Assessment of left atrial fibrosis progression in canines following rapid ventricular pacing using 3D late gadolinium enhanced CMR images.
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ABSTRACT: Background
Atrial fibrillation (AF) is associated with extracellular matrix (ECM) remodelling and often coexists with myocardial fibrosis (MF); however, the causality of these conditions is not well established.Objective
We aim to corroborate AF to MF causality by quantifying left atrial (LA) fibrosis in cardiac magnetic resonance (CMR) images after persistent rapid ventricular pacing and subsequent AF using a canine model and histopathological validation.Methods
Twelve canines (9 experimental, 3 control) underwent baseline 3D LGE-CMR imaging at 3T followed by insertion of a pacing device and 5 weeks of rapid ventricular pacing to induce AF (experimental) or no pacing (control). Following the 5 weeks, pacing devices were removed to permit CMR imaging followed by excision of the hearts and histopathological imaging. LA myocardial segmentation was performed manually at baseline and post-pacing to permit volumetric %MF quantification using the image intensity ratio (IIR) technique, wherein fibrosis was defined as pixels > mean LA myocardium intensity + 2SD.Results
Volumetric %MF increased by an average of 2.11 ± 0.88% post-pacing in 7 of 9 experimental dogs. While there was a significant difference between paired %MF measurements from baseline to post-pacing in experimental dogs (P = 0.019), there was no significant change in control dogs (P = 0.019 and P = 0.5, Wilcoxon signed rank tests). The median %MF for paced animals was significantly greater than that of non-paced dogs at the 5-week post-insertion time point (P = 0.009, Mann Whitney U test). Histopathological imaging yielded an average %MF of 19.42 ± 4.80% (mean ± SD) for paced dogs compared to 1.85% in one control dog.Conclusion
Persistent rapid ventricular pacing and subsequent AF leads to an increase in LA fibrosis volumes measured by the IIR technique; however, quantification is limited by inherent image acquisition parameters and observer variability.
SUBMITTER: Farrag NA
PROVIDER: S-EPMC9269919 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeTo develop an accelerated three-dimensional (3D) late gadolinium enhancement (LGE) pulse sequence using balanced steady-state free precession readout with stack-of-stars k-space sampling and extra motion-state golden-angle radial sparse parallel (XD-GRASP) reconstruction and test the performance for detecting atrial scar and fibrosis in patients with atrial fibrillation (AF).Materials and methodsTwenty-five patients with AF (20 paroxysmal and five persistent; 65 years ± 7 [standard deviation]; 18 men) were imaged at 1.5 T using the proposed LGE sequence with 1.3 mm × 1.3 mm × 2-mm spatial resolution and predictable imaging time. The resulting images were compared with historic images of 25 patients with AF (18 paroxysmal and seven persistent; 67 years ± 10; 14 men) obtained using a reference 3D left atrial (LA) LGE sequence with 1.3 mm × 1.3 mm × 2.5-mm spatial resolution. Two readers visually graded the 3D LGE images (conspicuity, artifact, noise) on a five-point Likert scale (1 = worst, 3 = acceptable, 5 = best), in which the summed visual score (SVS) of 9 or greater was defined as clinically acceptable. Appropriate statistical analyses (Cohen κ coefficient, Mann-Whitney U test, t tests, and intraclass correlation) were performed, where a P value < .05 was considered significant.ResultsMean imaging time was significantly shorter (P < .01) for the proposed pulse sequence (5.9 minutes ± 1.3) than for the reference pulse sequence (10.6 minutes ± 2). Median SVS was significantly higher (P < .01) for the proposed (SVS = 11) than reference (SVS = 9.5) 3D LA LGE images. Interrater reproducibility in visual scores was higher for the proposed (κ = 0.78-1) than reference 3D LA LGE (κ = 0.44-0.75). Intrareader repeatability in fibrosis quantification was higher for the reference cohort (intraclass correlation coefficient [ICC] = 0.94) than the prospective cohort (ICC = 0.79).ConclusionThe proposed 3D LA LGE method produced clinically acceptable image quality with 1.5 mm × 1.5 mm × 2-mm nominal spatial resolution and 6-minute predictable imaging time for quantification of LA scar and fibrosis in patients with AF. Supplemental material is available for this article. © RSNA, 2020.
| S-EPMC7605361 | biostudies-literature
Project description:Sustained atrial tachycardia leads to multiple molecular and cellular effects collectively defined as atrial tachycardia remodeling (ATR). ATR is thought to play a major role in the self-perpetuating nature of atrial fibrillation (AF) and has been a subject of intense research in large mammalian models of AF. Recently, rodents are increasingly used to gain insight on the pathophysiology AF. However, little is known regarding the effects of rapid pacing on the atria of rats and mice mainly due to technical challenges in electrophysiological studies of unanesthetized rodents. Using an implantable device for electrophysiological studies in unanesthetized rodents we examine, on a daily basis, the effects of continuous rapid atrial pacing (RAP) for at least 4 consecutive days on the developed AF substrate of Sprague-Dawley rats and C57BL6 mice. AF induction protocol consisted 10 aggressive bursts (20 seconds, double diastolic threshold, 10 ms cycle length [CL]). This protocol failed to induce AF at baseline in both species, but repeatedly induced AF episodes in rats following 2 days of sustained RAP. Microarray study of left atrial tissue from rats exposed for 2 days to RAP (70 ms CL) vs control pacing (140 ms CL) identified 304 differentially expressed genes (155 upregulated and 149 downregulated). Real-time qt-PCR confirmed the validity of the microarray. Enrichment analysis and comparison with a dataset of atrial tissue from AF patients revealed indications of increased carbohydrate metabolism, and changes in pathways that are thought to have critical role in human AF including TGF-beta and IL-6 signaling. Among 19 commonly affected genes in comparison with human AF, downregulation of FOXP1 and upregulation of the KCNK2 gene encoding the Kir2.1 potassium channel were conspicuous finding suggesting NFAT activation. Further results in line with NFAT activation included reduced expression of MIR-26, MIR-101, which were linked to upregulation of the KCNK2 in human AF. Our results demonstrate electrophysiological evidence for AF promoting effects of RAP in rats and some important molecular similarities between the effects of RAP in large and small mammalian models. The effects of atrial tachypacing are well documented in large mammals but very little is know regarding the effects of tacypacing on the rodent atria.
2019-08-01 | GSE126711 | GEO
Project description:ObjectiveArrhythmogenic mitral valve prolapse (MVP) is an important cause of sudden cardiac death characterized by fibrosis of the papillary muscles or left ventricle (LV) wall, and an association between late gadolinium enhancement (LGE) of the LV papillary muscles and ventricular arrhythmia in MVP has been reported. However, LGE of the papillary muscles may be observed in other causes of mitral regurgitation, and it is not limited to patients with MVP. This study was to evaluate the association of LGE of the LV papillary muscles or ventricular wall on cardiac magnetic resonance imaging (CMR) and ventricular arrhythmia in patients with mitral regurgitation.Materials and methodsThis study included 88 patients (mean age ± standard deviation, 58.3 ± 12.0 years; male, 42%) with mitral regurgitation who underwent CMR. They were allocated to the MVP (n = 43) and non-MVP (n = 45) groups, and their LGE images on CMR, clinical characteristics, echocardiographic findings, and presence of arrhythmia were compared.ResultsLV myocardial wall enhancement was more frequent in the MVP group than in the non-MVP group (28% vs. 11%, p = 0.046). Papillary muscle enhancement was observed in 7 (7.9%) patients. Of the 43 patients with MVP, 15 (34.8%) showed LGE in the papillary muscles or LV myocardium, including 12 (27.9%) with LV myocardial wall enhancement and 4 (9.3%) with papillary muscle enhancement. One patient with bilateral diffuse papillary muscle enhancement experienced sudden cardiac arrest due to ventricular fibrillation. Univariable logistic regression analysis showed that high systolic blood pressure (BP; odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.09; p = 0.027) and ventricular arrhythmia (OR, 6.84; 95% CI, 1.29-36.19; p = 0.024) were significantly associated with LGE of the papillary muscles.ConclusionLGE of the papillary muscles was present not only in patients with MVP, but also in patients with other etiologies of mitral regurgitation, and it was associated with high systolic BP and ventricular arrhythmia. Papillary muscle enhancement on CMR should not be overlooked.
| S-EPMC8484157 | biostudies-literature
Project description:BackgroundLeft atrial (LA) late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging is indicative of fibrosis, and has been correlated with reduced LA function, increased LA volume, and poor procedural outcomes in cohorts with atrial fibrillation (AF). However, the role of LGE as a prognostic biomarker for arrhythmia in cardiac disease has not been examined.MethodsIn this study, we assessed LA LGE using a 3D LGE CMR sequence to examine its relationships with new onset atrial arrhythmia, and LA and left ventricular (LV) mechanical function.ResultsLA LGE images were acquired in 111 patients undergoing CMR imaging, including 66 patients with no prior history of an atrial arrhythmia. During the median follow-up of 2.7?years (interquartile range (IQR) 1.8-3.7?years), 15/66 (23%) of patients developed a new atrial arrhythmia. LA LGE ?10% of LA myocardial volume was significantly associated with an increased rate of new-onset atrial arrhythmia, with a hazard ratio of 3.16 (95% CI 1.14-8.72), p =?0.026. There were significant relationships between LA LGE and both LA ejection fraction (r =?-?0.39, p <?0.0005) and echocardiographic LV septal e' (r =?-?0.24, p =?0.04) and septal E/e' (r =?0.31, p =?0.007).ConclusionsElevated LA LGE is associated with reduced LA function and reduced LV diastolic function. LA LGE is associated with new onset atrial arrhythmia during follow-up.
| S-EPMC6317232 | biostudies-literature
Project description:This is a proof-of-principle study investigating the feasibility of using late gadolinium enhancement magnetic resonance imaging (LGE-MRI) to detect left atrium (LA) radiation damage.LGE-MRI data were acquired for 7 patients with previous external beam radiation therapy (EBRT) histories. The enhancement in LA scar was delineated and fused to the computed tomography images used in dose calculation for radiation therapy. Dosimetric and normal tissue complication probability analyses were performed to investigate the relationship between LA scar enhancement and radiation doses.The average LA scar volume for the subjects was 2.5 cm3 (range, 1.2-4.1 cm3; median, 2.6 cm3). The overall average of the mean dose to the LA scar was 25.9 Gy (range, 5.8-49.2 Gy). Linear relationships were found between the amount of radiation dose (mean dose) (R2 = 0.8514, P = .03) to the LA scar-enhanced volume. The ratio of the cardiac tissue change (LA scar/LA wall) also demonstrated a linear relationship with the level of radiation received by the cardiac tissue (R2 = 0.9787, P < .01). Last, the normal tissue complication probability analysis suggested a dose response function to the LA scar enhancement.With LGE-MRI and 3-dimensional dose mapping on the treatment planning system, it is possible to define subclinical cardiac damage and distinguish intrinsic cardiac tissue change from radiation induced cardiac tissue damage. Imaging myocardial injury secondary to EBRT using MRI may be a useful modality to follow cardiac toxicity from EBRT and help identify individuals who are more susceptible to EBRT damage. LGE-MRI may provide essential information to identify early screening strategy for affected cancer survivors after EBRT treatment.
| S-EPMC5506699 | biostudies-other
Project description:IntroductionLate gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI) can be used to detect postablation atrial scar (PAAS) but its reproducibility and reliability in clinical scans across different magnetic flux densities and scar detection methods are unknown.MethodsPatients (n = 45) having undergone two consecutive MRIs (3 months apart) on 3T and 1.5T scanners were studied. We compared PAAS detection reproducibility using four methods of thresholding: simple thresholding, Otsu thresholding, 3.3 standard deviations (SD) above blood pool (BP) mean intensity, and image intensity ratio (IIR). We performed a texture study by dividing the left atrial wall intensity histogram into deciles and evaluated the correlation of the same decile of the two scans as well as to a randomized distribution of intensities, quantified using Dice Similarity Coefficient (DSC).ResultsThe choice of scanner did not significantly affect the reproducibility. The scar detection performed by Otsu thresholding (DSC of 71.26 ± 8.34) resulted in a better correlation of the two scans compared with the methods of 3.3 SD above BP mean intensity (DSC of 57.78 ± 21.2, p < .001) and IIR above 1.61 (DSC of 45.76 ± 29.55, p <.001). Texture analysis showed that correlation only for voxels with intensities in deciles above the 70th percentile of wall intensity histogram was better than random distribution (p < .001).ConclusionsOur results demonstrate that clinical LGE-MRI can be reliably used for visualizing PAAS across different magnetic flux densities if the threshold is greater than 70th percentile of the wall intensity distribution. Also, atrial wall-based thresholding is better than BP-based thresholding for reproducible PAAS detection.
| S-EPMC9205620 | biostudies-literature
Project description:AimsThis study aimed to evaluate the clinical parameters including late gadolinium enhancement (LGE) of cardiovascular magnetic resonance to predict re-worsening of left ventricular ejection fraction (LVEF) in patients with dilated cardiomyopathy (DCM).Methods and resultsWe included 138 patients with recent-onset DCM who had an LVEF <45% and underwent LGE of cardiovascular magnetic resonance imaging at diagnosis and echocardiography at the yearly follow-up [median 6 (4-8.3) years]. Initial LVEF recovery was defined as LVEF increase >10% from baseline, resulting in LVEF ?45% after treatment. The patients were divided into three groups: (i) improved (n = 83, 60%), defined as those with sustained LVEF ?45%; (ii) re-worsening (n = 39, 28%), those with >5% decrease and LVEF <45% after the initial LVEF recovery; and (iii) not-improved (n = 16, 12%), those without initial LVEF recovery. The primary endpoint was a composite of hospitalization for heart failure or sudden cardiac death. In baseline, LGE was observed in 70 patients. The LGE area was significantly larger in the re-worsening and not-improved groups than that in the improved group (P < 0.001). Loess curves of long-term LVEF trajectories showed that LVEF in the re-worsening group increased in the first 2 years and slowly declined thereafter. Multivariate logistic regression analysis demonstrated that LGE area [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.03-1.16, P = 0.004], B-type natriuretic peptide (OR 1.49, 95% CI 1.05-2.21, P = 0.030) level at the initial recovery, and LVEF (OR 0.91, 95% CI 0.86-0.97, P = 0.004) at the initial LVEF recovery were independent predictors of re-worsening of LVEF. During a median follow-up of 2273 (interquartile range: 1634-3191) days, the primary endpoint was observed in 31 (22%) patients. Univariate Cox proportional hazards analysis demonstrated that the risk of experiencing the primary event in the re-worsening group was significantly higher (hazard ratio: 4.30, 95% CI 1.63-11.31, P = 0.003) than that in the improved group and was lower than that in the not-improved group (hazard ratio: 0.33, 95% CI 0.15-0.72, P = 0.006).ConclusionsRe-worsening of LVEF was observed in 28% of patients with recent-onset DCM who showed an initial improvement in LVEF. High LGE burden, higher B-type natriuretic peptide level, and lower LVEF at the initial LVEF recovery were independent predictors of re-worsening of LVEF in patients with DCM. Careful observation is recommended for patients with a high risk for re-worsening of LVEF, even in those with an initial LVEF recovery.
| S-EPMC7835548 | biostudies-literature
Project description:BackgroundAccurate measurement of left atrial (LA) volumes is needed in cardiac diagnostics and the follow up of heart and valvular diseases. Geometrical assumptions with 2D methods for LA volume estimation contribute to volume misestimation. In this study, we test agreement of 3D and 2D methods of LA volume detection and explore contribution of 3D LA axis orientation and LA shape in introducing error in 2D methods by cardiovascular magnetic resonance imaging.Methods30 patients with prior first-ever ischemic stroke and no known heart disease, and 30 healthy controls were enrolled (age 18-49) in a substudy of a prospective case-control study. All study subjects underwent cardiac magnetic resonance imaging and were pooled for this methodological study. LA volumes were calculated by biplane area-length method from both conventional long axis (LAVAL-LV) and LA long axis-oriented images (LAVAL-LA) and were compared to 3D segmented LA volume (LAVSAX) to assess accuracy of volume detection. 3D orientation of LA long axis to left ventricular (LV) long axis and to four-chamber plane were determined, and LA 3D sphericity indices were calculated to assess sources of error in LA volume calculation. Shapiro-Wilk test, Bland-Altman analysis, intraclass and Pearson correlation, and Spearman's rho were used for statistical analysis.ResultsBiases were - 9.9 mL (- 12.5 to - 7.2) for LAVAL-LV and 13.4 (10.0-16.9) for LAVAL-LA [mean difference to LAVSAX (95% confidence interval)]. End-diastolic LA long axis 3D deviation angle to LV long axis was 28.3 ± 6.2° [mean ± SD] and LA long axis 3D rotation angle to four-chamber plane 20.5 ± 18.0°. 3D orientation of LA axis or 3D sphericity were not correlated to error in LA volume calculation.ConclusionsCalculated LA volume accuracy did not improve by using LA long axis-oriented images for volume calculation in comparison to conventional method. We present novel data on LA axis orientation and a novel metric of LA sphericity and conclude that these measures cannot be utilized to assess error in LA volume calculation.Trial registrationMain study Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) has been registered previously.
| S-EPMC8579555 | biostudies-literature
Project description:Atrial remodeling with fibrosis has been well-described in patients with atrial fibrillation (AF). We hypothesized that the left atrial (LA)-late gadolinium enhancement (LGE) extent on cardiac magnetic resonance (CMR) imaging is associated with LA pressure and can be a marker for suitable candidates for non-paroxysmal AF ablation. A total of 173 AF patients with an LA-LGE area on CMR imaging were enrolled. The clinical parameters, including invasively measured LA pressure, were compared between the patients with extensive LA-LGE (E-LGE, LGE extent ≥ 20%, n = 78) and those with small LA-LGE (S-LGE, LGE extent < 20%, n = 95). The E-LGE group had higher peak LA pressures than the S-LGE group (23 versus 19 mmHg, p < 0.001). The E-LGE group had more patients with non-paroxysmal AF (non-PAF) (51% vs. 34%), heart failure (9% vs. 0%), and higher NT pro-B-type natriuretic peptide (472 vs. 265 pg/ml) (all p < 0.05). LA pressure ≥ 21 mmHg was an independent predictor of E-LGE (OR = 2.218; p = 0.019). In the paroxysmal AF (PAF) subgroup, freedom from atrial arrhythmia after catheter ablation was not different (81% vs 86%, log-rank p = 0.529). However, in the non-PAF subgroup, it was significantly higher in the S-LGE group than in the E-LGE group (81% vs 55%, log-rank p = 0.014). Increased LA pressure was related to the LA-LGE extent. LA-LGE was a good predictor of outcome after catheter ablation, but only in patients with non-PAF.
| S-EPMC7536288 | biostudies-literature
Project description:BACKGROUND:Myocardial fibrosis occurs in aortic stenosis (AS) as part of the hypertrophic response. It can be detected by LGE, which is associated with an adverse prognosis in the form of increased mortality and morbidity. OBJECTIVES:To assess the prevalence of LGE patterns using cardiac magnetic resonance (CMR) in severe AS patients and to study its prognostic significance. METHODS:Patients enrolled into the study from June 2012 to November 2014. All the patients underwent CMR and various patterns of LGE studied. These patients if symptomatic were advised AVR and others were managed conservatively. All patients were followed up and watched for outcomes like mortality, heart failure/hospitalization for cardiovascular cause, fall in left ventricular ejection fraction (LVEF) ?20% and arrhythmia. RESULTS:A total of 109 patients (mean age-57.7±12.5yrs) underwent CMR with 63 males. These patients were followed up for a mean of 13 months. Among 38 patients who underwent AVR, 6 died (5-cardiovascular cause, 1-non cardiovascular). 71 patients were managed conservatively out of which 18 died (17-cardiovascular cause, 1-non cardiovascular cause). LGE patterns were seen in 46 patients (43%); mid myocardial enhancement was seen in 31.1% of cases (33 patients). No LGE pattern was seen in 57%(63 patients). Basal and mid regions were maximally involved with mid myocardial enhancement in 66% & 68.3% respectively. LV ejection fraction (p=0.002), peak aortic systolic velocity (p=0.01) and peak aortic systolic gradient (p=0.02) were the main predictors of LGE. Main predictors of primary outcome were NYHA class [OR- 13.4(2.8-26.1), p?0.001], age- 62±?9.6yrs(p=0.001), EF simpson-50.9±13%(p??0.001), LGE[OR 2.8 (1.27-6.47),p=0.01], number of segments involved [2.37±2.1,P?0.001] & CMR LV mass (151.73±32gms, p=0.007). LGE predicted heart failure/hospitalization for cardiovascular cause [OR- 3.8(1.2-11.9), p=0.01] and fall in LVEF [OR- 5.8(1.5-22.5), p=0.005]. Patients with LGE had 2.87 times risk of adverse outcomes and patients with more than 3 segment LGE involvement had again increased chances for adverse outcomes. CONCLUSIONS:LGE was detected by CMR in 43% of patients with severe AS. It predicted recurrent heart failure, hospitalization for cardiovascular cause and fall in LV ejection fraction. Our study has laid a path to larger prospective studies with long term follow up to assess the prognostic impact of CMR in patients with severe AS.
| S-EPMC5717299 | biostudies-other