Mohammadali Habibi

Association of CMR-Measured LA Function With Heart Failure Development: Results From the MESA Study

OBJECTIVES The goal of this study was to assess the association between left atrial (LA) volume and function measured with feature-tracking cardiac magnetic resonance (CMR) and development of heart failure (HF) in asymptomatic individuals. BACKGROUND Whether alterations of LA structure and function precede or follow HF development remains incompletely understood. We hypothesized that significant alterations of LA deformation and architecture precede the development of HF in the general population. METHODS In a case-control study nested in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA volume and function assessed using CMR feature-tracking were compared between 112 participants with incident HF (mean age 68.4 ± 8.2 years; 66% men) and 224 age- and sex-matched controls (mean age 67.7 ± 8.9 years; 66% men). Participants were followed up for 8 years. All individuals were in normal sinus rhythm at the time of imaging, without any significant valvular abnormalities and free of clinical cardiovascular diseases. RESULTS Individuals with incident HF had greater maximal and minimal LA volume indexes (LAVImin) than control subjects (40 ± 13 mm(3)/m(2) vs. 33 ± 10 mm(3)/m(2) [p <0.001] for maximal LA index and 25 ± 11 mm(3)/m(2) vs. 17 ± 7 mm(3)/m(2) [p <0.001] for LAVImin). The HF case subjects also had smaller global peak longitudinal atrial strain (PLAS) (25 ± 11% vs. 38 ± 16%; p <0.001) and lower LA emptying fraction (40 ± 11% vs. 48 ± 9%; p <0.001) at baseline. After adjustment for traditional cardiovascular risk factors, left ventricular mass, and N-terminal pro-B-type natriuretic peptide, global PLAS (odds ratio: 0.36 per SD [95% confidence interval: 0.22 to 0.60]) and LAVImin (odds ratio: 1.65 per SD [95% confidence interval: 1.04 to 2.63]) were independently associated with incident HF. CONCLUSIONS Deteriorations in LA structure and function preceded development of HF. Lower global PLAS and higher LAVImin, measured using CMR feature-tracking, were independent markers of incident HF in a multiethnic population of asymptomatic individuals.

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.

Multi-Ethnic Study of Atherosclerosis: Association between Left Atrial Function Using Tissue Tracking from Cine MR Imaging and Myocardial Fibrosis

PURPOSE To investigate the association between left atrial ( LA left atrium ) function and left ventricular myocardial fibrosis using cardiac magnetic resonance (MR) imaging in a multi-ethnic population. MATERIALS AND METHODS For this HIPAA-compliant study, the institutional review board at each participating center approved the study protocol, and all participants provided informed consent. Of 2839 participants who had undergone cardiac MR in 2010-2012, 143 participants with myocardial scar determined with late gadolinium enhancement and 286 age-, sex-, and ethnicity-matched control participants were identified. LA left atrium volume, strain, and strain rate were analyzed by using multimodality tissue tracking from cine MR imaging. T1 mapping was applied to assess diffuse myocardial fibrosis. The association between LA left atrium parameters and myocardial fibrosis was evaluated with the Student t test and multivariable regression analysis. RESULTS The scar group had significantly higher minimum LA left atrium volume than the control group (mean, 22.0 ± 10.5 [standard deviation] vs 19.0 ± 7.8, P = .002) and lower LA left atrium ejection fraction (45.9 ± 10.7 vs 51.3 ± 8.7, P < .001), maximal LA left atrium strain ( Smax maximum LA strain ) (25.4 ± 10.7 vs 30.6 ± 10.6, P < .001) and maximum LA left atrium strain rate ( SRmax maximum LA strain rate ) (1.08 ± 0.45 vs 1.29 ± 0.51, P < .001), and lower absolute LA left atrium strain rate at early diastolic peak ( SRE LA strain rate at early diastolic peak ) (-0.77 ± 0.42 vs -1.01 ± 0.48, P < .001) and LA left atrium strain rate at atrial contraction peak ( SRA LA strain rate at atrial contraction peak ) (-1.50 ± 0.62 vs -1.78 ± 0.69, P < .001) than the control group. T1 time 12 minutes after contrast material injection was significantly associated with Smax maximum LA strain (β coefficient = 0.043, P = .013), SRmax maximum LA strain rate (β coefficient = 0.0025, P = .001), SRE LA strain rate at early diastolic peak (β coefficient = -0.0016, P = .027), and SRA LA strain rate at atrial contraction peak LA strain rate at atrial contraction peak (β coefficient -0.0028, P = .01) in the regression model. T1 time 25 minutes after contrast material injection was significantly associated with SRmax maximum LA strain rate (β coefficient = 0.0019, P = .016) and SRA LA strain rate at atrial contraction peak (β coefficient = -0.0022, P = .034). CONCLUSION Reduced LA left atrium regional and global function are related to both replacement and diffuse myocardial fibrosis processes. Clinical trial registration no.: NCT00005487

Safety of Novel Oral Anticoagulants Compared With Uninterrupted Warfarin for Catheter Ablation of Atrial Fibrillation

Background: The novel oral anticoagulants (NOACs) are used for stroke prevention in atrial fibrillation (AF), but their safety and efficacy in the periablation period are not well established. Additionally, no standard procedure for managing periprocedural and intraprocedural anticoagulation has been established. Objective: To evaluate the frequency of hemorrhagic and thrombotic events as well as periprocedural management strategies of NOACs compared with warfarin as anticoagulation therapy for AF ablation. Methods: This was a retrospective cohort study from a prospective AF ablation registry maintained at a large, academic medical center. Results: A total of 374 cases (173 warfarin, 123 dabigatran, 61 rivaroxaban, and 17 apixaban) were included in the analysis. The overall hemorrhagic/thrombotic event rate was 14.2 % (major hemorrhage 2.7%, minor hemorrhage 11.2%, thrombotic stroke 0.5%). The frequency of minor hemorrhage was significantly higher with warfarin compared with dabigatran (15% vs 5.7%, P = 0.012). The average heparin dose required to reach the goal activated clotting time (ACT) was 5600 units for warfarin, 12 900 units for dabigatran (P < 0.001), 15 100 units for rivaroxaban (P < 0.001), and 14 700 units for apixaban (P < 0.001). The average time in minutes to reach the goal ACT was significantly longer, compared with warfarin, for dabigatran (57 vs 28, P < 0.001), rivaroxaban (63 vs 28, P < 0.001), and apixaban (72 vs 28, P < 0.001). Conclusions: Compared with warfarin, periprocedural anticoagulation with dabigatran resulted in fewer minor hemorrhages and total adverse events after AF ablation. Patients anticoagulated with NOACs required larger doses of heparin and took longer to reach the goal ACT compared with patients anticoagulated with warfarin.

Lack of regional association between atrial late gadolinium enhancement on cardiac magnetic resonance and atrial fibrillation rotors

BACKGROUND The extent of left atrial (LA) late gadolinium enhancement (LGE), as a surrogate for fibrosis, has been associated with atrial fibrillation (AF) recurrence after catheter ablation. Furthermore, there is ex vivo evidence that islands of fibrosis may anchor fibrillatory rotors. OBJECTIVE The purpose of this study was to examine the anatomical association of AF rotors with LA and right atrial (RA) LGE on cardiac magnetic resonance. METHODS The cohort included 9 patients with persistent AF (mean age 61.1 ± 9.7 years) who underwent LGE cardiac magnetic resonance before AF ablation using the focal impulse and rotor modulation system. The extent of LA and RA LGE was quantified globally and in each of the 7 sectors: LA posterior/inferior wall, anterior wall, roof, left and right pulmonary vein antra, and RA lateral and septal regions. The multivariable association of rotor incidence with global and per sector LGE extent was examined using multivariable Bernoulli logistic regression estimated by generalized estimating equations. RESULTS The mean RA and LA volumes were 113.2 ± 37.31 and 143.03 ± 58.25 mL, respectively. The mean RA and LA LGE burden was 17.2% ± 11.0% and 17.4% ± 14.4%, respectively. A total of 18 LA rotors and 9 RA rotors were identified in all patients. No univariable or multivariable association was observed between global or per sector LGE extent and focal impulse and rotor modulation rotor incidence. CONCLUSION In this cohort of patients, there was no association between AF rotor incidence and the global or regional extent of RA and LA LGE.

Quantitative Tissue‐Tracking Cardiac Magnetic Resonance (CMR) of Left Atrial Deformation and the Risk of Stroke in Patients With Atrial Fibrillation

Background Recent evidence suggests that left atrial (LA) dysfunction may be mechanistically contributing to cerebrovascular events in patients with atrial fibrillation (AF). We investigated the association between regional LA function and a prior history of stroke during sinus rhythm in patients referred for catheter ablation of AF. Methods and Results A total of 169 patients (59±10 years, 74% male, 29% persistent AF) with a history of AF in sinus rhythm at the time of pre‐ablation cardiac magnetic resonance (CMR) were analyzed. The LA volume, emptying fraction, strain (S), and strain rate (SR) were assessed by tissue‐tracking cardiac magnetic resonance. The patients with a history of stroke or transient ischemic attack (n=18) had greater LA volumes (Vmax and Vmin; P=0.02 and P<0.001, respectively), lower LA total emptying fraction (P<0.001), lower LA maximum and pre‐atrial contraction strains (Smax and SpreA; P<0.001 and P=0.01, respectively), and lower absolute values of LA SR during left ventricular (LV) systole and early diastole (SRs and SRe; P=0.005 and 0.03, respectively) than those without stroke/transient ischemic attack (n=151). Multivariable analysis demonstrated that the LA reservoir function, including total emptying fraction, Smax, and SRs, was associated with stroke/transient ischemic attack (odds ratio 0.94, 0.91, and 0.17; P=0.03, 0.02, and 0.04, respectively) after adjusting for the CHA2DS2‐VASc score and LA Vmin. Conclusions Depressed LA reservoir function assessed by tissue‐tracking cardiac magnetic resonance is significantly associated with a prior history of stroke/transient ischemic attack in patients with AF. Our findings suggest that assessment of LA reservoir function can improve the risk stratification of cerebrovascular events in AF patients.

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.

Pulmonary vascular volume, impaired left ventricular filling and dyspnea: The MESA Lung Study

Background Evaluation of impaired left ventricular (LV) filling has focused on intrinsic causes of LV dysfunction; however, pulmonary vascular changes may contribute to reduced LV filling and dyspnea. We hypothesized that lower total pulmonary vascular volume (TPVV) on computed tomography (CT) would be associated with dyspnea and decrements in LV end-diastolic volume, particularly among ever-smokers. Methods The Multi-Ethnic Study of Atherosclerosis recruited adults without clinical cardiovascular disease in 2000–02. In 2010–12, TPVV was ascertained as the volume of arteries and veins in the lungs detectable on non-contrast chest CT (vessels ≥1 mm diameter). Cardiac measures were assessed by magnetic resonance imaging (MRI). Dyspnea was self-reported. Results Of 2303 participants, 53% had ever smoked cigarettes. Among ever-smokers, a lower TPVV was associated with a lower LV end-diastolic volume (6.9 mL per SD TPVV), stroke volume, and cardiac output and with dyspnea (all P-values <0.001). Findings were similar among those without lung disease and those with 0–10 pack-years but were mostly non-significant among never-smokers. TPVV was associated smaller left atrial volume but not with LV ejection fraction or MRI measures of impaired LV relaxation. In a second sample of ever-smokers, a lower pulmonary microvascular blood volume on contrast-enhanced MRI was also associated with a lower LV end-diastolic volume (P-value = 0.008). Conclusion Reductions in pulmonary vascular volume were associated with lower LV filling and dyspnea among ever-smokers, including those without lung disease, suggesting that smoking-related pulmonary vascular changes may contribute to symptoms and impair cardiac filling and function without evidence of impaired LV relaxation.

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.

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

Background—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. Methods and Results—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. Conclusions—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.