 ± 0.5% to 7.7 ± 0.5% (95% confidence interval for the difference 1.5% to 2.3%, p < 0.001). Bicycle training also resulted in a substantial improvement of endothelial function. FMD increased from 6.2 ± 0.4% to 9.2 ± 0.4% (95% confidence interval for the difference 2.5% to 3.5%, p < 0.001). FES was associated with a 41% relative increase in FMD, compared to 57% with bicycle exercise (95% confidence interval for the difference between the relative changes 1.2% to 30.5%, p = 0.034). This resulted in attaining a significantly higher FMD value after bicycle training compared to FES (9.2 ± 0.4% vs 7.7 ± 0.5%, p < 0.001). In conclusion, the effect of muscle FES in patients with heart failure on endothelial function, although not equivalent to that of conventional exercise, is substantial. Muscle FES protocols may prove very useful in the treatment of patients with heart failure who cannot or will not adhere to conventional exercise programs.

Effect of radiographic contrast media on markers of complement activation and apoptosis in patients with chronic coronary artery disease undergoing coronary angiography.

The effects of radiographic contrast media on markers of complement activation and apoptosis in patients with chronic coronary artery disease (CAD) are unknown. The purpose of this study was to assess the comparative effects of ionic high-osmolar and non-ionic iso-osmolar radiographic contrast media on plasma markers of complement activation and apoptosis in patients with chronic CAD undergoing coronary angiography. Forty-four patients undergoing coronary angiography for chronic CAD were randomly assigned to receive the ionic high-osmolar radiographic contrast agent diatrizoate (Group A), or the non-ionic iso-osmolar contrast agent iodixanol (Group B) during angiography. Complement component 5 (C5a) and apoptotic markers sFas and sFasL were measured just prior to angiography and 1 hour after completion of angiography. Comparison of mean pre- and post-angiography plasma marker levels showed significantly greater increases in plasma levels in Group A than in Group B of C5a (29.30 +/- 5.45 ng/ml for Group A and 0.47 +/- 0.70 ng/ml for Group B (p < 0.00001), sFas (2.36 +/- 1.63 ng/ml for Group A and 0.23 +/- 0.90 ng/ml for Group B (p < 0.00001) and sFasL (14.00 +/- 5.41 pg/ml for Group A and 0.01 +/- 1.00 pg/ml for Group B (p < 0.00001). The results suggest that in patients with chronic CAD, the use of ionic high-osmolar radiographic contrast media during coronary angiography is associated with a more robust inflammatory and apoptotic milieu than that associated with the use of non-ionic iso-osmolar radiographic contrast media.