Long-term prognostic value of myocardin expression levels in non-ischemic dilated cardiomyopathy.

The mortality of patients with non-ischemic dilated cardiomyopathy (NIDCM) remains substantial. We evaluated gene expression levels of myocardin, an early cardiac gene, in the peripheral blood cells of NIDCM patients as a prognostic biomarker in their long-term outcome and mortality from congestive HF (CHF). We retrospectively analyzed 101 consecutives optimally treated NIDCM patients of Cretan origin who were enrolled from the HF clinic of our hospital from November 2005 to December 2008. Our patient data were either taken from their medical files or recorded during visits to the HF unit or hospitalizations. Follow-up was carried out by telephone interview and by accessing information from general practitioners and cardiologists in private practice. The median follow-up period was 8 years (mean follow-up 7 ± 3.4 years). The overall mortality during follow-up was 61.4%, while mortality due to congestive heart failure (CHF) was 49.5%. Higher CHF and all-cause mortality were observed in patients with myocardin levels < 14.26 (p < 0.001 for both CHF and all-cause mortality). A multivariate Cox regression analysis showed that myocardin level of expression had independent significant prognostic value for the risk of death from CHF (HR 14.5, 95% confidence interval (CI) 5.3-39) in those patients. Peripheral blood cells gene expression of myocardin, an early myocardial marker, may serve as prognostic biomarkers of the long-term outcome of patients with NIDCM. Our findings open new prospects in the risk stratification of these patients.

Impact of Sustained Cardiac Tachyarrhythmias Recorded in Coronary Intensive Care Unit on Short- and Long-Term Mortality and Duration of Hospitalization.

BACKGROUND: Studies conducted in coronary intensive care units (CICUs) have demonstrated that tachyarrhythmias are associated with increased mortality after acute coronary syndromes (ACSs). However, the data for tachyarrhythmias occurred in CICUs due to a variety of cardiovascular disorders are limited. METHODS: We conducted a single-center prospective observational study, which included consecutive CICU patients (January 1, 2014 to May 31, 2018). We recorded the ventricular arrhythmias (VAs), supraventricular tachycardias (SVTs), and days of CICU hospitalization. The patients were followed up for 6 months after CICU discharge. RESULTS: A total of 943 patients (age: 66.37 ±15.4 years; 673 males [71.4%]) were included. Patients with tachyarrhythmias had higher in-CICU mortality (8.0% vs 4.1%, P = .029, odds ratio [OR]: 2.04, 95% confidence interval [CI]: 1.08-3.86) and higher 6-month all-cause mortality (12.8% vs 6.1%, P = .002, OR: 2.27, 95% CI: 1.35-3.83) than those who did not develop tachyarrhythmias. Ventricular arrhythmias was significantly associated with higher all-cause mortality than no tachyarrhythmia (15.4% vs 6.1%; P = .001) or SVTs (15.4% vs 7.0%; P = .001). The mean duration of hospitalization for the patients with tachyarrhythmias was 3.89 ± 4.90 days, while for the patients without was 2.79 ± 3.31 days (P < .001). Patients without ACS had higher short- and long-term mortality compared to patients with ACS (9.2% vs 2.9%, P < .001 and 12.9% vs 4.9%, P < .001). CONCLUSIONS: Tachyarrhythmias were associated with prolonged CICU hospitalization, while non-ACS cardiovascular disorders and the occurrence of VAs were associated with increased short- and long-term mortality.

The impact of paced QRS duration on the expression of genes related to contractile function of the left ventricle in chronically paced patients from the right ventricular apex.

BACKGROUND: Right ventricular (RV) apex has proven to induce abnormal left ventricular (LV) activation pattern leading to pacing-induced cardiomyopathy (PICM) in a substantial percentage of paced patients. This study assessed the impact of paced QRS duration on the expression in the peripheral blood of sarcoplasmic reticulum calcium ATPase (SERCA) and investigated whether its width is related to the extend of LV remodelling. METHODS: We enrolled 52 consecutive patients with preserved ejection fraction (EF) who underwent pacemaker implantation for bradycardic indications. Group A consisted of 24 patients paced for atrioventricular conduction disturbances with QRS = 142 ± 12 ms post-implant and group B of 28 patients paced for sinus node disease with QRS = 94 ± 2%ms post-implant. mRNA levels of SERCA were assesed at implantation, 3, 6 and 12 months follow-up, while echocardiographic parameters at implantation, 1, 2 and 4 years. RESULTS: In group A, mRNA levels of SERCA decreased significantly at 3 months and remained low at 6 and 12 months' follow-up and were associated to the deterioration of LV function and geometry. Paced QRS duration was associated to both the alteration in the expression of SERCA and to the extend of LV remodelling. In group B no statistically significant change was demonstrated. CONCLUSIONS: Permanent RV pacing in patients with preserved EF and wide QRS post-implant is associated with a significant reduction of mRNA levels of SERCA. Paced QRS duration is associated to alterations in the expression of SERCA which precede adverse LV remodelling.

Bradykinin receptors gene expression in white adipose tissue in nondiabetic patients with coronary artery disease.

OBJECTIVES: Adipose tissue plays a key role in cardiovascular physiology. Kinin receptors are important determinant of the effect of adiposity on endothelial function and cardiovascular function. We examined the gene expression levels of kinin receptors in the subcutaneous white adipose tissue (sWAT) of nondiabetic patients with and without coronary artery disease (CAD). PATIENTS AND METHODS: We evaluated 21 patients with CAD (13 men, age: 68±8 years) and 23 patients without CAD (15 men, age: 66±5 years) who underwent catheterization through the femoral route. sWAT biopsies were obtained from the site of vessel puncture before the procedure and analyzed for bradykinin receptor type 1 (BKR1) and 2 (BKR2) gene expression by real-time quantitative PCR. RESULTS: Although BKR2 expression levels did not differ significantly (413.12±532.41 in CAD patients vs. 378.33±534.45 in controls, P=NS), BKR1 expression in sWAT was significantly greater in patients with CAD (352.69±455.12 vs. 46.5±46.7, P<0.05). Notably, BKR1 gene expression levels showed a significant positive correlation with BMI (r=0.45, P<0.002) and total cholesterol levels (r=0.53, P<0.001), and a negative correlation with fasting blood glucose (r=-0.4, P=0.006). CONCLUSION: There is a divergence in BKR1 gene expression in sWAT between patients with and without CAD and is associated with metabolic parameters. More studies are needed to determine the pathophysiological role of BKRs in adipogenesis, fat expansion, and atheromatous disease.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.