Midwall Fibrosis Research Articles

Abstract 11908: Osteoprotegerin and Myocardial Fibrosis in Patients With Aortic Stenosis

Introduction: Understanding the mechanistic role of valve calcification and myocardial fibrosis in patients with aortic stenosis (AS) remains challenging. Osteoprotegerin (OPG), a member of the TNF receptor family, is known to mediate valve calcification in AS; however its role on myocardial fibrosis has not been evaluated. Hypothesis: We hypothesized that OPG stimulates common pathways for valve calcification and myocardial fibrosis and investigated the association of OPG and presence of myocardial fibrosis. Methods: Between 2011 and 2015, consecutive consenting patients with moderate (1.0-1.5cm2) or severe (<1cm2) AS who had cardiovascular magnetic resonance (CMR) with late gadolinium enhancement were included. CMR parameters were analysed by blinded observers and patients characterized into 3 groups according to the pattern of fibrosis: presence of midwall fibrosis, presence of chronic infarction or absence of fibrosis. OPG levels were measured using ELISA and compared between the 3 groups. Results: 113 patients (76±10 years, 78 male) were included. 37 patients had no fibrosis, 40 patients had midwall fibrosis and 34 had chronic infarction. Max OPG level was 23.01 pmol/, min 2.22 pmol/L and mean 7.24± 3.45pmol/L. OPG per group was: no fibrosis= 6.29 pmol/L, midwall fibrosis=7.13 pmol/L and chronic infarction=8.42 pmol/L. There was no association between OPG level and presence of midwall fibrosis compared to no fibrosis (p=0.114). However, patients with chronic myocardial infarction had higher OPG than patients with no fibrosis (p=0.007). Conclusions: OPG is known to promote valve calcification in patients with AS. This is the first study to demonstrate that there is no association between the level of OPG and presence of myocardial midwall fibrosis. However higher OPG was observed in patients with chronic ischemia when compared to patients with no fibrosis.

Midwall Fibrosis: Cardiac Magnetic Resonance Imaging in Risk Stratifying Cardiomyopathies

The United Kingdom’s National Institute for Health and Care Excellence guidance on implantable cardiac defibrillator (ICD) therapy recommend ICD in those with left ventricular dysfunction and a high risk of sudden cardiac death (SCD). SCD accounts for 30% deaths in non-ischaemic dilated cardiomyopathy (DCM), however risk stratifying and predicting SCD in DCM is a major management challenge. We present two cases demonstrating the potential role of cardiac magnetic resonance imaging in risk stratifying DCM.

A clinical risk score of myocardial fibrosis predicts adverse outcomes in aortic stenosis.

AimsMidwall myocardial fibrosis on cardiovascular magnetic resonance (CMR) is a marker of early ventricular decompensation and adverse outcomes in aortic stenosis (AS). We aimed to develop and validate a novel clinical score using variables associated with midwall fibrosis.Methods and resultsOne hundred forty-seven patients (peak aortic velocity (Vmax) 3.9 [3.2,4.4] m/s) underwent CMR to determine midwall fibrosis (CMR cohort). Routine clinical variables that demonstrated significant association with midwall fibrosis were included in a multivariate logistic score. We validated the prognostic value of the score in two separate outcome cohorts of asymptomatic patients (internal: n = 127, follow-up 10.3 [5.7,11.2] years; external: n = 289, follow-up 2.6 [1.6,4.5] years). Primary outcome was a composite of AS-related events (cardiovascular death, heart failure, and new angina, dyspnoea, or syncope). The final score consisted of age, sex, Vmax, high-sensitivity troponin I concentration, and electrocardiographic strain pattern [c-statistic 0.85 (95% confidence interval 0.78–0.91), P < 0.001; Hosmer–Lemeshow χ2 = 7.33, P = 0.50]. Patients in the outcome cohorts were classified according to the sensitivity and specificity of this score (both at 98%): low risk (probability score <7%), intermediate risk (7–57%), and high risk (>57%). In the internal outcome cohort, AS-related event rates were >10-fold higher in high-risk patients compared with those at low risk (23.9 vs. 2.1 events/100 patient-years, respectively; log rank P < 0.001). Similar findings were observed in the external outcome cohort (31.6 vs. 4.6 events/100 patient-years, respectively; log rank P < 0.001).ConclusionWe propose a clinical score that predicts adverse outcomes in asymptomatic AS patients and potentially identifies high-risk patients who may benefit from early valve replacement.

Mid wall fibrosis on CMR with late gadolinium enhancement may predict prognosis for LVAD and transplantation risk in patients with newly diagnosed dilated cardiomyopathy-preliminary observations from a high-volume transplant centre.

BackgroundPatients with newly diagnosed dilated cardiomyopathy (DCM) and advanced heart failure have a very high morbidity and mortality with an unpredictable clinical course. We investigated the role of cardiovascular magnetic resonance (CMR) imaging using late gadolinium enhancement (LGE) in this cohort of high‐risk patients. We hypothesized that LGE has high prognostic value in primary DCM patients referred for possible transplantation/left ventricular assist device (LVAD) consideration.MethodsOver 49 consecutive months, 61 consecutives DCM patients were referred for standard CMR(1.5T, GE) to interrogate the LV pattern, distribution, and extent of LGE (MultiHance, Princeton, NJ). Inclusion criteria for a primary non‐ischaemic DCM and EF <45% were met in 31 patients. DCM patients were categorized into: (i) presence of midwall LV stripe (+Stripe) and (ii) absence of midwall stripe (−Stripe) groups. Primary outcome was defined by the composite of death, need for LV assist device (LVAD), and urgent orthotopic cardiac transplantation (Tx) during a 12‐month follow‐up period. Kaplan–Meier survival analysis was conducted grouping patients by +Stripe and −Stripe.ResultsThere were no differences between groups for demographics, blood pressure, labs, baseline LVEF, NYHA class, or invasive haemodynamics. There were 18 patients (58%) with +Stripe. Nine events occurred: seven patients required urgent Tx and/or LVAD implantation and two patients died. The +Stripe categorization strongly predicted the need for LVAD, urgent Tx surgery, and death (log‐rank = 9, P = 0.002). All the events occurred in the +Stripe patients with no MACE experienced in the −Stripe group. The −Stripe group experienced marked signs of improvement in LVEF (P = 0.01) at follow‐up. LVEDD was predictive of need for LVAD/Tx and death by univariate analysis. Otherwise, no common clinical metric such as LVEF, LVEDV, RVEF, RVEDV, or any invasive haemodynamic parameter predicted MACE.ConclusionsThe presence of +Stripe on CMR is strongly predictive of LVAD, transplant need, and death during a 12‐month follow‐up period in DCM patients in this proof of concept study. All −Stripe patients survived without experiencing any events. Incorporating CMR imaging into routine clinical practice may have prognostic value in DCM patients; indicating conservative management in low‐risk patients while expectantly managing high‐risk patients.

Focal myocardial fibrosis assessed by late gadolinium enhancement cardiovascular magnetic resonance in children and adolescents with dilated cardiomyopathy.

BackgroundDifferent patterns of late gadolinium enhancement (LGE) including mid-wall fibrosis using cardiovascular magnetic resonance (CMR) have been reported in adult patients presenting with non-ischemic dilated cardiomyopathy (DCM). In these studies, LGE was associated with pronounced LV remodelling and predicted adverse cardiac outcomes. Accordingly, the purpose of our study was to determine the presence and patterns of LGE in children and adolescents with DCM.MethodsPatients <18 years of age presenting with severe congestive heart failure who were admitted for evaluation of heart transplantation at our centre underwent CMR examination which consisted of ventricular functional analysis and assessment of LGE for detection of myocardial fibrosis. Ischemic DCM was excluded by coronary angiography, and right ventricular endomyocardial biopsies ruled out acute myocarditis.ResultsThirty-one patients (mean age 2.1 ± 4.2 years) with severe LV dilatation (mean indexed LVEDV 136 ± 48 ml/m2) and LV dysfunction (mean LV-EF 23 ± 8%) were examined. LGE was detected in 5 of the 31 patients (16%) appearing in various patterns characterized as mid-wall (n = 1), focal patchy (n = 1), RV insertion site (n = 1) and transmural (n = 2). Based on histopathological analysis, 4 of the 5 LGE positive patients had lymphocytic myocarditis, whereas one patient was diagnosed with idiopathic DCM.ConclusionsIn children and adolescents with DCM, focal histologically proven myocardial fibrosis is rarely detected by LGE CMR despite marked LV dilatation and severely depressed LV function. LGE occurred in various patterns and mostly in patients with inflammatory cardiomyopathy. It remains unclear whether myocardial fibrosis in childhood DCM reflects different endogenous repair mechanisms that enable favourable reverse remodelling. Larger trials are needed to assess the prognostic implications of LGE in childhood DCM.

FEATURE TRACKING-BASED STRAIN ANALYSIS PREDICTS THE PRESENCE OF MYOCARDIAL FIBROSIS AMONG PATIENTS WITH NON-ISCHEMIC CARDIOMYOPATHY

Abnormal myocardial deformation has been described in the presence of regional fibrosis, as detected by late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (CMR) in patients with previous infarction, Fabry’s disease and hypertrophic cardiomyopathy. Mid-wall striae pattern fibrosis on LGE imaging has been shown to predict adverse cardiovascular outcomes among patients with non-ischemic cardiomyopathy. However, macroscopic mid-wall fibrosis is a late pathologic finding and requires administration of gadolinium based contrast agent. Non-contrast dependent markers heralding adverse remodeling are desired. In this study we describe a novel strain analysis tool employing feature tracking to predict the presence of mid-wall fibrosis in patients with non-ischemic cardiomyopathy. CMR imaging was performed in 117 patients with idiopathic non-ischemic cardiomyopathy, defined as a left ventricular ejection fraction (LVEF) <55% by CMR with no prior history of myocardial infarction and no CMR findings of ischemic or other specific cardiomyopathy states (ie. hypertrophic cardiomyopathy, amyloidosis, sarcoidosis). Blinded quantitative analysis was performed using a prototype version of a commercial software (cvi42, version 4.1.5 M192, Calgary, Alberta, Canada). Left ventricular regional strain analysis was performed to obtain both radial and circumferential strain of a mid-ventricular short axis slice cine image (Figure 1). Volumetric analysis of sequential short axis cine images was also performed. LGE images were visually scored for the presence of mid-wall striae fibrosis. Mean age was 57.8 +/- 14.5 years and 60 % of patients were male. CMR characteristics are summarized in Table 1. Mid-wall striae fibrosis was identified in 48 patients (41 %). These patients had greater indexed LV end diastolic and systolic volumes and total scar volume with lower LV and RV ejection fraction. Compared to patients without midwall striae fibrosis, radial and circumferential strain values were significantly lower in the mid anteroseptal segments among patients with midwall striae fibrosis despite corresponding anterolateral strain values being similar (Table 1). On multivariate analysis, patients with midwall striae fibrosis had a significantly lower anteroseptal to anterolateral strain ratio (AASR) for both radial (0.61±0.41 vs. 0.37±0.32, p=0.024) and circumferential strain (0.66±0.36 vs. 0.42±0.29, p=0.015). Of note, 15 (22%) patients had a low AASR despite having no midwall striae fibrosis on LGE imaging. AASR is strongly associated with the presence of midwall striae fibrosis in patients with non-ischemic cardiomyopathy. The prognostic utility of this novel imaging marker warrants future study within a prospective multi-centre study.View Large Image Figure ViewerDownload (PPT)

Late gadolinium enhancement CMR in primary mitral regurgitation.

The appropriate timing for surgery in severe asymptomatic primary mitral regurgitation (MR) remains controversial. It has been shown that late gadolinium enhancement on cardiovascular magnetic resonance (LGE CMR), which may identify myocardial fibrosis, is associated with a worse outcome in various cardiomyopathies. We sought to investigate the prevalence and significance of delayed enhancement in primary MR. We prospectively included 41 patients with at least moderate primary MR and without overt signs of left ventricular (LV) dysfunction. Patients with evidence of coronary artery disease, arrhythmias or significant concomitant valvular disease were excluded. All patients were scheduled for transthoracic echocardiography and LGE CMR. A total of 39 patients had interpretable LGE CMR images. Among them, 12 (31%) had late contrast uptake of the LV wall. LGE CMR showed an infarct pattern in three patients, a pattern of mid-wall fibrosis in seven patients and two patients had a combined pattern. Patients with delayed enhancement on CMR had significant higher LV diameters (LV end-systolic diameter 39±4 vs. 34±5mm, P=0·002; LV end-diastolic diameter 57±5 vs. 50±5mm, P=0·001). There was a trend towards a higher indexed left atrial volume (55±21 vs. 44±13mL/m², P=0·06). By contrast, there was no significant association between myocardial contrast uptake and age, LV ejection fraction and MR severity. Left ventricular remodelling seems to be associated with the presence of delayed enhancement on CMR in primary MR. Further data are needed to determine whether LGE CMR can predict a less favourable outcome or could improve risk stratification in asymptomatic primary MR.

Mid-wall fibrosis on delayed enhancement CMR - a marker for adverse left ventricular chamber remodeling independent of cardiomyopathic etiology

Background Mid-wall fibrosis (MWF) is a hallmark of non-ischemic cardiomyopathy (NICM) that confers increased risk for sudden cardiac death and mortality. The relationship between MWF and left ventricular (LV) remodeling is unknown. Methods The population comprised patients with advanced systolic dysfunction (LVEF ≤ 40%) undergoing CMR (1.5T, General Electric Signa). Ischemic vs. NICM etiology was classified in accordance with established convention based on obstructive CAD on invasive angiography. Delayed enhancement CMR (IR-GRE acquired 10-30 minutes post gadolinium [0.2 mmol/kg]) was used to identify MWF, defined as hyperenhancement confined to the mid-myocardial or epicardial aspect of the interventricular septum. LV mass and chamber volume were quantified by planimetry of contiguous SSFP cine-CMR short axis slices, with ejection fraction (EF) calculated as the proportional difference between end-diastolic (EDV) and end-systolic (ESV) volumes. Results 523 patients (61 ± 14 yo, 72% M, 66% ischemic CM) were studied: MWF was present in 16%, and was 6-fold more common in patients with angiographically classified NICM (37% vs. 6%; p < 0.001). Regarding LV remodeling, MWF was associated with higher EDV (134 ± 39 ml vs. 114 ± 34 ml; p < 0.001) and LV mass (102 ± 24 vs. 96 ± 28 gm; p < 0.001) and lower LVEF (26 ± 8% vs. 30 ± 8%; p ≤ 0.05). MWF was nearly 3-fold more common among patients in the highest tertile of EDV vs. the remainder of the population (29% vs. 10%; p < 0.001). Multivariate regression analysis was performed to further assess markers for MWF: Restricted to imaging indices, results (Table 1A) demonstrated EF and EDV to be independently associated with MWF (OR = 1.46, CI 1.03-2.10; p < 0.05, OR = 1.13, CI 1.04-1.20; p < 0.05, respectively) after controlling for mass (OR = 0.95, CI 0.85-1.00; p = 0.29). Regarding clinical variables, results (Table 1B) confirmed a strong association with NICM (OR = 8.4, CI 4.78-14.72; p < 0.001), independent of other clinical indices. A combined model incorporating both clinical and imaging variables demonstrated both NICM and LV volume to be independently associated with MWF even after controlling for EF (Table 1C). Overall strength of the combined clinical/imaging (c 2 = 91.2; p < 0.001) model for MWF was higher than that of isolated clinical (c 2 = 76.7; p < 0.001) and imaging (c 2 = 26.0; p < 0.001) models.

Mechanical effects of midwall fibrosis in non-ischemic dilated cardiomyopathy

Background In patients with non-ischemic dilated cardiomyopathy (NIDCM), mid-wall fibrosis (MWF) is associated with a higher risk of hospitalizations and death from pump failure and sudden cardiac death. The mechanical effects of MWF remain unexplored. Strain measures derived from feature tracking-CMR (FT-CMR) have been validated against myocardial tagging. Methods Patients (n = 84, age: 57.7 ± 14.7 yrs, [mean ± SD], LVEF: 25.7 ± 11.1%) with newly diagnosed NIDCM underwent late gadolinium enhancement CMR (inversion-recovery technique 10 min after the administration of gadolinium-DTPA (0.1 mmol/kg). Peak systolic cir

Titin: a phenotype-genotype descriptive comparison of dilated cardiomyopathy

Background Cardiovascular magnetic resonance (CMR) imaging is the gold standard imaging modality for characterization of dilated cardiomyopathy (DCM). We recently identified genetic variants that truncate the giant protein Titin (TTN) accounting for up to 25% of DCM cases: a discovery that will increase the utility of genetic testing and family screening in DCM. However, the clinical consequences of TTN truncating variants (TTNtv) are unknown. Here, we integrated the power of CMR and capacity of next generation sequencing (NGS) to assess the relationship between genotype and phenotype in a non-ischemic DCM population. Methods 319 patients referred for characterization of DCM were recruited and underwent quantitative CMR study with detailed phenotyping (Siemens Avanto or Siemens Sonata 1.5T scanners). Additional clinical data were collected. TTN genotypes were determined by target enrichment using SureSelect and NGS sequencing using the SOLiD 5500 platform. Results TTN truncating variants (TTNtv) were identified in 13% (n = 42) of cases, the commonest genetic cause of DCM. Table 1 compares the CMR and clinical characteristics of TTNtv-positive and TTNtv-negative cohorts. TTNtv-positive DCM patients had lower left ventricular (LV) ejection fraction (EF) (p = 0.02), thinner LV walls (p < 0.02) and higher incidence of sustained ventricular tachycardia (VT) (p = 0.001) which was independent of EF. No statistically significant difference in the prevalence of midwall fibrosis existed between the two groups. Multivariate linear regression models that considered age, sex, TTNtv presence and position (distance from the protein N-terminus) indicated that TTNtv position was significantly correlated with biventricular ejection fraction and indexed stroke volumes such that more distal truncations had worse indices of cardiac function. For example, a C-terminal TTNtv would be associated with an absolute reduction in LV EF of 18 ± 7%, (p = 0.005), as compared with an N-terminal TTNtv. Conclusions These data highlight the prevalence of TTNtv in this unselected DCM cohort and suggest that TTNtvpositive DCM patients may benefit from tailored clinical management. Sustained VT, LV wall thickness and LVEF influence DCM outcomes. The increased risk of sustained VT in TTNtv-positive DCM may warrant a lower threshold for device therapy, as recommended for DCM caused by LMNA mutations. As distal TTNtv were associated with worse LV function, more aggressive clinical management may be appropriate in patients carrying these variants. The phenotypic expression of genetic substrates can be highly variable, and CMR is central to the accurate phenotypic description of this common yet heterogenous condition. Enhanced molecular understanding may lead to strategies to alter disease course beyond current pharmacological and device based therapy.

Letter by Taylor et al Regarding Article, “Myocardial Fibrosis as a Key Determinant of Left Ventricular Remodeling in Idiopathic Dilated Cardiomyopathy: A Contrast-Enhanced Cardiovascular Magnetic Study”

HomeCirculation: Cardiovascular ImagingVol. 6, No. 6Letter by Taylor et al Regarding Article, “Myocardial Fibrosis as a Key Determinant of Left Ventricular Remodeling in Idiopathic Dilated Cardiomyopathy: A Contrast-Enhanced Cardiovascular Magnetic Study” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Taylor et al Regarding Article, “Myocardial Fibrosis as a Key Determinant of Left Ventricular Remodeling in Idiopathic Dilated Cardiomyopathy: A Contrast-Enhanced Cardiovascular Magnetic Study” Robin J. Taylor, Fraz Umar and Francisco Leyva Robin J. TaylorRobin J. Taylor Centre for Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom Search for more papers by this author , Fraz UmarFraz Umar Centre for Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom Search for more papers by this author and Francisco LeyvaFrancisco Leyva Centre for Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom Search for more papers by this author Originally published1 Nov 2013https://doi.org/10.1161/CIRCIMAGING.113.001230Circulation: Cardiovascular Imaging. 2013;6:e78To the Editor:Masci et al1 should be commended for providing new evidence with respect to late gadolinium enhancement (LGE) cardiovascular MRI in patients with idiopathic dilated cardiomyopathy (IDCM). After categorizing patients by LGE status, they demonstrated that every patient remained in the same cohort during the 2 years of follow-up, a novel finding strongly suggestive of 2 distinct phenotypes. The observed progression in myocardial fibrosis, in association with a reduction in left ventricular systolic function, adds to the growing evidence of the malignant natural history of IDCM with fibrosis.Although we concur with the authors’ view that LGE-cardiovascular MRI is key to the assessment of patients with suspected IDCM, this study did not include patients undergoing cardiac resynchronization therapy (CRT). Therefore, we do not agree with the authors’ view that patients with fibrosis should be selected for CRT at an earlier point. The experience in patients with ischemic cardiomyopathy is that scar burden relates to a poor outcome after CRT.2,3 Moreover, we have recently shown that in patients with IDCM managed with CRT, the presence of midwall fibrosis is associated with unsuccessful reverse remodeling and a dramatically higher risk of cardiovascular mortality (hazard ratio, 18.6).4 This relationship was mediated through both sudden cardiac death and pump failure.The authors also argue that the positive response of patients without LGE to optimal medical therapy should influence the clinician to delay CRT. Clearly, this group of patients has a particularly favorable outcome.4,5 Nevertheless, the authors have not provided information on the outcome in patients who would be appropriate for CRT. It is reported that 59% of patients without LGE underwent reverse left ventricular remodeling, but it would be useful to know the further specific influence of QRS duration on this. Importantly, 14% of the study population were excluded from follow-up analyses because they received device therapy. Arguably, CRT may be paramount to left ventricular reverse remodeling in this subgroup.In essence, Masci et al1 have shown that patients with IDCM and myocardial fibrosis have a worse outcome than patients without fibrosis after medical therapy. However, because the study cohort did not include patients undergoing CRT, no conclusions can be drawn as to the eligibility or timing of CRT.Robin J. Taylor, MBChB, MRCPFraz Umar, MRCPFrancisco Leyva, MBChB, MDCentre for Cardiovascular SciencesUniversity of BirminghamEdgbaston, Birmingham, United KingdomDisclosuresNone.

Advanced diffuse fibrosis is associated with mid-wall fibrosis in patients with aortic stenosis

Purpose: To determine the association between diffuse fibrosis by T1 mapping and mid-wall fibrosis (MwF) by delayed enhancement in patients with aortic stenosis (AS). Methods: In a prospective study, patients with AS and no myocardial infarction underwent cardiovascular magnetic resonance (CMR) at 3T. Using modified look-locker inversion sequences, T1 maps were generated pre- and 20 min post-contrast (gadobutrol, 0.1 mmol/kg). Contrast volume of distribution (Vd; ΔRmyocardium/ΔRbloodx[1-hematocrit], where ΔR=1/post-contrast T1–1/pre-contrast T1) was measured at the short-axis, mid-cavity level in patients without MwF. In patients with MwF, Vd was measured at the short-axis level of MwF, excluding regions of enhancement. AS severity was assessed with echocardiography [aortic valve area, mean pressure gradient, trans-aortic velocity (Vm)]. Indices of left ventricular hypertrophy were evaluated with CMR [indexed left ventricular mass (LVMi) and mass/volume ratio (M/V; LVM/end-diastolic volume)]. Logistic regression was used to determine the association between Vd and MwF, adjusting for potential confounders. Results: Sixty patients were studied (70% males; 71±9 years, Vm 3.6±0.9m/s). MwF was identified in 33%. Patients with MwF had higher LVMi (91±22 vs. 79±16g/m2, p=0.03), M/V (1.21±0.22 vs. 1.08±0.19, p=0.02), Vm (3.9±0.7 vs. 3.5±0.9m/s, p=0.04) and Vd (28.7±2.5 vs. 26.7±2.0%, p<0.01). After adjusting for age, gender, AS severity and left ventricular remodeling indices, Vd was independently associated with MwF (odds ratio 1.55, 95% confidence interval 1.04-2.32). ![Figure][1] Conclusions: MwF is independently associated with an increased level of diffuse fibrosis. Diffuse fibrosis by T1 mapping is an early marker of myocardial response to ventricular hypertrophy. [1]: pending:yes

Association of Fibrosis With Mortality and Sudden Cardiac Death in Patients With Nonischemic Dilated Cardiomyopathy

Risk stratification of patients with nonischemic dilated cardiomyopathy is primarily based on left ventricular ejection fraction (LVEF). Superior prognostic factors may improve patient selection for implantable cardioverter-defibrillators (ICDs) and other management decisions. To determine whether myocardial fibrosis (detected by late gadolinium enhancement cardiovascular magnetic resonance [LGE-CMR] imaging) is an independent and incremental predictor of mortality and sudden cardiac death (SCD) in dilated cardiomyopathy. Prospective, longitudinal study of 472 patients with dilated cardiomyopathy referred to a UK center for CMR imaging between November 2000 and December 2008 after presence and extent of midwall replacement fibrosis were determined. Patients were followed up through December 2011. Primary end point was all-cause mortality. Secondary end points included cardiovascular mortality or cardiac transplantation; an arrhythmic composite of SCD or aborted SCD (appropriate ICD shock, nonfatal ventricular fibrillation, or sustained ventricular tachycardia); and a composite of HF death, HF hospitalization, or cardiac transplantation. Among the 142 patients with midwall fibrosis, there were 38 deaths (26.8%) vs 35 deaths (10.6%) among the 330 patients without fibrosis (hazard ratio [HR], 2.96 [95% CI, 1.87-4.69]; absolute risk difference, 16.2% [95% CI, 8.2%-24.2%]; P < .001) during a median follow-up of 5.3 years (2557 patient-years of follow-up). The arrhythmic composite was reached by 42 patients with fibrosis (29.6%) and 23 patients without fibrosis (7.0%) (HR, 5.24 [95% CI, 3.15-8.72]; absolute risk difference, 22.6% [95% CI, 14.6%-30.6%]; P < .001). After adjustment for LVEF and other conventional prognostic factors, both the presence of fibrosis (HR, 2.43 [95% CI, 1.50-3.92]; P < .001) and the extent (HR, 1.11 [95% CI, 1.06-1.16]; P < .001) were independently and incrementally associated with all-cause mortality. Fibrosis was also independently associated with cardiovascular mortality or cardiac transplantation (by fibrosis presence: HR, 3.22 [95% CI, 1.95-5.31], P < .001; and by fibrosis extent: HR, 1.15 [95% CI, 1.10-1.20], P < .001), SCD or aborted SCD (by fibrosis presence: HR, 4.61 [95% CI, 2.75-7.74], P < .001; and by fibrosis extent: HR, 1.10 [95% CI, 1.05-1.16], P < .001), and the HF composite (by fibrosis presence: HR, 1.62 [95% CI, 1.00-2.61], P = .049; and by fibrosis extent: HR, 1.08 [95% CI, 1.04-1.13], P < .001). Addition of fibrosis to LVEF significantly improved risk reclassification for all-cause mortality and the SCD composite (net reclassification improvement: 0.26 [95% CI, 0.11-0.41]; P = .001 and 0.29 [95% CI, 0.11-0.48]; P = .002, respectively). Assessment of midwall fibrosis with LGE-CMR imaging provided independent prognostic information beyond LVEF in patients with nonischemic dilated cardiomyopathy. The role of LGE-CMR in the risk stratification of dilated cardiomyopathy requires further investigation.

Prediction of ventricular arrhythmias using cardiovascular magnetic resonance

Ventricular tachycardia (VT) is the commonest cause of sudden cardiac death (SCD) in developed countries. Coronary artery disease (CAD) is the most frequent cause of VT in individuals over the age of 30, while hypertrophic cardiomyopathy (HCM), myocarditis and congenital heart disease in those below 30 years of age. Cardiac magnetic resonance (CMR), a non-invasive, non-radiating technique, can reliably detect the changes in ventricular volumes and the ejection fraction that can be predictive of VT/SCD. Furthermore, the capability of CMR to perform tissue characterization and detect oedema, fat and fibrotic substrate, using late gadolinium enhanced images (LGE), can predict VT/SCD in both ischaemic and non-ischaemic cardiomyopathy. The extent of LGE in HCM is correlated with risk factors of SCD and the likelihood of inducible VT. In idiopathic-dilated cardiomyopathy, the presence of midwall fibrosis, assessed by CMR, also predicts SCD/VT. Additionally, in arrhythmogenic right ventricle (RV) dysplasia/cardiomyopathy, CMR has an excellent correlation with histopathology and predicted inducible VT on programmed electrical stimulation, suggesting a possible role in evaluation and diagnosis of these patients. A direct correlation between LGE and VT prediction has been identified only in chronic Chagas' heart disease, but not in viral myocarditis. In CAD, infarct size is the strongest predictor of VT inducibility. The peri-infarct zone may also play a role; however, further studies are needed for definite conclusions. Left ventricle, RV, right ventricular outflow tract (RVOT) function, pulmonary regurgitation and LGE around the infundibular patch and RV anterior wall play an important role in the VT prediction in repaired Tetralogy of Fallot. Finally, in treated transposition of great arteries, the extent of LGE in the systemic RV correlates with age, ventricular dysfunction, electrophysiological parameters and adverse clinical events, suggesting prognostic importance.

Left Ventricular Midwall Fibrosis as a Predictor of Mortality and Morbidity After Cardiac Resynchronization Therapy in Patients With Nonischemic Cardiomyopathy

The aim of this study was to determine whether left ventricular (LV) midwall fibrosis, detected by midwall hyperenhancement (MWHE) on late gadolinium enhancement cardiovascular magnetic resonance (CMR) imaging, predicts mortality and morbidity in patients with dilated cardiomyopathy (DCM) undergoing cardiac resynchronization therapy (CRT). Midwall fibrosis predicts mortality and morbidity in patients with DCM. Patients with DCM with (+) or without (-) MWHE (n = 20 and n = 77, respectively) as well as 161 patients with ischemic cardiomyopathy (ICM) undergoing CRT (n = 258) were followed up for a maximum of 8.7 years. Among patients with DCM, +MWHE predicted cardiovascular mortality (hazard ratio [HR]: 18.6; 95% confidence intervals [CI]: 3.51 to 98.5; p = 0.0008), total mortality or hospitalization for major adverse cardiovascular events (HR: 7.57; 95% CI: 2.71 to 21.2; p < 0.0001), and cardiovascular mortality or heart failure hospitalizations (HR: 9.56; 95% CI: 2.72 to 33.6; p = 0.0004), independent of New York Heart Association class, QRS duration, atrial fibrillation, LV volumes, LV ejection fraction, and a CMR-derived measure of dyssynchrony. Among patients with DCM and ICM, the risk of cardiovascular mortality for DCM +MWHE (adjusted HR: 18.5; 95% CI: 3.93 to 87.3; p = 0.0002) was similar to that for ICM (adjusted HR: 21.0; 95% CI: 5.06 to 87.2; p < 0.0001). Both DCM +MWHE and ICM were predictors of pump failure death as well as sudden cardiac death. LV reverse remodeling was observed in DCM -MWHE and in ICM but not in DCM +MWHE. Midwall fibrosis is an independent predictor of mortality and morbidity in patients with DCM undergoing CRT. The outcome of DCM with midwall fibrosis is similar to that of ICM. This relationship is mediated by both pump failure and sudden cardiac death.

Prognostic significance of midwall fibrosis in dilated cardiomyopathy

Methods Consecutive patients with DCM referred for CMR between 2002-2008 were prospectively enrolled. The diagnosis of DCM was made using clinical, CMR and coronary angiographic findings. Patients with ischemic heart disease, primary valvar disease and infiltrative CM were excluded. LGE-CMR at 1.5T (Siemens Sonata or Avanto, Germany) was performed in 2 phase-encoding directions. The presence of midwall LGE was determined by a specialist blinded to all outcome data. The primary endpoint was all-cause mortality. The secondary endpoint was a composite of cardiovascular (CV) mortality or cardiac transplantation.

Midwall Fibrosis Is an Independent Predictor of Mortality in Patients With Aortic Stenosis

Midwall Fibrosis Is an Independent Predictor of Mortality in Patients With Aortic Stenosis

Evaluation of Sudden Cardiac Death, Using Cardiovascular Magnetic Resonance

Coronary artery disease is the most frequent cause of SCD in individuals over the age of 30, while hypertrophic cardiomyopathy in those below 30 years of age. Cardiac magnetic resonance (CMR), a noninvasive, non-radiating technique, can reliably perform evaluation of 1) cardiac function through assessment of ventricular volumes and ejection fraction and 2) tissue characterization through oedema, fat and fibrotic substrate assessment. The presence of scar has been linked to ventricular arrhythmias, which is believed to be the major cause of SCD in both ischemic and nonischemic cardiomyopathy. The extent of late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy is correlated with risk factors of SCD. In idiopathic dilated cardiomyopathy, the presence of midwall fibrosis, assessed by CMR, also predicts SCD. In coronary artery disease, infarct size is the strongest predictor of SCD. LGE around infundibular patch and RV anterior wall, among other functional parameters, also play an important role in SCD prediction in repaired Tetralogy of Fallot (TOF). Finally, in treated transposition of great arteries (TGA), the extent of LGE in systemic RV also correlates with SCD development.

Midwall Fibrosis Is an Independent Predictor of Mortality in Patients With Aortic Stenosis

The goal of this study was to assess the prognostic significance of midwall and infarct patterns of late gadolinium enhancement (LGE) in aortic stenosis. Myocardial fibrosis occurs in aortic stenosis as part of the hypertrophic response. It can be detected by LGE, which is associated with an adverse prognosis in a range of other cardiac conditions. Between January 2003 and October 2008, consecutive patients with moderate or severe aortic stenosis undergoing cardiovascular magnetic resonance with administration of gadolinium contrast were enrolled into a registry. Patients were categorized into absent, midwall, or infarct patterns of LGE by blinded independent observers. Patient follow-up was completed using patient questionnaires, source record data, and the National Strategic Tracing Service. A total of 143 patients (age 68 ± 14 years; 97 male) were followed up for 2.0 ± 1.4 years. Seventy-two underwent aortic valve replacement, and 27 died (24 cardiac, 3 sudden cardiac deaths). Compared with those with no LGE (n = 49), univariate analysis revealed that patients with midwall fibrosis (n = 54) had an 8-fold increase in all-cause mortality despite similar aortic stenosis severity and coronary artery disease burden. Patients with an infarct pattern (n = 40) had a 6-fold increase. Midwall fibrosis (hazard ratio: 5.35; 95% confidence interval: 1.16 to 24.56; p = 0.03) and ejection fraction (hazard ratio: 0.96; 95% confidence interval: 0.94 to 0.99; p = 0.01) were independent predictors of all-cause mortality by multivariate analysis. Midwall fibrosis was an independent predictor of mortality in patients with moderate and severe aortic stenosis. It has incremental prognostic value to ejection fraction and may provide a useful method of risk stratification.

407 Tissue injury and stress hypo-perfusion in hypertrophic cardiomyopathy: Spatial correlation of T2-wieghted imaging, first-pass stress perfusion imaging and delayed enhancement imaging using cardiovascular magnetic resonance

407 Tissue injury and stress hypo-perfusion in hypertrophic cardiomyopathy: Spatial correlation of T2-wieghted imaging, first-pass stress perfusion imaging and delayed enhancement imaging using cardiovascular magnetic resonance