ABSTRACT: The myocardial longitudinal relaxation time (T1) on cardiac magnetic resonance imaging (CMR) can quantify myocardial fibrosis in the presence or absence of visually detectable late gadolinium (Gd) enhancement (LGE). Mineralocorticoid receptor antagonist (MRA) treatment produces beneficial remodeling in nonischemic dilated cardiomyopathy (NIDCM). We assessed the hypothesis that interstitial myocardial fibrosis measured with the use of CMR predicts left ventricular (LV) beneficial remodeling in NIDCM after heart failure (HF) treatment including MRAs.Twelve patients with NIDCM, on stable beta-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor-blocking therapy, were studied before and after 6-29 months of treatment with MRAs, by means of CMR assessment of LV structure, function, and T1 from standard Look-Locker sequences (T1LL). All patients had depressed cardiac function, dilated left ventricles, and no visual LGE. After adding MRA to HF treatment, the LV ejection fraction increased and the LV end-systolic volume index (LV end-systolic volume/m2) decreased in all patients (P?
Project description:BACKGROUND:Mineralocorticoid receptor antagonist (MRA) treatment produces beneficial left ventricular (LV) remodeling in nonischemic dilated cardiomyopathy (NIDCM). This study addressed the timing of maximal beneficial LV remodeling in NIDCM when adding MRA. MATERIALS AND METHODS:We studied 12 patients with NIDCM on stable ?-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor-blocking therapy who underwent cardiac magnetic resonance imaging before and after 6-31 months of continuous MRA therapy. RESULTS:At baseline, the LV ejection fraction (LVEF) was 24% (19-27); median [interquartile range]. The LV end-systolic volume index (LVESVI) was 63 ml (57-76) and the LV stroke volume index (LVSVI) was 19 ml (14-21), all depressed. After adding MRA to the HF regimen, the LVEF increased to 47% (42-52), with a decrease in LVESVI to 36 ml (33-45) and increase in LVSVI to 36 ml (28-39) (for each, P ?< 0?.0001). Using generalized least squares analysis, the maximal beneficial remodeling (defined by maximal increase in LVEF, the maximal decrease in LVESVI and maximal increase in LVSVI) was achieved after approximately 12-16 months of MRA treatment. CONCLUSIONS:Adding MRA to a standard medical regimen for NIDCM resulted in beneficial LV remodeling. The maximal beneficial remodeling was achieved with 12-16 months of MRA therapy. These results have implications for the timing of other advanced therapies, such as placing internal cardioverter-defibrillators.
Project description:Left ventricular (LV) energy supply-demand imbalance is postulated to cause "energy starvation" and contribute to heart failure (HF) in nonischemic dilated cardiomyopathy (NIDCM). Using cardiac magnetic resonance (CMR) and [(11)C] acetate positron emission tomography (PET), we evaluated LV perfusion and oxidative metabolism in NIDCM and the effects of spironolactone on LV supply-demand relations.Twelve patients with NIDCM underwent CMR and PET at baseline and after ≥6 months of spironolactone therapy added to a standard HF regimen. The myocardial perfusion reserve index (MPRI) was calculated after gadolinium injection during adenosine, as compared to rest. The monoexponential clearance rate of [(11)C] acetate (kmono) was used to calculate the work metabolic index (WMI), an index of LV mechanical efficiency, and kmono/RPP (rate-pressure product), an index of energy supply/demand. At baseline, the subendocardium was hypoperfused versus the subepicardium (median MPRI, 1.63 vs. 1.80; P<0.001), but improved to 1.80 (P<0.001) after spironolactone. The WMI increased (P=0.001), as did kmono/RPP (P=0.003). These improvements were associated with reverse remodeling, increased LV ejection fraction, and decreases in LV mass and systolic wall stress (all P<0.002).NIDCM is associated with subendocardial hypoperfusion and impaired myocardial oxidative metabolism, consistent with energy starvation. Antifailure therapy improves parameters of energy starvation and is associated with augmented LV performance.http://www.clinicaltrials.gov/ Unique identifier: ID NCT00574119.
Project description:BACKGROUND:It has been reported that left ventricular (LV) myocardial strain and late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging have prognostic value in patients with heart failure (HF). However, previous studies included patients with various systolic functions. This study aimed to investigate the prognostic value of LV myocardial strain and LGE on CMR imaging in patients with idiopathic dilated cardiomyopathy (DCM) with reduced ejection fraction (EF?<?40%). METHODS:From a prospectively followed cohort who underwent CMR between November 2008 and December 2015, subjects with LV EF?<?40% and a diagnosis of idiopathic DCM were eligible for this study. The CMR images were analyzed for LV and right ventricular (RV) function, presence and extent of LGE, and LV myocardial strain. The primary outcome was a composite of all-cause death and heart transplantation. The secondary outcome was hospitalization for HF. RESULTS:A total of 172 patients were included, in whom mean LV EF was 23.7?±?7.9% (EF 30-40% n?=?47; EF?<?30% n?=?125). During a median follow-up of 47 months, the primary outcome occurred in 43 patients (16 heart transplantations, 29 all-cause deaths), and there were 41 hospitalizations for HF. Univariate Cox proportional hazard regression analysis showed that mean arterial pressure, serum sodium concentration, log of plasma NT-proBNP level, and presence of LGE (HR 2.277, 95% CI: 1.221-4.246) were significantly associated with the primary outcome. However, LV strain had no significant association (HR 1.048, 95% CI: 0.945-1.163). Multivariable analysis showed that presence of LGE (HR 4.73, 95% CI: 1.11-20.12) and serum sodium (HR 0.823, 95% CI: 0.762-0.887) were independently associated with the primary outcome. CONCLUSIONS:LGE in CMR imaging was a good predictor of adverse outcomes for patients with idiopathic DCM and reduced EF. Identification of LGE could thus improve risk stratification in high-risk patients. LV strain had no significant prognostic value in patients with moderate to severe systolic dysfunction.
Project description:OBJECTIVES:In patients with nonischemic dilated cardiomyopathy (NIDCM), native T1, partition coefficient (?Gd), and extracellular volume fraction (ECV) mapping may offer prognostic values beyond late gadolinium enhancement (LGE), by scaling the range of myocardial changes. BACKGROUND:In patients with NIDCM, LGE is seen in 30% of patients and it indicates adverse prognosis. METHODS:The study mapped 6 anatomical locations using all 4 cardiac magnetic resonance (CMR) tissue-characterizing methods and associated with outcome. The authors performed T1 mapping of the myocardium and the blood pool, before and serially after contrast injection, using a Look-Locker cine gradient-echo technique to obtain T1 and the corresponding reciprocal R1 values. ?Gd values were derived from the slopes of the least-squares regression lines for myocardial versus blood R1, then adjusted to serum hematocrit to yield ECV. RESULTS:Consecutive 240 NIDCM patients (49 ± 16 years of age; 38% women) underwent CMR for cardiac function, LGE, native T1, ?Gd, and ECV. After a median of 3.8 years, 36 (15%) experienced major adverse cardiac events (MACE), including 22 heart failure hospitalizations and 14 deaths. Nonischemic LGE was detected in 34%, whereas ECV was elevated (?1 location) in 58%. Comparing the 4 methods, mean ECV and ?Gd both demonstrated strong association with MACE (both p < 0.001). In contrast to native T1 and LGE, ECV values from all 6 locations were associated with MACE and death, with the anteroseptum being the most significant (p < 0.0001). The number of abnormal ECV locations correlated linearly with annual MACE rates (p = 0.0003). Mean ECV was the only predictor to enter a prognostic model that contained age, sex, New York Heart Association functional class, and left ventricular ejection fraction. For every 10% increase, mean ECV portended to a 2.8-fold adjusted increase risk to MACE (p < 0.001). CONCLUSIONS:In this study of patients with NIDCM, mapping the myocardial extent of abnormality using ECV offers prognostication toward heart failure outcomes incremental to LGE or native T1 mapping.
Project description:OBJECTIVE:To evaluate the reproducibility of first-pass contrast-enhanced cardiac MR (CMR) myocardial perfusion imaging in patients with non-ischaemic dilated cardiomyopathy (NIDCM). DESIGN:Prospective observational study. SETTING:Single centre, tertiary care hospital. PARTICIPANTS:6 outpatient participants with NIDCM. OUTCOME:Reproducibility of semiquantitative myocardial perfusion analysis by CMR. METHOD:6 patients with NIDCM were studied twice using first-pass of contrast transit through the left ventricular (LV) myocardium with a saturation-recovery gradient echo sequence at rest and during adenosine-induced hyperaemia. The anterior wall was divided into endocardial (Endo) and epicardial (Epi) segments. The Myocardial Perfusion Index (MPI) was calculated as the myocardial signal augmentation rate normalised to the LV cavity rate. The Myocardial Perfusion Reserve Index (MPRI) was calculated as hyperaemic/resting MPI. RESULTS:Between study 1 and 2, median MPI was similar for resting Endo (0.076 vs 0.077), hyperaemic Endo (0.143 vs 0.143), resting Epi (0.073 vs 0.074), and hyperaemic Epi (0.135 vs 0.134). Median MPRI was similar for Endo (1.84 vs 1.87) and Epi (1.90 vs 2.00). Combining Endo and Epi MPI (N=12), there was excellent agreement between Study 1 and 2 for resting MPI (r=0.998, intraclass correlation coefficient (ICC) 0.998, coefficients of variation (CoV) 1.4%), hyperaemic MPI (r=0.979, ICC 0.963, CoV 3.3%) and MPRI (r=0.989, ICC 0.94, CoV 3.8%). CONCLUSIONS:Resting and hyperaemic myocardial perfusion using a normalised upslope analysis during adenosine CMR is a highly reproducible technique in patients with NIDCM. TRIAL REGISTRATION NUMBER:Clinical Trials.Gov ID NCT00574119.
Project description:Aims: Patients who present with non-ischemic dilated cardiomyopathy (NIDCM) and enhancement on late gadolinium magnetic resonance imaging (LGE-CMR), are at high risk of sudden cardiac death (SCD). Further risk stratification of these patients based on LGE-CMR may be improved through better understanding of fibrosis microstructure. Our aim is to examine variations in fibrosis microstructure based on LGE imaging, and quantify the effect on reentry inducibility and mechanism. Furthermore, we examine the relationship between transmural activation time differences and reentry. Methods and Results: 2D Computational models were created from a single short axis LGE-CMR image, with 401 variations in fibrosis type (interstitial, replacement) and density, as well as presence or absence of reduced conductivity (RC). Transmural activation times (TAT) were measured, as well as reentry incidence and mechanism. Reentries were inducible above specific density thresholds (0.8, 0.6 for interstitial, replacement fibrosis). RC reduced these thresholds (0.3, 0.4 for interstitial, replacement fibrosis) and increased reentry incidence (48 no RC vs. 133 with RC). Reentries were classified as rotor, micro-reentry, or macro-reentry and depended on fibrosis micro-structure. Differences in TAT at coupling intervals 210 and 500ms predicted reentry in the models (sensitivity 89%, specificity 93%). A sensitivity analysis of TAT and reentry incidence showed that these quantities were robust to small changes in the pacing location. Conclusion: Computational models of fibrosis micro-structure underlying areas of LGE in NIDCM provide insight into the mechanisms and inducibility of reentry, and their dependence upon the type and density of fibrosis. Transmural activation times, measured at the central extent of the scar, can potentially differentiate microstructures which support reentry.
Project description:BACKGROUND:Hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) are both associated with an increased left ventricular (LV) wall thickness. Whilst LV ejection fraction is frequently normal in both, LV strain assessment could differentiate between the diseases. We sought to establish if cardiovascular magnetic resonance myocardial feature tracking (CMR-FT), an emerging method allowing accurate assessment of myocardial deformation, differentiates between both diseases. Additionally, CMR assessment of fibrosis and LV hypertrophy allowed association analyses and comparison of diagnostic capacities. METHODS:Two-hundred twenty-four consecutive subjects (53 HHD, 107 HCM, and 64 controls) underwent 1.5T CMR including native myocardial T1 mapping and late gadolinium enhancement (LGE). Global longitudinal strain (GLS) was assessed by CMR-FT (CVi42, Circle Cardiovascular Imaging Inc.). RESULTS:GLS was significantly higher in HCM patients (-14.7±3.8 vs. -16.5±3.3% [HHD], P = 0.004; or vs. -17.2±2.0% [controls], P<0.001). GLS was associated with LV mass index (HHD, R = 0.419, P = 0.002; HCM, R = 0.429, P<0.001), and LV ejection fraction (HHD, R = -0.493, P = 0.002; HCM, R = -0.329, P<0.001). In HCM patients, GLS was also associated with global native T1 (R = 0.282, P = 0.003), and LGE volume (? = 0.380, P<0.001). Discrimination between HHD and HCM by GLS (c = 0.639, 95% confidence interval [CI] 0.550-0.729) was similar to LV mass index (c = 0.643, 95% CI 0.556-0.731), global myocardial native T1 (c = 0.718, 95% CI 0.638-0.799), and LGE volume (c = 0.680, 95% CI 0.585-0.775). CONCLUSION:CMR-FT GLS differentiates between HHD and HCM. In HCM patients GLS is associated with myocardial fibrosis. The discriminatory capacity of CMR-FT GLS is similar to LV hypertrophy and fibrosis imaging markers.
Project description:Left ventricular (LV) trabeculation has been studied in certain forms of cardiomyopathy. However, the changes of LV endocardial trabeculation during the remodeling process leading to heart failure (HF) are unclear. Seventy-four patients with systolic heart failure (SHF), 65 with heart failure with preserved ejection fraction (HFpEF) and 61 without HF were prospectively enrolled. All subjects received magnetic resonance imaging (MRI) study including cine, T1 and late gadolinium enhancement (LGE) images. Trabecular-papillary muscle (TPM) mass, fractal dimension (FD) and extracellular volume (ECV) were derived. The results showed that TPM mass index was higher in patients with SHF than that in patients with HFpEF and non-HF. The TPM mass-LV mass ratio (TPMm/LVM) was higher in SHF group than that in HFpEF and non-HF. FD was not different among groups. The presence of LGE was inversely associated with TPM mass index and TPMm/LVM while the ECV were positively associated with TPMm/LVM. The FD was positively associated with LV chamber size. In conclusion, TPM increases in patients with SHF and are probably related to myocardial cell hypertrophy and fibrotic repair during remodeling. The FD increases with the dilatation of LV chamber but remain unchanged with the deterioration of LV function.
Project description:INTRODUCTION:The presence of late gadolinium enhancement (LGE) at the right ventricular insertion point (RVIP) on cardiac magnetic resonance (CMR) is generally believed to be nonspecific, but the clinical implication of this unique LGE pattern in patients with non-ischemic dilated cardiomyopathy (NICM) has not been elucidated. OBJECTIVES:We investigated the prognostic significance of RVIP-LGE in NICM patients. METHODS:A total of 360 consecutive NICM patients referred for CMR (102 with no LGE, 50 with RVIP-LGE, 121 with left ventricular [LV]-LGE, and 87 with both an LV and RVIP-LGE) were studied. The primary endpoint was a composite of the all-cause death, hospitalization due to worsening of heart failure, and major arrhythmic events. RESULTS:During a mean follow-up of 45.2 ± 36.5 months, 149 (41.4%) patients (22 [21.6%] no LGE vs. 16 [32.0%] RVIP-LGE vs. 62 [51.2%] LV-LGE vs. 49 [56.3%] both LV and RVIP-LGE, P < 0.0001) reached the primary endpoint. A Kaplan Meier curve demonstrated that RVIP-LGE patients had an intermediate trend of an event free survival rate for the composite endpoint (log-rank P < 0.0001). In a multivariable Cox regression model, LV-LGE (P = 0.008) and both LV and RVIP-LGE (P = 0.003) were significantly associated with a worse outcome, whereas RVIP-LGE was not (P = 0.101). In addition, RVIP-LGE patients (n = 32) had a more favorable outcome compared to LV-LGE patients (n = 32) even after matching the extent of the LGE (median 3.4% [interquartile range, 3.1-3.8], 8 [25.0%] RVIP-LGE vs. 20 [62.5%] LV-LGE, P = 0.002). CONCLUSIONS:LGE confined to the RVIP among NICM patients did not significantly increase the risk of adverse cardiac events, and also showed a better outcome than the same extent of LGE located in the LV. Identification of this unique LGE distribution may help refine the current risk stratification.
Project description:BACKGROUND: Cocaine is an addictive, sympathomimetic drug with potentially lethal effects. The prevalence and features of cocaine cardiotoxicity are not well known. We aimed to assess these effects using a comprehensive cardiovascular magnetic resonance (CMR) protocol in a large group of asymptomatic cocaine users. METHODS: Consecutive (n?=?94, 81 males, 36.6 ±7 years), non-selected, cocaine abusers were recruited and had a medical history, examination, ECG, blood test and CMR. The CMR study included measurement of left and right ventricular (LV, RV) dimensions and ejection fraction (EF), sequences for detection of myocardial oedema and late gadolinium enhancement (LGE). Images were compared to a cohort of healthy controls. RESULTS: Years of regular cocaine use were 13.9?±?9. When compared to the age-matched healthy cohort, the cocaine abusers had increased LV end-systolic volume, LV mass index and RV end-systolic volume, with decreased LVEF and RVEF. No subject had myocardial oedema, but 30% had myocardial LGE indicating myocardial damage. CONCLUSIONS: CMR detected cardiovascular disease in 71% of this cohort of consecutive asymptomatic cocaine abusers and mean duration of abuse was related to probability of LV systolic dysfunction.