Anika Afroz

P wave area for quantitative electrocardiographic assessment of left atrial remodeling.

Background Left atrial (LA) dilation provides a substrate for mitral regurgitation (MR) and atrial arrhythmias. ECG can screen for LA dilation but standard approaches do not assess LA geometry as a continuum, as does non-invasive imaging. This study tested ECG-quantified P wave area as an index of LA geometry. Methods and Results 342 patients with CAD underwent ECG and CMR within 7 (0.1±1.4) days. LA area on CMR correlated best with P wave area in ECG lead V1 (r = 0.42, p<0.001), with lesser correlations for P wave amplitude and duration. P wave area increased stepwise in relation to CMR-evidenced MR severity (p<0.001), with similar results for MR on echocardiography (performed in 86% of patients). Pulmonary arterial (PA) pressure on echo was increased by 50% among patients in the highest (45±14 mmHg) vs. the lowest (31±9 mmHg) P wave area quartile of the population. In multivariate regression, CMR and echo-specific models demonstrated P wave area to be independently associated with LA size after controlling for MR, as well as echo-evidenced PA pressure. Clinical follow-up (mean 2.4±1.9 years) demonstrated ECG and CMR to yield similar results for stratification of arrhythmic risk, with a 2.6-fold increase in risk for atrial fibrillation/flutter among patients in the top P wave area quartile of the population (CI 1.1–5.9, p = 0.02), and a 3.2-fold increase among patients in the top LA area quartile (CI 1.4–7.0, p = 0.005). Conclusions ECG-quantified P wave area provides an index of LA remodeling that parallels CMR-evidenced LA chamber geometry, and provides similar predictive value for stratification of atrial arrhythmic risk.

Q wave area for stratification of global left ventricular infarct size: comparison to conventional ECG assessment using Selvester QRS-score.

ObjectivesLeft ventricular (LV) infarct size is a prognostic determinant after acute myocardial infarction (AMI). ECG data have been used to measure infarct size, but conventional approaches use multiparametric algorithms that have limited clinical applicability. This study tested a novel ECG approach – based solely on Q wave area – for calculation of LV infarct size. MethodsSerial 12-lead ECGs were performed in AMI patients. Computerized software was used to quantify Q wave area (summed across surface ECG leads) and Selvester QRS-score components. ECG analysis was compared to the reference of myocardial infarct size quantified by delayed enhancement cardiac magnetic resonance. ResultsOverall, 158 patients underwent ECG during early (4±0.4) and follow-up (29±5 days) post-AMI time points. Selvester QRS-score and Q wave area increased stepwise with LV infarct size (P<0.001). Whereas both methods manifested marked increases at a threshold of 10% LV infarction, magnitude was greater for Q wave area (>2.5-fold) than Selvester QRS-score (<two-fold). In receiver operating characteristic analysis, Q wave area (area under the curve=0.83–0.86) and Selvester QRS-score (0.82–0.87) manifested similar performance in relation to a 10% infarct cutoff. When Selvester QRS-score and Q wave area thresholds were selected to optimize sensitivity, both methods yielded similar negative predictive value (Q wave area: 89–91%, Selvester QRS-score: 92–94%) although specificity was higher for Q wave area (44–45 vs. 17–25%; P⩽0.01). ConclusionQ wave area provides an index for stratification of LV infarct size that performs similarly to conventional ECG assessment via the Selvester QRS-score for exclusion of large infarction.

Geometry-Independent Inclusion of Basal Myocardium Yields Improved Cardiac Magnetic Resonance Agreement with Echocardiography and Necropsy Quantified Left Ventricular Mass

Objectives: Left-ventricular mass (LVM) is widely used to guide clinical decision-making. Cardiac magnetic resonance (CMR) quantifies LVM by planimetry of contiguous short-axis images, an approach dependent on reader-selection of images to be contoured. Established methods have applied different binary cut-offs using circumferential extent of left-ventricular myocardium to define the basal left ventricle (LV), omitting images containing lesser fractions of left-ventricular myocardium. This study tested impact of basal slice variability on LVM quantification. Methods: CMR was performed in patients and laboratory animals. LVM was quantified with full inclusion of left-ventricular myocardium, and by established methods that use different cut-offs to define the left-ventricular basal-most slice: 50% circumferential myocardium at end diastole alone (ED50), 50% circumferential myocardium throughout both end diastole and end systole (EDS50). Results: One hundred and fifty patients and 10 lab animals were studied. Among patients, fully inclusive LVM (172.6 ± 42.3 g) was higher vs. ED50 (167.2 ± 41.8 g) and EDS50 (150.6 ± 41.1 g; both P < 0.001). Methodological differences yielded discrepancies regarding proportion of patients meeting established criteria for left-ventricular hypertrophy and chamber dilation (P < 0.05). Fully inclusive LVM yielded smaller differences with echocardiography (&Dgr; = 11.0 ± 28.8 g) than did ED50 (&Dgr; = 16.4 ± 29.1 g) and EDS50 (&Dgr; = 33.2 ± 28.7 g; both P < 0.001). Among lab animals, ex-vivo left-ventricular weight (69.8 ± 13.2 g) was similar to LVM calculated using fully inclusive (70.1 ± 13.5 g, P = 0.67) and ED50 (69.4 ± 13.9 g; P = 0.70) methods, whereas EDS50 differed significantly (67.9 ± 14.9 g; P = 0.04). Conclusion: Established CMR methods that discordantly define the basal-most LV produce significant differences in calculated LVM. Fully inclusive quantification, rather than binary cut-offs that omit basal left-ventricular myocardium, yields smallest CMR discrepancy with echocardiography-measured LVM and non-significant differences with necropsy-measured left-ventricular weight.

Routine cine-CMR for assessment of prosthesis-associated mitral regurgitation - a multicenter, multivendor study

Background Mitral regurgitation (MR) is clinically important for patients with prosthetic mitral valves (PMV). While CMR can quantify MR based on flow, this requires dedicated imaging. Cine-CMR (SSFP) provides an alternative approach, whereby MR can be graded based on regurgitation-associated intervoxel dephasing. As cine-CMR is a standard component of nearly all exams, it could be used to screen for patients who warrant further quantitative imaging. Diagnostic performance of cine-CMR for prosthesis-associated MR has not been evaluated. Methods Databases at 6 sites were queried for all patients with PMV in whom CMR and echocardiography were performed within 10 days. Cine-CMR images were retrieved and interpreted using a uniform protocol: MR was visually graded based solely on jet size (mild 2/3) in relation to the left atrium. MR was graded in each long axis plane (2-,3-, 4-chamber), with overall severity based on mean grade. Additional parameters included jet directionality, signal intensity (3-grade scale), and pulmonary vein flow reversal. Echocardiography (TTE, TEE) was used as a comparator for MR based on clinically reported data. Cine-CMR was interpreted blinded to patient history and TTE/TEE. Results 56 patients with PMV (70% mechanical, 30% bio) underwent cine-CMR and echo (TTE 70%, TEE 48%) within 2.5±2.6 days. Cine-CMR (1.5T, typical TR=3msec, TE=1msec, BW=977Hz/pixel) was performed using commercial scanners (Siemens 59%/GE 36%/Philips 5%). MR was present on cine-CMR in 77% of patients (mild 43%, moderate 14%, severe 20%), and varied in direction (central 88%, eccentric 12%). Patients with severe MR had higher prevalence of dense regurgitant jets (73% vs. 3%, p<0.001), more frequent pulmonary vein reversal (55% vs. 3%, p<0.001), and larger left atria (5.7±1.0cm vs. 4.7±1.4cm, p=0.03) than did those with lesser MR, but did not differ based on LVEF (53±14% vs. 49±15%, p=0.4). Compared to TEE, cine-CMR yielded excellent diagnostic accuracy (96%) for severe MR (Table); accuracy was also high (93%) when a broader TEE threshold (≥moderate MR) was applied. Among patients with TTE

Marked variability in published CMR criteria for left ventricular basal slice selection - impact of methodological discrepancies on LV mass quantification

Background Left ventricular mass (LVM) quantification by cine-CMR is typically performed by planimetry of contiguous LV short axis images. This approach relies on use of anatomic landmarks or quantitative binary cutoffs to define the basal-most aspect of the LV. Methodological discordance concerning criteria for LV basal slice selection has the potential to alter cine-CMR quantified LVM. This study assessed frequency of methodological variability in published LV basal slice definitions, as well as its impact on cine-CMR quantification of LVM.

Cine-CMR quantified left atrial diameter - a simple index of left atrial remodeling that closely parallels chamber area and stratifies longitudinal atrial arrhythmic risk

Methods The study comprised patients with coronary artery disease (CAD) included in a multimodality registry. CineCMR (1.5T) was performed using a standard 2-dimensional steady state free precession (SSFP) pulse sequence (typical TR 3.5 msec, TE 1.6 msec, flip angle 60°, temporal resolution 30-50 msec). Cine-CMR evidenced mitral regurgitation (MR) severity was graded in accordance with established conventions based on size of MR associated inter-voxel dephasing of the regurgitant jet. LA size was measured on cine-CMR at atrial end-diastole using two established methods: [1] linear diameter (measured in 3-chamber long axis orientation), [2] area (planimetered in 4-chamber long axis orientation), with both indices indexed to body surface area. Clinical follow-up was performed via medical record review, with atrial fibrillation (AF) or flutter (AFl) verified based on physician documentation. Results 336 patients with CAD were studied (60 ± 12 yo, 79% M, 34% DM, 58% HTN); LA diameter (mean 2 ± 0.4 cm/m2) and area (12 ± 3 cm2/m2) yielded similar prevalence of chamber dilation (20% vs. 21%, p = 0.76) assigned using established cine-CMR population-based cutoffs. LA indices correlated highly (r = 0.74, p < 0.001; Figure 1), with similar magnitude of correlation among subgroups at risk for LA remodeling, such as patients

Mid-wall fibrosis on delayed enhancement CMR - a marker for adverse left ventricular chamber remodeling independent of cardiomyopathic etiology

Background Mid-wall fibrosis (MWF) is a hallmark of non-ischemic cardiomyopathy (NICM) that confers increased risk for sudden cardiac death and mortality. The relationship between MWF and left ventricular (LV) remodeling is unknown. Methods The population comprised patients with advanced systolic dysfunction (LVEF ≤ 40%) undergoing CMR (1.5T, General Electric Signa). Ischemic vs. NICM etiology was classified in accordance with established convention based on obstructive CAD on invasive angiography. Delayed enhancement CMR (IR-GRE acquired 10-30 minutes post gadolinium [0.2 mmol/kg]) was used to identify MWF, defined as hyperenhancement confined to the mid-myocardial or epicardial aspect of the interventricular septum. LV mass and chamber volume were quantified by planimetry of contiguous SSFP cine-CMR short axis slices, with ejection fraction (EF) calculated as the proportional difference between end-diastolic (EDV) and end-systolic (ESV) volumes. Results 523 patients (61 ± 14 yo, 72% M, 66% ischemic CM) were studied: MWF was present in 16%, and was 6-fold more common in patients with angiographically classified NICM (37% vs. 6%; p < 0.001). Regarding LV remodeling, MWF was associated with higher EDV (134 ± 39 ml vs. 114 ± 34 ml; p < 0.001) and LV mass (102 ± 24 vs. 96 ± 28 gm; p < 0.001) and lower LVEF (26 ± 8% vs. 30 ± 8%; p ≤ 0.05). MWF was nearly 3-fold more common among patients in the highest tertile of EDV vs. the remainder of the population (29% vs. 10%; p < 0.001). Multivariate regression analysis was performed to further assess markers for MWF: Restricted to imaging indices, results (Table 1A) demonstrated EF and EDV to be independently associated with MWF (OR = 1.46, CI 1.03-2.10; p < 0.05, OR = 1.13, CI 1.04-1.20; p < 0.05, respectively) after controlling for mass (OR = 0.95, CI 0.85-1.00; p = 0.29). Regarding clinical variables, results (Table 1B) confirmed a strong association with NICM (OR = 8.4, CI 4.78-14.72; p < 0.001), independent of other clinical indices. A combined model incorporating both clinical and imaging variables demonstrated both NICM and LV volume to be independently associated with MWF even after controlling for EF (Table 1C). Overall strength of the combined clinical/imaging (c 2 = 91.2; p < 0.001) model for MWF was higher than that of isolated clinical (c 2 = 76.7; p < 0.001) and imaging (c 2 = 26.0; p < 0.001) models.

ROUTINE CINE-CMR FOR PROSTHESIS ASSOCIATED MITRAL REGURGITATION: A MULTICENTER COMPARISON TO ECHOCARDIOGRAPHY

BACKGROUND AND AIM OF THE STUDY Mitral regurgitation (MR) is an important complication after prosthetic mitral valve (PMV) implantation. Transthoracic echocardiography is widely used to screen for native MR, but can be limited with PMV. Cine-cardiac magnetic resonance (CMR) holds the potential for the non-invasive assessment of regurgitant severity based on MR-induced inter-voxel dephasing. The study aim was to evaluate routine cine-CMR for the visual assessment of PMV-associated MR. METHODS Routine cine-CMR was performed at nine sites. A uniform protocol was used to grade MR based on jet size in relation to the left atrium (mild < 1/3, moderate 1/3-2/3, severe > 2/3). MR was graded in each long-axis orientation, with overall severity based on cumulative grade. Cine-CMR was also scored for MR density and pulmonary vein systolic flow reversal (PVSFR). Visual interpretation was compared to quantitative analysis in a single-center (derivation) cohort, and to transesophageal echocardiography (TEE) in a multicenter (validation) cohort. RESULTS The population comprised 85 PMV patients (59% mechanical valves, 41% bioprostheses). Among the derivation cohort (n = 25), quantitative indices paralleled visual scores, with stepwise increases in jet size and density in relation to visually graded MR severity (both p = 0.001). Patients with severe MR had an almost three-fold increase in quantitative jet area (p = 0.002), and a two-fold increase in density (p = 0.04) than did other patients. Among the multicenter cohort, cine-CMR and TEE (Δ =. 2 ± 3 days) demonstrated moderate agreement (κ = 0.44); 64% of discordances differed by ≤ 1 grade (Δ = 1.2 ± 0.5). Using a TEE reference, cine-CMR yielded excellent diagnostic performance for severe MR (sensitivity, negative predictive value = 100%). Patients with visually graded severe MR also had more frequent PVSFR (p < 0.001), denser jets (p < 0.001), and larger left atria (p = 0.01) on cine-CMR. CONCLUSION Cine-CMR is useful for the assessment of PMV-associated MR, which manifests concordant quantitative and qualitative changes in size and density of inter-voxel dephasing. Visual MR assessment based on jet size provides an accurate non-invasive means of screening for TEE-evidenced severe MR.

Established binary cutoffs for cine-CMR basal slice selection - an unrecognized source of CMR discordance with echocardiography and necropsy derived LV mass

Background Left ventricular mass (LVM) is widely used to guide clinical decision-making. CMR is well suited to measure LVM as it provides high-resolution delineation of myocardial contours. CMR quantification of LVM is typically performed via planimetry of contiguous short axis images, an approach fundamentally dependent on reader selection of short axis images to be contoured. Established methods have applied different binary cutoffs using circumferential extent of LV myocardium to define the basal LV, while omitting short axis images containing lesser fractions of LV myocardium. This study compared LVM, quantified using different established methods for basal slice selection, to independent references of LVM measured by echocardiography and necropsy. Methods