Effects of Cilazapril on atrial electrical, structural and functional remodeling in atrial fibrillation dogs

Background and purpose

The effects of angiotensin-converting enzyme inhibitor on long-term atrial electrophysiologic and structural remodeling are still unclear. The purpose of this study is to investigate the effects of Cilazapril on atrial electrical, structural, and functional remodeling in atrial fibrillation (AF) dogs induced by chronic rapid atrial pacing.

Methods

Twenty dogs were randomly divided into sham-operated group (n = 6), control group (n = 7), and Cilazapril group (n = 7). One thin silicon plaque containing 4 pairs of electrodes was sutured to each atrium. A pacemaker was implanted in a subcutaneous pocket and attached to a screw-in epicardial lead in the right atrial appendage. The dogs in control group and Cilazapril group were paced at 400 beats per minute for 6 weeks. The dogs in Cilazapril group received Cilazapril (0.5 mg•kg⁻¹•d⁻¹) 1 week before rapid atrial pacing until pacing stop. Before and after 6-week rapid atrial pacing, atrial effective refractory period (AERP) at 8 sites, AERP dispersion, intraatrium conduction time, inducibility, and duration of AF were measured. Transthoracic and transesophageal echocardiographic examinations included left atrium (LA) maximal volume, LA minimal volume, LA ejection fraction, left atrial appendage (LAA) maximal volume, LAA minimal volume, LAA ejection fraction, LAA maximal forward flow velocity, and LAA minimal backward flow velocity were performed. Atrial collagen volume fraction was analyzed by Masson staining.

Results

After 6-week rapid atrial pacing, although there was no significant difference in AERP shortening and AERP rate adaptation reduction between the control group and the Cilazapril group, the inducibility and duration of AF were found to be dramatically lower in the Cilazapril group than those in the control group (AF inducibility, 65.7% vs 95.7%, P < .05; AF duration, 531.5 ± 301.2 vs 1432.2 ± 526.5 s, P < .01).The post-tachycardia intraatrium conduction times after 6 weeks with Cilazapril were significantly shorter than those in the control group. Cliazapril could partially prevent AERP dispersion increase induced by chronic rapid atrial pacing. Compared with the control group, the LA and LAA volumes were significantly smaller; LA ejection fraction, LAA ejection fraction, LAA maximal forward flow velocity, and LAA minimal backward flow velocity were dramatically higher in the Cilazapril group. The Cilazapril group had a significantly lower percentage of interstitial fibrosis than the control group.

Conclusions

Cilazapril can suppress structural and functional remodeling and prevent the induction and promotion of AF in chronic rapid atrial pacing dogs.     

Epicardial ablation of right pulmonary artery ganglionated plexi for the prevention of atrial fibrillation originating in the pulmonary veins

Problem Presented

A novel study of catheter ablation of the right pulmonary artery ganglionated plexi (RPA GP) to reduce atrial fibrillation (AF) originating in the pulmonary veins (PVs) is presented.

Studies Undertaken

In 20 dogs, atrial effective refractory periods (AERPs), PVERP, and the dispersion of AERP (dAERP) were measured at baseline during RPA GP stimulation and after ablation. Programmed stimulation and burst stimulation protocols were performed at 4 distal PVs to measure the percentage of AF induced before and after ablation.

Results

Stimulation of the RPA GP shortened AERP (116 ± 16 vs 130 ± 10 milliseconds, P < .01) and PVERP (122 ± 14 vs 136 ± 12 milliseconds, P < .01), and increased dAERP (31 ± 6 vs 23 ± 6 milliseconds, P < .01). However, the above indices revealed an adverse change after excision (AERP, 138 ± 7 vs 130 ± 10 milliseconds; PVERP, 146 ± 18 vs 136 ± 12 milliseconds; and dAERP, 19 ± 5 vs 23 ± 6 milliseconds; P < .05). Furthermore, the percentage of AF induced from PVs was significantly reduced with vagosympathetic stimulation (40% vs 90%, P < .01).

Conclusions

Ablation of the RPA GP changes the electrophysiologic properties of both the atria and the PVs and decreases AF inducibility arising from the PVs.     

Improvement in sympatho-vagal imbalance and heart rate variability in patients with mitral stenosis after percutaneous balloon commissurotomy.

Elevated sympathetic nerve activity in patients with mitral stenosis (MS) may be an index of the severity of the disease. Percutaneous mitral balloon commissurotomy (PMBC) is now a standard treatment for many patients with symptomatic MS. We aimed to show the effects of PMBC on autonomic nervous system activity in the patients with MS by heart rate variability (HRV) analysis. Fifty-four consecutive patients with mitral stenosis and sinus rhythm who underwent percutaneous mitral commissurotomy were enrolled. Apart from significant haemodynamic improvements, mean heart rate (HR), LF day, LF night, LF/HF day and night significantly decreased and SDNN, RMSSD, PNN50, HF day and night significantly increased in the early period after PMBC and these changes were preserved for up to one month. SDNN was positively correlated with left ventricle ejection fraction (LVEF) but negatively correlated with mean valve area (MVA), left atrial (LA) diameter and pressure, right atrial (RA) pressure; LF/HF day ratio was positively correlated with LA diameter and pressure, mean transmitral gradient and negatively correlated with LVEF; LF/HF night ratio was positively correlated with LA pressure and mean transmitral gradient. The increase in SDNN was correlated with the change in LA and RA pressure. The decrease in LF/HF ratio after PMBC was significantly correlated with the changes in the mean transmitral gradient, LA pressure and RA pressure. As a result, the heart rate variability and autonomic nervous system function in patients with mitral stenosis are correlated with the atrial pressures and left ventricular function. These parameters significantly change in the early period after PMBC and are preserved at one month. The improvement in the heart rate variability and sympatho-vagal balance are significantly affected by the early changes in atrial pressures after PMBC.     

Expression of spliceosome assembly factor SC-35 in TUNEL-positive atrial cardiomyocytes in mitral and tricuspid regurgitation: Viability of atrial cardiomyocytes

Background

Most of the atrial cardiomyocytes with positive terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end-labelling (TUNEL) reaction are not apoptotic in patients with mitral and tricuspid valve diseases. The TUNEL-positive myocytes with expression of spliceosome assembly factor SC-35, an indicator of increased RNA synthesis, should be living cardiomyocytes.

Methods

This study analyzed twenty-three patients with significant mitral and tricuspid regurgitation. Fifteen patients had persistent atrial fibrillation, and eight had sinus rhythm. Atrial appendageal tissues were obtained during surgery. Immunohistochemical study was performed.

Results

Immunohistochemical study of fibrillating right atrial myocardium demonstrated that 44.8 ± 24.6% of myocytes had TUNEL-positive nuclei whereas 39.4 ± 21.4% of myocytes had TUNEL-positive nuclei in sinus right atrial myocardium (p = 0.682). However, most (81.6%) nuclei of TUNEL-positive myocytes in the fibrillating right atria also expressed proliferating cell nuclear antigen (PCNA), an indicator of DNA replication and repair, and most nuclei (91.8%) of TUNEL-positive myocytes also expressed SC-35. In fibrillating left atria, most (88.1%) nuclei of TUNEL-positive myocytes also expressed SC-35. Similarly, in sinus right atrial myocardium, most (78.0%) nuclei of TUNEL-positive myocytes expressed PCNA, and most (91.4%) nuclei of TUNEL-positive myocytes also expressed SC-35, but none expressed Ki-67, a replication-associated antigen. Additionally, the percentage of TUNEL-positive myocytes in the right atria significantly and positively correlated with the percentage of PCNA-positive myocytes (r = 0.826, p < 0.001) and SC-35 positive myocytes (r = 0.713, p < 0.001).

Conclusions

Most TUNEL-positive atrial cardiomyocytes in patients with mitral and tricuspid regurgitation are living cardiomyocytes.     

Serial monitoring of reverse left-atrial remodeling after pulmonary vein isolation in patients with atrial fibrillation: A magnetic resonance imaging study

Purpose

To prospectively determine the impact of sinus rhythm restoration on left-atrial (LA) volumes and function assessed by cardiac magnetic resonance (CMR) imaging within the first year after pulmonary vein isolation (PVI).

Methods

Forty-one patients (28 men; age: 57 ± 10 years) with paroxysmal or non-paroxysmal atrial fibrillation were studied serially using CMR at baseline and at 1-, 3-, 6- and 12-month intervals following PVI. LA diastolic and systolic volumes were determined by cine imaging with full gapless LA coverage applying Simpson's rule. Successful PVI was defined by a persisting sinus rhythm during the 12-month follow-up after a 3-month blanking period; patients with a relapse of atrial fibrillation after the blanking period were censored (4 patients at 6-month follow-up and additional 6 patients at 12-month follow-up).

Results

In all patients, LA diastolic and systolic volumes decreased significantly and progressively during the 12-month follow-up (p < 0.001 and p = 0.001, respectively). At baseline patients with successful PVI demonstrated a significantly smaller LA diastolic volume compared to patients with relapsed atrial fibrillation (p = 0.009). During the 3-month blanking period, patients with successful PVI showed a significant decrease of LA diastolic and systolic volumes (p = 0.026 and p = 0.006, respectively) and a significant increase of LA ejection fraction (p = 0.028); patients with subsequent relapse of atrial fibrillation, however, exhibited no significant change of LA diastolic and systolic volumes or LA ejection fraction.

Conclusion

Restoration of sinus rhythm led to a significant and progressive decrease of left-atrial diastolic and systolic volumes during one year following pulmonary vein isolation.     

Role of atrial electrophysiology and autonomic nervous system in patients with supraventricular tachycardia and paroxysmal atrial fibrillation

Objectives. The purposes of this study were to evaluate the atrial electrophysiology and autonomic nervous system in patients who had paroxysmal supraventricular tachycardia (PSVT) associated with paroxysmal atrial fibrillation (PAF).Background. PAF frequently appeared in patients with PSVT. However, the critical determinants for the occurrence of PAF were not clear.Methods. This study population consisted of 50 patients who had PSVT with (n = 23) and without (n = 27) PAF. Atrial pressure, atrial size, atrial effective refractory periods (AERPs), and AERP dispersion were evaluated during baseline and PSVT, respectively. Twenty-four hour heart rate variability and baroreflex sensitivity (BRS) were also examined.Results. There was greater baseline AERP dispersion in patients with PAF than in those without PAF. The atrial pressure, atrial size, AERPs in the right posterolateral atrium and distal coronary sinus, and AERP dispersion were increased during PSVT as compared with those during baseline. Patients with PAF had greater AERP dispersion than those without PAF during PSVT. The differences of atrial size, right posterolateral AERP, and AERP dispersion between baseline and PSVT were greater in patients with PAF than in those without PAF. BRS, but not heart rate variability, was higher in patients with PAF than in those without PAF. Univariate analysis showed that higher BRS (>4.5 ms/mm Hg, p = 0.0002, odds ratio = 16.1), AERP dispersion during PSVT (>40 ms, p = 0.0008, odds ratio = 9.7), and increase of right atrial area during PSVT (>2 cm², p = 0.016, odds ratio = 10.7) were significantly correlated with the occurrence of PAF in patients with PSVT.Conclusions. Disturbed atrial electrophysiology and higher vagal reflex could play important roles in the genesis of PAF in patients with PSVT.     

风心病二尖瓣狭窄合并窦性心律患者经皮球囊二尖瓣成形术后即刻P波离散度变化与左房平均压变化之间的关系

目的探讨风心病二尖瓣狭窄合并窦性心律患者经皮球囊二尖瓣成形术(PBMV)后即刻P波离散度(Pd)变化与左心房(左房)平均压(LMAP)变化之间的关系。方法选取成功进行PBMV风心病二尖瓣狭窄合并窦性心律患者32例,测量PBMV术前、术后即刻Pd、LMAP、二尖瓣口面积(MVA)及左房大小(LAS),计算Pd变化值,并与LMAP、MVA和LAS变化值行相关性分析。结果PBMV术后即刻Pd与LMAP明显减小(P<0.05)、MVA明显增加(P<0.05)、LAS无明显变化(P>0.05);Pd变化值仅与LMAP变化值之间具有相关性。结论风心病二尖瓣狭窄合并窦性心律患者PBMV术后即刻Pd变化与LMAP变化可能有关,提示心房牵张可能是引起风心病二尖瓣狭窄合并窦性心律患者Pd变化的原因。     

Regional differences in the recovery course of tachycardia-induced changes of atrial electrophysiological properties

BACKGROUND: Regional differences in recovery of tachycardia-induced changes of atrial electrophysiological properties have not been well studied. METHODS AND RESULTS: In the control group (5 dogs), atrial effective refractory period (AERP) and inducibility of atrial fibrillation (AF) were assessed before and every 4 hours for 48 hours after complete atrioventricular junction (AVJ) ablation with 8-week VVI pacing. In experimental group 1 (15 dogs), AERP and inducibility of AF were assessed before and after complete AVJ ablation with 8-week rapid right atrial (RA) pacing (780 bpm) and VVI pacing. In experimental group 2 (7 dogs), AERP and inducibility of AF were assessed before and after 8-week rapid left atrial (LA) pacing and VVI pacing. AERP and inducibility and duration of AF were obtained from 7 epicardial sites. In the control group, atrial electrophysiological properties obtained immediately and during 48-hour measurements after pacing did not show any change. In the 2 experimental groups, recovery of atrial electrophysiological properties included a progressive recovery of AERP shortening, recovery of AERP maladaptation, and decrease of duration and episodes of reinduced AF. However, recovery of shortening and maladaptation of AERP and inducibility of AF was slower at the LA than at the RA and Bachmann's bundle. CONCLUSIONS: The LA had a slower recovery of tachycardia-induced changes of atrial electrophysiological properties, and this might play a critical role in initiation of AF.     

Midterm results of left atrial bipolar radiofrequency ablation combined with a mitral valve procedure in persistent atrial fibrillation

Introduction

The aim of the study was to assess the midterm results of left atrial bipolar radiofrequency ablation combined with a mitral valve procedure in patients with mitral valve disease and persistent atrial fibrillation.

Methods

Between October 2006 and July 2009, 95 patients with mitral valve disease and persistent atrial fibrillation underwent a mitral valve procedure and left atrial bipolar radiofrequency ablation. The postoperative data of the combined procedure were collected at the time of discharge and at one, three, six and 12 months after the operation.

Results

Hospital mortality rate was 6.3% (six patients). Normal sinus rhythm was achieved in 77.2% of patients during the early postoperative period in hospital, and in 73.3, 72.0 and 75% of patients at three, six and 12 months postoperatively, respectively. Patients were followed up for a mean duration of 14.02 ± 5.71 months (range: 6–19 months). During this midterm follow-up period, nine patients had late recurrence of atrial fibrillation. No risk factor was identified for late recurrence of atrial fibrillation.

Conclusion

Our midterm follow-up results suggest that the addition of left atrial bipolar radiofrequency ablation to mitral valve surgery is an effective and safe procedure to restore sinus rhythm in patients with chronic atrial fibrillation.     

Long-term changes in sequence of atrial activation and refractory periods: no evidence for "atrial memory".

OBJECTIVES: The purpose of this study was to test whether the spatial distribution of the atrial refractory period (AERP) and the vulnerability to atrial fibrillation (AF) are altered by long-term changes in the sequence of atrial activation. BACKGROUND: The spatial distribution of the AERP plays an important role in AF. Changes in the activation sequence have been postulated to modulate atrial repolarization ("atrial memory"). METHODS: Six goats were chronically instrumented with epicardial atrial electrodes to determine activation time and AERP at 11 different areas of the right (RA) and left (LA) atrium and the Bachmann bundle. Activation time and AERP were measured during sinus rhythm and during prolonged RA and LA pacing (1 week RA pacing, 2 weeks LA pacing, 1 week RA pacing; 150 bpm). Inducibility of AF was determined by the number of atrial sites where single premature stimuli induced AF paroxysms >1 second. RESULTS: During sinus rhythm (106 +/- 4 bpm), AERP was longest at the Bachmann bundle and shortest at the LA free wall (185 +/- 6 ms and 141 +/- 5 ms, P < .001). In five of six goats, an inverse correlation between local activation time and AERP was found during sinus rhythm (r = -0.53 +/- 0.05; P < .05). The increase in atrial rate during RA and LA pacing caused an overall shortening of AERP from 167 +/- 6 ms to 140 +/- 6 ms (P < .001). However, a switch between long-term RA and LA pacing did not significantly change AERP at any of the 11 atrial regions and had no significant effect on AF inducibility. CONCLUSIONS: During sinus rhythm, an inverse relationship exists between the sequence of atrial activation and the local refractory period. However, long-term changes in the sequence of atrial activation do not alter the spatial distribution of AERP or the inducibility of AF.     

Net atrioventricular compliance can predict persistent pulmonary artery hypertension after percutaneous mitral balloon commissurotomy

Background

Pulmonary hypertension is a common complication of rheumatic mitral stenosis (MS). Patients with similar mitral valve (MV) areas may have different pulmonary artery pressures. Net atrioventricular compliance (Cn) was found to play an important role in the development of pulmonary hypertension.

C-reactive protein elevation independently influences the procedural success of percutaneous balloon mitral valve commissurotomy

Background

Markers of systemic inflammation including C-reactive protein (CRP) appear to predict morbidity and mortality in various clinical conditions. The presence of systemic inflammation and its impact on the procedural success of percutaneous balloon mitral valve commissurotomy (PBMC) in patients with rheumatic mitral stenosis has not been previously demonstrated.

Methods

Measurements of CRP with a high-sensitivity assay were performed at the time of PBMC or during post-procedural follow-up in 119 patients with mitral stenosis of rheumatic morphology. Patients were questioned to exclude confounders of CRP elevation and categorized into undetectable (≤0.10 mg/L) and detectable (>0.10 mg/L) CRP levels. Detectable levels were further classified into assay range (>0.10 and ≤6.0 mg/L) and elevated (>6.0 mg/L).

Results

CRP was detectable in 76% of patients and elevated (>6.0 mg/L) in 36% of patients studied. Procedural success occurred in 89% of patients with undetectable CRP, as compared with only 67% in patients with detectable CRP (P = .028). This effect remained after controlling for age and valve score (previously described predictors of PBMC success).

Conclusions

Systemic inflammation is common in patients with rheumatic mitral valve stenosis, and the relationship between procedural success and CRP suggests persistent inflammation may affect the results of PBMC.     

Effect of electrical and structural remodeling on spatiotemporal organization in acute and persistent atrial fibrillation

INTRODUCTION: Atrial fibrillation (AF) may originate from discrete sites of periodic activity. We studied the effect of structural and electrical remodeling on spatiotemporal organization in acute and persistent AF. METHODS AND RESULTS: Atrial effective refractory periods (AERPs) were recorded from five different sites at baseline and after pacing in acute AF (n = 8 dogs) and persistent AF (n = 8). Four persistent AF dogs subsequently were cardioverted to sinus rhythm to allow AERP recovery. Periodicity was quantified by calculating power spectra on left atrial electrograms obtained from a 64-electrode basket catheter. Left atrial size was measured by intracardiac echocardiography and structural changes were assessed by electron microscopy. Mean AERPs decreased after pacing in acute (128 +/- 16 msec to 108 +/- 29 msec, P < 0.001) and persistent AF (135 +/- 16 msec to 104 +/- 24 msec, P < 0.0001). AERP recovery was established after 7 days of sinus rhythm. Structural changes were mild in acute AF, severe in persistent AF, and remained severe after AERP recovery. A single dominant frequency was identified in 94% of acute AF bipoles, 57% in persistent AF, and 76% after AERP recovery. Average correlation coefficient was 0.82 among acute AF bipoles, 0.63 in persistent AF, and 0.73 after AERP recovery. CONCLUSION: Transition from acute to persistent AF is associated with loss of spatiotemporal organization. A single dominant frequency recruits the majority of the left atrium in acute AF. Persistent AF, however, is associated with structural remodeling and dominant frequency dispersion. Recovery of refractoriness only partially restores spatiotemporal organization, indicating a major role for structural remodeling in the maintenance of persistent AF.     

Postnatal outcome of fetal bradycardia without significant cardiac abnormalities

Background

A heart rate <100 beats/min may be present in 5% of fetuses with arrhythmia. In this study, we sought to define the feasibility of in utero diagnosis of the underlying mechanisms and the postnatal outcome.

Methods

The types of fetal bradycardia were defined by fetal echocardiogram. Fetuses with transient sinus bradycardia were excluded.

Results

From 1995-2000, a total of 18 fetuses were found to have bradycardia. Postnatal 12-lead electrocardiograms made at least 3 times during follow-up confirmed the cardiac rhythm in all except those terminated during pregnancy. Sick sinus bradycardia was noted in 4 patients (22 %), of whom 1 had a positive family history and 2 received permanent pacemakers at age 4 and 5 years. Frequent nonconducted atrial premature beats or nonconducted atrial bigeminy or trigeminy were noted in 5 (28%). All of them revealed normal sinus rhythm after birth. Atrioventricular (AV) block was noted in 6 (33%), of whom 3 were terminated due to severe heart failure, and another 2 fetuses received permanent pacemaker implantation soon after birth. Only 1 fetus whose mother showed normal levels of C3 and C4 recovered at late gestation. Most importantly, 3 patients (17%) developed intermittent bradycardia (AV block) and ventricular tachycardia during the fetal stage. They were found to have long QT syndrome. Two of them died during early infancy. One received in utero propranolol and postnatal propranolol and nicorandil with satisfactory control.

Conclusion

The mechanisms responsible for fetal bradycardia were diverse and could be characterized by fetal echocardiography. The prognosis was poor in those with long QT syndrome manifested as intermittent fetal bradycardia and tachycardia with AV dissociation.     

Pulmonary venous structural remodeling in a canine model of chronic atrial dilation due to mitral regurgitation

OBJECTIVE:

Structural remodelling plays an important role in the genesis and maintenance of atrial fibrillation (AF). Although some studies that associate structural remodelling with atrial dilation have been reported, structural pulmonary venous (PV) remodelling due to chronic atrial dilation remains unclear.

METHODS:

Six sham dogs and five mitral regurgitation (MR) dogs (three months after partial mitral valve avulsion) were studied. Separate cryosections from the PV and left atrium (LA) were immunolabelled with antibodies against connexin (Cx) 40 and Cx43 and analyzed by confocal laser scanning microscopy. Tissue samples from the PV and LA were stained with hematoxylin and eosin, and Masson’s trichrome.

RESULTS:

In MR models, a decrease in Cx40 (0.57±0.2% versus 1.18±0.3%, P<0.05) and Cx43 (0.48±0.2% versus 1.56±0.5%, P<0.05) expression was observed compared with sham dogs. The distribution pattern of Cx40 and Cx43 changed from homogeneous to heterogeneous. Gap junction remodelling was not observed in the LA. In Masson’s trichrome-stained sections from MR dogs, regions with increased interstitial fibrosis were present in the PV. Thickness in the PV and the PV-LA junction did not change in the MR group.

CONCLUSION:

The present study demonstrated a decrease in Cx40 and Cx43 expression and increased interstitial fibrosis in PV due to MR. These changes may potentially be a mechanism that renders the dilated atria more susceptible to AF.     

Preferential conduction patterns along the coronary sinus during atrial fibrillation in humans and their modification by pulmonary vein isolation

Introduction

Correlation function analysis applied to endocardial electrograms has earlier been used for analysis of agreement between signals and direction of activation during atrial fibrillation (AF). This study was aimed at evaluating whether preferential activation patterns along the coronary sinus (CS) exist in patients with AF.

Methods

Twenty-seven patients (57 ± 10 years old) admitted for electrophysiological (EP) study (10 patients) and/or AF ablation (17 patients) were studied, 8 with permanent and 19 with persistent AF. Unipolar signals were recorded during 60 seconds from a 10-pole CS catheter during AF at baseline (BL) and after isolation of left and right pulmonary veins and after additional lines in the left atrium (LA) (End). Correlation function analysis was applied to signals from each pair of adjacent electrodes, and graphs of cumulated time delay were made to enable interpretation of direction of activation.

Results

Correlation between paired signals was highest in the distal and middle parts of CS and lowest in the proximal CS. In 21 patients, correlation values greater than 0.8 between closely spaced electrodes suggested uniform propagation of the fibrillatory waves. In 18 of 21 patients, preferential conduction pattern along CS was seen. Of those, 15 patients had left-to-right conduction, and 3 had right-to-left conduction. During ablation, atrial fibrillation cycle length increased from 184 ± 32 milliseconds at BL to 193 ± 39 milliseconds after pulmonary vein isolation and 215 ± 39 milliseconds at the end of ablation (P = .03, BL vs End). Because of ablation, preferential conduction along CS changed in 4 patients from left to right at BL to simultaneous CS activation or right to left. In 1 of 3 patients with simultaneous activation at BL, the direction changed to right to left. No direction change was observed in any of the 3 patients with right-to-left activation at BL.

Conclusions

Atrial activation during AF exhibits a high degree of organization in distal and middle CS. Preferential conduction patterns observed in most patients may indicate either relatively dominant stable reentry circuits in the LA or activation spread from a focal source. The changes in preferential conduction during ablation of AF may reflect modification of AF substrate and indicate persistent right atrial sources not affected by ablation in the LA only.     

Echocardiographic predictors of atrial fibrillation after mitral valve replacement

Objectives

Detection of the echocardiographic predictors of post-operative atrial fibrillation in patients with rheumatic mitral valve disease undergoing mitral valve replacement.

Immediate effect of balloon valvuloplasty on hemostatic changes in mitral stenosis

This study was conducted to assess right and left atrial hemostatic function in patients with mitral stenosis (MS) and to investigate the immediate effect of balloon mitral valvuloplasty (BMV) on hemostatic function. BMV was performed in 28 patients with MS (age 29 +/- 8 years) who had sinus rhythm and no left atrial (LA) thrombus. Right and left atrial biochemical markers of platelet activity (platelet factor 4 [PF4] and B thromboglobulin [BTG]), coagulation (thrombin-antithrombin III complex [TAT]), and fibrinolytic activity (D-dimer) were measured before and 30 minutes after BMV. Right atrial levels of these markers were also measured in 20 control subjects. Compared with control subjects, patients with MS had higher right atrial levels of PF4 (30 +/- 15 vs 5 +/- 2 IU/ml), BTG (231 +/- 53 vs 30 +/- 8 IU/ml), TAT (7 +/- 4 vs 2 +/- 0.3 microg/L), and D-dimer (380 +/- 145 vs 160 +/- 35 ng/ml, p < 0.0001 in all). TAT levels were higher in the left atrium than in the right atrium of patients before BMV (8 +/- 4 vs 7 +/- 4 microg/L, p < 0.0001). BMV was successful (final mitral valve area > or = 1.5 cm2 and > or = 50% increase of the initial valve area) in all patients. There was a significant reduction of LA levels of PF4 (35 +/- 8 to 26 +/- 9 IU/ml, p < 0.0001), BTG (225 +/- 41 to 196 +/- 28 IU/ml, p < 0.001), and TAT (10 +/- 5 to 7 +/- 1 microg/L, p < 0.05) in the 16 patients with LA pressure < 10 mm Hg after BMV, whereas these markers were not reduced in the 12 patients with left atrial pressure > or = 10 mm Hg after BMV. These data indicate that platelet function, coagulation status, and fibrinolytic activity are increased regionally in the left atrium and in the systemic circulation in patients with MS and sinus rhythm in the absence of LA thrombus. Successful BMV induces a significant reduction of prethrombotic status in patients with low LA pressure after the procedure. Patients with high LA pressure after BMV maintain a high prethrombotic state and may be considered at an increased risk of thromboembolism after the procedure.     

Changes in systemic sympathetic nervous system activity after mitral valve surgery and their relationship to changes in left ventricular size and systolic performance in patients with mitral regurgitation

Background

We have shown that the systemic sympathetic nervous system (SNS) is activated in patients with chronic mitral regurgitation (MR). However, the fate of systemic SNS activity after surgical correction of MR is currently unknown.

Methods

We examined 14 patients with MR who had normal sinus rhythm with an investigational, preoperative cardiac catheterization, including arterial norepinephrine (NE) sampling and [³H]-NE infusions and arterial blood sampling to determine NE kinetic parameters using a 2-compartment modeling analysis. The arterial NE and NE kinetic parameters were determined in all patients after mitral valve surgery (MVS) at a mean of 12 months. A 2-dimensional echocardiographic examination was also performed before and after MVS.

Results

The average extravascular NE release rates (NE₂) before and after MVS were 1.89 ± 0.66 and 2.26 ± 0.82 μg/min/m² (P = .24), respectively. The average left ventricular (LV) end-diastolic dimension, fractional shortening, and ejection fraction decreased, whereas the mean LV end-systolic dimension did not change between the pre- and post-MVS echocardiographic studies. However, these group averages were comprised of patients with MR in whom the NE₂ and echocardiographic values both increased and decreased. This lack of homogeneity was a reflection of our new observation that the pre- to post-MVS changes in NE₂ were directly proportional to the changes in LV end-systolic dimension (r = 0.91, P <.001) and inversely related to the changes in LV fractional shortening (r = −0.82, P <.001) and ejection fraction (r = −0.78, P <.001).

Conclusions

The response in systemic SNS activity in patients with MR after MVS is not homogeneous, and these changes are concordant with the post-MVS changes in LV size and systolic performance. These data further support our earlier observations and extend them to suggest that systemic SNS activation in patients with chronic MR is related to LV remodeling and impaired systolic performance.     

Imbalance between pro-angiogenic and anti-angiogenic factors in rheumatic and mixomatous mitral valves

Background

A balance between angiogenic and anti-angiogenic factors is critical in tissue development, tissue repair and homeostasis. Aberrant angiogenesis has been implicated in several pathologic conditions, including valvular heart disease. The aim of this study was to ascertain the pathogenetic role of angiogenesis in rheumatic and mixomatous mitral valve diseases.

Methods

Leaflets from mixomatous (n = 20) and rheumatic (n = 20) mitral valves removed from surgical patients, and normal mitral valve (n = 6) obtained at autopsy were collected. Immunohistochemical studies were performed on sequential valve sections, evaluating CD31, CD34, α smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR1), VEGF receptor-2 (VEGFR-2), and chondromodulin-I (Chm-I).

Results

Immunohistochemistry revealed significant differences among groups in CD31 (p = 0.001), CD34 (p < 0.001), α-SMA (p < 0.001), VEGF (p < 0.001), VEGFR1 (p = 0.007), VEGFR2 (p = 0.011), and Chm-I (p < 0.001) expressions. Rheumatic valves demonstrated a severe up-regulation and down-regulation in pro-angiogenic and anti-angiogenic factors, respectively, compared with mixomatous and normal mitral valves. On the contrary, mixomatous valves showed a significant up-regulation of anti-angiogenic factors with respect to rheumatic and normal valves.

Conclusions

These findings provide evidence that an imbalance between pro-angiogenic and anti-angiogenic factors is implicated in mitral valve disease. Pro-angiogenic factors are up-regulated in rheumatic disease, while anti-angiogenic ones in mixomatous mitral valves.