Left Ventricular Late Gadolinium Enhancement Research Articles

Left ventricular fibrosis by extracellular volume fraction and the risk of atrial fibrillation recurrence after catheter ablation.

Left ventricular (LV) extracellular volume fraction (ECV) provides prognostic information in patients with variety of cardiomyopathies. However, data on the clinical significance of LV ECV in patients with atrial fibrillation (AF), especially in patients without replacement fibrosis are sparse. This study sought to investigate whether the presence of LV fibrosis identified by cardiac magnetic resonance (CMR) ECV quantification would independently predict the recurrence of AF after first catheter ablation (CA) in patients with AF. A total of 130 consecutive patients who were referred for CA of AF underwent CMR examination prior to ablation. LV function, T1 mapping derived LV ECV, LV late gadolinium enhancement (LGE) were assessed. Patients were followed for arrhythmia recurrence after the CA procedure. Of 130 AF patients, 65 patients had paroxysmal AF, and 65 patients had persistent AF. There were 50 AF recurrences over a median follow-up period of 13 months. LV ECV were significantly higher in patients with recurrent AF compared to those with no recurrence (30.4%±3.3% vs. 27.4%±2.9%, P<0.001). In multivariable model, gender (HR: 0.348, 95% CI: 0.174-0.697, P=0.003), body mass index (BMI) (HR: 1.159, 95% CI: 1.050-1.279, P=0.003), AF duration (HR: 1.006, 95% CI: 1.001-1.011, P=0.017), and LV ECV (HR: 1.158, 95% CI: 1.071-1.251, P=0.000) were significantly associated with AF recurrence. In subgroup of patients without LGE, gender, BMI, AF duration and LV ECV were still the independent predictors of AF recurrence. LV ECV expansion is associated with AF recurrence after CA and is a strong independent predictor of AF recurrence.

Left Ventricular Hypertrophy and Late Gadolinium Enhancement at Cardiac MRI Are Associated with Adverse Cardiac Events in Fabry Disease.

Background Cardiac involvement is the leading cause of mortality in patients with Fabry disease. Identification of imaging findings that predict adverse cardiac events is needed to enable identification of high-risk patients. Purpose To establish the prognostic value of cardiac MRI findings in men and women with Fabry disease. Materials and Methods Consecutive women and men with gene-positive Fabry disease who had undergone cardiac MRI at a single large tertiary referral hospital between March 2008 and January 2019 were included in this retrospective cohort study. Evaluators of cardiac MRI studies were blinded to all clinical information. Adverse cardiac events were assessed as a composite end point, defined as ventricular tachycardia, bradycardia requiring device implantation, severe heart failure, and cardiac death. Statistical analysis included Cox proportional hazard models adjusted for age and Mainz Severity Score Index (a measure of the severity of Fabry disease). Results Ninety patients (mean age, 44 years ± 15 [standard deviation]; 59 women) were evaluated. After a median follow-up period of 3.6 years, the composite end point was reached in 21 patients (incidence rate, 7.6% per year). Left ventricular hypertrophy (LVH) and late gadolinium enhancement (LGE) were independent predictors of the composite end point in adjusted analysis (LVH hazard ratio [HR], 3.0; 95% confidence interval [CI]: 1.1, 8.1; P = .03; and LGE HR, 7.2; 95% CI: 1.5, 34; P = .01). Patients with extensive LGE (≥15% of left ventricular mass) were at highest risk (HR, 12; 95% CI: 2.0, 67; P = .006). Sex did not modify the relationship between the composite end point and any of the cardiac MRI parameters, including LVH (P = .15 for interaction term) and LGE (P = .38 for interaction term). Conclusion Cardiac MRI findings of left ventricular hypertrophy and late gadolinium enhancement can be used to identify patients with Fabry disease who are at high risk of adverse cardiac events. © RSNA, 2019 See also the editorial by Zimmerman in this issue.

1174Characterization of disease hot-phases using 18f-fluorodeoxyglucose positron emission tomography in arrhythmogenic cardiomyopathy caused by desmosomal gene mutations

Abstract Introduction Mutations in the genes encoding for desmosomal proteins are associated with Arrhythmogenic Cardiomyopathy (AC), a condition in which “hot-phases” reminiscent of myocarditis can develop and which represent active disease progression. Detection of hot-phase disease can offer novel treatment opportunities. Purpose We used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to determine the prevalence of myocardial inflammation during clinical hot phases in AC. Methods Nineteen (12 male; age 38±14 years) symptomatic desmosomal gene mutation carriers (PKP-2, n=6; DSG-2, n=3; DSC-2, n=1; DSP, n=9) underwent FDG-PET and cardiac magnetic resonance (CMR). AC was diagnosed according to the 2010 Task Force diagnostic criteria. The indication for FDG-PET was presentation with clinically suspected myocarditis in 10 (53%), increase in arrhythmic burden in 4 (21%), deteriorating left ventricular (LV) systolic function in 3 (16%) and as part of a diagnostic workup in 2. We compared regional distribution of FDG uptake and late gadolinium enhancement (LGE) on CMR using a standard 16-segment model. Concordance between the two tests was defined as &gt;50% of segment overlap and partial concordance as 1- 50%. Cohen's κ was used to evaluate the inter-method agreement between FDG and LGE. Results Nine (47%) patients (5 male) had LV heterogeneous FDG uptake. RV uptake was never observed. Eight of these cases had a definite and 1 had a borderline diagnosis of AC. FDG uptake associated with the presence of DSP gene mutations (7/9, 78% vs 2/10, 20%, p=0.02) and older age (44±12 vs 33±15 years, p=0.05). Concurrent CMR study was available in 15 patients, including all nine with a positive FDG-PET. RV LGE was present in 6 (40%) and LV LGE in 14 cases (93%). All nine (100%) patients with FDG uptake had LV LGE. The commonest segments with FDG-uptake were the basal-anterior, mid-inferolateral and mid-anterolateral (5 cases, 56%), whereas LGE was most commonly present in the mid-anteroseptal (8 cases, 89%) followed by the basal- and mid-inferior segments (6 cases, 67%). Concordance of FDG uptake and LGE was present in 2 cases (22%). There was no concordance in 1 case (11%). Partial concordance was present in 6 (67%). There was poor inter-method topographical agreement between FDG-PET and CMR, κ = 0.04, p=0.64. Conclusion Up to 50% of desmosomal gene positive AC patients, and especially those with DSP mutations, and clinical “hot phases” have evidence for myocarditis on FDG-PET. The topographical variation between PET and CMR highlight the underlying pathophysiological stage of disease (inflammation versus scar) and suggest that the imaging modalities provide complementary information on tissue characterisation in AC. Acknowledgement/Funding Alexandros Protonotarios is funded by a BHF Clinical Research Training Fellowship no. FS/18/82/34024

P5657Fibrosis detected by late-gadolinium enhancement cardiac MRI is associated with atrial fibrillation and poorer ablation outcome: A meta-analysis

Abstract Background Fibrosis is a hallmark of atrial fibrillation (AF) substrate. Recent data suggests that fibrosis detected by late-gadolinium enhancement (LGE) cardiac MRI (CMR) can predict AF. However, this relationship is not well described. Objective To delineate the association of cardiac fibrosis detected by LGE CMR with AF prevalence, AF recurrence after catheter ablation. Methods PubMed, Embase, Web of Science and Ovid MEDLINE were searched through November 2018, using the keywords: LGE AND Fibrosis AND CMR AND AF. Inclusion criteria: 1. LGE CMR of left atrial (LA LGE), ventricular wall (LV LGE) or right ventricular wall (RV LGE); 2. Studies reporting AF or recurrent arrhythmia after ablation; 3. Patient ≥18 years; and 4. ≥50 participants. Included studies were pooled in a random effects meta-analysis and reported as: mean difference (MD); unadjusted risk ratios (RR); adjusted hazard ratios (HR); and 95% confidence intervals (95% CI). Results After exclusions, we identified 9 studies (2,307 patients [65.9% males, 34.1% females]) conducted between 2003 and 2015 for LGE and AF. Fibrosis was present in 666 (35.1%) and detected by LV LGE in 7 (78%) and RV LGE in 2 (22%). The presence of AF was higher in patients positive for ventricular LGE than those negative, trending towards significance (RR: 1.51, 95% CI: 0.94–2.45, p=0.09). Pooled LV fibrosis associated with AF progression (RR [NPAF vs. PAF]: 2.2, 95% CI: 1.22–3.94, p=0.009). We identified 8 studies (2,041 patients [65.8% males, 34.2% females]) conducted between 2006 and 2016 reporting LGE and AF recurrence after catheter ablation, with fibrosis detected in 644 (31.6%) by LA LGE in 8 (88.9%, biased towards one centre). After 17.8±14.2 follow-up years, atrial fibrosis was significantly greater in recurrent AF than controls (MD: 4.97%, 95% CI: 1.23–8.7, p&lt;0.01), and predicted 16% increased risk of AF recurrence (RR: 1.16, 95% CI: 1.07–1.26, p&lt;0.05). Conclusion Myocardial fibrosis detected by LGE associates with prevalence and progress of AF and is predictive of AF recurrence post ablation. This further supports the proarrhythmic role of fibrosis and selection of patients for ablation therapy based on LGE.

4252Additional value of stress testing for evaluation of ventricular arrhythmias in athletes undergoing preparticipation screening

Abstract Introduction The optimal protocol of athletes pre-participation screening is a matter of debate. The aim of this study is to test the additional value of exercise testing (ET) for evaluation of ventricular arrhythmias (VA) in athletes with otherwise normal findings. Methods The study included 10,975 competitive athletes who underwent preparticipation screening including ECG and stress testing. Athletes with ≥3 isolated premature ventricular beats or ≥1 repetitive VA underwent second-line investigations (echocardiography and 24-hour ambulatory ECG monitoring with a training session) and, in case of frequent, complex or exercise-induced VA or echocardiographic abnormalities, also cardiac magnetic resonance (CMR). Results 451 (4,1%) athletes were excluded for abnormalities at history, physical examination and baseline ECG. Among the remaining 10524 athletes, 524 (5%)showed VA at ET, 87 of whom underwent CMR.Echocardiography identified major cardiac abnormalities in 5 athletes and regional ventricular systolic dysfunction in 7, which were confirmed by CMR in 6. Other 12 patients with normal echocardiography had a positive CMR. In particular, in 16 subjects the CMR showed left ventricular late gadolinium enhancement suggesting myocardial fibrosis with a non-ischemic distribution. At multivariate analysis, VA observed at high work load at ET, the presence of complex VA at ET and the presence of a morphology other than infundibular or fascicular predicted an underlying pathological myocardial substrate while the presence of frequent (&gt;500/24-hour) premature ventricular beats did not. Predictors of underlying pathological myocardial substrate Substrate Univariate Multivariable YES (n=23) NO (n=501) OR (95% IC) P OR (95% IC) P Age 17 [13–43] 15 [14–17] 1.03 [0.98 -1.06] 0.18 – Male gender 15 (65%) 184 (37%) 3.2 [1.3–7.7] &lt;0.001 1.6 [0.7–4.8] 0.28 &gt;500 PVBs/24-hour 7 (30%) 98 (20%) 1.8 [0.7–4.5] 0.21 – VA at high work-load 10 (44%) 78 (16%) 4.2 [1.8–9.8] &lt;0.001 1.6 [1.1–4.7] 0.02 Couplets/NSVT at ET 14 (61%) 117 (23%) 6.2 [2.5–15] &lt;0.001 8.5 [2.5–29] 0.01 PVBs other than infundibular/fascicular 17 (74%) 118 (24%) 6.1 [2.4–16] &lt;0.001 3.9 [1.4–11] 0.008 Conclusions VA at ET may represent the only sign of a pathological myocardial abnormalities, such as the “isolated nonischemic left ventricular scar”, that could be the substrate for life-threatening ventricular arrhythmias. Addition of ET to baseline ECG may increase the sensitivity of PPE of competitive athletes.

4088Diagnostic specificity of triangular basal inferoseptal late gadolinium enhancement for identification of cardiac sarcoidosis

Abstract Background/Introduction Sarcoidosis, a multisystem disorder characterized by infiltration of noncaseating granulomas, can manifest as left ventricular (LV) dysfunction and fatal ventricular arrhythmias. The clinical diagnosis of cardiac sarcoidosis (CS) can be challenging and often requires multiple imaging modalities including cardiac magnetic resonance (CMR). The characterization of unique late gadolinium enhancement (LGE) patterns may assist in the diagnosis on CMR. Purpose We sought to examine the diagnostic value of inferoseptal triangular LGE for CS. Methods The retrospective cohort included 149 non-ischemic cardiomyopathy (NICM) patients referred to our hospital for a CMR from January 2012 to December 2018. Left ventricular LGE was identified in 86 patients (56.4±10.4 years, 84.9% male). Amongst them, 73 patients with septal LGE. We classified the various septal LGE patterns into four categories: (A) Mid-wall septal and basal inferoseptal triangular LGE; (B) Endocardial right ventricular (RV) septal LGE; (C) Basal inferoseptal triangular with endocardial RV septal LGE; (D) Mid-wall septal LGE (Figure). The diagnosis of sarcoidosis was confirmed by the Japanese Circulation Society/Japanese Society of Nuclear Cardiology guidelines. Results Individual diagnoses and imaging characteristics of non-ischemic cardiomyopathy types with septal LGE are summarized in the Table. LV ejection fraction, LV end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) did not significantly differ between sarcoidosis and non-sarcoidosis patients. Pattern A and Pattern B were highly specific but insensitive (Specificity/Sensitivity- A: 98.4/8.3%, p=0.19; B: 95.1%/8.3%, p=0.64) for CS. The only pattern with statistically significantly diagnostic indices was pattern C: specificity of 100% and sensitivity of 58.3% (p&lt;0.001). Pattern D revealed both low specificity of 6.6% and sensitivity of 25% (p&lt;0.001). Imaging characteristics and diagnosis Septal LGE/Diagnosis Sarcoidosis Idiopathic Pulmonary hypertension Giant cell myocarditis Amyloidosis Systemic lupus erythematous Myeloproliferative neoplasm Large cell lymphoma Mid-wall septal and basal inferoseptal triangular LGE 1 1 0 0 0 0 0 0 Endocardial RV septal LGE 1 2 0 1 0 0 0 0 Basal inferoseptal triangular andendocardial RV septal LGE 7 0 0 0 0 0 0 0 Mid-wall septal LGE 3 50 3 0 1 1 1 1 Individual diagnosis and patterns of septal late gadolinium enhancement. Septal LGE patterns Conclusions The presence of basal inferoseptal triangular LGE pattern with endocardial RV involvement enables an accurate diagnosis of CS. The absence of this triangular septal LGE pattern, however, cannot exclude the diagnosis of CS. Acknowledgement/Funding Taipei Veterans General Hospital-National Yang-Ming University Excellent Physician Scientists Cultivation Program, No. 106-V-A-009

P3686A novel desmin gene variant as an important cause of biventricular arrhythmogenic cardiomyopathy

Abstract Introduction Arrhythmogenic Cardiomyopathy (AC) is typically caused by mutations in the desmosomal genes, however non-desmosomal genes have been increasingly implicated. Desmin gene (DES) mutations have been previously reported in AC, but in many cases there are insufficient data to support their pathogenicity. Purpose We assessed our AC cohort for DES gene mutations and describe the clinical phenotype associated with a recurring variant present in 3 unrelated families. Methods Genetic testing was performed using next-generation sequencing for 41 genes in a total of 138 AC probands with a definite diagnosis of AC based on the revised 2010 Task Force diagnostic criteria. All candidate variants were confirmed using Sanger sequencing. Clinical and genetic cascade screening were expanded to the first-degree relatives of the probands. Retained tissue from deceased individuals was used for genetic testing. All living mutation carriers underwent clinical assessment including physical examination, 12-lead ECG, signal-averaged ECG, echocardiography, cardiac magnetic resonance imaging (MRI) and 24h Holter-monitoring. Results Two DES gene variants, p.Ser298Leu (n=1) and p.Leu115Ile (n=3), were identified in 4 out of the 138 probands (3%). The former coexisted with a pathogenic DSP gene mutation and has not been further evaluated. The latter is a novel variant, absent in control databases (gnomAD) and was the only variant present in 3 unrelated families (see figure). One carrier required heart transplant (A-II-1), two died suddenly (A-III-1, B-II-1) and one died of non-cardiac causes (B-I-2). Detailed clinical information was present in 8 mutation carriers (2 male, age 45±19 years). Seven (88%) had a definite diagnosis and one had a borderline diagnosis of AC. All cases (100%) had right ventricular (RV) wall motion abnormalities, 6 (75%) had a dilated RV, 6 (75%) a dilated LV and 6 (75%) had LV dysfunction (mild in 5 and severe in 1). LV late gadolinium enhancement (LGE) was present in all 6 carriers that had a cardiac MRI with a circumferential sub-epicardial distribution (see figure, case A-III-2). Non-sustained ventricular tachycardia (VT) was present in 7 (88%) and sustained VT in 2 cases (25%). The ventricular ectopic burden per 24h ranged from 426 to 10583 with a median value of 820. Figure 1 Conclusion Variants of the DES gene are rare causes of AC. The novel p.Leu115Ile variant seems to be prevalent in a large UK-based cohort and it causes a biventricular form of AC, with a characteristic scar pattern on MRI and severe outcomes. Acknowledgement/Funding Alexandros Protonotarios is supported by a BHF Clinical Research Training Fellowship no. FS/18/82/34024

P4661Increased levels of sST2 in patients with mitral annulus disjunction and ventricular arrhythmias

Abstract Background Mitral annulus disjunction (MAD), a basal displacement of the mitral valve annulus, is described as a possible aetiology of sudden cardiac death. Stretch-induced fibrosis in the sub-valvular apparatus has been suggested as the substrate of arrhythmias. Purpose We hypothesized that the stretch related biomarker soluble Suppression of Tumorigenicity-2 (sST2) is a marker of ventricular arrhythmias in patients with MAD. Methods We included patients with ≥1 mm MAD on cardiac magnetic resonance imaging, and recorded left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) suggesting papillary muscle fibrosis. Circulating levels of sST2 were assessed by blood sampling. The occurrence of ventricular arrhythmias, defined as aborted cardiac arrest, sustained or non-sustained ventricular tachycardia, was assessed retrospectively. Results We included 72 patients with MAD [55 (35–62) years old, 48 (67%) female], of which 22 (31%) had ventricular arrhythmias. Patients with ventricular arrhythmias had lower LVEF (60±6% vs. 63±6%, p=0.04), more prevalent papillary muscle fibrosis [14 (64%) vs. 10 (20%), p&lt;0.001] and higher sST2 levels [31.6±10.1 ng/mL vs. 25.3±9.2 ng/mL, p=0.01] compared to those without. Combining sST2-level, LVEF and papillary muscle fibrosis optimally detected individuals with arrhythmias (area under the curve 0.82, 95% CI 0.73–0.92) and improved the risk model (p&lt;0.05) compared to individual parameters (Figure right panel). Conclusion Circulating sST2 levels were higher in patients with MAD and ventricular arrhythmias compared to patients without arrhythmias. Combining sST2, LVEF and LGE may improve risk stratification in patients with MAD. Acknowledgement/Funding This work was supported by public grant [203489/030] from the Norwegian Research Council, Oslo, Norway. E. Scheirlynck received an ESC research grant

P5270Impaired myocardial deformation assessed by cardiac magnetic resonance is associated with increased arrhythmic risk in hypertrophic cardiomyopathy

Abstract Background Strain techniques, such as feature tracking cardiac magnetic resonance (FT-CMR), have emerged as a promise for more accurate evaluation of cardiac function compared to ejection fraction. In hypertrophic cardiomyopathy (HCM) patients, impaired myocardial deformation measured by FT-CMR has been associated with severity of hypertrophy and presence of late gadolinium enhancement (LGE) but associations with clinical severity and prognosis are scarce. Purpose To analyse the association between left ventricular strain measured by FT-CMR, morphologic features and prognostic markers in patients with HCM. Methods Retrospective analysis of clinical, echocardiography, Holter and CMR data of HCM patients aged ≥16 years followed at two referral centres. Ventricular arrhythmias (VA) were defined as non-sustained or sustained ventricular tachycardia or sudden cardiac arrest. Sudden cardiac death (SCD) risk was evaluated using the score proposed by the European Society of Cardiology. LGE extension was evaluated using the American Heart Association 17-segment model. FT-CMR was used to evaluate global peak systolic longitudinal (GLS), radial (GRS) and circumferential (GCS) strains - GLS was averaged from three standard longitudinal views while GRS and GCS were averaged from the basal, mid and apical LV short-axis planes. Results A total of 109 HCM patients (59.2±16.2 years old; 60.6% males) were included; mean follow-up was 39±25 months. Mean LV mass was 170.6±70.3g, LVEF was 63.7±10.0% and the number of segments with LGE was 3.14±3.32. Mean GLS, GRS and GCS were −14.8±4.0%, 34.4±13.3% and −17.5±4.8%, respectively. Impaired strain was associated with higher LV mass (GLS: r=0.46, GRS: r=−0.46, GCS: r=0.47, p&lt;0.001 for all), reduced LVEF (GLS: r=−0,33, GRS: r=0,44, GCS: r=−0.41, p&lt;0.003 for all) and LGE extension (GLS: r=0.26, GRS: r=−0.38, GCS: r=0.38, p&lt;0.01 for all). SCD risk score was 3.12%±2.98 (8 patients scored as high risk) and VA were documented in 26 patients (26%). Patients with VA had worse strain values than those without (GLS −13.2±4.12 vs −15.5±3.71, p=0.011; GCS −15,8±5.22 vs −18.3±4.24, p=0.017). Patients with high estimated risk of SCD also had worse strain values than those at low/intermediate risk (GLS −12.2±3.57 vs −15.1±3.83, p=0.048; GCS −14.5±4.26 vs −17.9±4.54, p=0.047). A correlation between SCD risk and GLS and GCS was observed (r=0.32, p=0.004; r=0.23, p=0.03, respectively). Conclusions In our population, worse strain measurements were associated with a more severe HCM phenotype, presence of VA and a higher estimated risk of SCD. Strain assessed by FT-CMR may improve risk stratification in HCM patients.

Early Left Ventricular Involvement Detected by Cardiovascular Magnetic Resonance Feature Tracking in Arrhythmogenic Right Ventricular Cardiomyopathy: The Effects of Left Ventricular Late Gadolinium Enhancement and Right Ventricular Dysfunction.

BackgroundLeft ventricular (LV) involvement is common in arrhythmogenic right ventricular cardiomyopathy (ARVC). We aim to evaluate LV involvement in ARVC patients by cardiovascular magnetic resonance feature tracking.Methods and ResultsSixty‐eight patients with ARVC and 30 controls were prospectively enrolled. ARVC patients were divided into 2 subgroups: the preserved LV ejection fraction (LVEF) group (LVEF ≥55%, n=27) and the reduced LVEF group (LVEF <55%, n=41). Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) and cardiovascular magnetic resonance feature tracking were performed in all subjects. LV global and regional (basal, mid, apical) peak strain (PS) in radial, circumferential and longitudinal directions were assessed, respectively. Right ventricular global PS in three directions were also analyzed. Compared with the controls, LV global and regional PS were all significantly impaired in the reduced LVEF group (all P<0.05). However, only LV global longitudinal PS as well as mid and apical longitudinal PS were impaired in the preserved LVEF group (all P<0.05), and all these parameters were significantly associated with right ventricular global radial PS (r=−0.47, −0.47, and −0.49, respectively, all P<0.001). The reduced LVEF group showed significantly higher prevalence of LGE (95.10% versus 63.00%, P=0.002) than the preserved LVEF group. Moreover, LV radial PS was significantly reduced in LV segments with LGE (33.15±20.42%, n=46) than those without LGE (41.25±15.98%, n=386) in the preserved LVEF group (P=0.016).ConclusionsIn patients with ARVC, cardiovascular magnetic resonance feature tracking could detect early LV dysfunction, which was associated with LV myocardial LGE and right ventricular dysfunction.

Natural History of Cardiomyopathy in Adult Dogs With Golden Retriever Muscular Dystrophy.

BackgroundDuchenne muscular dystrophy (DMD) is an X‐linked disease that causes progressive muscle weakness. Affected boys typically die from respiratory or cardiac failure. Golden retriever muscular dystrophy (GRMD) is genetically homologous with DMD and causes analogous skeletal and cardiac muscle disease. Previous studies have detailed features of GRMD cardiomyopathy in mostly young dogs. Cardiac disease is not well characterized in adult GRMD dogs, and cardiac magnetic resonance (CMR) imaging studies have not been completed.Methods and ResultsWe evaluated echocardiography and CMR in 24 adult GRMD dogs at different ages. Left ventricular systolic and diastolic functions, wall thickness, and myocardial strain were assessed with echocardiography. Features evaluated with CMR included left ventricular function, chamber size, myocardial mass, and late gadolinium enhancement. Our results largely paralleled those of DMD cardiomyopathy. Ejection fraction and fractional shortening correlated well with age, with systolic dysfunction occurring at ≈30 to 45 months. Circumferential strain was more sensitive than ejection fraction in early disease detection. Evidence of left ventricular chamber dilatation provided proof of dilated cardiomyopathy. Late gadolinium enhancement imaging showed DMD‐like left ventricular lateral wall lesions and earlier involvement of the anterior septum. Multiple functional indexes were graded objectively and added, with and without late gadolinium enhancement, to give cardiac and cardiomyopathy scores of disease severity. Consistent with DMD, there was parallel skeletal muscle involvement, as tibiotarsal joint flexion torque declined in tandem with cardiac function.ConclusionsThis study established parallels of progressive cardiomyopathy between dystrophic dogs and boys, further validating GRMD as a model of DMD cardiac disease.

Dilated cardiomyopathy and arrhythmogenic left ventricular cardiomyopathy: a comprehensive genotype-imaging phenotype study.

Myocardial scar detected by cardiovascular magnetic resonance has been associated with sudden cardiac death in dilated cardiomyopathy (DCM). Certain genetic causes of DCM may cause a malignant arrhythmogenic phenotype. The concepts of arrhythmogenic left ventricular (LV) cardiomyopathy (ALVC) and arrhythmogenic DCM are currently ill-defined. We hypothesized that a distinctive imaging phenotype defines ALVC. Eighty-nine patients with DCM-associated mutations [desmoplakin (DSP) n = 25, filamin C (FLNC) n = 7, titin n = 30, lamin A/C n = 12, bcl2-associated athanogene 3 n = 3, RNA binding motif protein 20 n = 3, cardiac sodium channel NAv1.5 n = 2, and sarcomeric genes n = 7] were comprehensively phenotyped. Clustering analysis resulted in two groups: 'DSP/FLNC genotypes' and 'non-DSP/FLNC'. There were no significant differences in age, sex, symptoms, baseline electrocardiography, arrhythmia burden, or ventricular volumes between the two groups. Subepicardial LV late gadolinium enhancement with ring-like pattern (at least three contiguous segments in the same short-axis slice) was observed in 78.1% of DSP/FLNC genotypes but was absent in the other DCM genotypes (P < 0.001). Left ventricular ejection fraction (LVEF) and global longitudinal strain were lower in other DCM genotypes (P = 0.053 and P = 0.015, respectively), but LV regional wall motion abnormalities were more common in DSP/FLNC genotypes (P < 0.001). DSP/FLNC patients with non-sustained ventricular tachycardia (NSVT) had more LV scar (P = 0.010), whereas other DCM genotypes patients with NSVT had lower LVEF (P = 0.001) than patients without NSVT. DSP/FLNC genotypes cause more regionality in LV impairment. The most defining characteristic is a subepicardial ring-like scar pattern in DSP/FLNC, which should be considered in future diagnostic criteria for ALVC.

Association between Lifelong Physical Activity and Disease Characteristics in HCM.

Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate left ventricular (LV) wall thickness. Adaptations to exercise can occasionally mimic certain HCM characteristics. However, it is unclear whether physical activity affects HCM genotype expression and disease characteristics. Consequently, we compared lifelong physical activity volumes between HCM gene carriers with and without HCM phenotype, and compared disease characteristics among tertiles of physical activity in phenotypic HCM patients. We enrolled n = 22 genotype positive/phenotype negative (G+/P-) HCM gene carriers, n = 44 genotype positive/phenotype positive (G+/P+) HCM patients, and n = 36 genotype negative/phenotype positive (G-/P+) HCM patients. Lifelong physical activity was recorded using a questionnaire and quantified as metabolic equivalent of task hours per week. We included 102 participants (51 ± 16 yr, 49% male). Lifelong physical activity volumes were not different between G+/P+ and G+/P- subjects (16 [10-29] vs 14 [6-26] metabolic equivalent of task-hours per week, P = 0.33). Among phenotypic HCM patients, there was no difference in LV wall thickness, mass, and late gadolinium enhancement across physical activity tertiles. Patients with the highest reported physical activity volumes were younger at the time of diagnosis (tertile 1: 52 ± 14 yr, tertile 2: 49 ± 15 yr, tertile 3: 41 ± 18 yr; P = 0.03), and more often had a history of nonsustained ventricular tachycardia (4% vs 30% vs 30%, P = 0.03). Lifelong physical activity volumes are not associated with genotype-to-phenotype transition in HCM gene carriers. We also found no difference in LV wall thickness across physical activity tertiles. However, the most active HCM patients were younger at the time of diagnosis and had a higher arrhythmic burden. These observations warrant further exploration of the role of exercise in HCM disease development.

MON-438 A Novel Insight into the Pathophysiology of Acromegalic Cardiomyopathy: Integrating Serum FSTL1 Levels and FSTL1 Polymorphisms with Cardiac MRI Findings

Background: Despite prolonged survival, the mortality rate of acromegalic patients is still higher. Cardiovascular disorders continue to be the most common cause of death. The exact pathophysiologic mechanisms of acromegalic cardiomyopathy (AC) remain to be established. In this study, we investigated the role of FSTL1 levels and FSTL1 gene polymorphisms on AC and assessed the functional and structural properties of cardiac muscle by cardiac MRI. Finally, we examined the relationship between FSTL1 levels, FSTL1 gene polymorphism and cardiac MRI findings. Materials and Methods: Forty-six acromegalic patients (28F/18M, age: 50.3±12.1 yrs) with a median disease duration of eight years and 81 age-sex matched healthy controls (48F/33M, age: 48.4±7.2 yrs) were included in the study. The rs1259293 region of the FSTL1 gene was subjected to polymorphism analysis. SNPs were identified (TT, TC and CC). A 1.5 Tesla scanner was used to obtain cardiac images. Results: The median serum IGF- 1 level and IGF-1 index were 232.5 ng/mL (50-1278) and 0.69 (0.17-3.1), respectively. Acromegalic patients had significantly lower levels of FSTL1 (median, IQR; A: 0.88, 0.44-2.13 ng/mL, C: 1.54, 0.85-3.16 ng/mL, p=0.04). FSTL1 levels were not different among polymorphism groups (TT, TC and CC). Left ventricular (LV) mass was increased in 18 patients (41%). In 20 acromegalic patients (45.4%), regional late gadolinium enhancement (LGE) was determined. Serum IGF-1 index was positively correlated with LV end-diastolic volume index, end-systolic volume index, stroke volume index, cardiac index and cardiac mass index; r: 0.36, 0.34, 0.32, 0.31 and 0.42, p: 0.02, 0.03, 0.03, 0.04 and 0.004 respectively. The IGF-1 index was defined as an independent risk factor for LV hypertrophy (95 % CI OR: 0.89-18.84); on the other hand, the CC polymorphism was shown to be an independent protective factor (95 % CI OR: 0.06-0.87). Discussion: Our study is the first study that assesses the role of serum FSTL1 levels and FSTL1 polymorphisms in AC. We found low FSTL1 levels in patients with acromegaly. FSTL-1 prevents hypertrophy in cardiomyocytes. In a previous report, homozygous deletion of FSTL1 in mice was shown to result in enlargement of heart. The relatively low abundance of FSTL1 in acromegalic patients could be an underlying mechanism for AC. Almost half of the acromegalic patients had increased LV mass and LGE. Contrary to the previous report, we show that LV hypertrophy and regional fibrosis are common findings in acromegaly. The IGF-1 index was found to be associated with hyperdynamic cardiac functions. Furthermore, we demonstrate that high IGF-1 index is an independent risk factor for increased LV mass. Finally, we revealed that the CC polymorphism is a protective factor against the LV mass increase. Conclusions: FSTL1 can have roles in the pathogenesis of AC. Specific polymorphism at the FSTL1 gene may prevent the growth of the LV.

Left atrial fibrosis correlates with extent of left ventricular myocardial delayed enhancement and left ventricular strain in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is associated with increased left ventricular (LV) mass, decreased myocardial strain, and the presence of LV fibrosis and scar. The relationship between LV scar and fibrosis with left atrial (LA) fibrosis in the setting of HCM has not been examined. The purpose of this study is to demonstrate a correlation between the degree of LA fibrosis and LV parameters in subjects with HCM. Twenty-eight subjects with HCM were imaged on a 1.5T MRI scanner with cine, LV and LA late gadolinium enhancement (LGE) sequences. LA LGE and LA measurements were correlated with LV measurements of volumes, mass, strain, and LGE. Other clinical conditions and medication usage were also examined and evaluated for correlation with LA and LV parameters. LV LGE was identified in 24 (86%) of the cases and LA LGE was identified in all of the cases. Extent of LA fibrosis significantly correlated with percent LV LGE (r = 0.64, p = 0.001), but not with indexed LV mass or maximum wall thickness. Extent of LA fibrosis also moderately correlated with decreased LV global strain (radial, r = - 0.50, p = 0.013; circumferential, r = 0.47, p = 0.02; longitudinal, r = 0.52, p = 0.013). Increased LA systolic volume correlated moderately with LV end diastolic volume (r = 0.50, p = 0.006). Patients on therapy with Renin-Angiotensin-Aldosterone System (RAAS) Inhibition had significantly less LA LGE compared to those without (18.6% vs 10.8%, p = 0.023). LA fibrosis, as measured by LGE, is prevalent in HCM and is correlated with LV LGE. The correlation between LA and LV LGE might suggest either that LA fibrosis is a consequence of LV remodeling, or that LA and LV fibrosis are both manifestations of the same cardiomyopathic process. Further study is warranted to determine the causality of LA scar in this population.

Incremental Predictive Value of Longitudinal Axis Strain and Late Gadolinium Enhancement Using Standard CMR Imaging in Patients with Aortic Stenosis.

To analyse the predictive ability and incremental value of left ventricular longitudinal axis strain (LAS) and late gadolinium enhancement (LGE) using standard cardiovascular magnetic resonance (CMR) imaging for the diagnosis and prognosis of severe aortic stenosis (AS) in patients with an indication for aortic valve replacement. We conducted a prospective study on 52 patients with severe AS and 52 volunteers. The evaluation protocol included standard biochemistry tests, novel biomarkers of myocardial fibrosis, 12-lead electrocardiograms and 24-hour Holter, the 6-minute walk test and extensive echocardiographic and CMR imaging studies. Outcomes were defined as the composite of major cardiovascular events (MACEs). Among AS patients, most (n = 17, 77.2%) of those who exhibited LGE at CMR imaging had MACEs during follow-up. Kaplan–Meier curves for event-free survival showed a significantly higher rate of MACEs in patients with LGE (p < 0.01) and decreased LAS (p < 0.001). In Cox regression analysis, only reduced LAS (hazard ratio 1.33, 95% CI (1.01 to 1.74), p < 0.01) and the presence of LGE (hazard ratio 11.3, 95% CI (1.82 to 70.0), p < 0.01) were independent predictors for MACEs. The predictive value increased if both LGE and reduced LAS were added to left ventricular ejection fraction (LVEF). None of the biomarkers of increased collagen turnover exhibited any predictive value for MACEs. LAS by CMR is an independent predictor of outcomes in patients with AS and provides incremental value beyond the assessment of LVEF and the presence of LGE.

Relationship Between Electrocardiographic Findings and Cardiac Magnetic Resonance Phenotypes in Arrhythmogenic Cardiomyopathy.

BackgroundThe new designation of arrhythmogenic cardiomyopathy defines a broader spectrum of disease phenotypes, which include right dominant, biventricular, and left dominant variants. We evaluated the relationship between electrocardiographic findings and contrast‐enhanced cardiac magnetic resonance phenotypes in arrhythmogenic cardiomyopathy.Methods and ResultsWe studied a consecutive cohort of patients with a definite diagnosis of arrhythmogenic cardiomyopathy, according to 2010 International Task Force criteria, who underwent electrocardiography and contrast‐enhanced cardiac magnetic resonance. Both depolarization and repolarization electrocardiographic abnormalities were correlated with the severity of dilatation/dysfunction, either global or regional, of both ventricles and the presence and regional distribution of late gadolinium enhancement. The study population included 79 patients (60% men). There was a statistically significant relationship between the presence and extent of T‐wave inversion across a 12‐lead ECG and increasing values of median right ventricular (RV) end‐diastolic volume (P<0.001) and decreasing values of RV ejection fraction (P<0.001). The extent of T‐wave inversion to lateral leads predicted a more severe RV dilatation rather than a left ventricular involvement because of the leftward displacement of the dilated RV, as evidenced by contrast‐enhanced cardiac magnetic resonance. A terminal activation delay of >55 ms in the right precordial leads (V1‐V3) was associated with higher RV volume (P=0.014) and lower RV ejection fraction (P=0.053). Low QRS voltages in limb leads predicted the presence (P=0.004) and amount (P<0.001) of left ventricular late gadolinium enhancement.ConclusionsThe study results indicated that electrocardiographic abnormalities predict the arrhythmogenic cardiomyopathy phenotype in terms of severity of RV disease and left ventricular involvement, which are among the most important determinants of the disease outcome.

Smoking aggravates ventricular arrhythmic events in non-ischemic dilated cardiomyopathy associated with a late gadolinium enhancement in cardiac MRI

Smoking is known to increase cardiovascular events, but the association and mechanisms between smoking and ventricular arrhythmic events in dilated cardiomyopathy (DCMP) are unknown. The purpose of this study is to investigate the hypothesis that smoking is associated with sudden cardiac death (SCD) and ventricular arrhythmia in DCMP patients. We enrolled 378 patients who underwent cardiovascular magnetic resonance imaging (cMRI) and were diagnosed with DCMP at two general hospitals in Korea. The clinical data and left ventricular late-gadolinium enhancement (LV-LGE) of all patients were analyzed according to being never-smokers or smokers. Smokers were more likely to be male than never-smokers, but there was no other clinical difference between them. Smokers had a greater LV-LGE ratio, and multi-segment involvement of LV-LGEs. Smoking and a low left ventricular (LV) ejection fraction were significant predictors of the presence of LV-LGEs even after adjusting for optimal medical therapy. In addition, smokers had a higher fatal ventricular arrhythmic (FVA; sustained ventricular tachycardia, and ventricular fibrillation) and FVA + SCD, and ex-smokers had a similar FVA to never-smokers during 44.3 ± 36.4 months of follow-up. Finally, smoking independently increased the FVA + SCD even after adjusting for the clinical variables and LV-LGE. Smoking is associated with a multi-segmental involvement of LV-LGE and increased FVA + SCD in DCMP patients when compared to never-smokers.

Predictive value of exercise testing in athletes with ventricular ectopy evaluated by cardiac magnetic resonance

Exercise-induced ventricular arrhythmias (EIVA) in young athletes raise the suspicion of an underlying heart disease at risk of sudden death. We aimed to assess the prevalence and determinants of abnormal cardiac magnetic resonance (CMR) findings in athletes referred for EIVA vs non-EIVA with negative or inconclusive echocardiography. We performed CMR in a consecutive series of athletes aged 15-50 years referred for frequent (>500 per day) or repetitive premature ventricular beats. Clinical and CMR findings were compared between athletes with EIVA and those with non-EIVA, and predictors of abnormal CMR were assessed. We included 36 athletes with EIVA (median age 25 years; 27 (75%) males) and 24 with non-EIVA (median age 17 years; 18 (75%) males). CMR revealed cardiac abnormalities in 20 athletes with EIVA (56%) and in 5 with non-EIVA (21%) (P = .004). In particular, left ventricular late gadolinium enhancement was identified in 17 athletes with EIVA (47%) and in 3 with non-EIVA (13%) (P = .006), mostly with a nonischemic pattern. Predictors of abnormal CMR were T-wave inversion on electrocardiography (ECG) (odds ratio [OR] 5.2; 95% confidence interval [CI] 1.0-27.1; P = .05), complex ventricular arrhythmias on 24-hour ambulatory ECG monitoring (OR 4.5; 95% CI 1.1-18.7; P = .04), and complex EIVA with a right bundle branch block or polymorphic morphology on exercise testing (OR 5.3; 95% CI 1.4-19.4; P = .01). Pathological myocardial substrates on CMR were observed significantly more often in athletes with EIVA than in those with non-EIVA. Repolarization abnormalities on baseline ECG and complex EIVA with a right bundle branch block or polymorphic morphology identified the subgroup of athletes with the highest probability of CMR abnormalities.

Histogram Analysis of Native T1 Mapping and Its Relationship to Left Ventricular Late Gadolinium Enhancement, Hypertrophy, and Segmental Myocardial Mechanics in Patients With Hypertrophic Cardiomyopathy.

The use of native T1 mapping for evaluation of hypertrophic cardiomyopathy (HCM) is being explored, and its combination with histogram analysis may benefit the accuracy of such assessments. To investigate the relationship of segmental left ventricular wall thickness (LVWT), myocardial fibrosis, and strain parameters with segmental histogram parameters of native T1 mapping in HCM patients. Retrospective. Ninety-three HCM patients without previous cardiovascular diseases were included. 3.0T cardiac MR. Steady-state free precession cine imaging, modified Look-Locker inversion recovery, phase-sensitive inversion recovery. Images were assessed by three experienced radiologists. Mann-Whitney U-tests, area under the curve (AUC), Spearman's rank correlation, intraclass correlation coefficient, and Bland-Altman test were used for statistical analysis. A higher LVWT value correlated with higher means, minimums, 10th /25th /50th /75th /90th percentiles, maximums, kurtosis, entropy, and lower SD and energy of T1 mapping (P < 0.05 for all), with the correlation being stronger for entropy and energy (Spearman's rho = 0.439 and -0.413, respectively) than other parameters. Late gadolinium enhancement positive (LGE+) segments exhibited higher mean, minimum, 10th /25th /50th /75th /90th percentiles, maximum, entropy, and lower energy of T1 times than late gadolinium enhancement negative (LGE-) segments (P < 0.001 for all). Impaired strain function parameters (peak thickening and thickening rate in radial, circumferential, and longitudinal directions) demonstrated a weak correlation with higher entropy (P < 0.001 for all) and lower energy (P < 0.001 for all). Histogram parameters of native T1 mapping provide more information than mean T1 times alone. Among these parameters, entropy and energy may correlate better with LVWT, myocardial late gadolinium enhancement, and strain parameters than mean T1 times in HCM patients. 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;49:668-677.