Changes In Left Atrium Research Articles

Pacing cycle length–dependent electrophysiologic changes in left atrium: Poor validity of using low-voltage area and slow conduction area under specific pacing cycle length as absolute substrates of atrial fibrillation

BackgroundPacing cycle length (PCL)–dependent changes in left atrial (LA) electrophysiologic properties have not been fully elucidated. ObjectiveWe aimed to elucidate these changes using a high-resolution mapping system. MethodsForty-eight patients underwent atrial fibrillation ablation with RHYTHMIA HDx. Paired LA maps under a baseline PCL (600 ms) and rapid PCL (300 ms) were acquired after pulmonary vein isolation under right atrial appendage pacing. The PCL-dependent change in the low-voltage area (LVA; area with <0.5 mV bipolar voltage), LA activation time (interval from first LA activation to wavefront collision at lateral wall), regional mean voltage, regional mean wave propagation velocity, and slow conduction area (area with <0.3 m/s wave propagation velocity) were quantitatively analyzed. ResultsUnder the rapid PCL, the total LVA was significantly increased (7.6 ± 9.5 cm2 vs 6.7 ± 7.6 cm2; P = .031), especially in patients with a 10 cm2 LVA on the baseline PCL map (21.5 ± 9.1 cm2 vs 18.1 ± 6.5 cm2; P = .013). The LA activation time was also prolonged (87.9 ± 16.2 ms vs 84.0 ± 14.0 ms; P < .0001). Although the rapid PCL did not decrease the regional mean voltage, it significantly decreased the regional mean wave propagation velocity and increased the slow conduction area in all measured regions. ConclusionLVA and slow conduction area can be emphasized by rapid PCL LA mapping. There may be poor validity in using these areas as absolute atrial fibrillation substrates without considering the PCL-dependent changes.

Abstract Mo039: Risk of Structural and Hemodynamic changes in Left Atrium in Patients with Heart Failure undergoing Percutaneous Left Atrial Appendage Occlusion: A Retrospective Analysis

Background: Exclusion of left atrial appendage (LAA) in animals reduces compliance and increases left atrial pressure. We hypothesize that percutaneous left atrial appendage occlusion (LAAO) would lead to structural and hemodynamic changes in left atrium and assess the risk using echocardiographic cut-offs used for evaluating left atrial pressure in heart failure patients. Methods: We queried TriNetx database for adult patients with heart failure undergoing percutaneous LAAO. We excluded those who underwent surgical or alternative percutaneous procedures pertaining to LAA, procedures pertaining to mitral valve (MV), mitral valvular pathologies, mechanical circulatory support placement, pacemaker placement, and those with left bundle branch block. We calculated risk of meeting echocardiographic cut-offs used in evaluation of left atrial pressure; MV maximum E-wave velocity ≥50cm/s, left atrial end systolic volume index (LAESVI) indexed to body surface area ≥34 ml/m2, Tricuspid Regurgitation systolic jet velocity ≥ 2.8 m/s, Pulmonary vein Systole/Diastole ratio ≤ 1, mitral valve lateral annulus E/e' ≥ 13 and Mitral valve E/A ratio ≥2. Those meeting the respective cut-off before LAAO were excluded. All diagnoses, procedures, and echocardiographic parameters were identified using International Classification of Diseases, Current Procedural Terminology, and Logical Observation Identifiers Names and Codes. Results: We identified 4,046 patients with heart failure undergoing percutaneous LAAO. Baseline demographics and diagnosis were; mean (SD) age 75.4 (8.1) years, 37% females, 92% hypertension, 67% ischemic heart disease, 42% diabetes mellitus, 41% chronic kidney disease, and 42% were overweight or obese. Risk of meeting echocardiographic cut-offs used in evaluating left atrial pressure was low with 0.24% (10) patients having LAESVI indexed to body surface area ≥34 ml/m2, Tricuspid Regurgitation systolic jet velocity ≥ 2.8 m/s, Pulmonary vein Systole/Diastole ratio ≤ 1, and Mitral valve E/A ratio ≥ 2. Risk of having MV maximum E-wave velocity ≥50cm/s was 0.58% and no patients had mitral valve lateral annulus E/e' ≥ 13. (Figure 1) Conclusion: Risk of meeting echocardiographic cut-offs used in evaluation of left atrial pressure in patients with heart failure undergoing percutaneous LAAO is low.

Analysis of Factors Influencing Changes in Left Atrium and Left Ventricle Size in Adults

Analysis of Factors Influencing Changes in Left Atrium and Left Ventricle Size in Adults

Clinical Characteristics and Features of Idiopathic Premature Ventricular Contractions with an Enlarged Left Atrium in Patients Without Structural Heart Diseases

Background and aims: Idiopathic premature ventricular contractions (PVCs) may cause subtle changes in left atrium (LA) structure and function. Here, we investigated whether serum sodium, body mass index (BMI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other characteristics might be associated with LA in these patients. Methods: A total of 268 consecutive patients diagnosed with idiopathic PVCs were retrospectively analyzed. We assessed associations of enlarged LA and with the clinical features obtained from 24-hour Holter monitoring, electrocardiography and serum data in patients with PVCs. Results: Patients with an enlarged LA (n = 101), compared with a normal LA (n = 167), had significantly lower serum sodium (140.9 ± 3.0 mmol/L vs 141.7 ± 2.8 mmol/L; P = 0.022), higher BMI (24.5 ± 2.7 kg/m2 vs 21.7 ± 2.5 kg/m2; P &lt; 0.001), higher NT-proBNP [99.3 (193.6) pg/mL vs 77.8 (68.8) pg/mL; P &lt; 0.001] and lower average heart rates (73.0 ± 8.0 bpm vs 75.3 ± 7.6 bpm; P = 0.019). No significant differences were observed in P-wave dispersion, QRS duration, PVC coupling interval, pleomorphism, circadian rhythm, non-sustained ventricular tachycardia, serum potassium, serum magnesium, hypersensitive C-reactive protein, low-density lipoprotein cholesterol, symptoms and PVC duration. Conclusions: Beyond the burden of PVCs, attributes such as serum sodium, BMI, NT-proBNP and average heart beats may potentially correlate with LA enlargement in individuals with idiopathic PVCs.

Volume and function changes of left atrium and left ventricle in patients with ejection fraction preserved heart failure measured by a three dimensional dynamic heart model.

The accurate diagnosis of HFpEF is still challenging and controversial. In this study, we used 3D-DHM technology to compare the differences of cardiac structure and function between HFpEF patients and healthy controls, as well as the differences of two-dimensional and three-dimensional cardiac function in HFpEF patients. Echocardiography with 3D-DHM and conventional two-dimensional (2D) methods were applied to measure the volume and function parameters of left atrium and ventricle of patients with HFpEF and healthy controls. Significant differences of 3D cardiac function indexes including LVESV, 3D-LVEF, ESL, SV, CI, EDmass, LAVmax, LAVmin, LAEF, and LAVI were observed between patients with HFpEF and controls (P < 0.05). However, no significant difference of LVEDV and EDL were observed (P > 0.05). In addition, we found no significant between-group difference in 2D cardiac function indexes such as LVDD and 2D-LVEF (P > 0.05), but the LAD, LVSD, LVPW, IVS, E, E/A, and E/e ' were significantly different between groups (P < 0.05). There was no significant difference between 3D-LVEF and 2D-LVEF in the control group (P > 0.05), while 3D-LVEF in the HFpEF group was lower than 2D-LVEF(P < 0.05). Among the two-dimensional and three-dimensional parameters of HFpEF patients, the parameters related to diastolic function changed more significantly than those of the normal group, and the three-dimensional LVEF of HFpEF patients decreased. The three-dimensional cardiac function parameters analyzed by DHM can provide more information regarding myocardial mechanics.

Diabetic microvascular complications are associated with left atrial structural alterations in asymptomatic type 2 diabetes patients: A cross-sectional study

AimsWe used 4D-Auto LAQ to quantitatively evaluate the morphological and functional changes of left atrium in patients with asymptomatic type 2 diabetes mellitus (T2DM), and explored its correlations with diabetic microvascular complications (MICRO). MethodsThis study included 319 patients with asymptomatic T2DM. According to the occurrence of MICRO, these patients were divided into 3 groups: patients with no complication, 1 complication, and 2–3 complications. 4D-Auto LAQ was used to evaluate left atrial volume (LAVImin, LAVImax, LAVIpre) and calculate the left atrial function (DEI, PEI, AEI) in different phases. Multiple linear regression was used to analyze the correlation between changes in left atrial volume and function and the number of MICROs in DM patients. ResultsA total of 279 patients with asymptomatic T2DM were included in this study. (1) The ultrasound data of the three T2DM groups showed that there was no significant difference in left ventricular size and function among the three groups; (2) with the increase of MICRO number, the left atrial volume (LAVImin, LAVImax, LAVIpre) progressively increased, the left atrial storage function index (DEI) gradually decreased, and the differences were significant (P < 0.05). (3) Multiple linear regression analysis showed that: with the increase of MICRO number (no complication→1 complication→2–3 complications), the left atrial volume (LAVImin, LAVIpre) showed an increasing trend (both P < 0.05). ConclusionIn asymptomatic T2DM patients, MICRO number showed a significant positive correlation with LAVImin and LAVIpre (P < 0.05). Therefore, the increase in left atrial volume can dynamically reflect the severity of microvascular lesions in patients with asymptomatic T2DM.

Early Detection of Iron Overload Cardiomyopathy in Transfusion Dependent Thalassemia Patients in Sulaimaniyah City, Iraq.

BackgroundLifelong blood transfusion is recommended for patients with transfusion-dependent thalassemia (TDT) that lead to iron overload and results in cardiomyopathy (CM).AimTo assess the accuracy of several electrocardiographic (ECG) data in patients at high risk of arrhythmia, early detection of structural and functional changes in left atrium and ventricle using ECG and echocardiography (two dimensional, M-mode echocardiography along with Doppler studies), and to observe the correlations between plasma B-type atrial natriuretic peptide (BNP)/serum ferritin and ECG with Doppler as well as echocardiographic changes in patients with TDT.MethodsThe current prospective case-control study included 75 TDT patients and 74 control subjects with the mean age of 9.55 and 9.93 years, respectively. Participants were assessed for the socio-demographic, physical examinations, serum ferritin, plasma BNP, ECG, 2D echocardiography, and tissue/pulse wave Doppler.ResultsThe mean of serum ferritin and plasma BNP were significantly (p<0.001) higher in the cases (1475.19 ng/mL and 47.63 pg/mL, respectively) than controls (41.3 ng/mL and BNP 23.37 pg/mL, respectively). ECG findings showed significant higher P-wave dispersion, QRS duration, QT duration and dispersion, and JTc dispersion in cases than controls. Echocardiography findings revealed diastolic dysfunction with preserved ejection fraction (EF) in thalassemia cases, as well as significant higher left ventricular (LV) mass, LV internal diameters during systole and diastole (LVIDs and d) and LV posterior wall thickness during diastole (LVPWd) in cases than controls (p<0.05). Also, a significant (p<0.05) correlation between BNP and QT dispersion was found in patients.ConclusionThese findings suggest the usefulness of ECG, 2D echocardiographic, Doppler studies and plasma BNP, with no significant beneficial effect of serum ferritin level in detecting early cardiac changes in patients with TDT.

Left atrial remodeling in heart failure: coexistence and additive prognostic power of atrial dilation and dysfunction

Abstract Background Heart failure (HF) is associated with volumetric and functional changes of left atrium (LA). Purpose It is still unclear whether the two atrial abnormalities necessarily coexist and if they have additive prognostic implications. Methods 690 patients with HF due to reduced left ventricular ejection fraction (EF) formed the study population. Each patients underwent comprehensive echocardiographic evaluation; atrial function was assessed by means of strain analysis during reservoir (PALS). End-point of the study was overall survival free of hospitalization. Results Patients were divided in 4 groups according to left atrial size (34 ml/mq) and function (PALS 20%). 64 patients (10%) were characterized by completely normal left atrium (group 1), 150 (25%) by dilated LA by normal PALS (group 2), 130 (20%) by normal LA volume but abnormal PALS (group 3) and 200 patients with dilated LA and decreased PALS (group 4). Clinical and echocardiographic characteristics of the groups are presented in the table. Decreased PALS was associated with worse survival both in patients with normal and abnormal LA volume (p&amp;lt;0.0001 for each group). Conclusions Increased volume and decreased function of LA frequently but not necessarily coexist. LA functional impairment affects prognosis independently of LA volume. Funding Acknowledgement Type of funding source: None

Impact of Pregnancy on Maternal Cardiac Atria.

Objective The aim of this study was to assess atrial changes across pregnancy and postpartum using cardiac magnetic resonance imaging (cMRI) to measure atrial end-diastolic volume (EDV). Study Design This was a 2-year prospective observational study of healthy nulliparous women. Each underwent serial cMRI in both maternal left lateral and supine positions at five epochs: 12 to 16 weeks, 26 to 30 weeks, 32 to 36 weeks, within 48 hours after delivery, and 12 weeks postpartum. EDV was calculated and compared with 12-week postpartum values. Results A total of 24 women completed the study. One woman developed preeclampsia, and her data were excluded. Mean age was 27 ± 2.8 years, and mean body mass index was 25.4 ± 3.8 kg/m2. Left atrial EDV increased by 12 weeks (p = 0.045) and remained significantly elevated through 32 to 36 (p &lt; 0.0001) weeks. Maternal lateral positioning was associated with larger left atrial EDV after 12 weeks. Right atrial EDV was significantly elevated at 26 to 30 (p = 0.04) and 32 to 36 (p = 0.02) weeks in the lateral position, though there was no difference in the supine position. Conclusion We documented a significant increase in EDV for both atria during pregnancy. Volume changes were greater in the lateral compared with the supine position, with the most dramatic changes in left atrium at 32 to 36 weeks.

Cardiac Magnetic Resonance-Measured Left Atrial Volume and Function and Incident Atrial Fibrillation: Results From MESA (Multi-Ethnic Study of Atherosclerosis).

Early detection of structural changes in left atrium (LA) before atrial fibrillation (AF) development could be helpful in identification of those at higher risk for AF. Using cardiac magnetic resonance imaging, we examined the association of LA volume and function, and incident AF in a multiethnic population free of clinical cardiovascular diseases. In a case-cohort study embedded in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA size and function assessed by cardiac magnetic resonance feature-tracking were compared between 197 participants with incident AF and 322 participants randomly selected from the whole MESA cohort. Participants were followed up for 8 years. Incident AF cases had a larger LA volume and decreased passive, active, and total LA emptying fractions and peak global LA longitudinal strain (peak LA strain) at baseline. In multivariable analysis, elevated LA maximum volume index (hazard ratio, 1.38 per SD; 95% confidence interval, 1.01-1.89) and decreased peak LA strain (hazard ratio, 0.68 per SD; 95% confidence interval, 0.48-0.96), and passive and total LA emptying fractions (hazard ratio for passive LA emptying fractions, 0.55 per SD; 95% confidence interval, 0.40-0.75 and hazard ratio for active LA emptying fractions, 0.70 per SD; 95% confidence interval, 0.52-0.95), but not active LA emptying fraction, were associated with incident AF. Elevated LA volumes and decreased passive and total LA emptying fractions were independently associated with incident AF in an asymptomatic multiethnic population. Including LA functional variables along with other risk factors of AF may help to better risk stratify individuals at risk of AF development.

Left atrial function in heart failure with impaired and preserved ejection fraction.

Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

Subclinical left atrium remodelling in patients with frequent premature ventricular contractions.

Premature ventricular contractions (PVCs) may cause subtle changes in left atrium (LA) structure and function which may not be readily detected by conventional parameters. To explore the relationship between PVCs and LA shape and size remodelling in patients without known structural heart disease. PVC frequency per 24 h was divided into tertiles. Echocardiographic measurements included left ventricular ejection fraction (LVEF) and volume, LA volume (LAV), mid-LA transverse diameter (LAt), and basal LA maximal transverse diameter (LAb). Trapezoidal LA shape was defined by LAt less than LAb. The association between PVCs and LA shape was explored by multivariable adjusted logistic regression. The 121 patients had a mean age of 43.1 years (63% male) and mean LVEF of 56%. Mean LAV was 57.7 mL in the lowest PVC tertile, 70.9 mL in the middle, and 87.1 mL in the highest PVC tertile (p < 0.001). Trapezoidal LA shape was documented in 32 patients. Five per cent of patients in the lowest and 65% in the highest PVC tertile had trapezoidal LA shape (p < 0.001). PVC frequency correlated with LAV (r = 0.87, p < 0.001) and LAb (r = 0.56, p < 0.001). Each 10% increase in PVCs was significantly associated with trapezoidal LA shape (OR = 1.32, 95% CI 1.17-1.48), after adjustment for age, sex, mean blood pressure, LVEF, and LV end-diastolic diameter. Frequent PVCs are associated with larger LAV and trapezoidal LA shape in otherwise healthy patients, suggesting LA remodelling in response to increased LV filling pressure.

Comparison between left atrial features in well-controlled hypertensive patients and normal subjects assessed by three-dimensional speckle tracking echocardiography

BackgroundThree-dimensional speckle tracking echocardiography (3D-STE) has a major advantage in the improvement of accuracy in the evaluation of cardiac chamber volume without any geometrical assumption. Thus, the aim of this study was to use 3D-STE to elucidate the features of left atrial (LA) volume and function that are altered by hypertension (HTN) by comparing well-controlled HTN patients with normal subjects. MethodsConventional echocardiographic parameters and LA phasic volume and function were measured from apical view by 3D-STE in 40 patients with well-controlled HTN [systolic blood pressure (BP) <140 and diastolic BP <90mmHg for more than one year] and 40 normotensive subjects. ResultsThe passive LA emptying function (EF) in the patients with well-controlled HTN significantly decreased (16±7% vs. 22±8%, p=0.0013) and the active LAEF in patients with well-controlled HTN significantly increased (35±10% vs. 30±9%, p=0.029) compared with the values in normotensive subjects. Multivariate logistic regression analysis revealed that E/e′ was an independent determinant of well-controlled HTN. The maximum LA volume index was correlated with elevated E/e′ (r=0.30, p=0.0064), whereas the maximum LA volume index was not correlated with LV mass index or systolic BP. This change was independent of age. ConclusionsThese results suggest that LV diastolic dysfunction occurs before structural changes of left atrium and left ventricle even in patients with well-controlled HTN.

Worsened diastology after radiofrequency catheter ablation in AF patients: More touches more stiff left atrium

We were grateful for the interesting article by Kosiuk et al. [1] investigating the prevalence and predictors of worsened left ventricular diastolic dysfunction (LVDD) after radiofrequency (RF) ablation of atrial fibrillation in a total of 70 patients (age 61±10years, 66% male, 57.1% paroxysmal AF and 38% LVDD at baseline). The study results revealed that the rate of late AF recurrence is 14% during 12month follow-up and also while there were no significant changes in left atrium (LA) and LV morphologic parameters (LA diameter, LV wall thickness or LV systolic function), the worsening of LVDD has been found in 19 (27%) patients which was significantly associated with total ablation time (OR: 1.611/10min ablation time, 95% CI: 1.088–2.386, p=0.017).

LEFT ATRIUM AND MODERN VIEWS ON PATHOGENESIS OF ESSENTIAL HYPERTENSION

The reviewed data concerning modern performance about the changes of left atrium in hypertension are cited in the paper. Haemodynamic, neurohumoral, molecular, electrophysiologic pathogenic factors of left atrium structural and functional remodeling in this disease are discussed. Changes of left atrium as hypertensive target organ presents an essential (and as a rule the earliest) sign of cardiovascular continuum.

47: Clinical Implications of Anatomical Changes in Left Atrium and Pulmonary Vein After Catheter Ablation for Atrial Fibrillation; Study with 64-row Multislice Computed Tomography

47: Clinical Implications of Anatomical Changes in Left Atrium and Pulmonary Vein After Catheter Ablation for Atrial Fibrillation; Study with 64-row Multislice Computed Tomography

Differences in atrial versus ventricular remodeling in dogs with ventricular tachypacing-induced congestive heart failure.

Congestive heart failure (CHF) causes arrhythmogenic remodeling in both atria and ventricles, but differences between atrial and ventricular remodeling in CHF have not been well characterized. We examined atrial and ventricular tissues from dogs with CHF induced by ventricular tachypacing (220-240/min) for 0 (control) or 24 h, or 1, 2 or 5 weeks. Histopathology was used to assess apoptosis, fibrosis, white blood cell infiltration and cell death, ELISA to measure angiotensin-II concentration and Western blot to evaluate protein expression. Ventricular tachypacing-induced CHF was associated with substantially more fibrosis in left atrium (maximum 10 +/- 1% at 5 weeks) than in left ventricle (0.4 +/- 0.1% at 5 weeks, P < 0.01 versus left atrium). Tissue angiotensin-II concentration increased to steady state in atrial tissue at 24 h but increased more slowly in left ventricle, with a maximum that was significantly higher in atrium than ventricle. Ventricular tachypacing caused tissue apoptosis, inflammatory cell infiltration and cell death, with maximum changes in left atrium being faster, transient and larger than in left ventricle. Mitogen activated protein kinase activation was rapid (within 24 h) in left atrium, but smaller and slower (p38, c-Jun N-terminal kinase) or non-significant (extracellular signal-related kinase) in left ventricle. The 25-kDa activated form of transforming growth factor-beta1, a particularly important profibrotic mediator in atrium, increased significantly in left atrium, from 2.6 +/- 0.6 (control) to 9.2 +/- 1.7 (24 h) and 8.1 +/- 1.8 optical density units (1 week), but was not significantly changed in ventricle. There are qualitative and quantitative differences in atrial versus ventricular remodeling in experimental ventricular tachypacing-induced CHF, with potentially important consequences for understanding underlying mechanisms and developing new therapeutic approaches.

Increase in atrial size in long-term survivors of heart transplant

Atrial size in recipients of orthotopic heart transplant (OHTX) who have long-term survival is not well described in the literature. We reviewed 2-dimensional echocardiograms of 14 recipients of OHTX who survived at least 5 years. Apical 4-chamber images were used for measurements starting at 1-year post-OHTX. The recipients of OHTX were 8 (57%) men and 6 (43%) women with a mean age of 43.6 ± 12.1 (20-60) years and mean survival of 9.5 ± 2.6 (5.8-14.4) years. All chambers increased with time post-OHTX ( r > 0.83, P < .002). The changes in left atrium (LA) and right atrium (RA), remnants of donor LA and RA, and remnants of recipients' LA areas correlated inversely with patient survival post-OHTX ( r > 0.83, P < .002). The change in RA recipient remnant area did not correlate with survival ( r = 0.58, P = .06). In recipients of OHTX with long-term survival, there is a significant correlation between the echocardiographic size of LA and RA, and donor and recipient remnants with time and survival.

Spatial Correlation Analysis of the Pharmacological Conversion of Sustained Atrial Fibrillation in Conscious Goats by Cibenzoline

The nonlinear spatial redundancy and the linear spatial correlation function were used to investigate to what extent non-linearity was involved in the coupling of atrial regions and how organization in activation patterns of sustained atrial fibrillation (AF) had been modified by administration of the class IC agent cibenzoline in the experimental model of sustained AF in instrumented conscious goats. Electrograms were measured in five goats during sustained AF and when the fibrillation interval had been prolonged to about 25%, 50% and 85% (CIB25, CIB50, CIB85) with respect to control. The nonlinear association length and linear correlation length were estimated along the principal axes of two-dimensional correlation maps estimated from the spatial redundancy and the spatial correlation function, respectively. The estimated short axis association length in the right atrium increased already shortly after the start of infusion (CIB25, +61%), and remained significantly different from control during the experiment, including the effects of non-simultaneous interaction. At CIB85 the association length had almost become twice as long with respect to control (increase from 16 to 29 mm, 89%), while in the left atrium changes were less pronounced (increase from 9 to 12 mm, +32%). The linearized association length which was estimated using multivariate surrogate data increased more gradually and was less sensitive to changes in spatial organization. The results of the spatial correlation analysis suggest that the drug-induced nonlinearity in the spatio-temporal dynamics of sustained AF is related to activation patterns which are characterized by extended uniformly propagating fibrillation wavefronts (AF type I). We conclude that cibenzoline enhanced the spatial organization of sustained AF associated with a transition from type II to type I AF activation patterns. This may destabilize the perpetuation of AF since an increase in association length is equivalent to a reduction of atrial tissue mass available to support reentrant circuits. The results are consistent with the hypothesis that larger association lengths result from fewer and larger reentrant circuits. It is argued that effects of diminished curvature of fibrillation wavefronts are anti-arrhythmic under conditions of suppressed excitability imposed by cibenzoline. Termination of AF may be mediated by a mechanism resembling a bifurcation of the dynamics which sets in when the ends of fractionated wavefronts cannot sufficiently curve anymore to maintain a positive balance of newly generated wavelets needed to sustain AF.