Median Late Gadolinium Enhancement Research Articles

Myocardial scar in end-stage hypertrophic cardiomyopathy: correlation with systolic function and prognostic significance

Abstract Background Hypertrophic cardiomyopathy with systolic impairment, often referred to as end-stage HCM (ES-HCM), has a poor prognosis. Scar is a significant contributor but the patterns and prognostic significance are unknown. Aim To understand role of scar in ES-HCM and investigate potential predictors of outcome. Methods A retrospective 4 centre study of ES-HCM (LVEF≤55%) who had undergone CMR between 2006 and 2022 for unexplained LVH. Exclusion criteria were: scaring therapies (septal reduction), phenocopies (amyloidosis, storage) and dual pathologies (severe aortic valve disease, previous infarction). CMR followed standardized protocols. All images were core-lab analysed de-novo with scar quantified using the full width at half maximum technique for late gadolinium enhancement (LGE) quantification in grams (LGEm) and percentage of total LV mass (LGE%). Cox models used to identify risk factors for all-cause mortality. Results From 3810 HCM CMR scans, 128 were ES-HCM pts (3%), 25(20%) were excluded due to known infarction. 103 (male n=82, 81%; age 57yrs[IQR51–68]) formed the study cohort. Of the 54% genotyped, 62% carried a (likely)pathogenic sarcomere mutation: MYBPC3 (n=20), MYH7 (n=7), TNNT2 (n=4), TMP1 (n=2),ALPK3 (n=1). Heart morphology was: 38(37%) isolated basal septal hypertrophy, 30(29%) reverse septal curvature, 7(7%) mid-cavity LVH with apical aneurysm, 3(3%) apical HCM, 24%other. The median EF was 46%(IQR 39-50). In only one third (34%) the ventricle was dilated (LVEDd mean 97ml/m2 IQR 79-112). The RV was impaired in 19(18%). Median max wall thickness was 17mm(IQR15-20) and LVmass 74mg/Kg(IQR65-90). Scar was present in 94(93%) and was typically extensive: median LGE% 23%(IQR 13-33), LGEm 31g(IQR 16-45) – although 7% had no scar. The LGE pattern was diffuse in 38%, patchy in 35%, ring-like in 9%, and infarct-like in 7% (all without coronary narrowing at invasive/non-invasive coronary artery assessment). LGE and cardiac function were effectively independent with low or no correlation between scar and LVEF% or global longitudinal strain (r2=0.015,p=0.227 or r2= 0.048,p=0.028 for LGE% and LGEm against LVEF; r2=0.059,p=0.021 or r2=0.196,p<0.001 for LGE% and LGEm against GLS) with poor correlation also with indexed stroke volume. During a 5 year (IQR 3-7) follow-up (516patient-years), 30 deaths occurred: mean age at death was 62(52-74). Using multivariate Cox regression analysis EF and demographics such as age were not predictive, but LGE% (HR 1.046, 95%IC 1.007-1.086, p=0.019 and GLS (HR 1.172, 95%IC 1.004-1.368, p=0.044) were independent all-cause mortality predictors (C-index 0.708; table). Conclusion Myocardial scar is almost always present in ES-HCM and is typically extensive – but with some unexpected features: 7% of patients have no LGE, dual pathology(infarction) is not rare, and ringlike LGE (ALVClike) may occur. LGE correlates poorly with any measure of LV impairment but is a strong predictor of mortality, as is GLS.

Higher subclinical cardiac fibrosis in South African youth with HIV: results from the CTAAC-heart study

Abstract Background Few data exist on cardiac fibrosis and inflammation in youth with HIV, particularly in sub-Saharan Africa. Purpose Our objective was to assess the association between HIV status and cardiovascular magnetic resonance (CMR) measures of subclinical cardiac fibrosis, inflammation, and function. Methods We performed CMR on a cross-section of youth in South Africa: youth with perinatally acquired HIV (YPHIV), youth with non-perinatally acquired HIV (YNPHIV), and HIV-seronegative youth (YHIV-). Subclinical fibrosis [late gadolinium enhancement (LGE) mass and fraction, extracellular volume (ECV)], inflammation [native T1 and T2 mapping], and cardiac function (cine, strain, and strain rate) were assessed. CD4, viral load (VL), and fasting glucose, insulin [for Homeostatic Model Assessment-Insulin Resistance (HOMA)] and lipids were obtained. Unadjusted and adjusted quantile regression models were used to assess the association between HIV status and CMR outcomes. In sub-group analyses of youth with HIV, we additionally adjusted for HIV factors. Results Of 464 youth, 287 were YPHIV, 87 YNPHIV, and 90 YHIV-. YNPHIV were older with a higher proportion self-identifying as female than YPHIV and YHIV- (median age 20 vs 18 and 17 years; 85% vs 50% and 49%, respectively). YPHIV had lower body surface area (1.6 vs 1.7 and 1.7m2) and a higher proportion with prior TB disease (70% vs. 20% vs 8%) compared to YNPHIV and YHIV-. Tobacco use, HOMA, total cholesterol, and low-density lipoproteins were similar between groups. Among youth with HIV, YPHIV had a higher proportion with CD4<200 cells/mm3 (10% vs 4%) or VL>50 copies/mL (39% vs 13%) but lower proportion on integrase inhibitors (33% vs 84%). LGE mass (0.13 vs 0.12 vs 0.07g respectively) and fraction (0.3% vs 0.3% vs. 0.2% respectively) were higher in YPHIV and YNPHIV than YHIV-; native T1 was highest in YNPHIV compared to YPHIV and YHIV- (Table). In adjusted analyses, compared to YHIV-, median LGE mass was higher in YPHIV and YNPHIV (β:0.06, p=0.01 for YPHIV, β:0.05, p=0.03 for YNPHIV) and LGE% was higher in YPHIV (β:0.14, p=0.02); native T1 and ECV did not differ between groups in adjusted analyses. Among youth with HIV, CMR outcomes did not differ significantly for persons with perinatal vs non-perinatal HIV. Findings did not vary in analyses restricted to females. Conclusion In one of the largest studies of CMR among youth with HIV in sub-Saharan Africa, we found that despite their young age, YPHIV and YNPHIV appear to have higher subclinical cardiac fibrosis than YHIV- and healthy adults in South Africa. Youth with HIV may benefit from early screening and long-term monitoring for cardiovascular disease.TableFigure

Correlations between high sensitive troponin I and acute myocarditis extent in cardiac magnetic resonance imaging.

To assess the correlation between high sensitive troponin I (HsTnI) levels and myocardial damage on cardiac magnetic resonance (CMR) represented by late gadolinium enhancement (LGE) percentage in patients diagnosed with myocarditis. Retrospective analysis of consecutive patients who underwent CMR following a suspected diagnosis of acute myocarditis, comparing CMR findings viewed as LGE percentage and HsTnI levels. Between February 2016 and December 2021, 101 patients underwent CMR for suspected myocarditis in Rambam Medical Center. Seventy-six (75.2%) patients with a documented diagnosis of acute myocarditis in the medical records based on clinical history and lab work were included in the final analysis. The median age was 30 years [interquartile range (IQR) 22,42] and 62 patients (81.6%) were male. Thirty-four patients (44.7%) had a history of fever and 26 (34.2%) had upper respiratory tract symptoms. The median maximal HsTnI was 3935 ng/l (1165,10 380) and the median C-reactive protein (CRP) was 7.97 mg/l (2.35,19.28). The median LGE percentage was 4.65% (2.6,8.5) and ventricular ejection fraction 60% (56.00,64.75).Linear association was found between LGE (%) and maximal HsTnI (ng/l) value with r = 0.49 ( P < 0.001). After including only patients in whom the CMR was performed within 5 days of the maximal HsTnI the correlation improved to r = 0.67 ( P < 0.001). HsTnI is an indicator for myocardial damage extent resulting from inflammation in patients with acute myocarditis.

LGE prevalence and patterns in severe aortic stenosis: When “junctional” means the same

BackgroundLeft ventricular (LV) remodeling in severe aortic valve stenosis (AS) is a complex process that goes beyond hypertrophic response. Reparative/replacement fibrosis is considered irreversible and has recognized value in both risk stratification and prognosis. Currently, cardiac magnetic resonance (CMR) is the gold-standard imaging technique for fibrosis identification through late gadolinium enhancement (LGE) assessment. However, its prevalence and distribution are quite variable among series. Our goal was to assess LGE prevalence and patterns in severe AS. MethodologySingle-center prospective cohort of 140 patients with severe symptomatic high-gradient AS (mean age 72 ± 8 years; mean valvular transaortic gradient 61 ± 18 mmHg; mean LV ejection fraction by echocardiogram 58 ± 9%) undergoing surgical aortic valve replacement. Those with previous myocardial infarction and/or non-ischemic cardiomyopathy were excluded. All patients performed 1.5 T LGE-CMR prior to surgery. ResultsOverall, 103 patients (74%) had non-ischemic LGE (median LGE mass 2.8 g [IQR 0.0–7.8] g), many of them with combined mid-wall and junctional enhancement pattern (36%). LGE was most frequently observed in the mid-basal segments of the interventricular septum. Seventy-four patients (53%) had non-exclusively junctional LGE. Contrary to those with junctional enhancement, patients with non-exclusively junctional LGE had higher LV volumes/mass, worse LV ejection fraction and worse global longitudinal strain. ConclusionAmong patients with severe, symptomatic, high-gradient AS, LGE is frequent, primarily affecting the mid-basal interventricular septum. Contrary to junctional LGE, the presence of non-junctional LGE seems to correlate with adverse markers of LV remodeling.

Impact of late gadolinium enhancement extent, location, and pattern on ventricular tachycardia and major adverse cardiac events in patients with ischemic vs. non-ischemic cardiomyopathy.

Left ventricular late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) has been associated with increased risk for life-threatening ventricular tachyarrhythmias. The differences in association between LGE characteristics and prognosis in patients with ischemic (ICM) vs. non-ischemic (NICM) cardiomyopathy is incompletely understood. A total of 168 consecutive patients who underwent CMR imaging with either ICM or NICM were included in our study. LGE extent, location and pattern were examined for association to the primary endpoint of ventricular tachycardia (VT) and secondary endpoint of major adverse cardiac events (MACE). Of 68 (41%) patients with ICM and 97 (59%) patients with NICM, median LGE mass was 15% (IQR 9-28) for the ICM group and 10% (IQR 6-15) for the NICM group. On multivariate analysis for both groups, LGE characteristics were prognostic while LVEF was not. In patients with ICM, septal and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median) and inferior wall LGE independently predicted the primary endpoint. In patients with NICM, anterior, inferior and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median, number of LGE segments, LGE stratified per 5% increase) and midwall LGE were independent predictors of the primary endpoint. Although LGE was an independent predictor of prognosis in both groups, LGE extent, location, and pattern characteristics were more powerful correlates to worse outcomes in patients with NICM than ICM.

Myocarditis following COVID-19 vaccination in adolescents: Cardiac magnetic resonance imaging study.

IntroductionVaccination-associated myocarditis was reported following COVID-19 vaccine initially among persons aged 16 or older and recently among adolescents aged 12–15.ObjectivesTo describe the clinical and cardiac magnetic resonance (CMR) characteristics of adolescents aged 12–15 with myocarditis following the administration of the BNT162b2 mRNA COVID-19 vaccine.MethodsCMR of adolescents (age 12–15) with a clinical diagnosis of myocarditis within 42 days following the first COVID-19 vaccine were analyzed.ResultsA total of 182,605 adolescent were vaccinated, out of which 9 were diagnosed with clinically adjudicated myocarditis while CMR was performed in 5/9 patients (56%). Median age was 15 years (range 13–15), 4/5 (80%) males. All the patients we previously healthy. The ECG upon presentation was abnormal in 3/5 (60%) of patients. All cases were classified as clinically mild and no patient required inotropes or mechanical circulatory support treatment. The median follow-up time, for the 5-included patients, was 206 (IQR 192–229, range 179–233) days. During the follow-up, no re-admissions, deaths, or any other cardiac events have occurred.The median time between the diagnosis to the CMR was 104 days (range 27–149). The median left ventricular ejection fraction was within normal range 65% (range 62–69). Native T1 was available in four patients, the local T1 value was increased in three of them. T2 values were available in two patients and were all within normal range. The median late gadolinium enhancement (LGE) was 2% (range 0–6%) with inferolateral wall being the most common location (3/5). The patterns of the LGE were as following: (i) mid-wall in 3 patients; (ii) epicardial in 1-patient. LGE in the pericardium was present in 2/5 patients with pericardial effusion present in 4/5 patients with a median diameter of 4 mm (range 3–5 mm) at end-systole.ConclusionsCMR findings and clinical course of adolescents with COVID-19 vaccination associated myocarditis, are similar to those of older patients, being relatively mild and potentially implying favorable outcomes.

Late gadolinium enhancement patterns in severe symptomatic high-gradient aortic stenosis

Abstract Background Left ventricular (LV) remodeling in patients with severe aortic valve stenosis (AS) is a complex process that goes beyond hypertrophic response and may involve reparative/replacement fibrosis. Currently, cardiac magnetic resonance (CMR) is the gold-standard imaging technique for detecting focal myocardial fibrosis through late gadolinium enhancement (LGE). However, myocardial fibrosis prevalence and distribution is quite variable among series. Our goal was to assess LGE prevalence and distribution pattern in severe symptomatic high-gradient AS. Methodology Single-center prospective cohort of 132 patients with severe symptomatic high-gradient AS (mean age 73±11 years; 48% male, mean valvular transaortic gradient 60±20 mmHg; mean aortic valve area 0.7±0.2 cm2/m2; mean LV ejection fraction by 2D echocardiogram 58±9%), all with normal flow (except one) undergoing surgical aortic valve replacement. Those with previous history of acute myocardial infarction, ischemic cardiomyopathy or other cardiomyopathy were excluded. All patients performed 1.5T CMR assessment with LV myocardium tissue characterization prior to surgery. Segmental LGE presence was assessed by two independent operators and classified according to the AHA 16 segment model, using 5-standard deviations from remote myocardium as the signal intensity cut-off for LGE identification and quantification. Results Overall, 96 patients (74%) had non-ischemic LGE (median LGE mass 3.2 g [IQR 0.2–8.3] g; median percentage of LGE myocardial mass 2.5% [IQR 0.1–6.1]%); 22 patients [17%] with exclusively junctional LGE); in one patient an incidental ischemic scar (subendocardial distribution) was identified. No cases of subepicardial distribution were found. Intramyocardial LGE was most frequently observed in basal and mid-anterior and inferior interventricular septum – see Figure 1. In these segments, LGE was most often junctional at right-ventricular insertion points (54%), followed by mid-wall LGE (32%) or both sites involvement (14%). Conclusion LGE is frequent in symptomatic high-gradient AS patients with preserved left ventricular ejection fraction, most often presenting as junctional enhancement in basal/mid-anterior and inferior interventricular septum. Future studies may address whether distinct LGE patterns may impact patient prognosis. Funding Acknowledgement Type of funding sources: None.

Histology-verified myocardial fibrosis and quantification in severe AS patients: correlation with non-invasive LV myocardial tissue assessment

Abstract Background Myocardial fibrosis (MF) is a common finding and a potential adverse prognostic marker in several cardiac diseases, including in severe aortic stenosis (AS). While histological analysis obtained through endomyocardial biopsy remains the gold-standard for MF assessment, non-invasive cardiac imaging may offer surrogate biomarkers for fibrosis. We tried to assess the correlation between MF quantification at histopathology and cardiac magnetic resonance (CMR)-derived tissue characterization data in patients with severe AS. Methodology Single-center prospective cohort enrolling 71 patients with severe symptomatic high-gradient AS undergoing surgical aortic valve replacement (SAVR) (mean age 71±9 years; 49% male, mean valvular transaortic gradient 60±20 mmHg; mean left ventricle [LV] ejection fraction 58±9%). Those with past history of myocardial infarction or cardiomyopathy were excluded. All patients underwent pre-operative CMR study with LV tissue characterization and quantification. Normal T1 mapping value was defined as &amp;gt;1021ms as per center protocol. Myocardial tissue was obtained during SAVR either through myocardial biopsy at basal LV septum or harvested from surgical myectomy specimens. Masson's trichrome stain was used for collagen/fibrosis assessment. Automatic quantification was obtained at QuPathTM digital pathology software after applying a dedicated artificial intelligence algorithm on ultra-high-resolution digital slide scanning images. Results Histology-confirmed MF was observed in all patients (median percentage of fibrotic myocardial tissue 15% [IQR 9–22%]). Median global T1 mapping and extracellular volume (ECV) percentage was 1048ms (IQR 1027–1078) and 24% (IQR 20–30%), respectively. Late gadolinium enhancement (LGE) with a non-ischemic pattern was present in 42 patients (59%) with a median LGE mass of 5.8g [IQR 1.0–10.2]; median percentage of 3.7% [IQR 0.6–10.4]. While neither T1 mapping (global or basal LV septum), ECV nor LGE had any significant correlation with histology-confirmed MF (Figure 1) the vast majority had significantly elevated global and basal LV septum T1 mapping – 81% and 92%, respectively. Conclusion In this single-center prospective study, microscopic MF was present in all patients with severe symptomatic high-gradient AS, was accompanied by elevated T1 mapping values but no correlation was found between myocardial fibrosis at histopathology analysis and CMR-derived LV tissue characterization parameters. This may not only stem from sampling (single point biopsy vs. whole myocardial tissue assessment) but also from distinct evaluation of different types of fibrosis by different methods. Funding Acknowledgement Type of funding sources: None.

A Case Series of Myocarditis Following Third (Booster) Dose of COVID-19 Vaccination: Magnetic Resonance Imaging Study.

BackgroundMyocarditis has been reported following the first two doses of Pfizer-BNT162b2 messenger RNA (mRNA) COVID-19 vaccination. Administration of a third dose (booster) of the vaccine was initiated recently in Israel.ObjectiveThe aim of this study was to describe the characteristics of patients referred for cardiac magnetic resonance (CMR) imaging with myocarditis following the booster.MethodsPatients referred for CMR imaging with a clinical diagnosis of myocarditis within 21 days following the booster, between July 13 and November 11, 2021, were analyzed.ResultsOverall, 4 patients were included, 3/4 (75%) were men, and the mean age was 27 ± 10 years. The time from booster administration to the onset of symptoms was 5.75 ± 4.8 days (range 2–14). Obstructive coronary artery disease was excluded in 3 of the patients (75%). CMR was performed 34 ± 15 days (range 8-47 days) following the 3rd vaccination. The mean left ventricular ejection fraction was 61 ± 7% (range 53–71%), and regional wall motion abnormalities were present in one of the patients. Global T1 was increased in one of the patients, while focal T1 values were increased in 3 of the patients. Global T2 was increased in one of the patients, while focal T2 values were increased in all the patients. Global ECV was increased in 3 of the patients, while focal ECV was increased in all the patients. Median late gadolinium enhancement (LGE) was 4 ± 3% (range 1–9%), with the inferolateral segment as the most common location (3 of the 4 patients). All the patients met the Updated Lake Louise Criteria.ConclusionsPatient characteristics and CMR imaging findings of myocarditis following the administration of the booster vaccine are relatively mild and consistent with those observed with the first two doses. Although larger-scale prospective studies are necessary, these initial findings are somewhat reassuring.

Predictors and prognostic value of left ventricle branch block in hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Conduction abnormalities as left bundle branch block (LBBB) are common in myocardial disease and contribute to LV dyssynchrony and adverse LV remodeling. The relevance of LBBB in the context of hypertrophic cardiomyopathy (HCM) is unclear. The aim of this study is to find factors that are associated to LBBB in HCM and its impact in prognosis. Methods Retrospective single-center study of 36 consecutive patients (pts) with HCM defined by wall thickness≥15 mm in≥1 myocardial segments in CMR; pts with history of uncontrolled hypertension (HTN) and significant valvular disease were excluded. Demographic, clinical, ECG and CMR data (including ventricular volumes, late gadolinium enhancement (LGE) and ventricular strain using feature tracking analysis (Circle CVi 42) were analyzed. For statistical analysis X2 test, Mann-Whitney and logistic regression model were used. Results Patient’s median age was 63 years (IQR: 49,5-74,8), 64% men. 69% had controlled hypertension, 46% dyslipidemia and 23% diabetes; family history of sudden death and HCM occurred in 16% and 46% respectively. 42% had genetic study and mutations were identified in 25% (TNNT2: 8%; MYBPC3: 6%). During a mean follow-up (FUP) of 17 ± 11 months, 24% had HF, 3% thromboembolic events, 26% new onset atrial fibrillation, 20% ventricular tachycardia (VT), 29% received an ICD and 3% died. On ECG evaluation, 33% had intraventricular disturbance conduction with 12% having LBBB, 49% had LVH criteria. On CMR, 81% had septal hypertrophy, 11% apical, 3% anterior-wall LVH and 6% lateral-wall hypertrophy. LVOTO was present in 33%. 69% of the patients had LGE (midwall: 61%, subendocardial: 11%, subepicardial: 3%; at segments with LVH: 47%, RV/LV insertion points: 25%, other:19.4%); the median LGE was 13.6g (IQR 6.7-22.4) corresponding to 7.4% of the LV mass (IQR 3.7-10.9). The median of the maximal wall thickness was 19mm (IQR 16.9-20.9), median LVEF was 70% (IQR 35-87); median LV indexed mass of 105 g/m2 (IQR 54.9-160.7). The median longitudinal strain in 4 and 2 chambers was -9.1 (IQR 15.6-4.6) and -9.1mm (IQR -16-2.6), respectively and the median radial strain in 4 and 2 chambers was 15.6 (IQR 6.5-28.2) and 13.7 (3.5-30.1), respectively. Patients with LBBB had more VT and ICD implantation in follow-up (p = 0.038). The presence of LGE in RV/LV insertion points (p = 0.019) and in the area of higher LVH (p = 0.033) were the only variables associated with LBBB. The area of LGE involving the RV/LV insertion points was an independent predictor of LBBB (p = 0.02, OR 36.0, IC:1.710-757.79). Conclusion In our sample, fibrosis in the RV/LV insertion points in CMR was an independent predictor of LBBB, which was associated with ventricular arrhythmias in follow-up. Further prospective studies with larger number of patients are needed to confirm our findings.

Nonsustained Ventricular Tachycardia Is Independently Associated With Sustained Ventricular Arrhythmias in Nonischemic Dilated Cardiomyopathy

Spontaneous nonsustained ventricular tachycardia (NSVT) on Holter, VT inducibility during electrophysiology study, and late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) have been associated with sustained ventricular arrhythmias (SVAs) in nonischemic dilated cardiomyopathy (DCM). This study aimed to analyze whether these parameters carry independent prognostic value for spontaneous SVA in DCM. Between 2011 and 2018, patients with the DCM clinical spectrum and documented SVA, suspected SVA, or considered to be at intermediate or high risk for SVA were enrolled in the prospective Leiden Nonischemic Cardiomyopathy Study. Patients underwent a comprehensive evaluation including 24-hour Holter, LGE-CMR, and electrophysiology study. Holters were assessed for the presence of NSVT (≥3 beats; rate, ≥120 bpm; lasting <30 s) and NSVT characteristics (coupling interval, duration, cycle length, morphology, regularity). Patients were followed at 6 to 12 monthly intervals. Of all 115 patients (age, 59±12 years; 77% men; left ventricular ejection fraction, 33±13%; history of SVA, 36%; LGE in 63%; median LGE mass, 13 g; interquartile range, 8-23 g), 62 (54%) had NSVT on Holter, and sustained monomorphic VT was inducible in 34 of 114 patients (30%). NSVT was not associated with LGE on CMR or VT inducibility during electrophysiology study nor were its features (all P>0.05). During 4.0±1.8 years of follow-up, SVA occurred in 39 patients (34%). NSVT (HR, 4.47 [95% CI, 1.87-10.72]; P=0.001) and VT inducibility (HR, 3.08 [95% CI, 1.08-8.81]; P=0.036) were independently associated with SVA during follow-up. A bivariable model including only noninvasively acquired parameters also allowed identification of a high-risk subgroup (ie, those with both NSVT and LGE on CMR). The findings remained similar when only patients without prior SVA were included. In patients with DCM, NSVT on Holter and VT inducibility during electrophysiology study predict SVA during follow-up independent of LGE on CMR. NSVTs may serve as an initiator, and sustained VT inducibility indicates the presence of the substrate for SVA in DCM. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01940081.

Long-term risk of sudden cardiac death in hypertrophic cardiomyopathy - a cardiac magnetic resonance outcome study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Robert Bosch Stiftung; Deutsche Forschungsgemeinschaft Background Sudden cardiac death (SCD) is an appalling complication of hypertrophic cardiomyopathy (HCM). There is an ongoing discussion about the optimal SCD risk stratification strategy in HCM since established SCD risk models have suboptimal discriminative power. Objective To evaluate the prognostic value of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) for SCD risk stratification compared to the ESC SCD risk score and traditional SCD risk factors in an &amp;gt;10-year follow-up study. Methods 220 consecutive patients with HCM and LGE-CMR were enrolled. Follow-up data was available in 203 patients (median age 58 years, 61% male) after a median follow-up period of 10.4 years. Results LGE was present in 70% of patients with a median LGE amount of 1.6%, the median ESC 5-year SCD risk score was 1.84. In the overall cohort, SCD rates were 2.3% at 5 years, 4.8% at 10 years, and 15.7% at 15 years, independent from established risk models. A LGE amount of &amp;gt;5% (LV mass) portends the highest risk for SCD with SCD prevalences of 5.5% at 5 years, 13.0% at 10 years and 33.3% at 15 years. Conversely, patients with no or ≤5% LGE amount (of LV mass) have favorable prognosis. Conclusions LGE-CMR in HCM patients allows effective 10-year SCD risk stratification beyond established risk factors. LGE amount might be added to established risk models to improve its discriminatory power. Specifically, patients with &amp;gt;5% amount of LGE should be carefully monitored and might be adequate candidates for primary prevention ICD during the clinical long-term course. Abstract Figure.

Long-term risk of sudden cardiac death in hypertrophic cardiomyopathy: a cardiac magnetic resonance outcome study.

AimsSudden cardiac death (SCD) is an appalling complication of hypertrophic cardiomyopathy (HCM). There is an ongoing discussion about the optimal SCD risk stratification strategy since established SCD risk models have suboptimal discriminative power. The aim of this study was to evaluate the prognostic value of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) for SCD risk stratification compared to the European Society of Cardiology (ESC) SCD risk score and traditional risk factors in an >10-year follow-up.Methods and resultsTwo hundred and twenty consecutive patients with HCM and LGE-CMR were enrolled. Follow-up data were available in 203 patients (median age 58 years, 61% male) after a median follow-up period of 10.4 years. LGE was present in 70% of patients with a median LGE amount of 1.6%, the median ESC 5-year SCD risk score was 1.84. In the overall cohort, SCD rates were 2.3% at 5 years, 4.8% at 10 years, and 15.7% at 15 years, independent from established risk models. An LGE amount of >5% left ventricular (LV) mass portends the highest risk for SCD with SCD prevalences of 5.5% at 5 years, 13.0% at 10 years, and 33.3% at 15 years. Conversely, patients with no or ≤5% LGE of LV mass have favourable prognosis.ConclusionsLGE-CMR in HCM patients allows effective 10-year SCD risk stratification beyond established risk factors. LGE amount might be added to established risk models to improve its discriminatory power. Specifically, patients with >5% LGE should be carefully monitored and might be adequate candidates for primary prevention implantable cardioverter-defibrillator during the clinical long-term course.

Long-term outcome of myocardial scarring and deformation with cardiovascular magnetic resonance in out of hospital cardiac arrest survivors

Cardiovascular magnetic resonance (CMR) is increasingly recognized as a diagnostic and prognostic tool in out of hospital cardiac arrest (OHCA) survivors. After assessing CMR findings early after ventricular fibrillation (VF) OHCA, we sought to explore the long-term outcome of myocardial scarring and deformation. We included 121 consecutive VF OHCA survivors (82% male, median 62 years) undergoing CMR within 2 weeks from cardiac arrest. Late gadolinium-enhancement (LGE) was quantified using the full width at half maximum method and tissue tracking analysis software was used to assess myocardial deformation. LGE was found in 71% of patients (median LGE mass 6.2% of the left ventricle, LV), mainly with an ischaemic pattern. Myocardial deformation was overall impaired and showed a significant correlation with LGE presence and extent (P < 0.001). A composite end-point of all-cause mortality and appropriate ICD discharge/anti-tachycardia pacing was met in 24% of patients. Patients meeting the end-point had significantly greater LGE extent (8.6% of LV myocardium vs. 4.1%, P = 0.02), while there was no difference with regards to myocardial deformation. Survival rate was significantly lower in patients with LGE (P = 0.05) and LGE mass >4.4% of the LV identified a group of patients at higher risk of adverse events (P = 0.005). We found a high prevalence of LGE, early after OHCA, and an overall impaired myocardial deformation. On long-term follow-up both LGE presence and extent showed a significant association with recurrent adverse events, while LV ejection fraction and myocardial deformation did not identify patients with an unfavourable outcome.

The amount of late gadolinium enhancement outperforms current guideline-recommended criteria in the identification of patients with hypertrophic cardiomyopathy at risk of sudden cardiac death

BackgroundIdentifying the patients with hypertrophic cardiomyopathy (HCM) in whom the risk of sudden cardiac death (SCD) justifies the implantation of a cardioverter-defibrillator (ICD) in primary prevention remains challenging. Different risk stratification and criteria are used by the European and American guidelines in this setting. We sought to evaluate the role of cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) in improving these risk stratification strategies.MethodsWe conducted a multicentric retrospective analysis of HCM patients who underwent CMR for diagnostic confirmation and/or risk stratification. Eligibility for ICD was assessed according to the HCM Risk-SCD score and the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) algorithm. The amount of LGE was quantified (LGE%) and categorized as 0%, 0.1–10%, 10.1–19.9% and ≥ 20%. The primary endpoint was a composite of SCD, aborted SCD, sustained ventricular tachycardia (VT), or appropriate ICD discharge.ResultsA total of 493 patients were available for analysis (58% male, median age 46 years). LGE was present in 79% of patients, with a median LGE% of 2.9% (IQR 0.4–8.4%). The concordance between risk assessment by the HCM Risk-SCD, ACCF/AHA and LGE was relatively weak. During a median follow-up of 3.4 years (IQR 1.5–6.8 years), 23 patients experienced an event (12 SCDs, 6 appropriate ICD discharges and 5 sustained VTs). The amount of LGE was the only independent predictor of outcome (adjusted HR: 1.08; 95% CI: 1.04–1.12; p < 0.001) after adjustment for the HCM Risk-SCD and ACCF/AHA criteria. The amount of LGE showed greater discriminative power (C-statistic 0.84; 95% CI: 0.76–0.91) than the ACCF/AHA (C-statistic 0.61; 95% CI: 0.49–0.72; p for comparison < 0.001) and the HCM Risk-SCD (C-statistic 0.68; 95% CI: 0.59–0.78; p for comparison = 0.006). LGE was able to increase the discriminative power of the ACCF/AHA and HCM Risk-SCD criteria, with net reclassification improvements of 0.36 (p = 0.021) and 0.43 (p = 0.011), respectively.ConclusionsThe amount of LGE seems to outperform the HCM Risk-SCD score and the ACCF/AHA algorithm in the identification of HCM patients at increased risk of SCD and reclassifies a relevant proportion of patients.

High Signal Intensity on T2-Weighted Cardiovascular Magnetic Resonance Imaging Predicts Life-Threatening Arrhythmic Events in Hypertrophic Cardiomyopathy Patients.

The prognostic value of high signal intensity on T2-weighted cardiovascular magnetic resonance imaging (T2 high signal) in hypertrophic cardiomyopathy (HCM) patients in a single-center cohort was investigated.Methods and Results:A total of 237 HCM patients (median age, 62 years; 143 male) underwent T2-weighted, cine and late gadolinium enhancement (LGE) imaging, and were followed (median duration, 3.4 years) for life-threatening arrhythmic events. The clinical and magnetic resonance imaging characteristics were extracted, and predictors of life-threatening arrhythmic events were assessed on multivariate analysis. LGE was present in 180 patients (75.9%). Median LGE score was 3 in a left ventricle 17-segment model. T2 high signal was present in 49 patients (20.7%). The annual events rate was significantly higher in patients with extensive LGE (score ≥4) than in those without (3.0%/year vs. 0.5%/year, P=0.011). On multivariate analysis, extensive LGE (hazard ratio, 5.650; 95% CI: 1.263-25.000, P=0.024) as an independent predictor for life-threatening arrhythmic events. In patients with extensive LGE, the annual events rate was significantly higher in patients with T2 high signal than in those without (5.8%/year vs. 0.9%/year, P=0.008). Extensive LGE was an independent predictor of life-threatening arrhythmic events in HCM patients. Furthermore, T2 high signal is useful for the risk stratification of serious arrhythmic events in patients with extensive LGE.

Extent of Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in Japanese Hypertrophic Cardiomyopathy Patients.

In addition to the presence of late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR), the extent of LGE is considered clinically important in hypertrophic cardiomyopathy (HCM). We evaluated the extent of LGE on CMR in a large series of Japanese HCM patients. CMR was performed in 317 HCM patients (147 male). The extent of LGE was scored as the sum of LGE-positive segments in a left ventricle (LV) 17-segment model. LGE was present in 246 patients (77.6%). LGE was detected in 3.5±3.1 segments on average. When the patients were divided according to maximum wall thickness (mild, <20 mm; moderate, 20-29 mm; severe, ≥30 mm), median LGE score increased as wall thickness increased (mild, 2 vs. moderate, 4 vs. severe, 5; P=0.000). When the patients were divided according to ejection fraction (EF) (reduced, <50%; low-normal, 50-65%; normal, >65%), median LGE score increased as EF decreased (reduced, 7 vs. low-normal, 4 vs. normal, 2; P=0.000). On multivariate analysis, reduced EF (OR, 0.947, P=0.015), pressure gradient <30 mmHg (OR, 0.359, P=0.000) and increased maximum wall thickness (OR, 1.236, P=0.000) were independent factors associated with extensive LGE. Progression of LGE was related to increased wall thickness, decreased contractility, and reduced intraventricular pressure gradient.

Myocardial biomarkers and delayed enhanced cardiac magnetic resonance relationship in clinically suspected myocarditis and insight on clinical outcome.

The relationship of cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) with myocardial biomarkers and markers of inflammation in acute viral myocarditis is not clearly defined. We assessed the relationship of LGE with myocardial and inflammatory biomarkers measured during the acute phase of myocarditis and their predictive value on clinical outcome. Patients with first clinical episode of acute viral myocarditis and complete CMR study, including cine and LGE images, were included. The peak values of troponin I, creatine kinase, C-reactive protein value at admission and LGE extent were reported for each case. A 29-month clinical follow-up was performed, and cardiac symptoms and adverse cardiac events (all-cause death, heart transplant, hospitalization for heart failure) were reported. Forty-one patients (39 ± 15 years and 78% men) were included. Median LGE extent was 13% [interquartile range (IQR) (9%, 19%)] of left-ventricular mass and mean left-ventricular ejection fraction was 56 ± 11%. There was a significant correlation between peak troponin I and LGE extent (r = 0.51, P < 0.001), and between peak creatine kinase and LGE extent (r = 0.66, P < 0.001). There was no correlation between C-reactive protein at admission and LGE extent (r = 0.27, P = 0.09). At follow-up, eight (20%) patients had an adverse clinical event. LGE extent was significantly associated with a worse New York Heart Association status at follow-up [odds ratio (OR) 1.21, 95% confidence interval (CI) 1.07, 1.37, P = 0.002]. After adjustment for left-ventricular ejection fraction, age and clinical presentation category, LGE extent remained an independent predictor of cardiovascular events (hazard ratio 1.42; 95% CI 1.05, 1.95, P = 0.027). LGE extent on CMR studies is significantly correlated to biomarkers of myocardial injury in patients with acute viral myocarditis, and is a significant independent predictor of adverse cardiovascular outcome.

Abstract 12145: Cardiac Magnetic Resonance Late Gadolinium Enhancement is Associated With Ventricular Elastance That May Predict Latent Ventricular Dysfunction After Fontan Procedure

Backgrounds: Systemic right ventricular circulation after Fontan procedures is known to have late hemodynamic complications. Although a number of studies have investigated the factors that may impact on survival, postoperative outcomes after palliations remain to be elucidated. Objective: The purpose of this study is to investigate the prognostic value of myocardial fibrosis identified by cardiac magnetic resonance imaging (cMRI) in patients with single ventricular physiology. Methods: Consecutive 23 patients undergoing Fontan procedures were prospectively scheduled to have cMRI study with late gadolinium enhancement (LGE) imaging and ventricle circumferential strain measurement before and 4 months after Fontan operation. Results: Of 23 patients (mean age 3.3±0.9 years), 7 were positive for LGE (LGE+) and median percent LGE was 3.0% (interquartile range 3.0% to 7.5%). Pre-Fontan examinations revealed that patients with LGE+ showed an increase in end-diastolic volume index (139.7±26.8 ml/BSA vs. 113.3±20.9 ml/BSA; P=0.02) and end-systolic volume index (ESVI: 99.9±32.2 ml/BSA vs. 70.8±20.0 ml/BSA; P=0.01) compared with those without LGE (LGE-). In contrast to LGE- group, LGE+ patients showed lower global circumferential strain (4.1±2.3% vs. 7.9±2.7%, P=0.006), decreased ejection fraction (EF: 29±9.1% vs. 38±8.7%; P=0.04), and reduced end-systolic elastance (1.1±0.3 mm Hg/ml/m2 vs. 1.7±0.5 mm Hg/ml/m2). In addition, LGE+ group had higher levels of BNP (91.0±72.4 pg/ml vs. 30.9±44.0 pg/ml, P=0.02) and New York University Pediatric Heart Failure Index (10.9±3.3 vs. 7.8±1.1, P=0.02) than LGE- group. This was validated by positive correlations between the area of LGE versus ESVI (r=0.85, P=0.01) and BNP levels (r=0.82, P=0.02), respectively. At 4 months after Fontan procedure, LGE- group showed higher EF (37.5±8.6% vs. 24.0±8.9%, P=0.02) compared with those in LGE+ patients, and increased global circumferential strain (6.5±2.0% to 7.4±2.7%, P=0.04). Conclusion: LGE identified by cMRI before operation may be associated with lower ventricular elastance that resulted in poorer functional recovery after staged palliation. This novel strategy may provide a prognostic value of latent myocardial dysfunction after Fontan procedure.

Abstract 78: Late Gadolinium Enhancement on Cardiac MRI Identifies Ventricular Dysfunction and Regional Myocardial Dyssynchrony in Patients with Univentricular Heart Diseases

Backgrounds: The impact of myocardial fibrosis on cardiac performance and clinical outcomes in patients with a functional single ventricle before stage-3 operation is unknown. Objective: The purpose of this study is to investigate the prognostic value of myocardial fibrosis identified by cardiac magnetic resonance imaging (cMRI) in patients with univentricular heart diseases. Methods: Consecutive 23 patients undergoing staged-3 surgical palliation with single ventricle physiology were prospectively scheduled to have cMRI study with late gadolinium enhancement (LGE) imaging and ventricle circumferential strain were examined. Results: Of 23 patients (mean age 3.3±0.9 years), 6 (26%) had positive late gadolinium enhancement (LGE+) in the ventricular myocardium, median percent LGE was 3.0% (interquartile range 3.0% to 14.0%). Pre-Fontan examinations revealed that patients with LGE+ had increased end-diastolic volume index (142.8 ml/BSA vs. 113.8 ml/BSA; P=0.02), increased end-systolic volume index (101.0 ml/BSA vs. 72.2 ml/BSA); P=0.01) compared with those without LGE (LGE-). Patients with LGE have shown to have lower ventricular circumferential strain compared with the area without LGE (basal: −1.9±1.9% vs. −4.0±3.0%, P=0.046; mid: −3.9±2.1% vs −8.0±3.9%, P=0.007; apical: −3.9±2.4% vs. −8.2±2.8%, P=0.004). In contrast to LGE- group, patients in LGE+ group had decreased right ventricular ejection fraction (27.7±8.8% vs. 38.2±8.4%; P=0.02) as well as higher levels of BNP (99.2±75.7 pg/ml vs. 32.6±44.3 pg/ml, P=0.02). In addition, patients with LGE+ had higher score of Ross classification (2.5±0.55 vs. 2.0±0, P=0.02) and New York University Pediatric Heart Failure Index (11.0±3.5 vs. 7.8±1.1, P=0.01) than in LGE- group. Age at stage-2 palliation was significantly older in patients with LGE+ group than LGE- subjects (16.8±16 months vs. 8.8±3.4 months, P=0.03). Conclusion: In this pre-stage-3 cMRI study, the age to stage-2 palliation may attribute to substantial myocardial fibrosis. The area of LGE was associated with impaired regional circumferential strain as well as disturbed ventricular performance. This novel strategy may provide a possible prognostic value of latent myocardial dysfunction after staged palliation.