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Background: The association of scar on late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) with local electrograms on electroanatomic mapping has been investigated. We aimed to quantify these associations to gain insights regarding LGE-CMR image characteristics of tissues and critical sites that support postinfarct ventricular tachycardia (VT).Methods and Results: LGE-CMR was performed in 23 patients with ischemic cardiomyopathy before VT ablation. Left ventricular wall thickness and postinfarct scar thickness were measured in each of 20 sectors per LGE-CMR short-axis plane. Electroanatomic mapping points were retrospectively registered to the corresponding LGE-CMR images. Multivariable regression analysis, clustered by patient, revealed significant associations among left ventricular wall thickness, postinfarct scar thickness, and intramural scar location on LGE-CMR, and local endocardial electrogram bipolar/unipolar voltage, duration, and deflections on electroanatomic mapping. Anteroposterior and septal/lateral scar localization was also associated with bipolar and unipolar voltage. Antiarrhythmic drug use was associated with electrogram duration. Critical sites of postinfarct VT were associated with >25% scar transmurality, and slow conduction sites with >40 ms stimulus-QRS time were associated with >75% scar transmurality.Conclusions: Critical sites for maintenance of postinfarct VT are confined to areas with >25% scar transmurality. Our data provide insights into the structural substrates for delayed conduction and VT and may reduce procedural time devoted to substrate mapping, overcome limitations of invasive mapping because of sampling density, and enhance magnetic resonance-based ablation by feature extraction from complex images. [ABSTRACT FROM AUTHOR]

Background: Recurrence of atrial fibrillation (AF) after catheter ablation has been associated with left atrial (LA) fibrosis. However, arbitrary units of measure limit the interpatient comparison of delayed enhancement intensity. We sought to quantify LA fibrosis using a novel normalized measure: the image intensity ratio (IIR) of late-gadolinium enhanced magnetic resonance imaging (LGE-MRI). Methods: LGE-MRI images (1.5 Tesla) were obtained in 30 patients (37% female, mean age 62 ± 8) prior to first (60%), second (23%), or third (17%) ablation procedure for AF. Multiplanar reformatted images were reconstructed from the stack of 3-D axial image data. Epicardial and endocardial contours were manually drawn around LA myocardium. The IIR, defined as local LA myocardial signal intensity divided by the mean LA blood pool image intensity, was measured for each of 20 sectors created on contiguous axial planes through the LA. Electroanatomic map (EAM) points were registered to the corresponding LGE-MRI images using custom software. Results: A total of 2569 EAM points were analyzed. The average bipolar voltage was 0.9 ± 1.0 mV (0.5 between and 0.9 within patient standard deviation). Local IIR was strongly associated with bipolar voltage (Figure, P <.001). Using a generalized estimating equations model clustered by patient and adjusting for age, LA volume, rhythm, gender, CHADS score, and type of AF, each unit increase in local IIR was associated with –1.4 mV decrease in bipolar LA voltage (P <.001). Conclusions: Higher IIR values were observed in areas with lower bipolar voltage on EAM. The IIR obtained from LGE-MRI may improve the quantification of LA fibrosis Display Omitted [ABSTRACT FROM AUTHOR]

Background: Left atrial (LA) late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) has varying protocols, which may limit interstudy comparisons. This study evaluates whether changes in image acquisition and reconstruction parameters affect quantification of LA LGE MRI. Methods: A total of 200 LGE MRI scans were prepared using various techniques from 5 subjects. 3D respiratory and ECG-gated LGE images were acquired at 15, 20, 25, and 30 minutes after contrast. Multiplanar reconstructions (MPR) and maximum intensity projections (MIP) were created from 3D data at various slice thicknesses. LA LGE was quantified with image intensity ratio (IIR, atrial wall signal intensity divided by blood pool). Mean IIR was calculated for the entire LA as a metric of LGE burden. Additionally, in 42 consecutive preablation patients, local IIR values from 3.5-mm MPR and MIP reconstructions were separately registered to LA electroanatomic voltage maps (EAM) obtained prior to ablation procedure. Results: Multitime point LGE-MRI showed a rise in baseline mean IIR of 0.5% ± 0.1% per minute (P <.001) in MPR and a rise of 0.6% ± 0.1% (P <.001) for MIP using regression analysis (Figure A). The MPR- and MIP-based mean IIRs diverged, showing change of –0.3% for MPR and +1.1% for MIP for 1-mm increase in slice thickness (P <.001 for both; Figure B). A total of 4428 EAM points were registered to local LA wall IIRs from both MPR and MIP techniques. An increase of a single unit of IIR was related to drop in 1.20 mV with MPR and 1.25 mV with MIP (P <.001 for both). Conclusions: Variations in timing of acquisition, image reconstruction methods, and slice thickness result in changes in LA LGE quantity. Display Omitted [Copyright &y& Elsevier]

Background: Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with the common –1306C/T matrix metalloproteinase-2 single nucleotide polymorphism (MMP2 SNP), which reduces the synthesis of matrix metalloproteinase-2 enzyme. Understanding the factors that mediate this association may improve current preventive and therapeutic strategies for AF. Methods: To test the hypothesis that MMP2 SNP is associated with atrial fibrosis, the study was designed as a single center, observational, cross-sectional study. One hundred consecutive patients with symptomatic drug-resistant AF who underwent catheter ablation between September 2009 and February 2011 were enrolled. The endocardial bipolar electrogram voltage was measured point by point in the left atrium as panel data clustered by patient and compared with the result of genetic testing for MMP2 SNP. Results: MMP2 SNP was present in at least 1 copy in 43% of patients, the minor allele frequency was 0.27, and genotype frequencies were in Hardy-Weinberg equilibrium (Χ2 = 2.34, P = .126). The overall mean atrial voltage for the 4878 measures in 87 patients was 0.89 ± 1.10 mV. MMP2 SNP was significantly associated with reduced bipolar voltage in codominant (–0.11 mV per T copy, P = .003) and dominant (–0.18 mV if CT or TT, P <.001) models clustered by patient and adjusted for age, ethnicity, gender, body mass index, coronary artery disease, hypertension, paroxysmal vs persistent AF, left atrial size, left ventricular ejection fraction, rhythm during voltage sampling, and previous ablations. The results were robust to exclusion of patients with nonsinus rhythm during voltage mapping (n = 13) and of those with prior ablation procedures (n = 5). Conclusions: We report a strong association between a common MMP2 promoter polymorphism and atrial scar fibrosis. Impaired tissue remodeling may mediate the previously reported association between the –1306C/T MMP2 polymorphism and AF. [Copyright &y& Elsevier]

Background: Pathogenicity of truncating or splice site mutations in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients has been widely accepted. However, pathogenicity of missense variants remains controversial. We assessed pathogenicity of ARVC-related missense variants and associated phenotype. Methods: Pathogenic mutations were found in 571 patients (239 families, age 43 ± 18 years) from US/Dutch ARVC cohorts by screening of desmosomal (PKP2, DSC2, DSG2, DSP, JUP) and/or nondesmosomal (PLN, TMEM43) genes. Patients with >1 mutation or variant were excluded. Missense variants were considered pathogenic when (1) algorithms SIFT and PolyPhen-2 predicted pathogenicity (SIFT: tolerance index score ≤0.05, PolyPhen-2: pathogenicity score >0.90) and (2) minor allele frequency in 1000 genomes was <0.014. Survival and arrhythmic outcome were compared between missense and non-missense mutation carriers. Results: A pathogenic missense mutation was found in 86/571 patients (15%). Frequently occurring mutation was PKP2 c.2386T>C (p.Cys796Arg; 34/86). Survival curves (P = .065) and, more importantly, sustained arrhythmia (ventricular tachycardia/fibrillation or appropriate ICD therapy) free survival curves (P = .810) of patients with a missense mutation were similar to those with pathogenic non-missense (330/571 truncating, 129/571 splice site) mutations (Figure). Conclusions: ARVC-related missense mutations have a similar pathogenic character as non-missense mutations regarding survival and substantial arrhythmic burden. Pathogenicity of missense mutations can be correctly predicted by combined criteria from SIFT, PolyPhen-2, and 1000 genomes. Display Omitted [ABSTRACT FROM AUTHOR]