Prevalence and Progression of Late Gadolinium Enhancement in Children and Adolescents With Hypertrophic Cardiomyopathy.
ABSTRACT: BACKGROUND:Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is believed to represent dense replacement fibrosis. It is seen in ?60% of adult patients with hypertrophic cardiomyopathy (HCM). However, the prevalence of LGE in children and adolescents with HCM is not well established. In addition, longitudinal studies describing the development and evolution of LGE in pediatric HCM are lacking. This study assesses the prevalence, progression, and clinical correlations of LGE in children and adolescents with, or genetically predisposed to, HCM. METHODS:CMR scans from 195 patients ?21 years of age were analyzed in an observational, retrospective study, including 155 patients with overt HCM and 40 sarcomere mutation carriers without left ventricular (LV) hypertrophy. The extent of LGE was quantified by measuring regions with signal intensity >6 SD above nulled remote myocardium. RESULTS:Patients were 14.3±4.5 years of age at baseline and 68% were male. LGE was present in 70 (46%) patients with overt HCM (median extent, 3.3%; interquartile range, 0.8-7.1%), but absent in mutation carriers without LV hypertrophy. Thirty-one patients had >1 CMR (median interval between studies, 2.4 years; interquartile range, 1.5-3.2 years). LGE was detected in 13 patients (42%) at baseline and in 16 patients (52%) at follow-up CMR. The median extent of LGE increased by 2.4 g/y (range, 0-13.2 g/y) from 2.9% (interquartile range, 0.8-3.2%) of LV mass to 4.3% (interquartile range, 2.9-6.8%) ( P=0.02). In addition to LGE, LV mass and left atrial volume, indexed to body surface area, and z score for LV mass, as well, increased significantly from first to most recent CMR. CONCLUSIONS:LGE was present in 46% of children and adolescents with overt HCM, in contrast to ?60% typically reported in adult HCM. In the subset of patients with serial imaging, statistically significant increases in LGE, LV mass, and left atrial size were detected over 2.5 years, indicating disease progression over time. Further prospective studies are required to confirm these findings and to better understand the clinical implications of LGE in pediatric HCM.
Project description:Aims:Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications. Methods and results:Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97-13.48 g] to 6.30 g (IQR 1.38-17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (<MPRI 1.40) and energetics (phosphocreatine/adenosine triphosphate <1.44) on baseline CMR (P ≤ 0.01 for both). Substantial LGE progression was associated with LV thinning, increased cavity size and reduced systolic function, and conferred a five-fold increased risk of subsequent clinical events (hazard ratio 5.04, 95% confidence interval 1.85-13.79; P = 0.002). Conclusion:Myocardial fibrosis is progressive in some HCM patients. Impaired energetics and perfusion abnormalities are possible mechanistic drivers of the fibrotic process. Fibrosis progression is associated with adverse cardiac remodelling and predicts an increased risk of subsequent clinical events in HCM.
Project description:BACKGROUND:Hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) are both associated with an increased left ventricular (LV) wall thickness. Whilst LV ejection fraction is frequently normal in both, LV strain assessment could differentiate between the diseases. We sought to establish if cardiovascular magnetic resonance myocardial feature tracking (CMR-FT), an emerging method allowing accurate assessment of myocardial deformation, differentiates between both diseases. Additionally, CMR assessment of fibrosis and LV hypertrophy allowed association analyses and comparison of diagnostic capacities. METHODS:Two-hundred twenty-four consecutive subjects (53 HHD, 107 HCM, and 64 controls) underwent 1.5T CMR including native myocardial T1 mapping and late gadolinium enhancement (LGE). Global longitudinal strain (GLS) was assessed by CMR-FT (CVi42, Circle Cardiovascular Imaging Inc.). RESULTS:GLS was significantly higher in HCM patients (-14.7±3.8 vs. -16.5±3.3% [HHD], P = 0.004; or vs. -17.2±2.0% [controls], P<0.001). GLS was associated with LV mass index (HHD, R = 0.419, P = 0.002; HCM, R = 0.429, P<0.001), and LV ejection fraction (HHD, R = -0.493, P = 0.002; HCM, R = -0.329, P<0.001). In HCM patients, GLS was also associated with global native T1 (R = 0.282, P = 0.003), and LGE volume (? = 0.380, P<0.001). Discrimination between HHD and HCM by GLS (c = 0.639, 95% confidence interval [CI] 0.550-0.729) was similar to LV mass index (c = 0.643, 95% CI 0.556-0.731), global myocardial native T1 (c = 0.718, 95% CI 0.638-0.799), and LGE volume (c = 0.680, 95% CI 0.585-0.775). CONCLUSION:CMR-FT GLS differentiates between HHD and HCM. In HCM patients GLS is associated with myocardial fibrosis. The discriminatory capacity of CMR-FT GLS is similar to LV hypertrophy and fibrosis imaging markers.
Project description:<h4>Background</h4>Cardiovascular Magnetic Resonance (CMR) provides valuable information in patients with hypertrophic cardiomyopathy (HCM) based on myocardial tissue differentiation and the detection of small morphological details. CMR at 7.0T improves spatial resolution versus today's clinical protocols. This capability is as yet untapped in HCM patients. We aimed to examine the feasibility of CMR at 7.0T in HCM patients and to demonstrate its capability for the visualization of subtle morphological details.<h4>Methods</h4>We screened 131 patients with HCM. 13 patients (9 males, 56 ±31 years) and 13 healthy age- and gender-matched subjects (9 males, 55 ±31years) underwent CMR at 7.0T and 3.0T (Siemens, Erlangen, Germany). For the assessment of cardiac function and morphology, 2D CINE imaging was performed (voxel size at 7.0T: (1.4x1.4x2.5) mm3 and (1.4x1.4x4.0) mm3; at 3.0T: (1.8x1.8x6.0) mm3). Late gadolinium enhancement (LGE) was performed at 3.0T for detection of fibrosis.<h4>Results</h4>All scans were successful and evaluable. At 3.0T, quantification of the left ventricle (LV) showed similar results in short axis view vs. the biplane approach (LVEDV, LVESV, LVMASS, LVEF) (p = 0.286; p = 0.534; p = 0.155; p = 0.131). The LV-parameters obtained at 7.0T where in accordance with the 3.0T data (pLVEDV = 0.110; pLVESV = 0.091; pLVMASS = 0.131; pLVEF = 0.182). LGE was detectable in 12/13 (92%) of the HCM patients. High spatial resolution CINE imaging at 7.0T revealed hyperintense regions, identifying myocardial crypts in 7/13 (54%) of the HCM patients. All crypts were located in the LGE-positive regions. The crypts were not detectable at 3.0T using a clinical protocol.<h4>Conclusions</h4>CMR at 7.0T is feasible in patients with HCM. High spatial resolution gradient echo 2D CINE imaging at 7.0T allowed the detection of subtle morphological details in regions of extended hypertrophy and LGE.
Project description:<h4>Background</h4>Left 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.<h4>Methods</h4>In 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.<h4>Results</h4>LA 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).<h4>Conclusions</h4>Elevated 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.
Project description:Microvascular ischemia is one of the hallmarks of hypertrophic cardiomyopathy (HCM) and has been associated with poor outcome. However, myocardial fibrosis, seen on cardiovascular magnetic resonance (CMR) as late gadolinium enhancement (LGE), can be responsible for rest perfusion defects in up to 30% of patients with HCM, potentially leading to an overestimation of the ischemic burden. We investigated the effect of left ventricle (LV) scar on the total LV ischemic burden using novel high-resolution perfusion analysis techniques in conjunction with LGE quantification.30 patients with HCM and unobstructed epicardial coronary arteries underwent CMR with Fermi constrained quantitative perfusion analysis on segmental and high-resolution data. The latter were corrected for the presence of fibrosis on a pixel-by-pixel basis.High-resolution quantification proved more sensitive for the detection of microvascular ischemia in comparison to segmental analysis. Areas of LGE were associated with significant reduction of myocardial perfusion reserve (MPR) leading to an overestimation of the total ischemic burden on non-corrected perfusion maps. Using a threshold MPR of 1.5, the presence of LGE caused an overestimation of the ischemic burden of 28%. The ischemic burden was more severe in patients with fibrosis, also after correction of the perfusion maps, in keeping with more severe disease in this subgroup.LGE is an important confounder in the assessment of the ischemic burden in patients with HCM. High-resolution quantitative analysis with LGE correction enables the independent evaluation of microvascular ischemia and fibrosis and should be used when evaluating patients with HCM.
Project description:<h4>Background</h4>Left atrial (LA) enlargement and dysfunction are related to clinical course in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate genetic contribution to LA structural and functional remodeling.<h4>Methods</h4>Two hundred twelve patients were consecutively enrolled, and echocardiography and extensive genetic analysis were performed. Cardiac magnetic resonance (CMR) was performed in 135 patients. Echocardiography was also performed in controls (n?=?30).<h4>Results</h4>Patients with HCM had lower late-diastolic mitral annular velocity (a') and higher LA volume index (LAVI) than controls. Patients with pathogenic or likely pathogenic sarcomere gene mutations (PSM, n =?67, 32%) had higher LAVI and lower CMR-derived LA total emptying fraction (37.0?±?18.5 vs. 44.2?±?12.4%, p =?0.025). In patients without AF (n =?187), the PSM had lower a' (6.9?±?2.0 vs. 7.8?±?1.9?cm/s, p =?0.004) than others. The PSM had higher prevalence and amount of late gadolinium enhancement (LGE) in the left ventricle (LV). In multivariate analysis, PSM was significantly related to lower a' independent of E/e', LV mass index, and LAVI. However, the relation significantly attenuated after adjustment for the extent of LGE in the LV, suggesting common myopathy in the LV and LA. In addition, PSM was significantly related to lower LA total emptying fraction independent of age, E/e', s', LV ejection fraction, LV myocardial global longitudinal strain and %LGE mass.<h4>Conclusions</h4>PSM was related to LA dysfunction independent of LV filling pressure and LAVI, suggesting its contribution to atrial myopathy in HCM.
Project description:INTRODUCTION:The presence of late gadolinium enhancement (LGE) at the right ventricular insertion point (RVIP) on cardiac magnetic resonance (CMR) is generally believed to be nonspecific, but the clinical implication of this unique LGE pattern in patients with non-ischemic dilated cardiomyopathy (NICM) has not been elucidated. OBJECTIVES:We investigated the prognostic significance of RVIP-LGE in NICM patients. METHODS:A total of 360 consecutive NICM patients referred for CMR (102 with no LGE, 50 with RVIP-LGE, 121 with left ventricular [LV]-LGE, and 87 with both an LV and RVIP-LGE) were studied. The primary endpoint was a composite of the all-cause death, hospitalization due to worsening of heart failure, and major arrhythmic events. RESULTS:During a mean follow-up of 45.2 ± 36.5 months, 149 (41.4%) patients (22 [21.6%] no LGE vs. 16 [32.0%] RVIP-LGE vs. 62 [51.2%] LV-LGE vs. 49 [56.3%] both LV and RVIP-LGE, P < 0.0001) reached the primary endpoint. A Kaplan Meier curve demonstrated that RVIP-LGE patients had an intermediate trend of an event free survival rate for the composite endpoint (log-rank P < 0.0001). In a multivariable Cox regression model, LV-LGE (P = 0.008) and both LV and RVIP-LGE (P = 0.003) were significantly associated with a worse outcome, whereas RVIP-LGE was not (P = 0.101). In addition, RVIP-LGE patients (n = 32) had a more favorable outcome compared to LV-LGE patients (n = 32) even after matching the extent of the LGE (median 3.4% [interquartile range, 3.1-3.8], 8 [25.0%] RVIP-LGE vs. 20 [62.5%] LV-LGE, P = 0.002). CONCLUSIONS:LGE confined to the RVIP among NICM patients did not significantly increase the risk of adverse cardiac events, and also showed a better outcome than the same extent of LGE located in the LV. Identification of this unique LGE distribution may help refine the current risk stratification.
Project description:<h4>Background</h4>Clinical data on myocardial function in HCM mutation carriers (carriers) is sparse but suggests that subtle functional abnormalities can be measured with tissue Doppler imaging before the development of overt hypertrophy. We aimed to confirm the presence of functional abnormalities using cardiovascular magnetic resonance (CMR), and to investigate if sensitive functional assessment could be employed to identify carriers.<h4>Results</h4>28 carriers and 28 controls were studied. Global left atrial (LA) and left ventricular (LV) dimensions, segmental peak systolic circumferential strain (SCS) and peak diastolic circumferential strain rate (DCSR), as well as the presence of late Gadolinium enhancement (LGE) were determined with CMR. Septal and lateral myocardial velocities were measured with echocardiographic tissue Doppler imaging. LV mass and volumes were comparable between groups. Maximal septal to lateral wall thickness ratio (SL ratio) was larger in carriers than in controls (1.3+/-0.2 versus 1.1+/-0.1, p<0.001). Also, LA volumes were larger in carriers compared to controls (p<0.05). Both peak SCS (p<0.05) and peak DCSR (p<0.01) were lower in carriers compared to controls, particularly in the basal lateral wall. Focal LGE was present in 2 carriers and not in controls. The combination of a SL ratio>1.2 and a peak DCSR<105%.s-1 was present in 45% of carriers and in none of the controls, yielding a positive predictive value of 100%. Two carriers and 18 controls had a SL ratio<1.2 and peak DCSR>105%.s-1, yielding a negative predictive value of 90%. With multivariate analysis, HCM mutation carriership was an independent determinant of reduced peak SCS and peak DCSR.<h4>Conclusions</h4>HCM mutation carriership is an independent determinant of reduced peak SCS and peak DCSR when LV wall thickness is within normal limits, and is associated with increased LA volumes and SL ratio. Using SL ratio and peak DCSR has a high accuracy to identify carriers. However, since carriers also display structural abnormalities and focal LGE, we advocate to also evaluate morphology and presence of LGE when screening for carriers.
Project description:BACKGROUND:Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is more sensitive than echocardiography for the detection of intracardiac thrombus because of its unique ability to identify thrombus based on tissue characteristics related to avascularity. The long-term prognostic significance of left ventricular (LV) thrombus detected by LGE CMR is unknown. METHODS:We performed a matched cohort study of consecutive adult patients with LV thrombus detected by LGE CMR who were matched on the date of CMR, age, and LV ejection fraction to up to 3 patients without LV thrombus. We investigated the long-term incidence of a composite of embolic events: stroke, transient ischemic attack, or extracranial systemic arterial embolism. We also compared outcomes among patients with LV thrombus detected by LGE CMR stratified by whether the LV thrombus was also detected by echocardiography or not. RESULTS:Of 157 LV thrombus patients, 155 were matched to 400 non-LV thrombus patients. During a median follow-up of 3.3 years, the cumulative incidence of embolism was significantly higher in LV thrombus patients compared with the matched non-LV thrombus patients (P<0.001), with annualized rates of 3.7% and 0.8% for LV thrombus and matched non-LV thrombus patients, respectively. LV thrombus was the only independent predictor of the composite embolic end point (hazard ratio, 3.99 [95% CI, 1.54-10.35]; P=0.004). The cumulative incidence of embolism was not different in patients with LV thrombus that was also detected by echocardiography versus patients with LV thrombus not detected by echocardiography (P=0.25). CONCLUSIONS:Despite contemporary antithrombotic treatment, LV thrombus detected by LGE CMR is associated with a 4-fold higher long-term incidence of embolism compared with matched non-LV thrombus patients. LV thrombus detected by LGE CMR but not by echocardiography is associated with a similar risk of embolism as that detected by both LGE CMR and echocardiography.
Project description:Regional variability of longitudinal strain (LS) has been previously described with echocardiography in patients with cardiac amyloidosis (CA), however, the reason for this variability is not completely evident. We sought to describe regional patterns in LS using feature-tracking software applied to cardiovascular magnetic resonance (CMR) cine images in patients with CA, hypertrophic cardiomyopathy (HCM), and Anderson-Fabry's disease (AFD) and to relate these patterns to the distribution of late gadolinium enhancement (LGE).Patients with CA (n = 45) were compared to LV mass indexed matched patients with HCM (n = 19) and AFD (n = 19). Peak systolic LS measurements were obtained using Velocity Vector Imaging (VVI) software on CMR cine images. A relative regional LS ratio (RRSR) was calculated as the ratio of the average of the apical segmental LS divided by the sum of the average basal and mid-ventricular segmental LS. LGE was quantified for the basal, mid, and apical segments using a threshold of 5SD above remote myocardium. A regional LGE ratio was calculated similar to RRSR.Patients with CA had significantly had worse global LS (-15.7 ± 4.6%) than those with HCM (-18.0 ± 4.6%, p = 0.046) and AFD (-21.9 ± 5.1%, p < 0.001). The RRSR was higher in patients with CA (1.00 ± 0.31) than in AFD (0.79 ± 0.24; p = 0.018) but not HCM (0.84 ± 0.32; p = 0.114). In CA, a regional difference in LGE burden was noted, with lower LGE in the apex (31.5 ± 19.1%) compared to the mid (38.2 ± 19.0%) and basal (53.7 ± 22.7%; p < 0.001 for both) segments. The regional LGE ratio was not significantly different between patients with CA (0.33 ± 0.15) and AFD (0.47 ± 0.58; p = 0.14) but lower compared to those with HCM (0.72 ± 0.43; p < 0.0001). LGE percentage showed a significant impact on LS (p < 0.0001), with a 0.9% decrease in absolute LS for every 10% increase in LGE percentage.The presence of marked "relative apical sparing" of LS along with a significant reduction in global LS seen in patients with CA on CMR cine analysis may provide an additional tool to differentiate CA from other cause of LVH. The concomitant presence of a base to apex gradient in quantitative LGE burden suggests that the regional strain gradient may be at least partially explained by the burden of amyloid deposition and fibrosis.