Myocardial Replacement Fibrosis Research Articles

Galectin-3 and Myocardial Fibrosis By Cardiac Magnetic Resonance in Thalassaemia Major

Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) technique is the only validated non-invasive approach used for detecting macroscopic myocardial fibrosis. Galectin-3 has been shown to participate in tissue fibrogenesis and was already associated with LGE-assessed myocardial replacement fibrosis in a cohort of patients with non-ischemic dilated cardiomyopathy (NICM).Our aim was to investigate the relationships between galectin-3 circulating level and myocardial fibrosis in patients with thalassemia major (TM) who underwent CMR technique during the Myocardial Iron Overload in Thalassemia (MIOT) project.All patients underwent also an extensive biohumoral characterization, including Troponin, NT Pro BnP, BNP, VES, PCR assay.At UOSD Malattie rare del globule Rosso of Cardarelli hospital (Naples, Italia), between January 2015 and March 2016, all patients who underwent contrast-enhanced CMR were progressively enrolled to test Galectin-3.Eighty-six patients were evaluated (males 43%; age 37, SD 8 years): six (7%) had diabetes mellitus (DM), 64 had anti-HCV antibodies and 28 (32%) were HCV RNA positive. Median galectin-3 value was 14.04ng/mL (5.26 ng/mL), and LGE was detected in 42 (49%) patients. Patients with LGE had higher galectin-3 than those without (14.48 ± 5.98, vs 13.63 ± 5.98), but without a statistically significant difference (p=0.109).Galectin-3 was significantly associated with age (R=0.34; p=0.001), but not with sex.Patients with DM, with anti-HCV antibodies and with HCV-RNA positivity, had significant higher level of Galectin 3 with respect to those without (22.5± 11.1 vs 13.4± 4, p=0.009; 14.9 ± 5.4 vs 11.5± 3.7, p=0.001; 16.2 ± 6.5 vs 13± 4.2, p=0.011, respectively).No correlation was found between Galectin 3 and other tested biochemical variables and iron overload and cardiac parameters.In conclusion, in our cohort of TM patients there was a great prevalence of myocardial fibrosis. In patients with myocardial fibrosis, the level of galectin-3 was higher and comparable to that found in a previous study performed in patients with NICM, but not significantly different with respect to those without fibrosis. The elevated prevalence of patients with previous exposure to HCV virus and/or DM and/or iron overload may significantly influence Galectin-3 level limiting the ability of the marker to identify patients without fibrosis. DisclosuresDe Franceschi:F. Hoffmann-La Roche Ltd, Basel, Switzerland: Research Funding. Pepe:Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc.

Characteristics, circumstances and pathology of sudden or unnatural deaths of cases with evidence of pathological hoarding

The study aimed to determine the characteristics and circumstances of cases sudden or unnatural death (n = 61) with evidence of pathological hoarding, their major organ pathology and toxicology. The mean age was 65·8 yrs (a mean of 16.1 years of potential life lost), 62·3% were male, and 28·2% were obese. 95·1% lived alone, and 96·7% died in their residence, with no medical intervention. In all cases severe squalor and extensive hoarding were noted. The direct cause of death was attributed to disease in 75·4%, heart disease being a significant factor in 52·5%. Accidents causing death directly related to hoarding occurred in two cases. Autopsy revealed extensive pathology: severe coronary artery narrowing (42·4%), myocardial replacement fibrosis (44·1%), emphysema (39·0%), nephrosclerosis (46·6%). Signs of hypothermia were present in 14·8%, and diabetes was diagnosed in 21·3%. The most commonly detected substance was alcohol (32·1%). Medications for heart disease (5·4%) or diabetes (7·1%) were rare. The overall clinical picture was of an isolated group, with a heavy burden of physical disease and, in all probability, a high level of psychiatric disorders, who died alone in their homes.

Abstract 12895: Characteristics and Outcome of Ventricular Tachycardia in Advanced Fabry Disease Cardiomyopathy

Introduction: Ventricular tachycardia (VT) are suspected the leading cause of premature death in patients with advanced Fabry cardiomyopathy. However, origin and outcome of respective tachyarrhythmic events have yet not been comprehensively investigated. Methods: All patients (n=261) in care at the Fabry Center for Interdisciplinary Therapy (FAZIT) Würzburg, Germany, with history of (n=17) or demand for (n=1) implantable cardioverter defibrillator (ICD) device therapy for primary or secondary prevention of ventricular tachyarrhythmic events due to advanced Fabry cardiomyopathy underwent comprehensive clinical investigations including analysis of 12-lead ECG, 24-hour Holter ECG, and ICD Holter chart reviews for documented VT episodes with special focus on characteristics and outcome of respective events. Results: Study subjects were mainly of male gender (14/18, 78%) and middle aged (55±10 years, range 33-74) at point of ICD demand. In total, 11/18 patients (61%) suffered from at least one episode of VT. All documented episodes were sustained monomorphic ventricular tachycardia. Most 12-lead ECG documented VT events (n=7) were self-terminated (n=6, 86%). Five subjects were in need of anti-tachycardia overdrive pacing and four of shocks for termination of respective VT events when followed over time. Analyzing VT episodes documented in 12-lead ECG showed a correlation of VT episode origination from the area of myocardial replacement fibrosis, mostly from the postero-lateral wall segments of the left ventricle. Radiofrequency catheter ablation was performed in three patients (17%), of whom two still suffered from VT episodes afterwards and both finally died due to end-stage heart failure complications. Three other subjects from this group also died due to cardiac events (in total 4/18, 22%), whereas one (6%) due to Fabry-associated stroke. Conclusions: VT is common in advanced Fabry disease. As all documented VT episodes were monomorphic, radiofrequency catheter ablation might represent a yet underestimated therapy option besides ICD device therapy. However, due to end-stage heart failure associated complications, cardiac mortality remains a substantial factor questioning the clinical impact and benefit in end-stage Fabry disease.

CARDIAC MYOSIN BINDING PROTEIN C IS A NOVEL CIRCULATING MARKER OF MYOCARDIAL INJURY AND FIBROSIS IN PATIENTS WITH AORTIC STENOSIS

Myocyte death characterises the transition from hypertrophy to replacement myocardial fibrosis in advanced aortic stenosis. Cardiac myosin binding protein C (cMyC) is a novel and highly specific marker of myocardial injury. We measured plasma cMyC in individuals with aortic stenosis and examined its

Myocardial Diseases: Current Views on Etiopathogenesis, Diagnostic Modalities, and Therapeutic Options

Myocardial Diseases: Current Views on Etiopathogenesis, Diagnostic Modalities, and Therapeutic Options

Prevalence and predictors of asymmetric hypertensive heart disease: insights from cardiac and aortic function with cardiovascular magnetic resonance.

We sought to determine the prevalence of asymmetric hypertensive heart disease (HHD) overlapping morphologically with hypertrophic cardiomyopathy (HCM) and to determine predictors of this pattern of hypertensive remodelling. One hundred and fifty hypertensive patients underwent 1.5 T cardiovascular magnetic resonance imaging. Twenty-one patients were excluded due to concomitant cardiac pathology that may confound the hypertrophic response, e.g. myocardial infarction, moderate-severe valvular disease, or other cardiomyopathy. Asymmetric HHD was defined as a segmental wall thickness of ≥15 mm and >1.5-fold the opposing wall in ≥1 myocardial segments, measured from short-axis cine stack at end-diastole. Ambulatory blood pressure, myocardial replacement fibrosis, aortic distensibility and aortoseptal angle were investigated as predictors of asymmetric HHD by multivariate logistic regression. Out of 129 hypertensive subjects (age: 51 ± 15 years, 50% male, systolic blood pressure: 170 ± 30 mmHg, diastolic blood pressure: 97 ± 16 mmHg), asymmetric HHD occurred in 21%. Where present, maximal end-diastolic wall thickness (EDWT) was 17.8 ± 1.9 mm and located exclusively in the basal or mid septum. In asymmetric HHD, aortoseptal angle (114 ± 10° vs. 125 ± 9° vs. 123 ± 12°, P < 0.05, respectively) was significantly reduced compared to concentric left ventricular hypertrophy (LVH) and compared to no LVH, respectively. Aortic distensibility in asymmetric HHD (1.01 ± 0.60 vs. 1.83 ± 1.65 mm2/mmHg × 103, P < 0.05, respectively) was significantly reduced compared to subjects with no LVH. Age (odds ratio [95th confidence interval]: 1.10 [1.02-1.18], P < 0.05) and indexed LV mass (1.09 [0.98-1.28], P < 0.0001) were significant, independent predictors of asymmetric HDD. Asymmetric HHD morphologically overlapping with HCM, according to the current ESC guidelines, is common. Postulating a diagnosis of HCM on the basis of EDWT of ≥15 mm should be made with caution in the presence of arterial hypertension particular in male subjects with elevated LV mass.

Abstract 18342: Development of Fibrotic Substrate for Atrial Fibrillation in Advanced Heart Failure is Driven Not by Inflammation but by Smad2/3 Dependent Replacement Fibrosis

Introduction: Fibrosis is an important contributor to atrial fibrillation (AF) substrate in heart failure, with TGF-β signaling generating atrial fibrosis. Inflammation is also known to contribute to AF. However, it is not known: a) if inflammation underlies the development of atrial fibrosis, b) if TGF-β signaling is involved in the generation of atrial inflammation and c) what is the relative role of canonical SMAD2/3 versus non-canonical TGF-β-activated kinase 1 (TAK) signaling in the creation of atrial inflammation/fibrosis. Methods: 21 dogs underwent transfection in the posterior left atria of either a plasmid expressing a dominant negative TGF-β type II receptor (pUBC-TGFβ-DN-RII) (N=9) or control vector (pUBC-LacZ) (N=12), followed by 3-4 weeks of right ventricular tachypacing (VTP) (240 bpm). After 3-4 weeks of VTP, the following were assessed: AF by open-chest mapping. Atrial tissue was assessed for signaling (pSMAD2/3 and pTAK) by western blot, fibrosis by trichrome staining and iflammation by CD68 staining. Results: The interstitial fibrosis in LacZ atria was replacement in character (Fig 1A). TGFβ-RII-DN dogs had a significant decrease in replacement fibrosis leading to a decrease in duration of inducible AF (LacZ 63.64 ± 12.12 s vs. TGFβ 26.52 ± 3.79 s, p &lt; 0.05). While both groups demonstrated evidence of inflammation (CD68 staining), there was no difference in inflammation between the groups (Fig 1B). TGFβ-RII-DN dogs had a significant decrease in pSMAD2/3 but not pTAK, compared to pUBC-LacZ dogs. Conclusion: The development of fibrotic substrate for AF in advanced HF is driven not by inflammation but primarily by SMAD2/3 mediated myocardial replacement fibrosis. These findings may have important implications for mechanism-guided therapies for AF, with canonical TGF-β signaling appearing to be an attractive therapeutic target in AF.

Prognostic significance of myocardial extracellular volume fraction in nonischaemic dilated cardiomyopathy.

In nonischaemic dilated cardiomyopathy (NICM), replacement myocardial fibrosis as detected by late gadolinium enhancement (LGE) at cardiovascular magnetic resonance (CMR) is associated with poor prognosis. We investigated the as-yet unexplored prognostic significance of interstitial fibrosis in NICM, using T1-mapping CMR. Eighty-nine NICM patients (63 men, age 59 ± 14 years) with left ventricular systolic dysfunction (ejection fraction 41 ± 13%) underwent comprehensive clinical and CMR evaluation, with extracellular volume fraction (ECV) estimation from pre and postcontrast T1 mapping. Fifteen healthy individuals (11 men, mean age 52 ± 11 years) were used as controls. The end-point was a composite of cardiovascular death, hospitalization for heart failure and appropriate defibrillator intervention. Myocardial ECV was higher in NICM patients (0.31 ± 0.05) than controls (0.25 ± 0.04, P < 0.01). In NICM patients, myocardial ECV correlated with left ventricular ejection fraction (R = 0.13), LGE extent (R = 0.17), Doppler E/E' (R = 0.17) and ventricular tachycardias (R = 0.21) at 24-h ECG monitoring (P < 0.05 for all). During a median follow-up of 24 months (interquartile range 12-42 months), 12 events occurred and higher myocardium ECV was independently associated with the occurrence of the composite end-point (P < 0.01). In NICM patients, myocardial ECV was increased compared with normal individuals, likely reflecting extracellular matrix remodelling and collagen deposition, and resulted an independent prognostic predictor beyond all other conventional clinical, electrocardiographic and echocardiographic parameters.

Myocardial interstitial remodelling in non-ischaemic dilated cardiomyopathy: insights from cardiovascular magnetic resonance.

Myocardial remodelling involves not only the myocytes, but also non-myocyte cells and the extracellular matrix, which constitutes around 6 % of the normal heart and includes fluid, collagen and glycoproteins. In non-ischaemic dilated cardiomyopathy (DCM), the cardiac interstitium increases as a result of diffuse interstitial (microscopic) fibrosis, post-necrotic replacement (macroscopic) fibrosis or myocardial oedema. The activation of the renin-angiotensin-aldosterone system is a major determinant of fibroblasts activation and collagen deposition, with the transforming growth factor β as the downstream signal mediator. Endomyocardial biopsy still represents the current reference method for interstitial and replacement myocardial fibrosis assessment, but cardiovascular magnetic resonance (CMR) allows in vivo detection of macroscopic fibrosis with post-contrast late enhancement imaging. Moreover, recent pre- and post-contrast T1 mapping techniques provide a quantitative estimation of myocardial interstitial remodelling, with potential diagnostic and prognostic clinical utility. Here, we review the pathophysiological mechanisms of myocardial interstitial remodelling in DCM, its non-invasive characterization with biomarkers and with CMR, as well as the most recent studies about their clinical utility.

Galectin-3 and myocardial fibrosis in nonischemic dilated cardiomyopathy

BackgroundLeft ventricular (LV) fibrosis, assessed by late gadolinium enhancement (LGE) at cardiac magnetic resonance imaging (MRI), is a marker of LV remodeling, and holds prognostic value in nonischemic dilated cardiomyopathy (NICM). Galectin-3 has been shown to participate in tissue fibrogenesis and to be a prognosticator in heart failure. Our aim was to investigate the relationships between galectin-3 circulating level and myocardial fibrosis at MRI in patients with NICM. Methods and resultsOne-hundred-fifty patients were enrolled (males 73%; age 58, SD 14years), with a NICM diagnosis according to the World Health Organization criteria. All patients underwent a comprehensive clinical assessment and biohumoral characterization, including galectin-3 assay, and cardiac MRI, with LGE assessment of fibrosis. Median galectin-3 value was 14.4ng/mL (IQR 11.7–19.0ng/mL), and LGE was detected in 106 (71%) patients. Patients with LGE had higher galectin-3 than those without (15.4, 11.8–21.0, vs 13.1, 11.7–16.4ng/mL, p=0.006). Among univariate predictors of LGE presence (galectin-3, male sex, disease duration, arterial hypertension, left and right ventricular ejection fraction, left ventricular stroke volume), galectin-3 maintained its predictive value at multivariate analysis, together with sex, hypertension, disease duration and right ventricular ejection fraction. At receiver operating characteristic analysis the optimal galectin-3 cut-off for LGE prediction was 14.6ng/mL (AUC 0.651, sensitivity 57%, specificity 73%). ConclusionsGalectin-3 is associated with LGE-assessed myocardial replacement fibrosis in patients with NICM. These results support the hypothesis that galectin-3 is involved in cardiac fibrosis and remodeling in NICM, and that its assay may help to select subgroups at higher risk.

In vivo diffusion-weighted MRI detection of myocardial fibrosis in hypertrophic cardiomyopathy patients

Background Recent studies have demonstrated the potential of in vivo diffusion-weighted MRI (DWI) in detecting myocardial replacement fibrosis for chronic myocardial infarction [1-3]. Despite the potential of this contrastfree technique, detecting diffuse myocardial fibrosis with DWI has not been established. Current cardiac MRI (CMR) techniques to detect diffuse myocardial fibrosis include late gadolinium enhancement (LGE) [4], pre/ post contrast T1 mapping [5], and extracellular volume (ECV) mapping [6]. We propose the application of a recently developed cardiac DWI technique [7] to detect diffuse myocardial fibrosis in HCM patients and compare its performance with established CMR techniques.

Examining the relationship between cardiac troponin T and cardiac morphology, function, and fibrosis - a cardiac magnetic resonance study

Background Elevated high sensitivity cardiac troponin (cTnT) levels, LVEF, and the degree of myocardial replacement fibrosis (RF) have been shown to be significantly associated with cardiovascular outcomes. However, the relationship amongst them has yet to be studied. Cardiac magnetic resonance (CMR) has become the gold standard for viability imaging and accurately characterizing RF. Recently, a new technique has been employed to quantify diffuse myocardial fibrosis via assessment of myocardial extracellular volume (ECV). The current study sought to investigate the association between ECV, RF, LVEF, LV mass (LVM) and cTnT levels.

Electrical Changes in Resting, Exercise, and Holter Electrocardiography in Fabry Cardiomyopathy.

In Fabry cardiomyopathy, little is known about the interaction between its key feature of myocardial replacement fibrosis and changes in resting, Holter, and exercise electrocardiography (-ECG). Resting ECG, 24-h Holter ECG, and exercise ECG were performed in 95 patients (50 women) with Fabry disease, staged using cardiac magnetic resonance imaging to measure left ventricular fibrosis. With resting ECG, T alterations were seen in patients with cardiac fibrosis, while time intervals and rhythm were unchanged (except for a longer QRS duration in patients with severe fibrosis). All patients with severe fibrosis showed T inversion, ST alteration, or both. With Holter ECG, maximum and minimum heart rate did not differ with fibrosis severity. Patients without fibrotic tissue showed less ventricular premature beats (VPB) (median 5/24h) compared to those with mild (median 11/24h) or severe fibrosis (median 115/24h; P < 0.05, respectively). Fibrosis was a strong predictor of VPB burden (r 2 = 0.5; P < 0.001). During exercise, patients with severe fibrosis had the least increase in systolic blood pressure (sBP) (47 ± 22mmHg vs. 62 ± 25mmHg, P < 0.05) and the lowest maximum heart rate (113 ± 18/min; P < 0.05). Patients with mild fibrosis had a high sBP during exercise (198 ± 37mmHg; P < 0.05). Decreased diastolic blood pressure (>10mmHg) occurred in some patients with no (3/41) or mild fibrosis (3/34) but not in patients with severe fibrosis (0/20; P < 0.01). Our data suggest that cardiac replacement fibrosis is responsible for repolarization abnormalities on resting ECG and increased VPB with Holter ECG. During exercise ECG, advanced cardiomyopathy is characterized by chronotropic incompetence with limitations on blood pressure and heart rate increase.

The Fabry cardiomyopathy - diagnostic approach and current treatment.

Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by alpha-galactosidase A deficiency. The intracellular storage of globotriaosylceramides in different tissues and organs leads to a multisystemic disease affecting kidneys, nervous system and the heart. Fabry cardiomyopathy is frequent and leads to concentric left-ventricular hypertrophy. Typical pattern in advanced stages is myocardial replacement fibrosis, first localized to mid myocardial layers of postero-lateral basal myocardium and then spreading to transmural fibrosis.Long term prognosis is dependent on timely initiation of specific and concomitant therapies, while therapy in advanced stages is only able to stabilize the organ affection. This review describes the characteristics of Fabry cardiomyopathy, shows the clinical assessment of cardiac involvement and highlights therapeutic issues aiming at the best outcome for patients with Fabry disease.

Multi-ethnic study of atherosclerosis: association between left atrial function using tissue tracking from cine MR imaging and myocardial fibrosis.

To investigate the association between left atrial ( LA left atrium ) function and left ventricular myocardial fibrosis using cardiac magnetic resonance (MR) imaging in a multi-ethnic population. For this HIPAA-compliant study, the institutional review board at each participating center approved the study protocol, and all participants provided informed consent. Of 2839 participants who had undergone cardiac MR in 2010-2012, 143 participants with myocardial scar determined with late gadolinium enhancement and 286 age-, sex-, and ethnicity-matched control participants were identified. LA left atrium volume, strain, and strain rate were analyzed by using multimodality tissue tracking from cine MR imaging. T1 mapping was applied to assess diffuse myocardial fibrosis. The association between LA left atrium parameters and myocardial fibrosis was evaluated with the Student t test and multivariable regression analysis. The scar group had significantly higher minimum LA left atrium volume than the control group (mean, 22.0 ± 10.5 [standard deviation] vs 19.0 ± 7.8, P = .002) and lower LA left atrium ejection fraction (45.9 ± 10.7 vs 51.3 ± 8.7, P < .001), maximal LA left atrium strain ( Smax maximum LA strain ) (25.4 ± 10.7 vs 30.6 ± 10.6, P < .001) and maximum LA left atrium strain rate ( SRmax maximum LA strain rate ) (1.08 ± 0.45 vs 1.29 ± 0.51, P < .001), and lower absolute LA left atrium strain rate at early diastolic peak ( SRE LA strain rate at early diastolic peak ) (-0.77 ± 0.42 vs -1.01 ± 0.48, P < .001) and LA left atrium strain rate at atrial contraction peak ( SRA LA strain rate at atrial contraction peak ) (-1.50 ± 0.62 vs -1.78 ± 0.69, P < .001) than the control group. T1 time 12 minutes after contrast material injection was significantly associated with Smax maximum LA strain (β coefficient = 0.043, P = .013), SRmax maximum LA strain rate (β coefficient = 0.0025, P = .001), SRE LA strain rate at early diastolic peak (β coefficient = -0.0016, P = .027), and SRA LA strain rate at atrial contraction peak LA strain rate at atrial contraction peak (β coefficient -0.0028, P = .01) in the regression model. T1 time 25 minutes after contrast material injection was significantly associated with SRmax maximum LA strain rate (β coefficient = 0.0019, P = .016) and SRA LA strain rate at atrial contraction peak (β coefficient = -0.0022, P = .034). Reduced LA left atrium regional and global function are related to both replacement and diffuse myocardial fibrosis processes. Clinical trial registration no.: NCT00005487

High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis

AimsHigh-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis. We sought to investigate the mechanism for troponin release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome.Methods and resultsPlasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay. First, in the Mechanism Cohort, 122 patients with aortic stenosis (median age 71, 67% male, aortic valve area 1.0 ± 0.4 cm2) underwent cardiovascular magnetic resonance and echocardiography to assess left ventricular (LV) myocardial mass, function, and fibrosis. The indexed LV mass and measures of replacement fibrosis (late gadolinium enhancement) were associated with cTnI concentrations independent of age, sex, coronary artery disease, aortic stenosis severity, and diastolic function. In the separate Outcome Cohort, 131 patients originally recruited into the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact of REgression (SALTIRE) study, had long-term follow-up for the occurrence of aortic valve replacement (AVR) and cardiovascular deaths. Over a median follow-up of 10.6 years (1178 patient-years), 24 patients died from a cardiovascular cause and 60 patients had an AVR. Plasma cTnI concentrations were associated with AVR or cardiovascular death HR 1.77 (95% CI, 1.22 to 2.55) independent of age, sex, systolic ejection fraction, and aortic stenosis severity.ConclusionsIn patients with aortic stenosis, plasma cTnI concentration is associated with advanced hypertrophy and replacement myocardial fibrosis as well as AVR or cardiovascular death.

Late gadolinium enhancement is common in patients with hypertrophic cardiomyopathy and no clinical risk factors for sudden cardiac death: A single center experience

Cardiac magnetic resonance (CMR) is used in the diagnosis and risk stratification of hypertrophic cardiomyopathy (HCM) and can detect myocardial replacement fibrosis (anindependent predictor of adverse cardiac outcomes) using late gadolinium enhancement (LGE). We retrospectively analysed CMR studies carried out over a 2 year period identifying those which were diagnostic of HCM. 117 cases were analysed. Mean age of subjects was 53 years and 78 (67%) were male. Mean ejection fraction (EF) was 68.3% with a mean left ventricular (LV) mass index of 89.4 g/m². Hypertrophy was predominantly asymmetric in 94 (80%). All subjects received gadolinium and 80 (68%) had evidence of LGE. LVEF was lower (67 vs. 71%; p = 0.015) and LV mass index higher (94 vs. 81 g/m²; p = 0.007) in the LGE group. The proportion of patients with at least 1 clinical risk factor for sudden cardiac death (SCD) was similar in groups with and without LGE (48% vs. 32%; p = 0.160). In this study, a significant proportion (62%) of patients without clinical risk factors for SCD were found to have LGE on CMR. These patients would not currently be considered for therapy with an implantable cardiac defibrillator. 1. Patients with HCM are at increased risk of SCD, but identifying patients who may benefit from implantable defibrillators is difficult. 2. LGE is associated with adverse cardiovascular outcomes in HCM, but is present in a large proportion of patients. 3. Many patients without clinical risk factors for SCD have LGE and would not currently be considered for an implantable cardiac device.

Relationship between CMR derived myocardial extracellular volume and myocardial replacement scarring in non-ischemic cardiomyopathy

Background The measurement of the extent of myocardial replacement fibrosis in non-ischemic cardiomyopathy (NICMP) has been shown to correlate with clinical cardiac outcomes Although delayed enhancement cardiovascular magnetic resonance (DE-CMR) has been established as the reference standard for assessing myocardial replacement fibrosis (RF), this imaging process is unable to identify more subtle diffuse interstitial fibrosis (IF) in the myocardium. Newer T1 mapping after the administration of gadolinium contrast has been shown to adequately assess increases in extracellular volume (ECV) fraction, which occurs in the setting of IF. In this study, we sought to evaluate the relationship between RF and IF in patients with NICMP. Methods Eighty consecutive patients with NICMP underwent DECMR and T1 mapping using a Modified Look-Locker Inversion recovery (MOLLI) technique. RF extent was determined by analysis of the DE-CMR images. The extracellular gadolinium contrast agent in the myocardium was compared to the amount of contrast in the blood in the dynamic steady state in order to estimate the ECV fraction. In order to decrease statistical variance, regions of localized RF detected on imaging were avoided when measuring the ECV. Results There was RF evident in 49 patients (61%). Patients with RF had higher ECV compared to those without RF (36.1 ± 10.7 and 31.9 ± 6.7 respectively; p = 0.04). The left ventricular ejection fraction (LVEF) and stroke volume (SV) were significantly lower in patients with ECV > 30% (p 30 has significantly lower LVEF (p = 0.02). There was a significant increase in ECV for patients with RF of more than 5% of LV myocardium (p 5% had ECV of 32.60 ± 6.20 and 44.70 ± 13.91%, respectively. In linear regression analysis, ECV is positively associated with scar burden (Beta weight = 0.527, p < 0.001). Conclusions The results of this study suggest that there is a positive relationship between increased RF and ECV in patients with NICMP. Our data shows that stroke volume and left ventricular ejection fraction are significantly decreased in patients with RF and in those with an increased ECV. Funding None.

Replacement fibrosis detected by CMR is a predictor of outcome in patients with non-ischemic cardiomyopathy

Background Left ventricular (LV) ejection fraction (EF) is important predictor of clinical outcomes in patients with nonischemic cardiomyopathy (NICMP). With the advent of gadolinium-enhanced cardiac magnetic resonance imaging (CMR), it has now become possible to discern the presence of myocardial replacement fibrosis (RF) with a high level of accuracy. The aim of our study is to investigate the predictive value of RF in patients with NICMP.

Abstract 18808: Relationship Between Myocardial Extracellular Volume and Myocardial Scar in Non-ischemic Cardiomyopathy Patients

Background: Delayed Enhancement (DE) Cardiovascular magnetic resonance (CMR) has been established as the reference standard for assessment of myocardial replacement fibrosis (RF) in ischemic heart disease. However DE-CMR is unable to identify diffuse interstitial fibrosis (IF). Recently, T1 mapping of the myocardium following the administration of gadolinium contrast has been shown to identify increased extracellular volume (ECV) which occurs in the setting of IF. For this study we sought to evaluate the relationship between RF and IF in patients with nonischemic cardiomyopathy (NICMP). Method: We enrolled 80 consecutive patients with NICMP who underwent DE-CMR and T1 mapping using a modified look-locker inversion recovery (MOLLI) technique. The extent of RF was determined by analysis of DE-CMR images. The ECV was estimated from the concentration of extracellular contrast agent in the myocardium relative to the blood in the dynamic steady state. Care was taken to avoid measuring ECV in regions with RF detected on DE-CMR. Results: The cohort consisted of 61.3% of patients with RF. In RF group, the mean scar burden was 7.4±9.9% of left ventricle myocardium. Patients with RF had higher ECV compared to those without RF (36.1±10.7 and 31.9±6.7 respectively; p=0.04). The left ventricular ejection fraction (LVEF) and stroke volume (SV) were significantly lower in patients with increased ECV (p&lt;0.005). Same relation held true for patients with RF (p&lt;0.005). There was a significant increase in ECV for patients with RF of more than 5% of LV myocardium (p&lt;0.001). In linear regression analysis, ECV is positively associated with scar burden (Beta weight=0.527, p&lt;0.001). Conclusion: This study suggests that LVEF and SV are significantly lower in patients with increased ECV and for those with RF. There is a positive relationship between increased ECV and RF in patients with NICMP. There appears to be a threshold effect where the largest increase in IF occurs when there is more than 5% RF.