Cardiac magnetic resonance derived left atrial strain after ST-elevation myocardial infarction: an independent prognostic indicator.

BACKGROUND: The prognostic value of cardiac magnetic resonance (CMR) derived left atrial (LA) strain, ejection fraction (LAEF) and indexed volumes (LAVImax and LAVImin) after ST-elevation myocardial infarction (STEMI) remains controversial. The aim of this study was to assess the relationship between LA function and major adverse cardiovascular events (MACE) after STEMI. METHODS: A total of 202 prospectively recruited patients who underwent CMR at median day 4 after STEMI had complete CMR data for feature tracking assessment. LA reservoir and booster strain were quantified based on the average of three independently repeated measurements. RESULTS: MACE occurred in 35 patients during a median follow up of 607 days. Patients with MACE had lower median LA reservoir strain (18.9% vs. 29.4%, P<0.001), LA booster strain (9.4% vs. 13.0%, P=0.002) and LAEF (41.5% vs. 49.2%, P<0.001) than patients without MACE. Kaplan-Meier analyses demonstrated a difference in MACE between high- and low-risk groups for LA reservoir strain (cutoff 19.2%, P<0.001), LA booster strain (cutoff 9.7%, P<0.001) and LAEF (cutoff 38.5%, P<0.001). The AUC increased from 0.713 (95% CI: 0.608-0.818) for LVEF to 0.775 (95% CI: 0.680-0.870) when LA reservoir strain was added to LVEF (P=0.047). Univariate Cox regression analysis showed that all LA parameters had a significant effect on MACE, while multivariate analysis found LA reservoir strain was an independent predictor of MACE (HR 0.905; 95% CI: 0.843-0.972, P=0.006). CONCLUSIONS: CMR derived LA reservoir strain independently predicted MACE after STEMI when adjusted for standard risk measures.

Direct comparison of multilayer left ventricular global longitudinal strain using CMR feature tracking and speckle tracking echocardiography.

BACKGROUND: Cardiac magnetic resonance feature tracking (CMR-FT) and speckle tracking echocardiography (STE) are well-established strain imaging modalities. Multilayer strain measurement permits independent assessment of endocardial and epicardial strain. This novel and layer specific approach to evaluating myocardial deformation parameters may provide greater insight into cardiac contractility when compared to whole-layer strain analysis. The aim of this study is to validate CMR-FT as a tool for multilayer strain analysis by providing a direct comparison between multilayer global longitudinal strain (GLS) values between CMR-FT and STE. METHODS: We studied 100 patients who had an acute myocardial infarction (AMI), who underwent CMR imaging and echocardiogram at baseline and follow-up (48 ± 13 days). Dedicated tissue tracking software was used to analyse single- and multi-layer GLS values for CMR-FT and STE. RESULTS: Correlation coefficients for CMR-FT and STE were 0.685, 0.687, and 0.660 for endocardial, epicardial, and whole-layer GLS respectively (all p < 0.001). Bland Altman analysis showed good inter-modality agreement with minimal bias. The absolute limits of agreement in our study were 6.4, 5.9, and 5.5 for endocardial, whole-layer, and epicardial GLS respectively. Absolute biases were 1.79, 0.80, and 0.98 respectively. Intraclass correlation coefficient (ICC) values showed moderate agreement with values of 0.626, 0.632, and 0.671 respectively (all p < 0.001). CONCLUSION: There is good inter-modality agreement between CMR-FT and STE for whole-layer, endocardial, and epicardial GLS, and although values should not be used interchangeably our study demonstrates that CMR-FT is a viable imaging modality for multilayer strain.

Intra- and inter-observer reproducibility of multilayer cardiac magnetic resonance feature tracking derived longitudinal and circumferential strain.

BACKGROUND: Multilayer strain measurement with cardiac magnetic resonance feature tracking (CMR-FT) allows independent assessment of endocardial and epicardial strain. This novel method of layer-specific quantification of myocardial deformation parameters provides greater insight into contractility compared to whole-layer strain analysis. The clinical utility of this technique is promising. The aim of this study is to investigate the intra- and inter- observer reproducibility of CMR-FT derived multilayer global longitudinal strain (GLS) and global circumferential strain (GCS) parameters in the setting of normal cardiac function, cardiac pathology, and differing MRI field strengths. METHODS: We studied 4 groups of 20 subjects, comprising of patients with dilated cardiomyopathy, ischemic heart disease, and patients without cardiac pathology at both 1.5 and 3 T. Quantitative measures of whole-layer and multi-layer longitudinal and circumferential strain were calculated using CMR-FT software. RESULTS: Intraclass correlation coefficients (ICC) for intraobserver reproducibility of endocardial, epicardial, and whole-layer measurements of GLS were 0.979, 0.980, and 0.978 respectively, and those for GCS were 0.986, 0.977, and 0.985. ICCs for inter-observer reproducibility of endocardial, epicardial, and whole-layer measurements of GLS were 0.976, 0.970, and 0.976, and those for GCS were 0.982, 0.969, and 0.981. Bland Altman analysis showed minimal bias and acceptable limits of agreement (LOA) within each patient subgroup and the overall cohort. Circumferential and longitudinal strain parameters were equally reproducible in the overall cohort. CONCLUSIONS: CMR-FT derived multilayer measurements of longitudinal and circumferential strain demonstrate high intra- and inter- observer reproducibility, with suitability for use in clinical practice.

Incidence and predictors of left ventricular thrombus formation following acute ST-segment elevation myocardial infarction: A serial cardiac MRI study.

AIMS: Left ventricular (LV) thrombus is a complication of acute ST-segment elevation myocardial infarction (STEMI). We determined the incidence and predictors of LV thrombus formation using serial cardiac magnetic resonance (CMR) and two-dimensional echocardiography studies. METHODS AND RESULTS: Two hundred and ten patients underwent CMR (median 4 days [IQR 3-7]) and transthoracic echocardiography (median 4 days [IQR 3-7]) early after STEMI presentation with serial follow-up CMR (median 55 days [IQR 46-64]) and echocardiography studies (median 54 days [IQR 45-64]) performed subsequently. The incidence of LV thrombus was 12.3% (26/210) by CMR and 6.2% (13/210) by two-dimensional echocardiography. Echocardiography had 50% sensitivity and 100% specificity for LV thrombus detection compared to CMR. LV thrombus was found in 23.6% of patients with anterior STEMI (22/93). Ischaemic stroke occurred in 1.4% of patients (3/210). Patients with LV thrombus had lower baseline LV ejection fraction (LVEF) (34.9% vs 47.4%, p < 0.001). Microvascular obstruction was more common in patients with LV thrombus (77% vs 39%, p < 0.001). Patients with LV thrombus had increased LV dimensions with larger LV end-diastolic (19 ml [IQR 9-44] vs 6 ml [IQR -4-18], p < 0.001) and end-systolic volumes (10 ml [IQR 0-22] vs -4 ml [IQR -12-4], p < 0.001). CONCLUSION: CMR increases the detection of LV thrombi which standard echocardiography may underestimate. Serial studies post-STEMI may improve detection of LV thrombus, which is more prevalent in patients with anterior infarction, moderate LV dysfunction and adverse LV remodelling. This subgroup of patients may represent a high-risk group for targeted serial screening with CMR.

Atrial Fibrillation and Sleep Apnoea: Guilt by Association?

Atrial fibrillation (AF) and obstructive sleep apnoea (OSA) are both common, often underdiagnosed conditions with serious sequelae. An association between these two conditions has been recognised but the nature of this relationship remains a topic of active debate. Despite that lack of strong, randomised controlled trials, there is a considerable body of data indicating that not only does untreated OSA provide the substrates and triggers for AF but that OSA, itself, is also a therapeutic target for the management of cardiovascular disease in general and of AF in particular.

Adverse diastolic remodeling after reperfused ST-elevation myocardial infarction: An important prognostic indicator.

OBJECTIVES: We sought to determine the relationship of adverse diastolic remodeling (ie, worsening diastolic or persistent restrictive filling) with infarct scar characteristics, and to evaluate its prognostic value after ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Severe diastolic dysfunction (restrictive filling) has known prognostic value post STEMI. However, ongoing left ventricular (LV) remodeling post STEMI may alter diastolic function even if less severe. METHODS AND RESULTS: There were 218 prospectively recruited STEMI patients with serial echocardiograms (transthoracic echocardiography) and cardiac magnetic resonance imaging (CMR) performed, at a median of 4 days (early) and 55 days (follow-up). LV ejection fraction and infarct characteristics were assessed by CMR, and comprehensive diastolic function assessment including a diastolic grade was evaluated on transthoracic echocardiography. 'Adverse diastolic remodeling' occurred if diastolic function grade either worsened (≥1 grade) between early and follow-up imaging, or remained as persistent restrictive filling at follow-up. Follow-up infarct scar size (IS) predicted adverse diastolic remodeling (area under the curve 0.86) and persistent restrictive filling (area under the curve 0.89). The primary endpoint of major adverse cardiovascular events (MACE) occurred in 48 patients during follow-up (mean, 710±79 days). Kaplan-Meier analysis showed that adverse diastolic remodeling (n=50) and persistent restrictive filling alone (n=33) were significant predictors of MACE (both P<.001). Multivariate Cox analysis, when adjusted for TIMI risk score and CMR IS, microvascular obstruction, and LV ejection fraction, showed adverse diastolic remodeling (HR 3.79, P<.001) was an independent predictor of MACE, as was persistent restrictive filling alone (HR 2.61, P=.019). CONCLUSIONS: Larger IS is associated with adverse diastolic remodeling. Following STEMI, adverse diastolic remodeling is a powerful prognostic marker, and identifies a larger group of 'at-risk' patients, than does persistent restrictive filling alone.

Simultaneous conduction mapping and intracellular membrane potential recording in isolated atria.

We describe a novel approach for simultaneously determining regional differences in action potential (AP) morphology and tissue electrophysiological properties in isolated atria. The epicardial surface of rat atrial preparations was placed in contact with a multi-electrode array (9 × 10 silver chloride electrodes, 0.1 mm diameter and 0.1 mm pitch). A glass microelectrode (100 MΩ) was simultaneously inserted into the endocardial surface to record intracellular AP from either of 2 regions (A, B) during pacing from 2 opposite corners of the tissue. AP duration at 80% of repolarisation and its restitution curve was significantly different only in region A (p < 0.01) when AP was initiated at different stimulation sites. Alternans in AP duration and AP amplitude, and in conduction velocity were observed during 2 separate arrhythmic episodes. This approach of combining microelectrode array and intracellular membrane potential recording may provide new insights into arrhythmogenic mechanisms in animal models of cardiovascular disease.

Prognostic value of high sensitivity troponin T after ST-segment elevation myocardial infarction in the era of cardiac magnetic resonance imaging.

AIMS: To determine if high sensitivity troponin T (hs-TnT) measurements performed during the 'plateau phase' of troponin release (≥48 h) following ST-segment elevation myocardial infarction (STEMI) can predict major adverse cardiovascular endpoints (MACE), and to evaluate its prognostic value compared with cardiac magnetic resonance imaging (CMRI) parameters. METHODS AND RESULTS: We prospectively recruited 201 first presentation STEMI patients. Serial hs-TnT levels were measured at admission, peak (highest), 24, 48 and 72 h. CMRI and transthoracic echocardiography were performed (4 days median) post-STEMI, evaluating infarct scar characteristics and left ventricular ejection fraction (LVEF). Associations were determined between hs-TnT levels and CMRI parameters early after STEMI with MACE (comprising mortality, re-infarction, new or worsening of heart failure, cerebrovascular accident, and sustained ventricular arrhythmias) at medium-term follow-up. After 602 days (median), 33 (17%) patients had MACE. Upper tertile hs-TnT levels at 48 and 72 h were associated with MACE (Kaplan-Meier P = 0.002 and P = 0.012, respectively). Multivariate Cox analyses, incorporating diabetes, CMRI scar size, LVEF and hs-TnT levels (applied at a single hs-TnT time point) showed that 48 and 72 h hs-TnT levels were independent predictors for MACE (HR = 1.20, P = 0.002, and HR = 1.21, P = 0.035 respectively). CONCLUSION: Measurement of hs-TnT in the plateau phase after STEMI is an inexpensive method of prognostic risk assessment.

High-sensitivity troponin T predicts infarct scar characteristics and adverse left ventricular function by cardiac magnetic resonance imaging early after reperfused acute myocardial infarction.

BACKGROUND: Late gadolinium enhancement cardiac magnetic resonance imaging (CMRI) is the current standard for evaluation of myocardial infarct scar size and characteristics. Because post-ST-segment elevation myocardial infarction (STEMI) troponin levels correlate with clinical outcomes, we sought to determine the sampling period for high-sensitivity troponin T (hs-TnT) that would best predict CMRI-measured infarct scar characteristics and left ventricular (LV) function. METHODS AND RESULTS: Among 201 patients with first presentation with STEMI who were prospectively recruited, we measured serial hs-TnT levels at admission, peak, 24 hours, 48 hours, and 72 hours after STEMI. Indexed LV volumes, LV ejection fraction (LVEF) and infarct scar characteristics (scar size, scar heterogeneity, myocardial salvage index, and microvascular obstruction) were evaluated by CMRI at a median of 4 days post-STEMI. Peak and serial hs-TnT levels correlated positively with early indexed LV volumes and infarct scar characteristics, and negatively correlated with myocardial salvage index and LVEF. Both 48- and 72-hour hs-TnT levels similarly predicted "large" total infarct scar size (odds ratios [ORs] 3.08 and 3.53, both P < .001), myocardial salvage index (ORs 1.68 and 2.30, both P < .001), and LVEF <40% (ORs 2.16 and 2.17, both P < .001) on univariate analyses. On multivariate analyses, 48- and 72-hour hs-TnT levels independently predicted large infarct scar size (ORs 2.05 and 2.31, both P < .001), reduced myocardial salvage index (OR 1.39 [P = .031] and OR 1.55 [P = .009]), and LVEF <40% (OR 1.47 [P = .018] and OR 1.43 [P = .026]). All measured hs-TnT levels had a modest association and similar capacity to predict microvascular obstruction. CONCLUSIONS: Levels of hs-TnT at 48 and 72 hours, measured during the "plateau phase" post-STEMI, predicted infarct scar size, poor myocardial salvage, and LVEF. These levels also correlated with scar heterogeneity and microvascular obstruction post-STEMI. Since ascertaining peak levels after STEMI is challenging in routine practice, based on the biphasic kinetics of hs-TnT, a measurement at 48 to 72 hours (during the plateau phase) provides a useful and simple method for early evaluation of LV function and infarct scar characteristics.

Atrial arrhythmia in ageing spontaneously hypertensive rats: unraveling the substrate in hypertension and ageing.

BACKGROUND: Both ageing and hypertension are known risk factors for atrial fibrillation (AF) although the pathophysiological contribution or interaction of the individual factors remains poorly understood. Here we aim to delineate the arrhythmogenic atrial substrate in mature spontaneously hypertensive rats (SHR). METHODS: SHR were studied at 12 and 15 months of age (n = 8 per group) together with equal numbers of age-matched normotensive Wistar-Kyoto control rats (WKY). Electrophysiologic study was performed on superfused isolated right and left atrial preparations using a custom built high-density multiple-electrode array to determine effective refractory periods (ERP), atrial conduction and atrial arrhythmia inducibility. Tissue specimens were harvested for structural analysis. RESULTS: COMPARED TO WKY CONTROLS, THE SHR DEMONSTRATED: Higher systolic blood pressure (p<0.0001), bi-atrial enlargement (p<0.05), bi-ventricular hypertrophy (p<0.05), lower atrial ERP (p = 0.008), increased atrial conduction heterogeneity (p = 0.001) and increased atrial interstitial fibrosis (p = 0.006) & CD68-positive macrophages infiltration (p<0.0001). These changes resulted in higher atrial arrhythmia inducibility (p = 0.01) and longer induced AF episodes (p = 0.02) in 15-month old SHR. Ageing contributed to incremental bi-atrial hypertrophy (p<0.01) and atrial conduction heterogeneity (p<0.01) without affecting atrial ERP, fibrosis and arrhythmia inducibility. The limited effect of ageing on the atrial substrate may be secondary to the reduction in CD68-positive macrophages. CONCLUSIONS: Significant atrial electrical and structural remodeling is evident in the ageing spontaneously hypertensive rat atria. Concomitant hypertension appears to play a greater pathophysiological role than ageing despite their compounding effect on the atrial substrate. Inflammation is pathophysiologically linked to the pro-fibrotic changes in the hypertensive atria.

Atrial remodeling in obstructive sleep apnea: implications for atrial fibrillation.

BACKGROUND: There is a known association between obstructive sleep apnea (OSA) and atrial fibrillation (AF); however, how OSA affects the atrial myocardium is not well described. OBJECTIVE: To determine whether patients with OSA have an abnormal atrial substrate. METHODS: Forty patients undergoing ablation of paroxysmal AF and in sinus rhythm (20 with OSA [apnea-hypopnea index ≥ 15] and 20 reference patients with no OSA [apnea-hypopnea index < 15] by polysomnography) were studied. Multipolar catheters were positioned at the lateral right atrium (RA), coronary sinus, crista terminalis, and RA septum to determine the effective refractory period at 5 sites, conduction time along linear catheters at the RA and the coronary sinus, conduction at the crista terminalis, and sinus node function (corrected sinus node recovery time). Biatrial electroanatomic maps were created to determine the voltage, conduction, and distribution of complex electrograms (duration ≥ 50 ms). RESULTS: The groups had no differences in the prevalence of established risk factors for AF. Patients with OSA had the following compared with those without OSA: no difference in effective refractory period (P = .9), prolonged conduction times along the coronary sinus and RA (P = .02), greater number (P = .003) and duration (P = .03) of complex electrograms along the crista terminalis, longer P-wave duration (P = .01), longer corrected sinus node recovery time (P = .02), lower atrial voltage (RA, P <.001; left atrium, P <.001), slower atrial conduction velocity (RA, P = .001; left atrium, P = .02), and more widespread complex electrograms in both atria (RA, P = .02; left atrium, P = .01). CONCLUSION: OSA is associated with significant atrial remodeling characterized by atrial enlargement, reduction in voltage, site-specific and widespread conduction abnormalities, and longer sinus node recovery. These features may in part explain the association between OSA and AF.

Characterization of atrial remodeling studied remote from episodes of typical atrial flutter.

Atrial electrical remodeling has been shown after termination of atrial flutter (AFL); however, whether abnormalities persist beyond an arrhythmic episode is not known. We aimed to characterize the atrial substrate, remote from arrhythmia, in patients with typical AFL. We compared 20 patients, studied remote from episodes of typical AFL and without a history of atrial fibrillation, to 20 reference patients. Multipolar catheters placed at the lateral right atrium (RA), coronary sinus, crista terminalis, and septal RA measured the effective refractory period at 5 sites; conduction characteristics at the crista terminalis; and the conduction time along the lateral RA and coronary sinus. Electroanatomic right atrial maps were created to determine regional differences in voltage and conduction. Patients with AFL demonstrated the following compared to the reference patients: a larger right atrial volume (121 +/- 30 vs 83 +/- 24 ml, p = 0.005); a prolonged P-wave duration (122 +/- 18 vs 102 +/- 11 ms, p = 0.007); a longer right atrial activation time (107 +/- 23 vs 85 +/- 14 ms, p = 0.02); a prolonged conduction time along the lateral RA (67 +/- 4 vs 47 +/- 3 ms, p <0.001); a slower mean conduction velocity (1.2 +/- 0.2 vs 2.1 +/- 0.6 mm/ms, p <0.001); a greater proportion of fractionated electrographic findings (16 +/- 4% vs 10 +/- 6%, p = 0.006); more frequent abnormal electrographic findings at the crista terminalis (4.1 +/- 2.6 vs 1.0 +/- 1.1, p = 0.001); a prolonged corrected sinus node recovery time (318 +/- 71 vs 203 +/- 94 ms, p = 0.02); a trend toward greater effective refractory period (232 +/- 29 vs 213 +/- 12 ms, p = 0.06); and a lower voltage (2.1 +/- 0.5 vs 3.0 +/- 0.5 mV, p <0.001). In conclusion, studied remote from arrhythmia, patients with AFL demonstrated significant and diffuse atrial abnormalities characterized by structural changes, conduction abnormalities, and sinus node dysfunction. These persisting abnormalities characterize the substrate underlying typical AFL and may account for the subsequent development of atrial fibrillation.

Feasibility of high-density electrophysiological study using multiple-electrode array in isolated small animal atria.

1. High-density cardiac electrophysiological study (EPS) of small animal atria has been limited to optical mapping techniques, which require complex and expensive equipment setup. We aim to evaluate the feasibility of carrying out EPS in isolated atrial tissues using a custom made high-density multiple-electrode array (MEA). 2. Isolated rat atrial preparations were studied. The MEA (4 × 5 mm) consisted of 90 silver chloride coated electrodes (0.1 mm diameter, 0.5 mm pitch) and was connected to a conventional EP system yielding 80 bipolar signals. Atrial tissues were placed over the MEA in a dish bubbled with 100% oxygen and superfused with modified HEPES solution at pH 7.35 and 37°C. Then, 1 mmol of 2,3-butanedione monoxime was added to suppress motion artifacts from muscle contractions. Custom plaque analysis software was used for offline conduction analysis. 3. Isolated atrial tissues showed good viability of > 30 min, allowing ample time for complete EPS. High quality electrograms with excellent signal to noise ratio were obtained. All electrophysiological parameters showed good reproducibility: effective refractory period, conduction velocity and heterogeneity index. Tachycardia was also inducible in these normal atria. 4. The present study shows the feasibility of performing high-density EPS of small isolated atrial tissues with a conventional electrode-based technique. The MEA system is compatible with standard electrophysiology recording systems and provides a novel, inexpensive option for detailed EPS in small animal models. In particular, it presents new research avenues to further explore the mechanisms of atrial arrhythmias in various transgenic and knockout rodent models.

Direction-dependent conduction in lone atrial fibrillation.

BACKGROUND: Patients with lone atrial fibrillation (AF) have an abnormal atrial substrate. OBJECTIVE: The purpose of this study was to determine the role of direction-dependent conduction in patients with lone AF. METHODS: Twenty-four patients with paroxysmal lone AF and 24 reference patients with left-sided accessory pathways were studied. Multipolar catheters placed at the lateral right atrium, crista terminalis, coronary sinus (CS), and left atrial roof were used to determine direction-dependent conduction characteristics. Biatrial electroanatomic maps were created during sinus rhythm and with distal CS pacing to characterize direction-dependent differences in conduction velocities, electrogram complexity, and voltage. RESULTS: Differing wavefront directions caused changes in conduction velocity (P <.001), biatrial activation times (P <.001), electrogram fragmentation (P <.001), site-specific conduction delays (P <.001), and voltage (P <.001) in both lone AF and reference patients. These direction-dependent abnormalities were amplified in lone AF patients compared to reference patients, who exhibited greater slowing in conduction velocities (P = .02), prolongation of biatrial activation time (P = .04), increase in number (P <.001) and length (P <.001) of lines of conduction block, increase in proportion of fractionated electrograms (P <.001), and decrease in voltage (P = .03) during distal CS pacing compared to sinus rhythm. CONCLUSION: This study demonstrates the marked direction-dependent conduction abnormalities present in patients with lone AF. These results provide further insights into the critical interplay between the underlying abnormal substrate and differing wavefront directions. The study suggests that direction-dependent conduction abnormalities may explain in part the greater arrhythmogenicity of ectopic triggers from the left atrium rather than the right atrium.

Cardiorespiratory phase-coupling is reduced in patients with obstructive sleep apnea.

Cardiac and respiratory rhythms reveal transient phases of phase-locking which were proposed to be an important aspect of cardiorespiratory interaction. The aim of this study was to quantify cardio-respiratory phase-locking in obstructive sleep apnea (OSA). We investigated overnight polysomnography data of 248 subjects with suspected OSA. Cardiorespiratory phase-coupling was computed from the R-R intervals of body surface ECG and respiratory rate, calculated from abdominal and thoracic sensors, using Hilbert transform. A significant reduction in phase-coupling was observed in patients with severe OSA compared to patients with no or mild OSA. Cardiorespiratory phase-coupling was also associated with sleep stages and was significantly reduced during rapid-eye-movement (REM) sleep compared to slow-wave (SW) sleep. There was, however, no effect of age and BMI on phase coupling. Our study suggests that the assessment of cardiorespiratory phase coupling may be used as an ECG based screening tool for determining the severity of OSA.

Paroxysmal lone atrial fibrillation is associated with an abnormal atrial substrate: characterizing the "second factor".

OBJECTIVES: The purpose of this study was to determine whether patients with paroxysmal "lone" atrial fibrillation (AF) have an abnormal atrial substrate. BACKGROUND: While "AF begets AF," prompt termination to prevent electrical remodeling does not prevent disease progression. METHODS: Twenty-five patients with paroxysmal lone AF, without arrhythmia in the week prior, and 25 reference patients with left-sided accessory pathways were studied. Multipolar catheters placed at the lateral right atrium (RA), crista terminalis, coronary sinus, septal RA, and sequentially within the left atrium (LA) determined the effective refractory period (ERP) at 10 sites, conduction time along linear catheters, and conduction characteristics at the crista terminalis. Bi-atrial electroanatomic maps were created to determine regional differences in conduction velocity and voltage. RESULTS: Patients with AF demonstrated the following compared with reference patients: larger atrial volumes (RA: 94 +/- 18 ml vs. 69 +/- 9 ml, p = 0.003; LA: 99 +/- 19 ml vs. 77 +/- 17 ml, p = 0.006); longer ERP (at 600 ms: 255 +/- 25 ms vs. 222 +/- 16 ms, p < 0.001; at 450 ms: 234 +/- 20 ms vs. 212 +/- 14 ms, p = 0.004); longer conduction time along linear catheters (57 +/- 18 ms vs. 47 +/- 10 ms, p = 0.01); longer bi-atrial activation time (128 +/- 17 ms vs. 89 +/- 10 ms, p < 0.001); slower conduction velocity (RA: 1.3 +/- 0.3 mm/ms vs. 2.1 +/- 0.5 mm/ms; LA: 1.2 +/- 0.2 mm/ms vs. 2.2 +/- 0.4 mm/ms, p < 0.001); greater proportion of fractionated electrograms (27 +/- 8% vs. 8 +/- 5%, p < 0.001); longer corrected sinus node recovery time (265 +/- 57 ms vs. 185 +/- 60 ms, p = 0.002); and lower voltage (RA: 1.7 +/- 0.4 mV vs. 2.9 +/- 0.4 mV; LA: 1.7 +/- 0.7 mV vs. 3.3 +/- 0.7 mV, p < 0.001). CONCLUSIONS: Patients with paroxysmal lone AF, remote from arrhythmia, demonstrate bi-atrial abnormalities characterized by structural change, conduction abnormalities, and sinus node dysfunction. These factors are likely contributors to the "second factor" that predisposes to the development and progression of AF.

Clinical validation and comparison of alternative methods for evaluation of entrainment mapping.

INTRODUCTION: Measuring the postpacing interval (PPI) and correcting for the tachycardia cycle length (TCL) is an important entrainment response (ER). However, it may be impossible to measure PPI due to electrical noise on the mapping catheter. To overcome this problem, 2 alternative methods for the assessment of ER have been proposed: N+1 difference (N+1 DIFF) and PPIR method. PPI-TCL difference (PPI-TCL) correlates very well with ER assessed by new methods, but the agreement with PPI-TCL was established only in relation to PPIR method. Moreover, it is not known which of these methods is superior in the assessment of ER. METHODS: We analyzed 155 episodes of ER in 21 patients with heterogeneous reentrant arrhythmias. ER was estimated by PPI-TCL and by both alternative methods. Agreement between methods was assessed by means of the Bland-Altman test, kappa coefficient (kappa), and correlation coefficient (r). Finally, a mathematical comparison of the alternative methods was performed. RESULTS: The agreement between PPI-TCL and alternative methods was very good. For N+1 DIFF the mean difference was -1.86 +/- 7.31 ms; kappa = 0.9; r = 0.98; for PPIR method the mean difference was -1.46 +/- 7.65 ms; kappa = 0.92; r = 0.99. Agreement between both alternative methods was also very high: the mean difference of 0.5 +/- 6.6 ms; kappa = 0.89; r = 0.99. The analysis of the equations used for calculation of ER by these methods revealed that essentially they were mathematically equivalent. CONCLUSION: Each of the alternative methods may be used for evaluation of ER when PPI-TCL cannot be assessed directly. Results obtained by both alternative methods are comparable.

High-density mapping of atrial fibrillation in humans: relationship between high-frequency activation and electrogram fractionation.

INTRODUCTION: Sites of complex fractionated atrial electrograms (CFAE) and dominant frequency (DF) have been implicated in maintaining atrial fibrillation (AF); however, their relationship is poorly understood. METHODS AND RESULTS: Twenty patients underwent biatrial high-density contact mapping (507 +/- 150 points/patient) during AF. CFAE were characterized using software to quantify electrogram complexity (CFE-mean). Spectral analysis determined the frequency with greatest power and sites of high DF with a frequency gradient. CFE-mean was higher (less fractionated) for right compared with left atria (P < 0.001) and in paroxysmal compared with persistent AF (P < 0.001). DF was lower for right compared with left atria (P = 0.02) and in paroxysmal compared with persistent AF (P < 0.001). There was significant regional variation in DF in paroxysmal (P < 0.001) but not persistent AF. Highest DF points clustered together with 5.2 +/- 1.7 clusters/patient. Correlation between CFE-mean and DF was poor on a point-by-point basis (r =-0.17, P < 0.001), but moderate on an individual basis (r =-0.50, P = 0.03). Exploration of their spatial relationship demonstrated CFAE areas in close proximity (median 5 mm, IQR 2-10) to high DF sites; within 10 mm in 80% and 10-20 mm in 10%. Simultaneous activation mapping at these sites further supports this observation. CONCLUSION: Greater fractionation and higher DF are seen in persistent AF and left atria during AF. Preferential areas of high DF are observed in paroxysmal but not persistent AF. CFAE and DF correlate within an individual but not point-by-point. Exploration of their spatial relationship demonstrates CFAE in areas adjacent to high DF, and this is supported by activation mapping at these sites.