Electrophysiological and Electroanatomical Mapping of the Right Atrium in Persistent Atrial Fibrillation: Relation to Collagen Turnover.

BACKGROUND: Atrial fibrillation (AF) is associated with abnormal atrial substrate. We investigated whether patients with persistent lone AF and patients with persistent AF and nonischemic dilated cardiomyopathy (NIDCM) exhibit any differences in electrophysiological and electroanatomical properties of right atrium (RA) and collagen turnover. We also investigated the relationship between mean RA bipolar voltage and collagen turnover. METHODS: Ten patients with a history of persistent lone AF and eight patients with a history of persistent AF and NIDCM were studied. Sinus node recovery times (SNRTs) and effective refractory periods (ERPs) at 600 ms, 500 ms, and 400 ms from the high (HLRA) and low (LLRA) lateral RA, proximal coronary sinus (pCS), and right atrial appendage (RAA) were evaluated, and RA electroanatomic mapping was created. Serum N-terminal propeptide of collagen type I (PINP), cross-linked C-terminal telopeptide of collagen type I (CTx), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinases (TIMP-1) were measured as markers of collagen synthesis and degradation. RESULTS: No differences were found in SNRTs, ERPs from the HLRA, LLRA at 600 ms, pCS and RAA, mean RA bipolar voltage, serum PINP, CTx, MMP-1, and TIMP-1 between the two groups. In persistent lone AF, serum levels of TIMP-1 were related with mean HLRA and HPRA bipolar voltage. CONCLUSIONS: Persistent AF patients with or without NIDCM, demonstrate similar changes in electrophysiological and electroanatomical properties of the RA, as well as similar structural changes. Moreover, serum markers of collagen synthesis are correlated with bipolar voltage in specific regions of RA in persistent lone AF.

Sinus rhythm restoration affects collagen turnover in patients with persistent atrial fibrillation.

AIMS: Collagen turnover and atrial fibrosis have been implicated in the generation and perpetuation of atrial fibrillation (AF). We evaluated the importance of serum markers of collagen turnover in predicting the outcome of electrical cardioversion (CV) of persistent AF and the relationship between AF and fibrosis. METHODS AND RESULTS: Serum C-terminal pro-peptide of collagen type-I (CICP) and C-terminal telopeptide of collagen type-I (CITP) were measured in 164 patients with AF before and 2 months after CV. All the patients were successfully cardioverted to sinus rhythm (SR) although in 38 of them AF recurred. Baseline CICP levels were comparable in patients in SR 60 days after CV and in those who experienced a relapse of AF (85.08 ± 16.99 vs. 87.55 ± 10.43 ng/mL, respectively, P = ns). Baseline CITP levels were significantly higher in patients with AF recurrence compared with those who remained in SR (0.48 ± 0.16 vs. 0.32 ± 0.17 ng/mL, respectively, P < 0.0001). In the 126 patients who maintained the SR, CICP levels were significantly lower at the end of the study as compared with the baseline (63.74 ± 15.92 vs. 85.08 ± 16.99 ng/mL P = 0.003), while there was a mild increase in plasma CITP levels (0.36 ± 0.21 vs. 0.32 ± 0.17 ng/mL, respectively, P = 0.03). CONCLUSION: Atrial fibrillation can result in alterations in atrial structure and architecture that make the atrial myocardium more susceptible to the maintenance of the arrhythmia. Sinus rhythm restoration could affect the fibrotic process occurring or exacerbating during AF course.

Mechanisms of arrhythmia recurrence after video-assisted thoracoscopic surgery for the treatment of atrial fibrillation: insights from electrophysiological mapping and ablation.

BACKGROUND: Video-assisted thoracoscopic bilateral pulmonary vein (PV) isolation with left atrial appendage (LAA) excision is a novel surgical treatment for patients who have atrial fibrillation (AF) but no indication for open heart surgery. However, the electrophysiological mechanisms of the recurrent atrial tachyarrhythmias after this procedure are unknown. METHODS: Eight consecutive patients with highly symptomatic atrial tachyarrhythmias after failed video-assisted thoracoscopic surgery were included in this study. A predetermined stepwise ablation protocol, aimed at termination of the arrhythmia and isolation of all PVs, was conducted. The conduction across the remnant of the LAA was also evaluated in 4 patients. RESULTS: Three patients had AF, which was converted into AT by complex fractionated atrial electrogram ablation in 2. Eleven sustained ATs in 7 patients were mapped during the procedure. A majority of ATs (10 of 11) were terminated by ablation before PV isolation. In total, 10 PV gaps in 7 patients were identified. All residual PV gaps were distributed exclusively in the roof or the bottom of the PV antrum. The conduction time across the remnant of the LAA was 90.7 +/- 11.5 ms. One patient underwent a repeat successful ablation procedure. After a mean follow-up of 10.1 +/- 5.0 months after the last ablation procedure, 7 of 8 patients were free of clinical atrial tachyarrhythmias recurrence. CONCLUSION: PV gaps are present, with a characteristic distribution, in the majority of patients who fail this surgical procedure, but these gaps are not responsible for the arrhythmias identified. Instead, most are macro-reentrant, isthmus-dependent arrhythmias related to clamp-associated or LAA excision-associated scars.

Cost-effectiveness of atrial fibrillation catheter ablation.

Radiofrequency catheter ablation has become an established treatment option for the management of patients with atrial fibrillation (AF). Although the concept of a rhythm control strategy devoid of the adverse events related to antiarrhythmic treatment seems highly attractive, further steps are needed in order to improve our understanding of the underlying pathophysiology, refine our ablative techniques, and increase our therapeutic efficacy. Furthermore, the increased cost of AF catheter ablation combined with the substantial number of potential candidates also mandates the evaluation of this invasive treatment through a cost-effectiveness prism. In the present review, we recapitulate the existing evidence pertaining to cost-effectiveness of AF catheter ablation as well as the shortcomings, peculiarities, and distinctive aspects of such a cost-to-benefit analysis.

Achievement of pulmonary vein isolation in patients undergoing circumferential pulmonary vein ablation: a randomized comparison between two different isolation approaches.

INTRODUCTION: Circumferential pulmonary vein ablation (CPVA) with the endpoint of pulmonary vein (PV) isolation has been developed as an effective therapy for atrial fibrillation (AF). This endpoint can be achieved either by closing gaps along circular lines or by segmental PV isolation inside the circular lines after creation of initial CPVA lesions. We investigated whether the clinical outcome depends on the PV isolation approach used during the first-time CPVA procedure. METHODS AND RESULTS: One hundred consecutive patients (69 male; age, 56.7 +/- 11.6 years) who underwent first-time CPVA for treatment of symptomatic AF were enrolled. PV isolation was randomly achieved either by CPVA alone (aggressive CPVA [A-CPVA] group, n = 50) or by a combination of CPVA with segmental PV ostia ablation (modified CPVA [M-CPVA] group, n = 50). Recurrence of atrial tachyarrhythmias (ATa) within 3 months after the initial procedure occurred in 30 patients (60%) in the M-CPVA group and in only 15 patients (30%) in the A-CPVA group (P < 0.01). ATa relapse after the first 3 months was detected in 21 patients (42%) in the M-CPVA group, compared with 9 patients (18%) in the A-CPVA group (P = 0.01). At 13 +/- 4 months, patients treated by the A-CPVA approach had greater freedom from ATa recurrence than patients who underwent M-CPVA (P = 0.01). The M-CPVA approach was the only independent predictor associated with procedural failure (RR 0.318; 95% CI 0.123-0.821; P = 0.02). CONCLUSIONS: When PV isolation is the endpoint of CPVA, the efficacy of the A-CPVA approach is better than that of M-CPVA.

Evidence of mechanoelectric feedback in the atria of patients with atrioventricular nodal reentrant tachycardia.

OBJECTIVE: Patients with atrioventricular nodal reentrant tachycardia (AVNRT) could serve as a clinical model to study the effects of mechanical stretch in the electrical properties of atrial myocardium. MATERIALS AND METHODS: We studied 14 patients with AVNRT. Peak, mean and minimal atrial pressures, atrial refractoriness (ERP) in the right atrial appendage and high right atrial lateral wall and monophasic action potential duration at 90% of repolarisation (MAPd90) in the right atrial appendage were assessed during atrial pacing at 500 and 400 ms and after 2 min of pacing at the tachycardia cycle length. Measurements were repeated from the same positions after ventricular pacing at the same cycle lengths and after 2 min of tachycardia. Susceptibility to atrial fibrillation (AF) was assessed by noting whether AF was induced during ERP evaluation. RESULTS: Atrial pressure showed a statistically significant increase during ventricular pacing compared to baseline. This increase remained substantially unchanged when the tachycardia was induced. A significant reduction in atrial ERP and MAPd90 was also observed during ventricular pacing at all cycle lengths compared to atrial pacing. Two minutes of spontaneous tachycardia were enough to change the atrial ERP and MAPd90 to values significantly lower than those during atrial pacing at the cycle length of tachycardia. During the ERP evaluation AF was induced more often during the tachycardia (28%) than during ventricular (14%) and atrial pacing (0%). CONCLUSION: In AVNRT patients, ventricular pacing and reentrant tachycardia significantly increase right atrial pressures and subsequently shorten ERP and MAPd90, leading to an enhanced propensity for AF.

Long-term clinical outcomes in implantable cardioverter defibrillator recipients on the island of Crete.

PURPOSE: The aim of the current study is to disseminate long-term "real-world" data on mortality and device therapies in primary and secondary prevention implantable cardioverter defibrillator (ICD) recipients on the island of Crete. METHODS: We analyzed data for all consecutive patients who received an ICD in our tertiary university hospital from 1993 until December 2013. Follow-up visits were performed every 6 months or more frequently when indicated. Survival status was recorded, and all stored episodes during interrogation were registered and classified as appropriate or inappropriate. RESULTS: In total, 854 patients received an ICD; 623 (73%) for primary and 231 (27%) for secondary prevention. Most of these patients (490) suffered from ischemic cardiomyopathy. During the mean follow-up of 12.4±7.8 years, 218 (25.5%) patients died; 19.7% in the primary prevention group (p=0.008) and 41.1% in the secondary prevention group. Overall, 248 patients (29%) received appropriate therapy; however, the percentage was significantly higher in the secondary prevention group (44.2%) than in primary prevention group (23.4%). The cumulative incidence of inappropriate therapies during the mean follow-up period was 11.6%. Lead-related complications were noted in 49 patients (5.7%), while only 13 patients (1.5%) suffered device-related infections. CONCLUSIONS: The long-term data related to clinical outcomes in ICD recipients in our center are in accordance with those of other international centers and confirm the high efficacy and safety of these devices in preventing sudden cardiac death.

Comparative efficacy of nebivolol versus carvedilol on left ventricular function and exercise capacity in patients with nonischemic dilated cardiomyopathy. A 12-month study.

PURPOSE: To compare the efficacy of nebivolol versus carvedilol on left ventricular (LV) function and exercise capacity in patients with nonischemic dilated cardiomyopathy (NIDC). METHODS: After enrollment in this double-blind trial, 72 patients, aged 55 +/- 9.5 years, with NIDC, LV ejection fraction (LVEF) < 45%, New York Heart Association classes II to III, were randomized to either nebivolol (34 patients) or carvedilol (38 patients) and were evaluated through echocardiography and exercise tests at baseline and 3 and 12 months after treatment. RESULTS: During follow-up, 4 patients discontinued nebivolol, although 3 patients stopped carvedilol. Patients in both the nebivolol and carvedilol groups showed a steady improvement in New York Heart Association class (P = .002 and < .001, at 12 months, respectively) and LVEF (P = .001 and < .001, at 12 months, respectively) that became significant from 3-month follow-up on. Intergroup analysis showed that carvedilol group had a greater increase in LVEF at 3 (P = .04) and 12 (P = .02) months' follow-up compared with nebivolol group. Advanced diastolic dysfunction regressed to earlier stages in carvedilol patients after 3 (P = .02) and 12 (P = .01) months' treatment, whereas in the nebivolol group, a significant improvement in diastolic dysfunction was found at the 12 months' follow-up (P = .02). Exercise duration improved in both groups at 12 months' follow-up (both P = .01), but in the nebivolol group, there was an initial deterioration at 3 months (P = .07). CONCLUSIONS: Both nebivolol and carvedilol appear relatively safe, with beneficial effects on LV systolic and diastolic function as well as exercise capacity in patients with NIDC after 12 months' treatment. However, carvedilol exhibits more favorable effects on LV function than does nebivolol.

Amino-terminal pro-brain natriuretic peptide predicts ventricular arrhythmogenesis in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators.

STUDY OBJECTIVES: Even in high-risk population groups, not all patients have the same risk of sudden cardiac death (SCD). Given the emerging data about the amino-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP) value in heart failure, we planned to evaluate the importance of NT-proBNP levels in predicting the occurrence of malignant arrhythmias in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators (ICDs). DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: Thirty five ambulatory patients with previous myocardial infarction, left ventricular ejection fraction < 35%, and ICDs for primary prevention of SCD according to Multicenter Automatic Defibrillator Implantation Trial I criteria. INTERVENTIONS: Venous blood samples for plasma NT-proBNP measurement were obtained after 30 min of supine rest from all patients at the beginning of the study. Patients were evaluated every 2 months, or sooner in cases of device discharges, during a 1-year follow-up period. Data concerning arrhythmias and device therapy were stored at the time of device interrogation on each follow-up visit. MEASUREMENTS AND RESULTS: During 1-year follow-up, 11 of 35 patients (31.4%) received 18 antiarrhythmic device therapies for ventricular tachyarrhythmia (VT). Patients who experienced such arrhythmias had NT-proBNP levels of 997.27 +/- 335.14 pmol/L (mean +/- SD), whereas those without VT had NT-proBNP levels of 654.87 +/- 237.87 pmol/L (p = 0.001). An NT-proBNP cutoff value of 880 pmol/L had a sensitivity of 73%, a specificity of 88%, a positive predictive value of 80%, and a negative predictive value of 88% for the prediction of occurrence-sustained VT events. CONCLUSION: To achieve the maximum benefit by ICD therapy, more precise risk stratification is required, even in high-risk, post-myocardial infarction patients. Plasma NT-proBNP levels comprise a promising method that could help in the better identification of a patient group with an even higher risk of sudden death.

Acute electrophysiologic effects of inhaled salbutamol in humans.

STUDY OBJECTIVES: Although inhaled beta2-agonists are in widespread use, several reports question their potential arrhythmogenic effects. The purpose of this study was to evaluate the cardiac electrophysiologic effects of a single, regular dose of an inhaled beta2-agonist in humans. DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: Six patients with bronchial asthma and 12 patients with mild COPD. INTERVENTIONS: All patients underwent an electrophysiologic study before and after the administration of salbutamol solution (5 mg in a single dose). MEASUREMENTS AND RESULTS: Sinus cycle length, sinus node recovery time (SNRT), interval from the earliest reproducible rapid deflection of the atrial electrogram in the His bundle recording to the onset of the His deflection (AH), interval from the His deflection to the onset of ventricular depolarization (HV), Wenckebach cycle length (WCL), atrial effective refractory period (AERP), and ventricular effective refractory period (VERP) were evaluated just before and 30 min after the scheduled intervention. Salbutamol, a selective beta2-agonist, administered by nebulizer had significant electrophysiologic effects on the atrium, nodes, and ventricle. The AH length decreased from 86.1 +/- 19.5 ms at baseline to 78.8 +/- 18.4 ms (p < 0.001), and the WCL decreased from 354.4 +/- 44.2 to 336.6 +/- 41.7 ms (p = 0.001). Salbutamol significantly decreased the AERP and VERP too while leaving the HV unchanged. Additionally, inhaled salbutamol increased heart rate (from 75.5 +/- 12.8 beats/min at baseline to 93.1 +/- 16 beats/min, p < 0.001) and shortened the SNRT (from 1,073.5 +/- 178.7 to 925.2 +/- 204.9 ms, p = 0.001). CONCLUSION: Inhaled salbutamol results in significant changes of cardiac electrophysiologic properties. Salbutamol enhances atrioventricular (AV) nodal conduction and decreases AV nodal, atrial, and ventricular refractoriness in addition to its positive chronotropic effects. These alterations could contribute to the generation of spontaneous arrhythmias.

Adding fentanyl to etomidate fails to reduce painful recall of external direct current cardioversion in adults: a randomised trial.

INTRODUCTION: External electrical cardioversion under hypnotics, even when combined with opioids, has been consistently described as distressing or painful. The main objective of the present study was to determine if adding an opioid to a hypnotic, in comparison to the same hypnotic alone, would decrease the incidence of unpleasant or painful recall during anaesthesia for external electrical cardioversion. METHODS: This was a single-centre, prospective, randomised, double-blinded clinical trial that took place from September 2011 to March 2012. Fifty-two adult patients with persistent atrial fibrillation, scheduled for external direct current cardioversion, were enrolled. Exclusion criteria were age >80 years, previous cardiac surgery, implanted pacemaker or defibrillator, and haemodynamic instability. Patients received intravenously either (group EF) fentanyl 50 g and after 60 s etomidate 0.1 mg/kg, or (group E) only etomidate 0.1 mg/kg. If the patients did not lose their eyelid reflex, repeated doses of etomidate 4 mg were given. Cardioversion was attempted with an extracardiac biphasic electrical shock from 200 to 300 J, at most three times. The primary endpoint was recall of something unpleasant or painful. Secondary outcome measures were predictors of the requirement for repeat doses of etomidate, and the number of shocks needed. RESULTS: Fifty-one patients (35 male, 16 female), aged 62.1 ± 10.2 years, completed the study. There were no differences between group EF and group E regarding recall (unpleasant recall 0 vs. 2 patients, p=0.235; painful recall 1 vs. 0 patients, p=0.510). The administration of etomidate alone was a significant predictor for subsequent repeated doses of etomidate (p=0.049, odds ratio 4.312, 95% confidence interval 1.007-18.460). The number of shocks needed to restore sinus rhythm did not differ between the groups (p=0.846). CONCLUSIONS: In the present study, the addition of fentanyl to etomidate did not diminish distressing or painful experience during anaesthesia for external cardioversion.

Comparative effects of carvedilol and amiodarone on conversion and recurrence rates of persistent atrial fibrillation.

Pretreatment with antiarrhythmic agents could improve cardioversion and recurrence rates in patients with persistent atrial fibrillation. In a prospective controlled trial, 145 patients were randomly assigned to treatment with carvedilol, amiodarone, or placebo for 4 weeks before electrical cardioversion. Although the 2 drugs had similar effects on cardioversion rates, amiodarone was superior in terms of sinus rhythm maintenance after conversion.

Pharmacological cardioversion of recent onset atrial fibrillation with intravenous amiodarone in patients receiving long-term amiodarone therapy: is it reasonable?

In clinical practice the use of intravenous amiodarone has been proposed for the conversion of recurrent atrial fibrillation in patients already under chronic treatment with the same drug. Given that intravenous amiodarone exhibits different electrophysiological properties than when the drug is taken orally over a long period, this approach seems reasonable, but its effectiveness and safety have not been investigated systematically before. Of 45 patients under chronic treatment with amiodarone for the maintenance of sinus rhythm who had atrial fibrillation of recent onset, 23 were given intravenous loading of the same drug for 24 hours and 22 received placebo. Nine patients underwent an electrophysiological study several months after the successful restoration of sinus rhythm, before and after another intravenous loading dose of amiodarone, in order to examine the possible electrophysiological changes. In the amiodarone group 20 patients were successfully converted to sinus rhythm, compared to 13 of the placebo group (p < 0.05). No serious side effects of the intravenous administration were observed. Prolongation of refractoriness was seen in all 9 patients who underwent electrophysiological study after intravenous loading, without any effect on repolarization, atrioventricular conduction or sinus node function. In conclusion an intravenous loading dose of amiodarone exerts an additional electrophysiological effect in patients already under chronic treatment with the same drug. Such a combined therapy could be used with a high efficacy and safety for the conversion of recent onset atrial fibrillation in patients who are receiving long-term amiodarone therapy.

Anaesthesia for cardioversion: a prospective randomised comparison of propofol and etomidate combined with fentanyl.

INTRODUCTION: External electrical cardioversion is mostly performed solely under sedatives or hypnotics, although the procedure is painful. The aim of this prospective randomised study was to compare two anaesthetic protocols that included analgesia. METHODS: Patients with persistent atrial fibrillation were randomised to receive intravenously either fentanyl 50 µg and propofol 0.5 mg/kg (group P) or fentanyl 50 µg and etomidate 0.1 mg/kg (group E), while breathing spontaneously 100% oxygen. In the case of inadequate anaesthesia, repeated doses of 20 mg propofol (group P) or 4 mg etomidate (group E) were given as often as necessary until loss of eyelid reflex. Cardioversion was achieved with an extracardiac biphasic electrical shock ranging from 200 to 300 J, performed three times at most. RESULTS: Forty-six patients (25 in group P, 21 in group E), aged 64 ± 9 years, were enrolled in the study. There were no differences between the study groups concerning left ventricular ejection fraction, the dimension of the left atrium, the number of shocks needed or the number of unsuccessful cardioversions. Patients in group E had a shorter time from injection of the induction agents until loss of consciousness (49 vs. 118 s, p=0.003) and until the first shock was given (61 vs. 135 s, p=0.004). Systolic blood pressure decreased significantly (repeated measurements ANOVA with Bonferroni adjustment) in group P when the baseline value was compared to that after anaesthesia induction (mean decrease 15.2 mmHg, 95% CI 5.6-24.8 mmHg, p=0.001) and to the value after recovery (mean decrease 15.2 mmHg, 95% CI 4.8-25.7 mmHg, p=0.002). Manual ventilation was required in 7 and 9 patients in groups P and E, respectively (p=0.360). CONCLUSION: Both anaesthetic regimens provided excellent conditions for external electric cardioversion. In addition, etomidate in combination with fentanyl had a shorter induction time and ensured haemodynamic stability.

Serum markers of collagen turnover predict future shocks in implantable cardioverter-defibrillator recipients with dilated cardiomyopathy on optimal treatment.

OBJECTIVES: We investigated prospectively whether serum markers of collagen turnover could be used as predictors for the occurrence of malignant ventricular arrhythmias in patients with nonischemic dilated cardiomyopathy (NIDC) who had received an implantable cardioverter-defibrillator (ICD) for primary prevention. BACKGROUND: Extracellular matrix alterations in NIDC might provide electrical heterogeneity, thus potentially contributing to the occurrence of ventricular arrhythmia and subsequent sudden cardiac death (SCD). METHODS: Serum C-terminal propeptide of collagen type-I, C-terminal telopeptide of collagen type-I, matrix metalloproteinase (MMP)-1, and tissue inhibitor of MMP-1 were measured as markers of collagen synthesis and degradation in 70 patients with mild to moderate symptomatic heart failure due to NIDC with left ventricular ejection fraction <35%, who received an ICD for primary prevention of SCD. Patients were evaluated for any appropriate ICD delivered therapy, whether shock or antitachycardia pacing, during a 1-year follow-up period. RESULTS: Appropriate device therapies were delivered in 14 of the 70 patients during the follow-up period, with antitachycardia pacing in 2, antitachycardia pacing with shocks in 4, and shocks in 8. Pre-implantation serum concentrations of C-terminal telopeptide of collagen type-I levels were significantly higher in patients who had appropriate ICD-delivered therapy than in those who did not have any therapy (0.46 +/- 0.19 ng/ml vs. 0.19 +/- 0.07 ng/ml, p < 0.001, respectively). The same was true for baseline MMP-1 and tissue inhibitor of MMP-1 (27.7 +/- 1.6 ng/ml vs. 24.1 +/- 2.5 ng/ml, p < 0.001, and 89 +/- 14 ng/ml vs. 58 +/- 18 ng/ml, p = 0.008, respectively). CONCLUSIONS: If the maximum benefit is to be achieved from ICD therapy in NIDC patients for the primary prevention of SCD, a more precise risk stratification is required. As extracellular matrix alterations affect the arrhythmogenic substrate in NIDC, we observed that serum markers of collagen turnover could predict arrhythmic events in ICD recipients.

Effect of sinus rhythm restoration after electrical cardioversion on apelin and brain natriuretic Peptide prohormone levels in patients with persistent atrial fibrillation.

Because humoral alterations have been implicated in the generation and perpetuation of atrial fibrillation (AF), we aimed to elucidate possible abnormalities in atrial endocrine function in the setting of lone AF. Levels of plasma apelin and amino terminal fragment of the brain natriuretic peptide prohormone (NT-pro-BNP) were measured in 40 patients with persistent AF, before and 1 month after electrical cardioversion, and in 15 controls in sinus rhythm (SR). All patients were successfully cardioverted to SR, although in 9 of them AF recurred. Baseline apelin levels were lower and NT-pro-BNP levels higher in patients with AF compared to controls (380 +/- 186 vs 700 +/- 151 pg/ml, p <0.001, and 615 +/- 611 vs 50 +/- 28 pg/ml, p <0.001, respectively). Maintenance of SR resulted in an increase of apelin and a decrease of NT-pro-BNP levels during the postcardioversion follow-up period compared to baseline (497 +/- 170 vs 368 +/- 178 pg/ml, p <0.001, and 206 +/- 106 vs 398 +/- 269 pg/ml, p <0.001 respectively). Patients who developed AF recurrence by the end of the follow-up period had similar values of apelin and NT-pro-BNP on final and initial evaluations (444 +/- 142 vs 422 +/- 217 pg/ml, p = 0.62, and 1,328 +/- 714 vs 1,362 +/- 862 pg/ml, p = 0.74, respectively). Stepwise logistic regression analysis showed that left atrial diameter (b =-0.49, p = 0.05), and baseline NT-pro-BNP (b = 0.006, p = 0.022), but not apelin, were independent predictors for AF recurrence. In conclusion, this study suggests that endocrine heart function, as judged from apelin and NT-pro-BNP levels, is reversibly modified in the setting of lone AF. This could influence systemic hemodynamics and pharmacologic measures designed to treat this arrhythmia.

Electrophysiological effects of carvedilol administration in patients with dilated cardiomyopathy.

PURPOSE: Several studies suggest the clinical efficacy of carvedilol in reducing atrial and ventricular arrhythmias in patients with left ventricular dysfunction (LVD) due to congestive heart failure (CHF) or following myocardial infarction. However, the mechanisms supporting its antiarrhythmic efficacy have been derived from experimental studies. In this prospective, placebo-controlled trial we examined the electrophysiological effects of a high oral dose of carvedilol in patients with CHF and LVD due to non-ischemic dilated cardiomyopathy. METHODS: Thirty-one patients with stable CHF underwent electrophysiological study and were randomly assigned to treatment with carvedilol or placebo. After 2 months of treatment the study was repeated. RESULTS: Carvedilol prolonged almost all conduction times. In the same group atrial and ventricular effective refractory periods were significantly prolonged, while the parameters of repolarization remained virtually unchanged. The prolongation of refractoriness was most pronounced in the atrium. The change in ventricular refractoriness was correlated with ejection fraction (r = 0.94, p < 0.01) suggesting that patients with more preserved left ventricular function responded to treatment with greater prolongation. CONCLUSION: Even after a short period of administration carvedilol has marked and diffused electrophysiological effects that would be beneficial for patients with CHF and may contribute to the positive outcome of clinical trials.

Extracellular matrix alterations in patients with paroxysmal and persistent atrial fibrillation: biochemical assessment of collagen type-I turnover.

OBJECTIVES: We investigated whether the serum markers of collagen turnover differed in various forms of atrial fibrillation (AF) and in sinus rhythm (SR) in humans. BACKGROUND: Structural alterations and fibrosis have been implicated in the generation and perpetuation of AF. METHODS: Serum C-terminal propeptide of collagen type-I (CICP), C-terminal telopeptide of collagen type-I (CITP), matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinases-1 were measured as markers of collagen synthesis and degradation in 70 patients with AF and 20 healthy control subjects in SR. RESULTS: C-terminal propeptide of collagen type-I and CITP were significantly higher in AF patients than in control subjects (91 +/- 27 ng/ml vs. 67 +/- 11 ng/ml, p < 0.001 and 0.38 +/- 0.20 ng/ml vs. 0.25 +/- 0.08 ng/ml, p < 0.001, respectively). Persistent AF patients had higher levels of CICP (105 +/- 28 ng/ml vs. 80 +/- 21 ng/ml, p < 0.001), but not CITP, compared with those with paroxysmal AF. Patients with persistent AF had lower levels of matrix metalloproteinase-1 but increased levels of tissue inhibitor of matrix metalloproteinases-1 compared with patients with paroxysmal AF (11.90 +/- 4.79 ng/ml vs. 14.98 +/- 6.28 ng/ml, p = 0.03 and 155 +/- 45 ng/ml vs. 130 +/- 38 ng/ml, p < 0.001, respectively). Tissue inhibitor of matrix metalloproteinases-1 levels were significantly lower in control subjects compared with those in both paroxysmal and persistent AF patients (102 +/- 15 ng/ml vs. 130 +/- 38 ng/ml vs. 155 +/- 45 ng/ml, respectively, p < 0.001). CONCLUSIONS: Serum markers of collagen type-I turnover differed significantly between patients with AF and SR. Furthermore, these markers also differed significantly between paroxysmal and persistent AF patients, suggesting that the intensity of the extracellular synthesis and degradation of collagen type-I may be related to the burden or type of AF.

Angiotensin II type 1 receptor inhibition is associated with reduced tachyarrhythmia-induced ventricular interstitial fibrosis in a goat atrial fibrillation model.

BACKGROUND: Using a goat animal model, we tested the hypothesis that angiotensin-II inhibition reduces fibrotic degeneration of both the atrial and ventricular myocardium as well as AF induction susceptibility. METHODS: We studied three groups of five goats over a 6-month period. The study animals in the first two groups were implanted with a pacemaker capable of maintaining AF with burst pacing. Additionally, in one group, goats were administered candesartan (AF+candesartan group). The third group (SR group) of animals served as control. Animals were tested for AF induction on day 0, 1, 30, 90 and 180. A "Vulnerability Index" (VI) for AF induction was calculated, defined as the ratio of total time in AF per number of bursts needed to induce sustained AF, in each session. At the end of the study, all four heart chambers were examined and fibrosis quantified. RESULTS: Both AF goat groups developed cardiomegaly due to tachy-cardiomyopathy. Although, the VI was significantly increased in AF group over time (28.8+/-43 to 284.7+/-291, p=0.045), this was not the case for AF+candesartan group (30.3+/-40 to 170.8+/-243, p=0.23). Histology revealed a significant increase of fibrous tissue in goats with induced AF, noticeable in all four heart chambers, compared to controls. However, the degree of fibrosis was significantly lower in AF animals on candesartan. CONCLUSIONS: Our study demonstrated a beneficial effect of angiotensin II inhibition on tachyarrhythmia-induced ventricular fibrosis. It is also consistent with previous studies indicating a reduction in burst-induced AF susceptibility in goats and confirms the favorable effects in atrial structural remodeling.

Late left ventricular color M-mode Doppler in the assessment of diastolic dysfunction in patients with dilated cardiomyopathy.

The ratio of early (Ep) to late (Ap) color M-mode Doppler flow propagation through the left ventricle helps in the differentiation between normal and pseudonormal (PSN) filling pattern in patients with preserved systolic function. We studied the value of this index in the assessment of diastolic dysfunction for patients with reduced left ventricular systolic function. We studied 80 patients with nonischemic dilated cardiomyopathy and 50 control subjects. According to echocardiography 53 patients had abnormal relaxation and 27 had PSN pattern. Patients had reduced Ep (P < .001) and Ep/Ap ratio (P < .001) and increased Ap (P = .001) compared to controls. Binary logistic regression analysis showed that Ep followed by Ep/Ap ratio (both P < .001) were the best determinants for the discrimination of PSN from normal filling pattern. Ep/Ap ratio, this novel echo-index, increases the diagnostic accuracy of color M-mode Doppler in discriminating normal from PSN filling pattern in patients with left ventricular systolic dysfunction.