Irfan M. Khurram

Initial experience with magnetic resonance imaging of atrial scar and co-registration with electroanatomic voltage mapping during atrial fibrillation: Success and limitations

BACKGROUND Ablation for atrial fibrillation (AF) frequently requires multiple procedures to achieve durable restoration of sinus rhythm. Early studies have suggested that delayed enhancement magnetic resonance imaging (DE-MRI) of the left atrium (LA) can assist in performing repeat ablation procedures. OBJECTIVE The purpose of this study was to investigate the utility of DE-MRI in delineating regions of LA low voltage and PV reconnection sites in patients undergoing repeat PV isolation for recurrent AF. METHODS We enrolled 10 patients undergoing repeat ablation for AF recurrence to undergo preprocedural DE-MRI of the LA in conjunction with high-density voltage mapping (>100 sites) of the LA during the ablation procedure. LA wall regions with hyperenhancement were segmented from DE-MRI images and retrospectively co-registered with the electroanatomic LA map. The association between scar on DE-MRI images and low-voltage regions of the LA was assessed, as was the association between scar gaps and electrogram-determined PV reconnection sites. RESULTS Ten patients underwent successful DE-MRI imaging and repeat AF ablation without complication. In all 10 patients, the majority of PVs were found to have regained electrical continuity with the LA (30/37 PVs electrically active); all patients underwent successful reisolation of all PVs using standard ablation techniques. There was a significant association between scar identified by DE-MRI and low-voltage regions of the LA (-0.7±0.1 mV in scar regions; generalized estimating equations model clustered by patient, P<.001). However, there was no association between scar gaps and PV reconnection sites. CONCLUSION We demonstrate the co-registration of DE-MRI scar imaging and electroanatomic LA mapping, with agreement between regions of scar on DE-MRI and low voltage by mapping. However, at our center, this technique did not provide accurate information on the location of PV reconnection sites in patients undergoing repeat ablation for AF.

Relationship between left atrial appendage morphology and stroke in patients with atrial fibrillation

BACKGROUND Atrial fibrillation (AF) is an important cause of stroke. Given the morbidity and mortality associated with stroke, the risk stratification of patients based on left atrial appendage (LAA) characteristics is of great interest. OBJECTIVE To explore the association between LAA morphology and LAA characteristics including the extent of trabeculations, orifice diameter, and length with prevalent stroke in a large cohort of patients with drug refractory AF who underwent AF ablation to develop mechanistic insight regarding the risk of stroke. METHODS An institutional cohort of 1063 patients referred for AF ablation from 2003 to 2012 was reviewed to identify patients that underwent preprocedural cardiac computed tomography (CT). LAA morphology was characterized as chicken wing, cactus, windsock, or cauliflower by using previously reported methodology. Left atrial size and LAA trabeculations, morphology, orifice diameter, and length were compared between patients with prevalent stroke and patients without prevalent stroke. RESULTS Of 678 patients with CT images, 65 (10%) had prior stroke or transient ischemic attack. In univariate analyses, prevalent heart failure (7.7% in cases vs 2.8% in controls; P = .033), smaller LAA orifice (2.26 ± 0.52 cm vs 2.78 ± 0.71 cm ; P < .001), shorter LAA length (5.06 ± 1.17 cm vs 5.61 ± 1.17 cm; P < .001), and extensive LAA trabeculations (27.7% vs 14.4%; P = .019) were associated with stroke. LAA morphologies were unassociated with stroke risk. In multivariable analysis, smaller LAA orifice diameter and extensive LAA trabeculations remained independently associated with thromboembolic events. CONCLUSIONS The extent of LAA trabeculations and smaller LAA orifice diameter are associated with prevalent stroke and may mediate the previously described association of cauliflower LAA morphology with stroke.

Magnetic resonance image intensity ratio, a normalized measure to enable interpatient comparability of left atrial fibrosis.

BACKGROUND The measurement of late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) intensity in arbitrary units limits the objectivity of thresholds for focal scar detection and interpatient comparisons of scar burden. OBJECTIVE To develop and validate a normalized measure, the image intensity ratio (IIR), for the assessment of left atrial (LA) scar on LGE-MRI. METHODS Electrocardiogram- and respiratory-gated 1.5 Tesla LGE-MRI was performed in 75 patients (75% men; 62 ± 8 years) before atrial fibrillation ablation. The local IIR was defined as LA myocardial signal intensity for each of the 20 sectors on contiguous axial image planes divided by the mean LA blood pool image intensity. Intracardiac point-by-point sampled electroanatomic map points were coregistered with the corresponding image sectors. RESULTS The average bipolar voltage for all 8153 electroanatomic map points was 0.9 ± 1.1 mV. In a mixed effects model accounting for within patient clustering, and adjusting for age, LA volume, mass, body mass index, sex, CHA2DS2-VASc score, atrial fibrillation type, history of previous ablations, and contrast delay time, each unit increase in local IIR was associated with 91.3% decrease in bipolar LA voltage (P < .001). Local IIR thresholds of >0.97 and >1.61 corresponded to bipolar voltage <0.5 and <0.1 mV, respectively. CONCLUSIONS Normalization of LGE-MRI intensity by the mean blood pool intensity results in a metric that is closely associated with intracardiac voltage as a surrogate of atrial fibrosis.

Cardiac magnetic resonance T1 mapping of left atrial myocardium.

BACKGROUND Cardiac magnetic resonance (CMR) T1 mapping is an emerging tool for objective quantification of myocardial fibrosis. OBJECTIVES To (a) establish the feasibility of left atrial (LA) T1 measurements, (b) determine the range of LA T1 values in patients with atrial fibrillation (AF) vs healthy volunteers, and (c) validate T1 mapping vs LA intracardiac electrogram voltage amplitude measures. METHODS CMR imaging at 1.5 T was performed in 51 consecutive patients before AF ablation and in 16 healthy volunteers. T1 measurements were obtained from the posterior LA myocardium by using the modified Look-Locker inversion-recovery sequence. Given the established association of reduced electrogram amplitude with fibrosis, intracardiac point-by-point bipolar LA voltage measures were recorded for the validation of T1 measurements. RESULTS The median LA T1 relaxation time was shorter in patients with AF (387 [interquartile range 364-428] ms) compared to healthy volunteers (459 [interquartile range 418-532] ms; P < .001) and was shorter in patients with AF with prior ablation compared to patients without prior ablation (P = .035). In a generalized estimating equations model, adjusting for data clusters per participant, age, rhythm during CMR, prior ablation, AF type, hypertension, and diabetes, each 100-ms increase in T1 relaxation time was associated with 0.1 mV increase in intracardiac bipolar LA voltage (P = .025). CONCLUSIONS Measurement of the LA myocardium T1 relaxation time is feasible and strongly associated with invasive voltage measures. This methodology may improve the quantification of fibrotic changes in thin-walled myocardial tissues.

Association of Left Atrial Function and Left Atrial Enhancement in Patients With Atrial Fibrillation Cardiac Magnetic Resonance Study

Atrial fibrillation (AF) is associated with extensive abnormalities in atrial structure and function1-3. It is well-established that structural atrial changes precede the development of AF and progress with increased duration of sustained AF4. The changes in atrial function impair not only the booster pump function but also the atrial reservoir and conduit functions during ventricular systole and early diastole 5, 6. Progressive atrial remodeling includes fibrotic changes that promote AF maintenance7. This idea is supported by observations of increased left atrial (LA) fibrosis in patients with long-standing persistent AF 4. LA structural and functional remodeling is associated with increased incidence of AF, as well as AF recurrence after cardioversion or ablation8-11. Late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR) can noninvasively quantify the extent of LA fibrosis12, 13. Atrial function is commonly evaluated by speckle-tracking echocardiography; however, the technique is limited for resolution of the thin and asymmetric LA myocardium and for the analysis of the posterior LA where most of the fibrosis is located7. In contrast, myocardial motion can be accurately tracked with CMR due to its ability to accurately define endocardial and epicardial borders14. CMR-feature tracking, a novel post–processing technique which tracks myocardial motion using cine CMR images, has recently been developed15-19. In this study, we sought to examine the association of LA fibrosis measured with LGE-CMR with phasic LA remodeling measured with feature-tracking CMR in patients with AF. We hypothesized that increased atrial LGE is associated with reduced LA function as assessed by feature tracking CMR.Background—Atrial fibrillation (AF) is associated with left atrial (LA) structural and functional changes. Cardiac magnetic resonance late gadolinium enhancement (LGE) and feature-tracking are capable of noninvasive quantification of LA fibrosis and myocardial motion, respectively. We sought to examine the association of phasic LA function with LA enhancement in patients with AF. Methods and Results—LA structure and function was measured in 90 patients with AF (age 61±10 years; 76% men) referred for ablation and 14 healthy volunteers. Peak global longitudinal LA strain, LA systolic strain rate, and early and late diastolic strain rates were measured using cine–cardiac magnetic resonance images acquired during sinus rhythm. The degree of LGE was quantified. Compared with patients with paroxysmal AF (60% of cohort), those with persistent AF had larger maximum LA volume index (56±17 versus 49±13 mL/m2; P=0.036), and increased LGE (27.1±11.7% versus 36.8±14.8%; P<0.001). Aside from LA active emptying fraction, all LA parameters (passive emptying fraction, peak global longitudinal LA strain, systolic strain rate, early diastolic strain rate, and late diastolic strain rate) were lower in patients with persistent AF (P<0.05 for all). Healthy volunteers had less LGE and higher LA functional parameters compared with patients with AF (P<0.05 for all). In multivariable analysis, increased LGE was associated with lower LA passive emptying fraction, peak global longitudinal LA strain, systolic strain rate, early diastolic strain rate, and late diastolic strain rate (P<0.05 for all). Conclusions—Increased LA enhancement is associated with decreased LA reservoir, conduit, and booster pump functions. Phasic measurement of LA function using feature-tracking cardiac magnetic resonance may add important information about the physiological importance of LA fibrosis.

Association Between Left Atrial Stiffness Index and Atrial Fibrillation Recurrence in Patients Undergoing Left Atrial Ablation

Background—Atrial fibrillation (AF) is associated with significant abnormalities of left atrial (LA) systolic and diastolic function. This study describes a novel measure, LA stiffness index, that estimates LA diastolic function and its association with clinical outcomes of catheter ablation. Methods and Results—A total of 219 AF patients referred for ablation (59% paroxysmal, mean CHA2DS2VASc score 1.7±1.4) were enrolled. Atrial pressure and volume loops were prepared from invasive pressure measures and cardiac magnetic resonance imaging volumetric data during sinus rhythm for all patients. An LA stiffness index was created, defined by the ratio of change in LA pressure to volume during passive filling of LA (&Dgr;P/&Dgr;V). Patients were followed prospectively. Mean LA stiffness index for AF patients was 0.6±0.5 mm Hg/mL (paroxysmal AF 0.51±0.4 and persistent AF 0.73±0.6; P<0.001). Linear regression analysis showed a rise in the stiffness index with age, increasing at a rate of 0.02 mm Hg/mL per year (P<0.001). The LA stiffness index was higher in patients with previous LA ablation(s) for AF (0.51±0.35 versus 0.83±0.70; P<0.001). Forty of 160 patients had recurrence after AF ablation with a mean follow-up of 10.4±7.6 months. Patients with recurrence had higher stiffness index than those without recurrence (0.83±0.46 versus 0.40±0.22; P<0.001). Conclusions—LA stiffness index, a novel measure to assess LA diastolic function, increases with age and is higher in persistent AF and in the setting of repeat AF ablation. Greater LA stiffness index was independently associated with recurrence of AF after LA ablation.

Association of Left Atrial Local Conduction Velocity With Late Gadolinium Enhancement on Cardiac Magnetic Resonance in Patients With Atrial Fibrillation

Background—Prior studies have demonstrated regional left atrial late gadolinium enhancement (LGE) heterogeneity on magnetic resonance imaging. Heterogeneity in regional conduction velocities is a critical substrate for functional reentry. We sought to examine the association between left atrial conduction velocity and LGE in patients with atrial fibrillation. Methods and Results—LGE imaging and left atrial activation mapping were performed during sinus rhythm in 22 patients before pulmonary vein isolation. The locations of 1468 electroanatomic map points were registered to the corresponding anatomic sites on 469 axial LGE image planes. The local conduction velocity at each point was calculated using previously established methods. The myocardial wall thickness and image intensity ratio defined as left atrial myocardial LGE signal intensity divided by the mean left atrial blood pool intensity was calculated for each mapping site. The local conduction velocity and image intensity ratio in the left atrium (mean±SD) were 0.98±0.46 and 0.95±0.26 m/s, respectively. In multivariable regression analysis, clustered by patient, and adjusting for left atrial wall thickness, conduction velocity was associated with the local image intensity ratio (0.20 m/s decrease in conduction velocity per increase in unit image intensity ratio, P<0.001). Conclusions—In this clinical in vivo study, we demonstrate that left atrial myocardium with increased gadolinium uptake has lower local conduction velocity. Identification of such regions may facilitate the targeting of the substrate for reentrant arrhythmias.

Comparison of preexisting and ablation-induced late gadolinium enhancement on left atrial magnetic resonance imaging

BACKGROUND Postablation atrial fibrillation recurrence is positively associated with the extent of preexisting left atrial (LA) late gadolinium enhancement (LGE) on magnetic resonance imaging (MRI), but negatively associated with the extent of postablation LGE regardless of proximity to the pulmonary vein antra. The characteristics of pre- vs postablation LA LGE may provide insight into this seeming paradox and inform future strategies for ablation. OBJECTIVE The purpose of this study was to define the characteristics of preexisting vs ablation-induced LA LGE. METHODS LGE-MRI was prospectively performed before and ≥3 months after initial ablation in 20 patients. The intracardiac locations of ablation points were coregistered with the corresponding sites on axial planes of postablation LGE-MRI. The image intensity ratio (IIR), defined as the LA myocardial MRI signal intensity divided by the mean LA blood pool intensity, and LA myocardial wall thickness were calculated on pre- and postablation images. RESULTS Imaging data from 409 pairs of pre- and postablation axial LGE-MRI planes and 6961 pairs of pre- and postablation image sectors were analyzed. Ablation-induced LGE revealed a higher IIR, suggesting greater contrast uptake and denser fibrosis, than did preexisting LGE (1.25 ± 0.25 vs 1.14 ± 0.15; P < .001). In addition, ablation-induced LGE regions had thinner LA myocardium (2.10 ± 0.67 mm vs 2.37 ± 0.74 mm; P < .001). CONCLUSION Regions with ablation-induced LGE exhibit increased contrast uptake, likely signifying higher scar density, and thinner myocardium as compared with regions with preexisting LGE. Future studies examining the association of postablation LGE intensity and nonuniformity with ablation success are warranted and may inform strategies to optimize ablation outcome.

The association of pre-existing left atrial fibrosis with clinical variables in patients referred for catheter ablation of atrial fibrillation.

Introduction Atrial fibrillation (AF) recurrence after ablation is associated with left atrial (LA) fibrosis on late gadolinium enhanced (LGE) magnetic resonance imaging (MRI). We sought to determine pre-ablation, clinical characteristics that associate with the extent of LA fibrosis in patients undergoing catheter ablation for AF. Methods and Results Consecutive patients presenting for catheter ablation of AF were enrolled and underwent LGE-MRI prior to initial AF ablation. The extent of fibrosis as a percentage of total LA myocardium was calculated in all patients prior to ablation. The cohort was divided into quartiles based on the percentage of fibrosis. Of 60 patients enrolled in the cohort, 13 had <5% fibrosis (Group 1), 15 had 5-7% fibrosis (Group 2), 17 had 8-13% fibrosis (Group 3), and 15 had 14-36% fibrosis (Group 4). The extent of LA fibrosis was positively associated with time in continuous AF, and the presence of persistent or longstanding persistent AF. However, no statistically significant difference was observed in the presence of comorbid conditions, age, BMI, LA volume, or family history of AF among the four groups. After adjusting for diabetes and hypertension in a multivariable linear regression model, paroxysmal AF remained independently and negatively associated with the extent of fibrosis (-4.0 ± 1.8, P = 0.034). Conclusion The extent of LA fibrosis in patients undergoing AF ablation is associated with AF type and time in continuous AF. Our results suggest that the presence and duration of AF are primary determinants of increased atrial LGE.

The association of left atrial low-voltage regions on electroanatomic mapping with low attenuation regions on cardiac computed tomography perfusion imaging in patients with atrial fibrillation

BACKGROUND Previous studies have shown that contrast-enhanced multidetector computed tomography (CE-MDCT) could identify ventricular fibrosis after myocardial infarction. However, whether CE-MDCT can characterize atrial low-voltage regions remains unknown. OBJECTIVE The purpose of this study was to examine the association of CE-MDCT image attenuation with left atrial (LA) low bipolar voltage regions in patients undergoing repeat ablation for atrial fibrillation recurrence. METHODS We enrolled 20 patients undergoing repeat ablation for atrial fibrillation recurrence. All patients underwent preprocedural 3-dimensional CE-MDCT of the LA, followed by voltage mapping (>100 points) of the LA during the ablation procedure. Epicardial and endocardial contours were manually drawn around LA myocardium on multiplanar CE-MDCT axial images. Segmented 3-dimensional images of the LA myocardium were reconstructed. Electroanatomic map points were retrospectively registered to the corresponding CE-MDCT images. RESULTS A total of 2028 electroanatomic map points obtained in sinus rhythm from the LA endocardium were registered to the segmented LA wall CE-MDCT images. In a linear mixed model, each unit increase in the local image attenuation ratio was associated with 25.2% increase in log bipolar voltage (P = .046) after adjusting for age, sex, body mass index, and LA volume, as well as clustering of data by patient and LA regions. CONCLUSION We demonstrate that the image attenuation ratio derived from CE-MDCT is associated with LA bipolar voltage. The potential ability to image fibrosis via CE-MDCT may provide a useful alternative in patients with contraindications to magnetic resonance imaging.