Nonatrial Fibrillation Patients With Complete P Wave Disappearance: An Overlooked Population With High Stroke Risk.

BACKGROUND AND PURPOSE: Complete P wave disappearance (CPWD) in patients without atrial fibrillation is an uncommon clinical phenomenon. We aimed to study the relationship between CPWD and thromboembolism. METHODS: Between July 2007 and December 2018, consecutive patients with CPWD on surface ECG and 24-hour Holter recording were recruited into the study from 4 centers in China. All recruited patients underwent transesophageal echocardiography or cardiac computed tomography to screen for atrial thrombus. Atrial electrical activity and scar were assessed by electrophysiological study (EPS) and 3-dimensional electroanatomic mapping. Cardiac structure and function were assessed by multimodality cardiac imaging. RESULTS: Twenty-three consecutive patients (8 male; mean age 48.5±14.7 years) with CPWD were included. Only 3 patients demonstrated complete atrial electrical silence with atrial noncapture. Thirteen patients who had invasive atrial endocardial mapping demonstrated extensive scar. Pulse-wave mitral inflow Doppler demonstrated absent and dampened A waves in 18 and 5 patients, respectively. Pulse-wave tricuspid inflow Doppler showed absent and dampened A waves in 19 and 4 patients, respectively. Upon recruitment, 8 patients had previous stroke and 3 patients had atrial thrombus. Warfarin was prescribed to all patients. During median follow-up of 42.0 months, 2 patients developed massive ischemic stroke due to warfarin discontinuation. CONCLUSIONS: Our study suggested that CPWD reflects extensive atrial electrical silence and significantly impaired atrial mechanical function. It was strongly associated with thromboembolism and the clinical triad of CPWD-atrial paralysis-stroke was proposed. Anticoagulation should be recommended in such patients.

Idiopathic isolated fibrotic atrial cardiomyopathy underlies unexplained scar-related atrial tachycardia in younger patients.

Aims: Unexplained scar-related atrial tachycardia (AT) has been frequently encountered in clinical practice. We hypothesized that idiopathic, isolated fibrotic atrial cardiomyopathy (ACM) underlies this rhythm disorder. This study was aimed to characterize the underlying substrate and to explore the aetiology of this unexplained scar-related AT. Methods and results: Twenty-six (11 men, aged 46 ± 13 years) of 52 non-surgical scar-related AT patients identified by three-dimensional voltage mapping were enrolled in this prospective observational study. Multimodality image examinations (echocardiography, cardiac magnetic resonance, 99Tc single-photon emission computed tomography), ventricular voltage mapping, and intracardiac pressure curve recording ruled out ventricular involvement. Catheter ablation was acutely successful for all the patients, and pacemaker implantation was performed in seven patients who presented sinus node dysfunction or atrial standstill after termination of the AT. In three patients with multiple AT recurrences, the diseased areas of the right atrium were resected and dechannelled via mini-invasive surgical interventions. Histological examinations revealed profound fibrosis without amyloidosis or adipose deposition. Viral and familial investigations yielded negative results. Fibrosis progression over a median of 45 (5-109) months of follow-up manifested as atrial arrhythmia recurrence in seven patients and atrial lead non-capture due to newly developed atrial standstill in two patients. Two patients suffered four ischaemic stroke events before receiving anticoagulation treatment. Conclusion: Isolated, fibrotic ACM may underlie the idiopathic scar-related ATs. This novel cardiomyopathy has unique clinical characteristics with high morbidity including stroke and warrants specific therapeutic strategies. Further investigations are required to determine the aetiology and mechanism.

An association analysis between mitochondrial DNA content, G10398A polymorphism, HPV infection, and the prognosis of cervical cancer in the Chinese Han population.

The aim was to analyze quantitative (mitochondrial DNA (mtDNA) content) and qualitative (G10398A polymorphism) mtDNA alterations as well as human papillomavirus (HPV) infection in cervical cancer prognosis. One hundred and twenty-two cases of formalin-fixed paraffin-embedded cervical carcinoma specimens were collected from the Yichang Tumor Hospital and Zhongnan Hospital of Wuhan University in the recent 10 years together with medical records. A quantitative real-time PCR (RT-PCR) was used to determine the copy number of the mitochondrial DNA and HPV expression levels. G10398A polymorphism was determined by PCR-RFLP assay. The overall survival of patients with higher mtDNA content was significantly reduced compared with lower mtDNA content patients (P = 0.029). But there was no difference of prognosis between the mtDNA 10398 A allele and G allele. However, the Kaplan-Meier survival curve illustrated a significantly reduced overall survival in the patients with 10398A plus high mtDNA copy number compared with the other groups (P < 0.05). Although no association between HPV expression level and cervical cancer prognosis was observed, 10398A got increased mtDNA content compared with 10398G (P < 0.05) and 10398G displayed an increased HPV-positive rate compared with 10398A. Furthermore, HPV-18 and mtDNA content were positively related in the younger subgroup (≤45 years) (correlation coefficient = 0.456, P = 0.022). This study indicated that mtDNA content and HPV infection status are associated with cervical cancer prognosis. High mitochondrial DNA content plus 10398 A may be a marker of poor prognosis in cervical cancer. And mtDNA variation may potentially influence the predisposition to HPV infection and cervical carcinogenesis.

Echocardiography in pericardial diseases: new developments.

Echocardiography is one of the most important clinical tools in the diagnosis and management of various pericardial diseases, including constrictive pericarditis, effusive constrictive pericarditis, pericardial effusion, tamponade, absence of the pericardium and cysts or tumors. During recent years, remarkable progress has been made in echocardiography: cardiac tissue Doppler analysis (TDI), strain and strain rate imaging by speckle tracking imaging (STE) and three-dimensional (3D) echocardiography. The assessment of early diastolic annulus velocity and annulus reversus by TDI improves the differentiation of constriction from restrictive myocardial disease, which can be further facilitated by STE as a complementary tool. 3D echocardiography may be useful for the more precise assessment of pericardial diseases, such as pericardial effusion or pericardial masses as it provides incremental value to 2D echocardiography by detecting anatomic structures with higher accuracy. Applications of these newer echocardiographic techniques in the assessment of pericardial diseases are discussed in this chapter.

Cardiac magnetic resonance imaging pericardial late gadolinium enhancement and elevated inflammatory markers can predict the reversibility of constrictive pericarditis after antiinflammatory medical therapy: a pilot study.

BACKGROUND: Constrictive pericarditis (CP) is a disabling disease, and usually requires pericardiectomy to relieve heart failure. Reversible CP has been described, but there is no known method to predict the reversibility. Pericardial inflammation may be a marker for reversibility. As a pilot study, we assessed whether cardiac magnetic resonance imaging pericardial late gadolinium enhancement (LGE) and inflammatory biomarkers could predict the reversibility of CP after antiinflammatory therapy. METHOD AND RESULTS: Twenty-nine CP patients received antiinflammatory medications after cardiac magnetic resonance imaging. Fourteen patients had resolution of CP, whereas 15 patients had persistent CP after 13 months of follow-up. Baseline LGE pericardial thickness was greater in the group with reversible CP than in the persistent CP group (4 ± 1 versus 2 ± 1 mm, P = 0.001). Qualitative intensity of pericardial LGE was moderate or severe in 93% of the group with reversible CP and in 33% of the persistent CP group (P = 0.002). Cardiac magnetic resonance imaging LGE pericardial thickness ≥ 3 mm had 86% sensitivity and 80% specificity to predict CP reversibility. The group with reversible CP also had higher baseline C-reactive protein and erythrocyte sedimentation rate than the persistent CP group (59 ± 52 versus 12 ± 14 mg/L, P = 0.04 and 49 ± 25 versus 15 ± 16 mm/h, P = 0.04, respectively). Antiinflammatory therapy was associated with a reduction in C-reactive protein, erythrocyte sedimentation rate, and pericardial LGE in the group with reversible CP but not in the persistent CP group. CONCLUSIONS: Reversible CP was associated with pericardial and systemic inflammation. Antiinflammatory therapy was associated with a reduction in pericardial and systemic inflammation and LGE pericardial thickness, with resolution of CP physiology and symptoms. Further studies in a larger number of patients are needed.

[Retracted] MicroRNA­379 acts as a tumor suppressor in non­small cell lung cancer by targeting the IGF­1R­mediated AKT and ERK pathways.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the cell migration and invasion assay data shown in Figs. 2F, 5D and 6D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 38: 1857­1866, 2017; DOI: 10.3892/or.2017.5835].

Intracardiac thrombosis and anticoagulation therapy in cardiac amyloidosis.

BACKGROUND: Primary amyloidosis has a poor prognosis as a result of frequent cardiac involvement. We recently reported a high prevalence of intracardiac thrombus in cardiac amyloid patients at autopsy. However, neither the prevalence nor the effect of anticoagulation on intracardiac thrombus has been evaluated antemortem. METHODS AND RESULTS: We studied all transthoracic and transesophageal echocardiograms of cardiac amyloid patients at the Mayo Clinic. The prevalence of intracardiac thrombosis, clinical and transthoracic/transesophageal echocardiographic risks for intracardiac thrombosis, and effect of anticoagulation were investigated. We identified 156 patients with cardiac amyloidosis who underwent transesophageal echocardiograms. Amyloidosis was the primary type (AL) in 80; other types occurred in 76 patients, including 56 with the wild transthyretin type, 17 with the mutant transthyretin type, and 3 with the secondary type. Fifth-eight intracardiac thrombi were identified in 42 patients (27%). AL amyloid had more frequent intracardiac thrombus than the other types (35% versus 18%; P=0.02), although the AL patients were younger and had less atrial fibrillation. Multivariate analysis showed that atrial fibrillation, poor left ventricular diastolic function, and lower left atrial appendage emptying velocity were independently associated with increased risk for intracardiac thrombosis, whereas anticoagulation was associated with a significantly decreased risk (odds ratio, 0.09; 95% CI, 0.01 to 0.51; P<0.006). CONCLUSIONS: Intracardiac thrombosis occurs frequently in cardiac amyloid patients, especially in the AL type and in those with atrial fibrillation. Risk for thrombosis increased if left ventricular diastolic dysfunction and atrial mechanical dysfunction were present. Anticoagulation therapy appears protective. Timely screening in high-risk patients may allow early detection of intracardiac thrombus. Anticoagulation should be carefully considered.

Intracardiac thrombosis and embolism in patients with cardiac amyloidosis.

BACKGROUND: Patients with primary amyloidosis (AL type) have a poor prognosis, in part due to frequent cardiac involvement. Although intracardiac thrombus has been reported in anecdotal cases, neither its frequency nor its role in causing mortality is known. Furthermore, the clinical and echocardiographic variables that may be associated with thromboembolism in cardiac amyloidosis have not been defined. METHODS AND RESULTS: A total of 116 autopsy or explanted cases of cardiac amyloidosis (55 AL and 61 other type) were identified in the Mayo Clinic. Forty-six fatal nonamyloid trauma cases served as controls. Each heart was examined for intracardiac thrombus. The cause of death was determined from autopsy and clinical notes. Intracardiac thrombosis was identified in 38 hearts (33%). Twenty-three had 1 thrombus, whereas 15 had 2 to 5 thrombi. Although subjects in the AL group were younger and had less atrial fibrillation than those with other types of amyloidosis, the AL group had significantly more intracardiac thrombus (51% versus 16%, P<0.001) and more fatal embolic events (26% versus 8%, P<0.03). Control hearts had no intracardiac thrombus. The presence of both atrial fibrillation and AL was associated with an extremely high risk for thromboembolism (odds ratio 55.0 [95% confidence interval 8.1 to 1131.4]). By multivariate analysis, AL type (odds ratio 8.4 [95% confidence interval 1.8 to 51.2]) and left ventricular diastolic dysfunction (odds ratio 12.2 [95% confidence interval 2.7 to 72.7]) were independently associated with thromboembolism. CONCLUSIONS: A high frequency of intracardiac thrombosis was present in cardiac amyloidosis. Furthermore, thromboembolism caused significant fatality. Several risk factors for thromboembolism were identified. Early screening, especially in high-risk patients, and early anticoagulation might reduce morbidity and mortality.

MR imaging of the pericardium.

Imaging of the pericardium requires understanding of anatomy and the normal and abnormal physiology of the pericardium. MR imaging is well-suited for answering clinical questions regarding suspected pericardial disease. Pericardial diseases that may be effectively imaged with MR imaging include pericarditis, pericardial effusion, cardiac-pericardial tamponade, constrictive pericarditis, pericardial cysts, absence of the pericardium, and pericardial masses. Although benign and malignant primary tumors of the pericardium may be occasionally encountered, the most common etiology of a pericardial mass is metastatic disease.

MR imaging of cardiac masses.

Cardiac MR imaging is the preferred method for assessment of cardiac masses. A comprehensive cardiac MR imaging examination for a cardiac mass consists of static morphologic images using fast spin-echo sequences, including single-shot techniques, with T1 and T2 weighting and fat suppression pulses as well as dynamic imaging with cine steady-state free precession techniques. Further tissue characterization is provided with perfusion and delayed enhancement imaging. Specific cardiac tumoral characterization is possible in many cases. When specific tumor characterization is not possible, MR imaging often can demonstrate aggressive versus nonaggressive features that help in differentiating malignant from benign tumors.

MicroRNA-379 acts as a tumor suppressor in non-small cell lung cancer by targeting the IGF­1R-mediated AKT and ERK pathways.

Lung cancer is one of the most common types of malignancy in humans and is a leading cause of cancer-related deaths among men and women worldwide. Aberrantly expressed microRNAs in non-small cell lung cancer (NSCLC) contribute to tumor occurrence and development as either tumor suppressors or promoters. MicroRNA-379 (miR­379) is dysregulated in several types of human cancer. However, its expression pattern, role and underlying mechanism in NSCLC progression and metastasis are poorly understood. In this study, assay of reverse transcription-quantitative polymerase chain reaction showed that miR­379 was downregulated in both NSCLC tissue and cell lines. Low miR­379 expression in NSCLC tissues was significantly correlated with TNM stage and lymph node metastasis. In addition, functional experiments revealed that restoring the expression of miR­379 inhibited cell proliferation, migration and invasion of NSCLC. The insulin-like growth factor receptor-1 (IGF­1R) was identified as a direct target of miR­379 in NSCLC. IGF­1R was highly expressed in NSCLC tissues and inversely correlated with miR­379 expression. Downregulation of IGF­1R had tumor suppressive roles similar to that of miR­379 overexpression on NSCLC cell proliferation, migration and invasion. Moreover, the upregulation of IGF­1R effectively rescued the tumor suppressive roles induced by miR­379 overexpression in NSCLC. The resumption of the expression of miR­379 inhibited the activation of AKT and ERK signaling pathways in NSCLC. These findings suggested that miR­379 acts as a tumor suppressor in NSCLC by directly targeting IGF­1R and indirectly regulating AKT and ERK signaling pathways. miR­379 provides novel therapeutic targets for the treatment of patients with this disease.

Complete sequence of a cholangiocarcinoma inbred Sprague-Dawley rat model mitochondrial genome.

In the present work we undertook the complete mitochondrial genome sequencing of an important cholangiocarcinoma model inbred rat strain for the first time. Its mitogenome was 16,312 bp and coding 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes. A total of 96 SNPs were examined when compared to reference BN sequence.

Novel Imaging Approaches for Predicting Arrhythmic Risk.

Determination of ventricular arrhythmic risk is crucial for guiding management of cardiac disease. Although for patients at increased risk an implantable cardioverter-defibrillator is recommended, it is widely acknowledged that current criteria for device use based predominantly on left ventricular ejection fraction are deficient. Genesis of ventricular arrhythmias involves a complex interaction of myocardial substrate abnormalities, precipitating triggers, and modulating factors. There are much data showing that by more directly assessing these factors, noninvasive imaging using echocardiography, radionuclide imaging, and cardiac magnetic resonance enhances arrhythmic risk stratification beyond ejection fraction and commonly used electrocardiographic and serum biomarkers. It is anticipated that further technological advancements studied in well-designed clinical trials will provide both more precise determination of risk and guide therapies to enhanced survival and patient well-being.

Expression of human protection of telomere 1 correlates with telomere length and radiosensitivity in the human laryngeal cancer Hep-2 cell line.

The close association between telomere length and radiosensitivity has been established by several studies. There is also a hypothesis that telomere length may be regulated by human protection of telomere 1 (hPOT1) in human carcinoma cells. In the present study, the hPOT1 level between the radioresistant Hep-2R cells and the wild-type were compared, and the results showed that the hPOT1 gene was upregulated in the radioresistant Hep-2R cell lines compared with the wild-type. This suggested that the expression level of hPOT1 correlates with radiosensitivity. Additionally, an hPOT1-directed short hairpin (sh)RNA plasmid was constructed and transferred into the Hep-2R cells, which lead to telomere shortening, an increase in apoptosis and markedly decreased growth of the RNAi-Hep-2R cell line. These results demonstrate that hPOT1-directed shRNAs are associated with telomere length and radiosensitivity, and maybe a potent sensitizer for laryngeal cancer radiotherapy.

The clinical significance of FSCN1 in non-small cell lung cancer.

Fascin actin-bundling protein 1 (FSCN1) plays significant roles in biological processes such as tumor cell invasion and metastasis. However, little is known about prognostic value of FSCN1 in non-small cell lung cancer (NSCLC). FSCN1 mRNA and protein expression were detected by real-time PCR and Western blot in NSCLC tissues and paired adjacent normal lung tissues. Furthermore, the association of FSCN1 protein expression with clinicopathological characteristics including the survival was explored in 156 NSCLC patients. In our results, FSCN1 mRNA and protein expression were obviously higher in NSCLC tissues than in normal lung tissues. High levels of FSCN1 protein were positively correlated with status of differentiated degree, clinical stage, N classification, and M classification in NSCLC. Meanwhile, higher FSCN1 protein expression was significantly associated with poor overall survival in patients with NSCLC. Multivariate analyses showed that increased FSCN1 protein expression was a poor independent prognostic biomarker for NSCLC patients. In conclusions, FSCN1 plays an important role on NSCLC progression and prognosis and may serve as a convictive prognostic biomarker for NSCLC patients.

Adenosine sensitivity is associated with ablation success rate and recurrence rate with nonirrigated catheters in patients with ventricular premature contractions/tachycardia from the ventricular outflow tract.

BACKGROUND: A high ablation success rate for ventricular arrhythmia (VA) from outflow tract has been achieved, but some of them cannot be eliminated from endocardium. We investigated the association between adenosine sensitivity and ablation success/recurrence rates with a nonirrigated or an irrigated catheter. METHODS: According to adenosine test, all patients were divided into a sensitive group (S group) or an insensitive group (I group). The patients of each group were randomized into a nonirrigated catheter (NA) subgroup or an irrigated catheter (IA) subgroup with a 2:1 ratio. RESULTS: In S group of 122 patients (84 in NA subgroup), the ablation success rate was similar between two subgroups (94.7% vs. 90.5%, P > 0.05), but in I group of 94 patients (60 in NA subgroup), it was higher in IA subgroup (94.1%) than that in NA subgroup (73.3%, P < 0.05). The success rate using nonirrigated catheter was significantly higher in S group (90.5%) than that in I group (73.3%, P < 0.01), and the recurrence rate was lower in S group than that in I group (1.3%, vs. 13.6%, P < 0.05). On the contrary, the success rate and the recurrence rate using irrigated catheter were similar between S group and I group (94.7%, 94.1%, P > 0.05, vs. 2.8%, 6.3%, P > 0.05). CONCLUSIONS: Adenosine insensitivity is associated with a lower success rate and a higher recurrence rate for VA patients undergoing nonirrigated catheter ablation. Thus, irrigated catheters should be the first choice for VA ablation in adenosine insensitive patients.

Absence of association between polymorphisms in the hemostatic factor pathway genes and carotid intimal medial thickness: the Framingham Heart Study.

BACKGROUND AND PURPOSE: Fibrinogen, plasminogen activator inhibitor-1, and other key proteins in the coagulation cascade have been implicated in the origin of cardiovascular disease. Polymorphisms in genes encoding these proteins have been associated with variability in plasma levels of these proteins. Carotid intimal medial thickness (IMT) is a heritable, quantitative measure of atherosclerosis that is predictive of subsequent myocardial infarction and stroke. We sought to test whether carotid IMT is associated with polymorphisms in several well-characterized genes in the hemostatic factor pathways. METHODS: Here, 867 men and 911 women (mean age, 57 years) in the Framingham offspring cohort underwent B-mode carotid ultrasonography to determine the mean internal (ICA) and common carotid artery (CCA) IMT. Age-, sex-, and multivariable-adjusted linear regression was used to estimate the association of the following variants with log-transformed CCA and ICA IMT: factor V Leiden, factor VII Arg/Gln, fibrinogen HindIII beta-148, plasminogen activator inhibitor-1 4G/5G, and the glycoprotein IIIa Pl(A2) polymorphism. RESULTS: Mean ICA IMT was 0.58 mm; mean CCA IMT was 0.60 mm. There were no differences in ICA or CCA IMT by genotype for any of the candidate genes in unadjusted, age- or sex-adjusted, and multivariable-adjusted models. CONCLUSIONS: There is no evidence for an association between well-studied polymorphisms in the hemostatic factor genes and carotid IMT. Whether other common genetic variants in hemostatic factor genes are associated with subclinical atherosclerosis remains to be determined.

A genome-wide search for genes affecting circulating fibrinogen levels in the Framingham Heart Study.

INTRODUCTION: Circulating levels of fibrinogen are associated with atherosclerosis and predict future coronary heart disease and stroke. Levels of fibrinogen are correlated among family members, suggesting a heritable component. Variants of the beta-fibrinogen gene subunit on 4q28 are associated with fibrinogen levels but explain only a small proportion of the total genetic variability. It remains unknown what role, if any, is played by other genetic variants in the inter-individual variability in levels of fibrinogen in the general population. MATERIALS AND METHODS: We conducted a 10-cM spaced genome-wide scan using 402 original cohort subjects and 1193 offspring subjects from 330 extended families of the Framingham Heart Study. Heritability and linkage analyses were carried out using variance component methods. Regression analyses were performed to adjust for traditional risk factors and HindIII beta-148 genotypes. RESULTS AND DISCUSSIONS: The total heritability was estimated as 0.24. The highest and second highest LOD scores of linkage were found on chromosomes 2 (LOD=1.5 at 243 cM) and 10 (LOD=2.4 at 87 cM) using only offspring subjects in the analysis, and on chromosomes 2 (LOD=2.1 at 242 cM) and 10(LOD=1.4 at 86 cM), 17 (LOD=1.4 at 96 cM) and 20 (LOD=1.4 at 80 cM) using both original cohort and offspring. These results suggest that there may be influential genetic regions on these chromosomes. While no linkage with genome-wide significance was detected, further research to confirm our findings is warranted.

Impact of myocardial scarring on outcomes of cardiac resynchronization therapy: extent or location?

UNLABELLED: Refining the criteria for patient selection for cardiac resynchronization therapy (CRT) may improve its outcomes. The study objective was to determine the effect of scar location, scar burden, and left ventricular (LV) lead position on CRT outcomes. METHODS: The study included 213 consecutive CRT recipients with radionuclide myocardial perfusion imaging before CRT between January 2002 and December 2008. Scar localization and myocardial viability were analyzed using a 17-segment model and a 5-point semiquantitative scale. New York Heart Association (NYHA) class and echocardiography were assessed before and after CRT. The anatomic LV lead location in the 17-segment model was assessed by review of fluoroscopic cinegrams in right and left anterior oblique views. As in published studies, clinical response was defined as an absolute improvement in LV ejection fraction of ≥5 percentage points after CRT. RESULTS: A total of 651 scar segments was identified in 213 patients. Eighty-three percent of scar segments were located in the LV anterior, posterior, septal, and apical regions, whereas 84% of LV leads were in the lateral wall. Only 11% of LV leads were positioned in scar segments. The extent of scarring was significantly higher in nonresponders than in responders (18.0% vs. 6%, P = 0.001). Compared with patients with scarring >22%, patients ≤70 y with scarring ≤22% of the left ventricle had a greater increase in LV ejection fraction (10.1% ± 10.5% vs. 0.8% ± 6.1%; P < 0.001) and improvement in NYHA class (-0.9 ± 0.7 vs. -0.5 ± 0.8; P = 0.02). CONCLUSION: LV leads were often located in viable myocardial regions. Less scar burden was associated with a greater improvement in heart failure but only in relatively younger CRT recipients.