Regional Myocardial Remodeling Characteristics Correlates With Cardiac Events in Sarcoidosis.

BACKGROUND: The poor prognosis of cardiac sarcoidosis (CS) underscores the need for risk stratification. PURPOSE: To investigate the prognostic significance of ventricular/myocardial remodeling features in sarcoidosis. STUDY TYPE: Retrospective. POPULATION: In all, 132 biopsy-proven sarcoidosis patients imaged from 2008 to 2018. The primary endpoint was a composite of cardiac mortality, new onset arrhythmias, hospitalization for heart failure, and device implantation. FIELD STRENGTH/SEQUENCE: No field strength or sequence restrictions. ASSESSMENT: Global and regional ventricular/myocardial remodeling features were assessed by standard volumetric measurements and automated function imaging postprocessing analysis. STATISTICAL TESTS: Student's t-test or Mann-Whitney test (chi2 test or Fisher's exact test for categorical variables) were used for comparisons. Cox-proportional hazards regression model, univariate /multivariate analyses, and receiver operating characteristic were performed to relate clinical/lab data, imaging parameters to the endpoints. RESULTS: Over a median follow-up of 40.7 (interquartile range 18.8-60.5) months, 41 (31.1%) patients developed adverse cardiac events. Abnormal left ventricular (LV) geometric remodeling alterations (measured by LV mass index and relative wall thickness) occurred 3.66-fold more frequently in patients with endpoints than patients without. The ratio of patients with endpoints increased as ventricular remodeling phenotype progressed. In patients with endpoints, regional myocardial wall thickness (RMWT) was significantly (P = 0.022) increased in six clustered LV segments located in the middle interventricular septum and basal/middle anterolateral walls. In all of the abnormal ventricular remodeling stages, patients with endpoints constantly had higher mean RMWT than those without. Among clinical, electrocardiographic, and imaging parameters, LV mass index (hazard ratio [HR] 1.010 95% confidence interval [CI] 1.002-1.018, P = 0.017) and mean RMWT (HR 3.482 95% CI 1.679-7.223, P = 0.001) were independently associated with endpoints. Sarcoidosis patients without this RMWT distribution pattern were significantly (P < 0.001) more likely to be free of the occurrence of subsequent cardiac events. DATA CONCLUSION: Regional myocardial remodeling characteristics are associated with subsequent adverse cardiac events in sarcoidosis. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:499-509.

Atrial fibrosis in non-atrial fibrillation individuals and prediction of atrial fibrillation by use of late gadolinium enhancement magnetic resonance imaging.

INTRODUCTION: Besides the traditional concept of atrial fibrillation (AF) perpetuating atrial structural remodeling, there is increasing evidence that atrial fibrosis might precede AF, highlighting the need for better characterization of the fibrotic substrate. We aimed to assess atrial fibrosis by use of late gadolinium enhancement magnetic resonance imaging (LGE-MRI) in non-AF individuals and to identify predisposing risk factors. A second aim was to establish a risk score for the prevalence of AF using atrial fibrosis in addition to established clinical variables. METHODS AND RESULTS: Non-AF individuals without structural heart disease (n = 91) and matched AF controls (n = 91) underwent MRI for assessment of LGE. According to the established UTAH classification, atrial LGE ≥20% was considered extensive. Mean left atrial (LA) fibrosis in non-AF and AF individuals were 8.8 ± 6.5% and 12.5 ± 5.8%, respectively. Body mass index (BMI) >30 kg/m 2 and LA volume were predictors of atrial fibrosis. Diastolic function was not significantly different with respect to atrial fibrosis. A novel scoring system for the prevalence of AF (2 points for arterial hypertension and/or left ventricular ejection fraction <55%; 3 points for atrial fibrosis >6%) was derived demonstrating that patients in the intermediate/high-risk group had a significantly increased risk of AF. CONCLUSION: This study reports unexpectedly high atrial fibrosis in non-AF patients without apparent heart disease, highlighting the concept that structural fibrotic alterations may precede AF onset in a significant proportion of individuals. BMI as a predictor of atrial fibrosis suggests that lifestyle and drug intervention, that is, weight reduction, could positively influence fibrosis development. The derived risk score for AF prevalence provides the basis for prospective studies on AF incidence.

Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD.

nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition - ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.g., energy expenditure, activity, or food intake). Furthermore, whether the consumption of liquid sugar exacerbates the development of glucose intolerance, insulin resistance, and adipose tissue dysfunction in the model is currently in question. In our study, a high-fat Western diet (HFWD) with liquid sugar [fructose and sucrose (F/S)] induced acute hyperphagia above that observed in HFWD-fed mice, yet without changes in energy expenditure. Liquid sugar (F/S) exacerbated HFWD-induced glucose intolerance and insulin resistance and impaired the storage capacity of epididymal white adipose tissue (eWAT). Hepatic TG, plasma alanine aminotransferase, and normalized liver weight were significantly increased only in HFWD+F/S-fed mice. HFWD+F/S also resulted in increased hepatic fibrosis and elevated collagen 1a2, collagen 3a1, and TGFß gene expression. Furthermore, HWFD+F/S-fed mice developed more profound eWAT inflammation characterized by adipocyte hypertrophy, macrophage infiltration, a dramatic increase in crown-like structures, and upregulated proinflammatory gene expression. An early hypoxia response in the eWAT led to reduced vascularization and increased fibrosis gene expression in the HFWD+F/S-fed mice. Our results demonstrate that sugary water consumption induces acute hyperphagia, limits adipose tissue expansion, and exacerbates glucose intolerance and insulin resistance, which are associated with NAFLD progression.

Interstudy repeatability of self-gated quantitative myocardial perfusion MRI.

PURPOSE: To evaluate the interstudy repeatability of multislice quantitative cardiovascular magnetic resonance myocardial blood flow (MBF), myocardial perfusion reserve (MPR), and extracellular volume (ECV). A unique saturation recovery self-gated acquisition was used for the perfusion scans. MATERIALS AND METHODS: An ungated golden angle radial turboFLASH pulse sequence was used to scan 10 subjects on two separate days on a 3T scanner. A single saturation pulse was followed by a set of four slices. Rest and hyperemia scans were acquired during free breathing. The images were reconstructed using an iterative algorithm with spatiotemporal constraints. The ungated images were retrospectively binned (self-gated) into near-systole and near-diastole. Deformable registration was performed to adjust for respiratory and residual cardiac motion, and the data were fit with a Fermi model to estimate the interstudy repeatability of quantitative self-gated MBF and MPR. RESULTS: The coefficient of variation (CoV) of the territorial MPR using the self-gated near-systole data was 18.6%. The self-gated near-diastole data gave less good CoV of MPR, equal to 46.2%. For MBFs, and using smaller (segmental) regions, the CoVs were 20.1% and 22.7% for the estimation of myocardial blood flow at stress and rest, respectively, using the self-gated near-systole data. The self-gated near-diastole data gave CoV = 48.6% and 44.9% for stress and rest. CONCLUSION: The self-gated free-breathing technique for quantification of myocardial blood flow showed good repeatability for near-systole, with results comparable to published studies on interstudy repeatability of quantitative myocardial perfusion MRI using ECG-gating and breath-holds. Self-gated near-diastole data results were less repeatable. J. Magn. Reson. Imaging 2016;43:1369-1378.

Decoding Postinfarction Left Ventricular Pseudoaneurysm.

Recognizing true from pseudo left ventricular aneurysm after myocardial infarction is paramount to guide clinical management and determine need for surgical urgency. We discuss a case of a postinfarction pseudoaneurysm that poses unique anatomic challenges and may hold a secret "DaVinci code" beyond current diagnostic criteria. (Level of Difficulty: Advanced.).

Predicting adverse cardiac events in sarcoidosis: deep learning from automated characterization of regional myocardial remodeling.

Recognizing early cardiac sarcoidosis (CS) imaging phenotypes can help identify opportunities for effective treatment before irreversible myocardial pathology occurs. We aimed to characterize regional CS myocardial remodeling features correlating with future adverse cardiac events by coupling automated image processing and data analysis on cardiac magnetic resonance (CMR) imaging datasets. A deep convolutional neural network (DCNN) was used to process a CMR database of a 10-year cohort of 117 consecutive biopsy-proven sarcoidosis patients. The maximum relevance - minimum redundancy method was used to select the best subset of all the features-24 (from manual processing) and 232 (from automated processing) left ventricular (LV) structural/functional features. Three machine learning (ML) algorithms, logistic regression (LogR), support vector machine (SVM) and multi-layer neural networks (MLP), were used to build classifiers to categorize endpoints. Over a median follow-up of 41.8 (inter-quartile range 20.4-60.5) months, 35 sarcoidosis patients experienced a total of 43 cardiac events. After manual processing, LV ejection fraction (LVEF), late gadolinium enhancement, abnormal segmental wall motion, LV mass (LVM), LVMI index (LVMI), septal wall thickness, lateral wall thickness, relative wall thickness, and wall thickness of 9 (out of 17) individual LV segments were significantly different between patients with and without endpoints. After automated processing, LVEF, end-diastolic volume, end-systolic volume, LV mass and wall thickness of 92 (out of 216) individual LV segments were significantly different between patients with and without endpoints. To achieve the best predictive performance, ML algorithms selected lateral wall thickness, abnormal segmental wall motion, septal wall thickness, and increased wall thickness of 3 individual segments after manual image processing, and selected end-diastolic volume and 7 individual segments after automated image processing. LogR, SVM and MLP based on automated image processing consistently showed better predictive accuracies than those based on manual image processing. Automated image processing with a DCNN improves data resolution and regional CS myocardial remodeling pattern recognition, suggesting that a framework coupling automated image processing with data analysis can help clinical risk stratification.

Relation of Left Atrial Appendage Remodeling by Magnetic Resonance Imaging and Outcome of Ablation for Atrial Fibrillation.

The left atrial appendage (LAA) is a nonpulmonary vein trigger site in atrial fibrillation (AF). The association of LAA structural remodeling (SRM) identified by late gadolinium enhancement magnetic resonance imaging (LGE-MRI) and AF ablation outcome has never been described. This study sought to investigate the clinical significance of LAA-SRM in AF patients who undergo ablation therapy. Consecutive patients with AF who underwent catheter ablation therapy within 14 days following MRI scan were included in this study. LAA-SRM was assessed using LGE-MRI images to quantify the extent of LAA-LGE. Patients were followed for arrhythmia recurrence after the ablation procedure. A total of 74 patients were included in the study, 68% were male, with a mean age of 72 years. Mean LAA-LGE extent was 9%. There were 37 arrhythmia recurrences (50%) observed over a mean follow-up period of 18 months. The recurrence rate was significantly higher (73.3% vs 37.5%; p = 0.045) in patients with LAA-LGE extent in the highest tier (T4) compared with the lowest tier (T1). LAA-LGE extent was independently associated with arrhythmia recurrence (adjusted hazard ratio [HR] 1.054; 95% confidence interval [CI] 1.008 to 1.103). In addition, there was an approximately fourfold increased risk of arrhythmia recurrence (adjusted HR 4.117, 95% CI 1.260 to 13.459) in patients with advanced LAA-SRM (T4 vs T1). In conclusion, the extent of LAA-SRM identified by LGE-MRI is associated with arrhythmia recurrence after AF ablation.

Right-to-left ventricular end diastolic diameter ratio in severe sepsis and septic shock.

PURPOSE: The ratio of right ventricular end-diastolic diameter (EDD) to left ventricular EDD (RV/LV) is a measure predictive of right ventricular failure. We hypothesized that an increase in RV/LV would be associated with poor prognosis in severe sepsis and septic shock. MATERIALS AND METHODS: This is a retrospective chart review of patients with severe sepsis and septic shock admitted to a medical intensive care unit (ICU) at a single tertiary care hospital. Patients were identified by ICD-9 codes: 995.92 for severe sepsis and 785.52 for septic shock; and had to have an echocardiogram within 48 h of ICU admission. Increased RV/LV was defined as RV/LV ≥ 0.9. Left and right-sided chamber dimensions were measured according to American Society of Echocardiography guidelines. RESULTS: We included 146 consecutive ICU patients admitted with septic shock (72) or severe sepsis (74). There was no significant difference in ICU mortality in patients with RV/LV ≥ 0.9 versus RV/LV < 0.9 (p = .49). CONCLUSIONS: An increased RV/LV does not predict mortality in severe sepsis or septic shock.

Atrial Fibrosis by Late Gadolinium Enhancement Magnetic Resonance Imaging and Catheter Ablation of Atrial Fibrillation: 5-Year Follow-Up Data.

Background Late gadolinium enhancement magnetic resonance imaging is an effective tool for assessment of atrial fibrosis. The degree of left atrial fibrosis is a good predictor of atrial fibrillation ( AF ) ablation success at 1 year, but the association between left atrial fibrosis and long-term ablation success has not been studied. Methods and Results Late gadolinium enhancement magnetic resonance images of sufficient quality to quantify atrial fibrosis were obtained before the first AF ablation in 308 consecutive patients. Left atrial fibrosis was classified in 4 Utah stages (I, 0-10%; II , 10-20%; III , 20-30%; and IV , >30%). Patients were followed up for up to 5 years until the time of first arrhythmia recurrence or second ablation. A total of 308 patients were included; the mean age was 64.5±12.1 years, and 63.4% were men. During follow-up, 157 patients experienced an arrhythmia recurrence and 106 patients underwent a repeated ablation. A graded effect was observed in which patients with more advanced atrial fibrosis were more likely to experience recurrent AF (hazard ratio for stage IV versus stage I, 2.73; 95% confidence interval, 1.57-4.75) and undergo a repeated ablation (proportional odds ratio for stage IV versus stage I, 5.19; 95% confidence interval, 2.12-12.69). Conclusions The degree of left atrial fibrosis predicts the success of AF ablation at up to 5 years follow-up. In patients with advanced atrial fibrosis, AF ablation is associated with a high procedural failure rate.

Estimating extraction fraction and blood flow by combining first-pass myocardial perfusion and T1 mapping results.

BACKGROUND: Quantifying myocardial perfusion is complicated by the complexity of pharmacokinetic model being used and the reliability of perfusion parameter estimates. More complex modeling provides more information about the underlying physiology, but too many parameters in complex models introduce a new problem of reliable estimation. To overcome the problem of multiple parameters, we have developed a technique that combines knowledge from two different cardiac magnetic resonance (MR) imaging techniques: dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and T1 mapping. Using extracellular volume (ECV) estimates from T1 mapping may allow more robust model parameter estimates. METHODS: Simulations and human scans were performed. The myocardial perfusion scans used an ungated saturation recovery prepared TurboFLASH pulse sequence. Four short-axis (SA) slices were acquired after a single saturation pulse with a saturation recovery time of ~25 ms before the first slice. Gadoteridol was injected and ~240 frames were acquired over a minute with shallow breathing and no electrocardiograph (ECG) gating. This was followed 20±5 minutes later by an injection of regadenoson to induce hyperemia. The data were acquired using an under-sampled golden angle radial acquisition. Modified look-locker inversion recovery (MOLLI) T1 mapping was performed in 3 slices pre- and post-contrast. The pre- and post-contrast T1 maps were used for ECV estimation. Quantification of perfusion was done using a 4-parameter model with additional information about ECV supplied during model fitting. Phase contrast scans of the coronary sinus (CS) were acquired at rest and immediately after the stress perfusion acquisition to estimate global flow. RESULTS: Without ECV information, the 5-parameter model fails to converge to a unique solution and often gives incorrect estimates for the perfusion parameters. The myocardial blood flow (MBF) estimates during rest and stress were 0.9±0.1 and 2.3±0.6 mL/min/g, respectively. The extraction fraction estimates were 0.49±0.04 and 0.34±0.05 during rest and stress, respectively. CONCLUSIONS: These results show that it is possible to successfully fit a dynamic perfusion model with an extraction fraction parameter by using information from T1 mapping scans. This hybrid approach is especially important when the 5-parameter model alone fails to converge on a unique solution. This work is a good example of exploiting information overlaps between various cardiac MR imaging techniques.

Left Atrial Fibrosis and Risk of Cerebrovascular and Cardiovascular Events in Patients With Atrial Fibrillation.

BACKGROUND: Severity of left atrial (LA) fibrosis is a strong predictor of atrial fibrillation (AF) ablation success and has been associated with a history of stroke, hypertension, and heart failure (HF). However, it is unclear whether more severe LA fibrosis independently increases the risk of major adverse cardiovascular and cerebrovascular events (MACCE) among those with AF. OBJECTIVES: The goal of this study was to evaluate the occurrence and frequency of MACCE by strata of LA fibrosis severity in patients with AF. METHODS: This was a retrospective cohort study of 1,228 patients with AF who underwent late gadolinium enhancement (LGE)-cardiac magnetic resonance imaging to quantify LA fibrosis severity between January 2007 and June 2015. Patients were stratified according to Utah stage of LA LGE criteria, and observed for the occurrence of MACCE, which included a composite of stroke or transient ischemic attack (TIA), myocardial infarction, acute decompensated HF, or cardiovascular death. Disease risk score (DRS) stratification was used to control for between-group differences in baseline characteristics and risk. RESULTS: During follow-up, 62 strokes or TIAs, 42 myocardial infarctions, 156 HF events, and 38 cardiovascular deaths occurred. In DRS stratified analysis, the hazard ratio comparing patients with stage IV versus stage I LA LGE was 1.67 (95% confidence interval: 1.01 to 2.76) for the composite MACCE outcome. The only individual component of the MACCE outcome to remain significantly associated with advanced LGE following DRS stratification was stroke or TIA (hazard ratio: 3.94; 95% confidence interval: 1.72 to 8.98). CONCLUSIONS: This retrospective analysis demonstrated that more severe LA LGE is associated with increased MACCE risk, driven primarily by increased risk of stroke or TIA.