Controls In Sinus Rhythm Research Articles

Interleukin-6, endothelial activation and thrombogenesis in chronic atrial fibrillation.

A prothrombotic or hypercoagulable state has been described in AF, which could increase the risk of thromboembolism. As inflammation has been related to thrombogenesis and endothelial activation, we hypothesised that the prothrombotic state in AF (as assessed by an index of thrombogenesis, prothrombin fragment 1+2 [F1+2]) and endothelial activation (soluble E-selectin (sEsel)) could be related to an index of inflammation (interleukin-6 (IL-6)). We studied 191 consecutive patients (98 male; mean age 72.3+/-9.2 years) with chronic non-rheumatic AF who were not on anticoagulant therapy. Plasma IL-6, sEsel and F1+2 were measured by ELISA. Research indices were compared to 74 controls in sinus rhythm matched for age and sex. In 43 patients with AF, the effects of introducing anticoagulation (INR 2.0-3.0) were also studied. Patients with AF had elevated levels of F1+2 (p<0.001) and IL-6 (p=0.045), but not sEsel. There was no significant correlation between F1+2 and IL-6. In multivariate analysis, only F1+2 levels were independently associated with the presence of AF (p=0.001). After oral anticoagulation, plasma levels of F1+2 and sEsel were significantly decreased (both p<0.01). High levels of IL-6 in AF suggest an inflammatory state, which appears to be more related to clinical variables of the patients, rather than to the presence of AF per se. There was no association of inflammation with endothelial activation (sEsel) or the presence of abnormal thrombogenesis (high F1+2 levels) in AF. Moreover, no changes in IL-6 levels were found despite the reduction of the other markers by oral anticoagulant therapy.

Anticoagulation in management of atrial fibrillation

Atrial fibrillation is the most common cardiac arrhythmia in adults. The prevalence of atrial fibrillation rises with age, reaching as high as 9% in those 70 years and older. Currently there are 2.2 million affected people in the United States, with twice the mortality rate of age-matched controls in sinus rhythm. Epidemiologic studies show atrial fibrillation to be responsible for as many as 15% of the total number of strokes, a higher incidence of dementia, cardiac function compromise, and decreased quality of life. Recent studies indicate that rate control and rhythm restoration are equally effective strategies in the treatment of atrial fibrillation, with a trend toward better survival in patients treated for rate control and anticoagulation. Data from several randomized controlled studies on stroke prophylaxis provided consistent evidence of the superiority of adjusted-dose warfarin over aspirin. Guidelines developed by the American College of Cardiology, the American Heart Association, the European Society of Cardiology, and ACCP provide a convenient decision-making framework for the practicing physician. The safety and effectiveness of anticoagulation in clinical practice were found to be equal to those in major trials with rigorous controls. Despite the proven effectiveness and safety of oral anticoagulation for thromboembolism prophylaxis in atrial fibrillation, warfarin remains underused, especially among the elderly (75 years and older), who are at the greatest risk of stroke and would likely benefit the most from prophylactic anticoagulation.

Anticoagulation in management of atrial fibrillation.

Atrial fibrillation is the most common cardiac arrhythmia in adults. The prevalence of atrial fibrillation rises with age, reaching as high as 9% in those 70 years and older. Currently there are 2.2 million affected people in the United States, with twice the mortality rate of age-matched controls in sinus rhythm. Epidemiologic studies show atrial fibrillation to be responsible for as many as 15% of the total number of strokes, a higher incidence of dementia, cardiac function compromise, and decreased quality of life. Recent studies indicate that rate control and rhythm restoration are equally effective strategies in the treatment of atrial fibrillation, with a trend toward better survival in patients treated for rate control and anticoagulation. Data from several randomized controlled studies on stroke prophylaxis provided consistent evidence of the superiority of adjusted-dose warfarin over aspirin. Guidelines developed by the American College of Cardiology, the American Heart Association, the European Society of Cardiology, and ACCP provide a convenient decision-making framework for the practicing physician. The safety and effectiveness of anticoagulation in clinical practice were found to be equal to those in major trials with rigorous controls. Despite the proven effectiveness and safety of oral anticoagulation for thromboembolism prophylaxis in atrial fibrillation, warfarin remains underused, especially among the elderly (75 years and older), who are at the greatest risk of stroke and would likely benefit the most from prophylactic anticoagulation.

A study of platelet activation in paroxysmal, persistent and permanent atrial fibrillation.

We hypothesized that the 'residual' thromboembolic risk in therapeutically anticoagulated patients undergoing cardioversion could potentially be related to abnormal haemorheology and platelet activation. To test this hypothesis, we firstly investigated the role of haemorheology and platelet activation in patients with paroxysmal and persistent atrial fibrillation (AF), who were compared with healthy controls and patients with permanent AF. Second, we compared these indices in patients with persistent AF, before and after successful cardioversion. We measured indices of haemorheology (haematocrit, plasma viscosity, and fibrinogen), fibrin D-dimer (an index of thrombogenesis and fibrin turnover) and platelet activation (as assessed by platelet aggregation and plasma levels of beta-thromboglobulin, and soluble P-selectin) in 29 patients with paroxysmal AF, 87 patients with permanent AF and 29 healthy controls in sinus rhythm. The effects of cardioversion were studied in 20 patients with persistent AF, who maintained sinus rhythm at 2 months follow-up. Plasma levels of beta-thromboglobulin (P = 0.03) and fibrin D-dimer (P = 0.001) were higher in patients with AF, when compared with controls; the highest levels were seen in those with permanent AF (Tukey's test, < 0.05). Plasma viscosity was significantly higher in the patients with paroxysmal AF compared with healthy controls (P = 0.02). Plasma soluble P-selectin levels and platelet aggregation responses to all four platelet agonists (adenosine diphosphate, collagen, epinephrine and thrombin) in patients with paroxysmal AF and permanent AF were similar to controls. Plasma fibrinogen, viscosity and other markers of platelet activation (including platelet aggregation) were not significantly different in patients with paroxysmal AF, during episodes of AF and sinus rhythm (P = not significant), although mean haematocrit was significantly higher during the episodes of AF compared with episodes of sinus rhythm (P = 0.03). Among the patients with persistent AF who remained in sinus rhythm at 2 months following successful cardioversion, there was a significant decrease in the plasma levels of soluble P-selectin at 2 weeks and 2 months, when compared with baseline (pre-cardioversion) levels (P < 0.001). Haemorheology and platelet aggregation response to agonists did not change significantly, except for a transient increase in platelet aggregation response to collagen at 2 weeks (P = 0.045). In conclusion. abnormal haemostatic and platelet activation in patients with permanent AF are not consistently observed in patients with paroxysmal and persistent AF. Abnormal haemorheology appears to play an important role in patients with paroxysmal AF, especially during the paroxysms of AF. Cardioversion of persistent AF to sinus rhythm appears to decrease the platelet activation, but whether this translates into a beneficial reduction in thromboembolic risk requires further study.

Activation of proteolysis by calpains and structural changes in human paroxysmal and persistent atrial fibrillation

Atrial fibrillation (AF) is accompanied by electrical, structural and ion-channel protein remodeling. We tested if proteolysis by calpain and proteasome is activated during AF, and studied the relation with the remodeling processes. Right atrial appendages were obtained from patients with paroxysmal (n=7) or persistent (n=10) lone AF and compared to controls (n=10) in sinus rhythm undergoing coronary artery bypass grafting (CABG). Proteolysis was measured using Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl-coumarin. Protein expression of calpain I and II was assessed by Western-blot and calpain I localization by immunohistochemistry. Structural changes were quantified by counting atrial myocytes with contraction bands or hibernation. Calpain activity was significantly increased in paroxysmal AF (2-fold, P<0.001) and persistent AF (3-fold, P<0.001), mainly due to calpain I activation. Increased calpain I protein expression was found in AF with Western blot and immunohistochemistry. Myocytes from all AF groups showed increased contraction bands, whereas hibernation was only found in persistent AF. Calpain activity correlated with L-type Ca(2+) channel and Kv1.5 protein amounts (r=-0.80, P<0.001 and r=-0.72, P<0.001, respectively), degree of structural changes (r=0.90, P<0.001), shortening of atrial effective refractory period (AERP) (basic cycle length 500 ms, r=-0.60, P<0.001) and AERP rate adaptation (r=-0.80, P<0.001). Calpain activity is induced during AF and correlates with parameters of ion-channel protein, structural and electrical remodeling. The results suggest that calpain activation represents an important mechanism linking calcium overload to cellular adaptation mechanisms in human AF.

Electrical remodeling of the atrium in an anatomic model of atrial flutter: relationship between substrate and triggers for conversion to atrial fibrillation.

Atrial flutter (AFL) and atrial fibrillation (AF) frequently coexist, yet the specific relationship between these arrhythmias, and particularly whether sustained AFL leads to AF, is unknown. We investigated the electrophysiological consequences of chronic AFL using an ovine anatomic right atrial Y-lesion model. AFL was induced in 7 animals, and 4 remained in sinus rhythm (controls). Sheep were monitored for spontaneous conversion of AFL to AF. Six of 7 sheep sustained AFL for 28 days. In 1 of 7 sheep, spontaneous conversion of AFL to AF occurred on day 5. AFL produced a highly significant fall in right and left atrial refractoriness (AERP, P<0.001), with 74+/-10% of the reduction occurring by day 3. Right atrial conduction velocity also fell significantly (baseline 89+/-9 cm/s versus day 28 64+/-14 cm/s, P<0.001) but over a slower time course. AERP and conduction velocity changes coincided with a characteristic biphasic decrease and increase in the AFL cycle length. The excitable gap (percent of AFL cycle length) increased from 13+/-3% at baseline to 46+/-8% by day 28 (P<0.001). Sustained AF (>30 seconds) was not inducible at baseline but after 28 days of AFL could be induced in 6 of 6 sheep by critically timed single or multiple extrastimuli delivered either in sinus rhythm or AFL. There was no significant change in any parameter in control sheep. In this model, AFL produced electrical remodeling and the substrate for sustained AF. However, spontaneous conversion to AF was uncommon, and the development of AF was dependent on specific triggers.

Asymptomatic embolisation in non-valvular atrial fibrillation and its relationship to anticoagulation therapy

Objective: A prospective study to determine the prevalence of embolic signals (ES) detected with transcranial Doppler ultrasound (TCD) in subjects with non-valvular atrial fibrillation (NVAF) who were and were not taking anticoagulants. Methods: Sixty-eight subjects with NVAF taking warfarin and sixty-three NVAF subjects not taking warfarin were recruited from the cardiology department. No patients had suffered a previous stroke or clinical systemic embolisation. Thirty subjects in sinus rhythm were recruited as controls. TCD recordings were performed bilaterally from the middle cerebral arteries for 1 h. In 126 subjects (96%) the recording was repeated 1 week later. All Doppler recordings were reviewed blindly by an observer for ES. Results: After one recording ES were detected in one warfarin NVAF subject (1.5%), four non-warfarin NVAF subjects (6.3%) and no sinus rhythm controls. Following both recordings ES were detected in one warfarin NVAF subject (1.5%) and seven non-warfarin NVAF subjects (11.9%) P=0.017. Conclusions: Asymptomatic ES can be detected in a minority of subjects with NVAF. These signals were significantly less common in NVAF subjects taking warfarin, and this is consistent with asymptomatic ES having clinical significance in this disease. TCD detection of ES may have application in patients with NVAF for risk stratification, and assessment of the efficacy of new anti-platelet and anti-thrombotic regimens in the condition. Further large prospective studies are required to determine whether ES predict stroke risk in this patient group.

Endothelin system in human persistent and paroxysmal atrial fibrillation.

Activation of the endothelin system is an important compensatory mechanism that is activated during left ventricular dysfunction. Whether this system plays a role at the atrial level during atrial fibrillation (AF) has not been examined in detail. The purpose of this study was to investigate mRNA and protein expression levels of the endothelin system in AF patients with and without concomitant underlying valve disease. Right atrial appendages of 36 patients with either paroxysmal or persistent AF were compared with 36 controls in sinus rhythm. The mRNA amounts of pro-endothelin-1 (pro-ET-1), endothelin receptor A (ET-A), and endothelin receptor B (ET-B) were studied by semiquantitative polymerase chain reaction. Protein amounts of the receptors were investigated by slot-blot analysis. mRNA amounts of pro-ET-1 were increased (+40%; P = 0.002) only in AF patients with underlying valve disease. ET-A and ET-B receptor protein amounts were significantly reduced in patients with paroxysmal AF (-39% and -47%, respectively) and persistent AF with underlying valve disease (-28% and -30%, respectively) and in persistent AF without valve disease (-20% and -40%, respectively). ET-A mRNA expression was unaltered in paroxysmal and persistent AF, whereas ET-B mRNA was reduced by 30% in persistent AF with (P < 0.001) or without (P = 0.04) valve disease, but unchanged in paroxysmal AF. Substantial changes in gene expression of the endothelin system were observed in human atria during AF, especially in the presence of underlying valve disease. Alterations in endothelin expression associated with AF could play a role in the pathophysiology of AF and the progression of underlying heart disease.

Effect of acute exercise on the raised plasma fibrinogen, soluble P-selectin and von Willebrand factor levels in chronic atrial fibrillation.

There is increasing evidence that chronic atrial fibrillation (AF) is associated with a prothrombotic or hypercoagulable state. This study was undertaken to determine whether short-term exercise in patients with chronic AF would shift the overall hemostatic balance toward a more prothrombotic state with a reduction in fibrinolytic potential. We recruited 20 patients (13 men; mean age 65 years +/- 11 standard deviation [SD]) with chronic AF who were not treated with antithrombotic therapy and exercised them to exhaustion using a multistage treadmill exercise (standard Bruce) protocol. Blood samples were taken pre exercise, immediately after cessation of exercise, and at 20 min post exercise. The prothrombotic state was quantified by fibrinogen (an index of hemorheology and a coagulation factor), soluble P-selectin (sP-sel, marking platelet activation), von Willebrand factor (vWF, an index of endothelial dysfunction), and plasminogen activator inhibitor-1 (PAI-1, a regulator of fibrinolytic activity) levels. There were two groups of age- and gender-matched controls in sinus rhythm: (1) healthy controls, and (2) "hospital controls" who were patients with vascular disease. Baseline levels of vWf (p = 0.034) and fibrinogen (p < 0.0001), but not sP-sel (p = 0.075) were significantly elevated in patients with AF compared with both control groups in sinus rhythm. The PAI-1 levels were highest in the hospital control patients, but not in chronic AF (p = 0.041). Following treadmill exercise, achieving a mean metabolic equivalent of 4.9 METS (+/- 1.75 SD) and total exercise duration of 4.9 min (+/- 2 SD), there was a significant rise in plasma fibrinogen (repeated measures analysis of variance [ANOVA] p = 0.047) and a reduction in PAI-1 levels (p = 0.025) in patients with AF. There were no significant changes seen in vWf (p = 0.308) or sP-sel (p = 0.071) levels. No significant changes in these indices were seen in hospital controls (all p = not significant), despite a much longer duration of exercise with greater workload. Patients with chronic AF have increased vWf and fibrinogen levels compared with sinus rhythm. Exercise to exhaustion influences the hypercoagulable state in chronic AF, with a rise in plasma fibrinogen and possible increase in fibrinolytic activity. Nevertheless, acute exercise does not appear to have a significant influence on endothelial dysfunction or platelet activation in patients with AF.

Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+channels

OBJECTIVESOur purpose was to determine whether patients with persistent atrial fibrillation (AF) and patients with paroxysmal AF show alterations in potassium channel expression.BACKGROUNDPersistent AF is associated with a sustained shortening of the atrial action potential duration and atrial refractory period. Underlying molecular changes have not been studied in humans. We investigated whether a changed gene expression of specific potassium channels is associated with these changes in patients with persistent AF and in patients with paroxysmal AF.METHODSRight atrial appendages were obtained from 8 patients with paroxysmal AF, 10 with persistent AF and 18 matched controls in sinus rhythm. All controls underwent coronary artery bypass surgery, whereas most AF patients underwent Cox’s MAZE surgery (atrial arrhythmia surgery to cure AF) (n = 12). All patients had normal left ventricular function. mRNA (ribonucleic acid) levels were measured by semiquantitative polymerase chain reaction and protein content by Western blotting.RESULTSmRNA levels of transient outward channel (Kv4.3), acetylcholine-dependent potassium channel (Kir3.4) and ATP-dependent potassium channel (Kir6.2) were reduced in patients with persistent AF (−35%, −47% and −36%, respectively, p < 0.05), whereas only Kv4.3 mRNA level was reduced in patients with paroxysmal AF (−29%, p = 0.03). No changes were found for Kv1.5 and HERG mRNA levels in either group. Protein levels of Kv4.3, Kv1.5 and Kir3.1 were reduced both in patients with persistent AF (−39%, −84% and −47%, respectively, p < 0.05) and in those with paroxysmal AF (−57%, −64%, and −40%, respectively, p < 0.05).CONCLUSIONSPersistent AF is accompanied by reductions in mRNA and protein levels of several potassium channels. In patients with paroxysmal AF these reductions were observed predominantly at the protein level and not at the mRNA level, suggesting a post-transcriptional regulation.

Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation.

Sustained shortening of the atrial effective refractory period (AERP), probably due to reduction in the L-type calcium current, is a major factor in the initiation and maintenance of atrial fibrillation (AF). We investigated underlying molecular changes by studying the relation between gene expression of the L-type calcium channel and potassium channels and AERP in patients with AF. mRNA and protein expression were determined in the left and right atrial appendages of patients with paroxysmal (n=13) or persistent (n=16) AF and of 13 controls in sinus rhythm using reverse transcription polymerase chain reaction and slot-blot, respectively. The mRNA content of almost all investigated ion channel genes was reduced in persistent but not in paroxysmal AF. Protein levels for the L-type Ca(2+) channel and 5 potassium channels (Kv4.3, Kv1.5, HERG, minK, and Kir3.1) were significantly reduced in both persistent and paroxysmal AF. Furthermore, AERPs were determined intraoperatively at 5 basic cycle lengths between 250 and 600 ms. Patients with persistent and paroxysmal AF displayed significant shorter AERPs. Protein levels of all ion channels investigated correlated positively with the AERP and with the rate adaptation of AERP. Patients with reduced ion channel protein expression had a shorter AERP duration and poorer rate adaptation. AF is predominantly accompanied by decreased protein contents of the L-type Ca(2+) channel and several potassium channels. Reductions in L-type Ca(2+) channel correlated with AERP and rate adaptation, and they represent a probable explanation for the electrophysiological changes during AF.

Effect of degree of blood pressure on the hypercoagulable state in chronic atrial fibrillation

To investigate the hypothesis that higher levels of blood pressure would further promote the hypercoagulable state in atrial fibrillation (AF) by increasing the degree of hemostatic abnormalities, we studied 82 consecutive patients with chronic nonvalvular AF who were not taking antithrombotic therapy. Patients with AF had higher levels of plasma fibrin D-dimer, von Willebrand factor, and fibrinogen than controls in sinus rhythm, and no differences between tertiles of either systolic, diastolic, or mean blood pressure were found, suggesting other mechanisms may be contributing to the hypercoagulable state in AF.

Gene expression of the natriuretic peptide system in atrial tissue of patients with paroxysmal and persistent atrial fibrillation.

Circulating cardiac natriuretic peptides play an important role in maintaining volume homeostasis, especially during conditions affecting hemodynamics. During atrial fibrillation (AF), levels of plasma atrial natriuretic peptide (ANP) becomes elevated. The aim of this study was to gather information about gene expression of the natriuretic peptide system on the atrial level in patients with AF. Right atrial appendages of 36 patients with either paroxysmal or persistent AF were compared with 36 case matched controls in sinus rhythm for mRNA expression of pro- atrial natriuretic peptide (pro-ANP), pro-brain natriuretic peptide (pro-BNP), and their natriuretic peptide receptor type-A (NPR-A). We investigated patients without (n = 36) and with (n = 36) valvular disease. Persistent AF was associated with higher mRNA expression of pro-BNP (+66%, P = 0.04, in patients without valvular disease, and +69%, P < 0.01, in patients with valvular disease) and lower mRNA expression of NPR-A (-58%, P = 0.02, in patients without valvular disease, and -62 %, P < 0.01, in patients with valvular disease). The mRNA content of pro-ANP was only increased in patients with valvular disease (+12%, P = 0.03). No changes were observed in patients with paroxysmal AF. This study demonstrates that persistent, but not paroxysmal, AF induces alterations in gene expression of pro-BNP and NPR-A on the atrial level. Although AF generally is associated with an increase of plasma ANP level, a change in mRNA content of pro-ANP is only observed in the presence of concomitant valvular disease and is of minor magnitude.

Gene expression of proteins influencing the calcium homeostasis in patients with persistent and paroxysmal atrial fibrillation.

Persistent atrial fibrillation (AF) results in an impairment of atrial function. In order to elucidate the mechanism behind this phenomenon, we investigated the gene expression of proteins influencing calcium handling. Right atrial appendages were obtained from eight patients with paroxysmal AF, ten with persistent AF (> 8 months) and 18 matched controls in sinus rhythm. All controls underwent coronary artery bypass grafting, whereas most AF patients underwent Cox's MAZE surgery (n = 12). All patients had a normal left ventricular function. Total RNA was isolated and reversely transcribed into cDNA. In a semi-quantitative polymerase chain reaction the cDNA of interest and of glyceraldehyde-3-phosphate dehydrogenase were coamplified and separated by ethidium bromide-stained gel electrophoresis. Slot blot analysis was performed to study protein expression. L-type calcium channel alpha 1 and sarcoplasmic reticulum Ca(2+)-ATPase mRNA (-57%, p = 0.01 and -28%, p = 0.04, respectively) and protein contents (-43%, p = 0.02 and -28%, p = 0.04, respectively) were reduced in patients with persistent AF compared to the controls. mRNA contents of phospholamban, ryanodine receptor type 2 and sodium/calcium exchanger were comparable. No changes were observed in patients with paroxysmal AF. Alterations in gene expression of proteins involved in the calcium homeostasis occur only in patients with long-term persistent AF. In the absence of underlying heart disease, the changes are rather secondary than primary to AF.

Indexes of hypercoagulability measured in peripheral blood reflect levels in intracardiac blood in patients with atrial fibrillation secondary to mitral stenosis

Systemic thromboembolism is a major complication in patients with mitral stenosis, especially in those who have atrial fibrillation (AF). It has been suggested that there may be increased regional left atrial coagulation activity in such patients, despite normal systemic coagulation activity on peripheral blood sampling. Our aim was to investigate whether there were significant differences between intracardiac versus peripheral indexes of hypercoagulability in 25 patients (5 men; mean age 60 years) with mitral stenosis who were undergoing percutaneous balloon mitral valvuloplasty and who were all in chronic AF. Two days after halting warfarin therapy, intracardiac (right and left atria) and peripheral (venous and arterial) blood samples from patients were obtained and compared with levels in matched healthy controls in sinus rhythm. Thrombogenicity was assessed by levels of fibrin D-dimer, fibrinogen, indexes of platelet activation (soluble P-selectin and β thromboglobulin [βTG]) and indexes of endothelial dysfunction (soluble thrombomodulin [sTM] and von Willebrand factor [vWF]). There were no statistically significant differences in the various markers between the femoral vein and artery, left and right atria, and between the femoral vein and both atria (all p = NS). Plasma fibrinogen, vWf (both p <0.005), and D-dimer (p = 0.011) were significantly higher and levels of sP-selectin and sTM were lower (both p <0.005) in patients when compared with controls. There was no significant difference in plasma βTG levels. Our results suggest that there is no significant variation in indexes of thrombogenesis, platelet activation, and endothelial dysfunction between left atrium, right atrium, and the peripheral artery or vein. Peripheral samples therefore do reflect atrial coagulation, platelet, and endothelial activities.

Cellular Basis of Biventricular Hypertrophy and Arrhythmogenesis in Dogs With Chronic Complete Atrioventricular Block and Acquired Torsade de Pointes

In the dog with chronic complete atrioventricular block (AVB), torsade de pointes arrhythmias (TdP) can be induced reproducibly by class III antiarrhythmic agents. In vivo studies reveal important electrophysiological alterations of the heart at 5 weeks of AVB, resulting in increased proarrhythmia. Autopsy studies indicate the presence of biventricular hypertrophy. In this study, the cellular basis of proarrhythmia and hypertrophy in chronic AVB was investigated. From chronic-AVB dogs with increased heart weights and TdP, left midmyocardial and right ventricular myocytes were isolated by enzymatic dispersion. These myocytes were significantly larger than sinus rhythm (SR) controls. In chronic AVB, the action potential spike-and-dome configuration was preserved. However, the action potential duration (APD) at 95% and 50% of repolarization of the left midmyocardium was significantly larger in chronic AVB than in SR, with little change in the right ventricle, causing enhanced interventricular dispersion of repolarization at slow pacing rates. Treatment with the class III agent almokalant increased the APD to a much larger extent in chronic-AVB than in SR myocytes and resulted in a higher incidence of early afterdepolarizations (EADs). EADs had their takeoff potential between -35 and 0 mV. There was no evidence that spontaneous sarcoplasmic reticulum Ca2+ release underlies these EADs. In the dog, chronic AVB leads to hypertrophy of both right and left ventricular myocytes. The repolarization abnormalities predisposing for class III-dependent TdP in vivo are the results of cellular electrophysiological remodeling.

Evaluation of left atrial filling using systolic pulmonary venous flow velocity measurements in patients with atrial fibrillation.

The pattern of pulmonary venous flow velocity is useful for understanding the hemodynamic relationship between the left atrium and left ventricle in patients with a variety of diseases, and the systolic flow wave, in particular, is considered a clinically important parameter that reflects left atrial filling. The study was undertaken to determine whether systolic pulmonary venous flow velocity patterns can be used to evaluate left atrial filling in patients with atrial fibrillation. We performed transesophageal pulsed Doppler echocardiography and cardiac catheterization in 34 patients with chronic atrial fibrillation (10 with hypertrophic cardiomyopathy, 5 with dilated cardiomyopathy, 7 with previous myocardial infarction, and 12 with isolated atrial fibrillation) and 15 normal controls in sinus rhythm. Mean pulmonary capillary wedge pressure, V-wave height in the pulmonary capillary wedge pressure curve, and left ventricular end-diastolic pressure were significantly higher in the hypertrophic cardiomyopathy and dilated failing heart (previous myocardial infarction and dilated cardiomyopathy) groups than in the isolated atrial fibrillation and normal groups. The peak velocity and time-velocity integral of the systolic pulmonary venous flow velocity, and percent left atrial emptying fraction were significantly lower in the dilated failing heart group than in the isolated atrial fibrillation, hypertrophic cardiomyopathy, and normal groups. The peak velocity and time-velocity integral of the systolic pulmonary venous flow velocity, percent left atrial emptying fraction, and V-wave height were comparatively constant when the preceding R-R intervals were relatively stable in the isolated atrial fibrillation group and in 4 of the 10 patients with hypertrophic cardiomyopathy. However, changes in these variables correlated with the preceding R-R interval in all patients with dilated failing hearts and in 6 of the 10 patients with hypertrophic cardiomyopathy. Transesophageal pulsed Doppler echocardiographic measurements of systolic pulmonary venous flow velocity are valid indicators of left atrial filling in patients with atrial fibrillation.

Transesophageal Pulsed Doppler Echocardiographic Study of Systolic Flow Velocity Patterns of the Pulmonary Vein in Patients with Atrial Fibrillation.

We recorded pulmonary venous flow velocity in 27 patients with atrial fibrillation using transesophageal pulsed Doppler echocardiography to investigate the cycle length-dependent characteristics and background of early systolic reversal and second systolic forward waves. The study group consisted of 15 patients with mitral stenosis, 5 patients with left atrial myxoma, and 7 patients without underlying organic heart disease; they were compared with 20 normal controls in sinus rhythm. The mean pulmonary capillary wedge pressure was significantly greater in patients with mitral stenosis and left atrial myxoma than in normal controls and in patients with isolated atrial fibrillation. The mean peak velocity of the early systolic reversal wave was also significantly greater in patients with mitral stenosis and left atrial myxoma than in patients with isolated atrial fibrillation. The mean peak velocity of the second systolic forward wave was significantly lower in patients with mitral stenosis and left atrial myxoma than in controls and in patients with isolated atrial fibrillation. The preceding RR interval had significant negative correlations with the peak early systolic reversal velocity, left atrial pressure during closure of the mitral valve, and peak V wave height of the pulmonary capillary wedge pressure in patients with mitral stenosis and left atrial myxoma. In the same patient groups, the preceding RR interval had significant positive correlations with the peak second systolic forward velocity and amplitudes of the mitral annular and interatrial septal motions during ventricular systole. The variations in the peak velocities of the early systolic reversal and second systolic forward waves with the preceding RR interval were smaller in patients with more severe mitral stenosis. In conclusion, early systolic reversal waves of the pulmonary venous flow velocity reflect left atrial pressure, and the second systolic forward waves reflect left atrial filling. Both velocities vary with disease conditions or preceding RR intervals in atrial fibrillation.

Left atrial spontaneous echo contrast in patients with permanent pacemakers.

OBJECTIVE: To determine the relations between left atrial appendage function, spontaneous echo contrast, and thromboembolism in patients with different modes of permanent pacemakers. PATIENTS AND METHODS: 88 patients with pacemaker...

Evaluation of left atrial appendage function by measurement of changes in flow velocity patterns after electrical cardioversion in patients with isolated atrial fibrillation

We investigated temporary changes in left atrial appendage (LAA) flow velocity patterns in patients undergoing electrical cardioversion for chronic isolated atrial fibrillation, and evaluated the role of active LAA contraction in directing blood flow to the left atrial main chamber and left ventricle. The study consisted of 26 patients with chronic isolated atrial fibrillation treated with electrical cardioversion and 20 normal controls in sinus rhythm. Using transthoracic and transesophageal Doppler echocardiography, we recorded transmitral, pulmonary venous, and LAA flow velocity patterns before, 24 hours, and 1 week after cardioversion in all subjects. In the 15 patients who underwent successful cardioversion, the maximal LAA area 24 hours after cardioversion was smaller than the area before cardioversion, whereas LAA ejection fraction during atrial systole and peak atrial systolic emptying velocity of the LAA flow were lower 24 hours after cardioversion than those in the control group. One week after cardioversion, maximal LAA area and LAA peak atrial systolic emptying velocity were restored to levels approximately equivalent to those in the control group, although LAA ejection fraction was lower than in the control group. Maximal LAA area and LAA peak atrial systolic emptying velocity correlated negatively and positively with LAA ejection fraction, respectively, 24 hours and 1 week after cardioversion. These results suggest that LAA and the left atrial main chamber show stunning 24 hours after cardioversion, and the atrial systolic emptying wave of LAA flow is generated by active LAA contraction.