Myocardial Fibrosis In Patients Research Articles

CMR-Verified Diffuse Myocardial Fibrosis Is Associated With Diastolic Dysfunction in HFpEF

ObjectivesThe purpose of this study was to investigate diffuse myocardial fibrosis in patients with systolic heart failure (SHF) and in patients with heart failure with preserved ejection fraction (HFpEF) and the association with diastolic dysfunction of the left ventricle (LV). BackgroundIncreased diffuse myocardial fibrosis may impair LV diastolic function. However, no study has verified the association between the degree of diffuse myocardial fibrosis and the severity of impaired diastolic function in SHF and HFpEF. MethodsForty patients with SHF, 62 patients with HFpEF, and 22 patients without HF underwent cardiac magnetic resonance (CMR), including T1 mapping and cine CMR on a 3-T system. Extracellular volume fraction (ECV), a measure of diffuse myocardial fibrosis, was quantified from T1 mapping. Systolic and diastolic functions of the LV were assessed by cine CMR. The ECV values and LV functional indexes were compared among the 3 groups. Associations between ECV and LV diastolic function were also investigated. ResultsCompared with patients without HF, significantly higher ECV was found in patients with SHF (31.2% [interquartile range (IQR): 29.0% to 34.1%] vs. 27.9% [IQR: 26.2% to 29.4%], p < 0.001) and HFpEF (28.9% [IQR: 27.8% to 31.3%] vs. 27.9% [IQR: 26.2% to 29.4%], p = 0.006). Peak filling rate, a diastolic functional index assessed by cine CMR, was significantly decreased in patients with SHF (1.00 s−1 [IQR: 0.79 to 1.49 s−1] vs. 3.86 s−1 [IQR: 3.34 to 4.48 s−1], p < 0.001) and HFpEF (2.89 s−1 [IQR: 2.13 to 3.50 s−1] vs. 3.86 s−1 [IQR: 3.34 to 4.48 s−1], p < 0.001). Myocardial ECV was significantly correlated with peak filling rate in the HFpEF group (r = −0.385, p = 0.002), but no correlation was found in the SHF and non-HF groups (r = 0.030, p = 0.856 and r = −0.238, p = 0.285, respectively). ConclusionsIn patients with HF, only those with HFpEF show a significant correlation between increased diffuse myocardial fibrosis and impaired diastolic function. Diffuse myocardial fibrosis plays a unique role in the pathogenesis of HFpEF.

Assessment of left ventricular twist mechanics by speckle tracking echocardiography reveals association between LV twist and myocardial fibrosis in patients with hypertrophic cardiomyopathy.

We aimed to investigate whether left ventricular (LV) twist analysis can detect the extent of myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM). This prospective case–control study recruited 81 consecutive patients with HCM examined between January 2012 and April 2013. Data of 76 patients were analyzed after excluding 5 patients whose echocardiographic images were of poor quality. Healthy volunteers (n = 46) served as controls. Both groups underwent comprehensive echocardiographic examination (i.e., Bas-Rotation, AP-Rotation, LVEF, LADs, IVST, LAVi, E/Em, LVMI, advanced LV-twist analysis by speckle tracking echocardiography) and magnetic resonance imaging. Between-group differences were analyzed by independent t test; logistic regression analysis was performed to identify effect factors. No significant differences were found between baseline characteristics of HCM and control groups (all p > 0.05). HCM patients had significantly higher Bas-Rotation, AP-Rotation, LV Twist, LVEF, LADs, IVST, LAVi, E/Em and LVMI than controls (all p < 0.0001) and significantly lower LVDd and E/A (both p < 0.001). Bas-Rotation, AP-Rotation, LV-Twist, LADs, IVST, LAVi, E/Em and LVMI were significantly higher in HCM patients with fibrosis than in those without fibrosis (p < 0.001), but no significant differences in other echocardiographic parameters were found between those with and without fibrosis. Age, Bas-Rotation, AP-Rotation, LV twist, LADs, IVST, LAVi, E/A, E/Em, and LVMI were significant effect factors for fibrosis. AUROC analysis showed that LV twist had high discriminatory power to detect extent of myocardial fibrosis (AUC 0.996, 95 % CI 0.989–1.004, p < 0.001). Left ventricular twist mechanics are associated with the extent of myocardial fibrosis. LV-twist assessment by STE may be clinically useful.Electronic supplementary materialThe online version of this article (doi:10.1007/s10554-014-0509-6) contains supplementary material, which is available to authorized users.

Myocardial fibrosis in patients with myotonic dystrophy type 1: a cardiovascular magnetic resonance study.

BackgroundMyotonic dystrophy type 1 (DM1) is associated with increased cardiac morbidity and mortality. Therefore, assessment of cardiac involvement and risk stratification for sudden cardiac death is crucial. Nevertheless, optimal screening-procedures are not clearly defined. ECG, echocardiography and Holter-monitoring are useful but insufficient. Cardiovascular magnetic resonance (CMR) can provide additional information of which myocardial fibrosis may be relevant.The purpose of this study was to describe the prevalence of myocardial fibrosis in patients with DM1 assessed by CMR, and the association between myocardial fibrosis and abnormal findings on ECG, Holter-monitoring and echocardiography.MethodsWe selected 30 unrelated patients with DM1: 18 patients (10 men, mean age 51 years) with, and 12 patients (7 men, mean age 41 years) without abnormal findings on ECG and Holter-monitoring.Patients were evaluated with medical history, physical examination, ECG, Holter-monitoring, echocardiography and CMR.ResultsMyocardial fibrosis was found in 12/30 (40%, 9 men). The presence of myocardial fibrosis was associated with the following CMR-parameters: increased left ventricular mass (median (range) 55 g/m2 (43–83) vs. 46 g/m2 (36–64), p = 0.02), increased left atrial volume (median (range) 52 ml/m2 (36–87) vs. 46 ml/m2 (35–69), p = 0.04) and a trend toward lower LVEF (median (range) 63% (38–71) vs. 66% (60–80), p = 0.06). Overall, we found no association between the presence of myocardial fibrosis and abnormal findings on: ECG (p = 0.71), Holter-monitoring (p = 0.27) or echocardiographic measurements of left ventricular volumes, ejection fraction or global longitudinal strain (p = 0.18).ConclusionPatients with DM1 had a high prevalence of myocardial fibrosis which was not predicted by ECG, Holter-monitoring or echocardiography. CMR add additional information to current standard cardiac assessment and may prove to be a clinically valuable tool for risk stratification in DM1.

Increased concentration of circulating angiogenesis and nitric oxide inhibitors induces endothelial to mesenchymal transition and myocardial fibrosis in patients with chronic kidney disease

BackgroundSudden cardiovascular death is increased in chronic kidney disease (CKD). Experimental CKD models suggest that angiogenesis and nitric oxide (NO) inhibitors induce myocardial fibrosis and microvascular dropout thereby facilitating arrhythmogenesis. We undertook this study to characterize associations of CKD with human myocardial pathology, NO-related circulating angiogenesis inhibitors, and endothelial cell behavior. MethodsWe compared heart (n=54) and serum (n=162) samples from individuals with and without CKD, and assessed effects of serum on human coronary artery endothelial cells (HCAECs) in vitro. Left ventricular fibrosis and capillary density were quantified in post-mortem samples. Endothelial to mesenchymal transition (EndMT) was assessed by immunostaining of post-mortem samples and RNA expression in heart tissue obtained during cardiac surgery. Circulating asymmetric dimethylarginine (ADMA), endostatin (END), angiopoietin-2 (ANG), and thrombospondin-2 (TSP) were measured, and the effect of these factors and of subject serum on proliferation, apoptosis, and EndMT of HCAEC was analyzed. ResultsCardiac fibrosis increased 12% and 77% in stage 3–4 CKD and ESRD and microvascular density decreased 12% and 16% vs. preserved renal function. EndMT-derived fibroblast proportion was 17% higher in stage 3–4 CKD and ESRD (Ptrend=0.02). ADMA, ANG, TSP, and END concentrations increased in CKD. Both individual factors and CKD serum increased HCAEC apoptosis (P=0.02), decreased proliferation (P=0.03), and induced EndMT. ConclusionsCKD is associated with an increase in circulating angiogenesis and NO inhibitors, which impact proliferation and apoptosis of cardiac endothelial cells and promote EndMT, leading to cardiac fibrosis and capillary rarefaction. These processes may play key roles in CKD-associated CV disease.

Incremental Prognostic Value of Myocardial Fibrosis in Patients With Non–Ischemic Cardiomyopathy Without Congestive Heart Failure

We conducted a prospective longitudinal study to investigate the yet unknown clinical significance of myocardial fibrosis in patients with non-ischemic cardiomyopathy without history of congestive heart failure (CHF). At 3 tertiary referral centers, 228 patients with non-ischemic cardiomyopathy without history of CHF were studied with cardiovascular magnetic resonance for late gadolinium enhancement (LGE) detection and quantification and prospectively followed up for a median of 23 months. The end point was a composite of cardiac death, onset of CHF, and aborted sudden cardiac death. LGE was detected in 61 (27%) patients. Thirty-one of 61 (51%) patients with LGE reached combined end point when compared with 18 of 167 (11%) patients without LGE (hazard ratio, 5.10 [2.78-9.36]; P<0.001). Patients with LGE had greater risk of developing CHF than patients without LGE (hazard ratio, 5.23 [2.61-10.50]; P<0.001) and higher rate of aborted sudden cardiac death (hazard ratio, 8.31 [1.66-41.55]; P=0.010). Multivariate analysis showed that LGE was associated with high likelihood of composite end point independent of other prognostic determinants, including age; duration of cardiomyopathy; and left ventricular volumes, mass, and ejection fraction (hazard ratio, 4.02 [2.08-7.76]; P<0.001). Improvement χ(2) analysis disclosed that LGE addition to models, including clinical data alone or in combination with parameters of left ventricular remodeling and function, yielded an improvement in outcome prediction (P<0.001). Addition of LGE to age and left ventricular ejection fraction improved risk stratification for composite end point (net reclassification improvement, 29.6%) and onset of CHF (net reclassification improvement, 25.4%; both P<0.001). In patients with non-ischemic cardiomyopathy without history of CHF, myocardial fibrosis is a strong and independent predictor of outcome, providing incremental prognostic information and improvement in risk stratification beyond clinical data and degree of left ventricular dysfunction.

Vitamin D Receptor Genetics on Extracellular Matrix Biomarkers and Hemodynamics in Systolic Heart Failure

Vitamin D deficiency has been associated with the development of myocardial hypertrophy and inflammation. These findings suggest that vitamin D status and vitamin D receptor (VDR) genomics may play a role in myocardial fibrosis. The aim of this pilot study was to determine the association between vitamin D levels, VDR polymorphisms, and biomarkers of left ventricular remodeling and hemodynamics. In a cross-sectional pilot study, patients with ejection fraction (EF) <40% (and New York Heart Association ≥ II) undergoing right heart catheterization were included in the study. Blood was collected for determination of 25-hydroxyvitamin D level (antibody competitive immunoassay), VDR genotypes (BsmI, ApaI, TaqI, and FokI), and biomarkers (N-terminal propeptide of collagen type III [PIIINP], matrix metalloproteinase 2, and galectin 3). The vitamin D genotypes were determined through the use of pyrosequencing. A total of 30 patients with a mean EF of 17% ± 8% were enrolled. There was a significant association between the BsmI C allele, ApaI G allele, and TaqI A allele, which formed a haplotype block (CGA) for analysis. There were no differences in baseline parameters between patients with the VDR haplotype block (n = 20) and those without (n = 10). Individual genotypes were not associated with any biomarker or hemodynamics. Patients with the CGA haplotype demonstrated significantly higher log PIIINP values (1.74 ± 0.32 mcg/mL vs 1.36 ± 0.31 mcg/mL, P = .0041). When evaluating vitamin D levels below and above the median level (19 ng/mL), there was no significant difference between these 2 groups in regard to biomarker levels for left ventricular remodeling. This study has shown that a biomarker for collagen type III synthesis, PIIINP, was associated with the CGA haplotype of BsmI, ApaI, and TaqI single nucleotide polymorphisms on the VDR. These findings suggest that VDR genetics may play a role in myocardial fibrosis in patients with systolic heart failure.

Evaluating the Utility of Circulating Biomarkers of Collagen Synthesis in Hypertrophic Cardiomyopathy

In hypertrophic cardiomyopathy (HCM), accumulation of myocardial collagen may play a central role in the pathogenesis of diastolic dysfunction and arrhythmia. Previous studies have suggested that peripheral levels of byproducts of collagen synthesis are reflective of myocardial extracellular matrix metabolism, although this has not been validated in detail. Given the potential clinical utility of such biomarkers, we sought to validate the assumed relationship between peripheral markers and myocardial fibrosis in HCM. Fifty patients with HCM and 25 healthy controls underwent peripheral venous sampling to determine plasma concentrations of key collagen precursors (procollagen I and III N-terminal propeptides [PINP, PIIINP]). Contrast-enhanced cardiac magnetic resonance imaging was performed to quantify regional (by late-gadolinium enhancement) and diffuse (by T1 mapping) myocardial fibrosis. Nineteen subjects also underwent simultaneous arterial and coronary sinus blood sampling (to derive transcardiac concentration gradients of PINP, PIIINP, and C-terminal telopeptide of type I collagen) and right heart catheterization. Despite cardiac magnetic resonance evidence of regional (late-gadolinium enhancement quantity, 6.4±8.0%) and diffuse (T1 time, 478±79 ms) myocardial fibrosis in patients with HCM, peripheral levels of collagen precursors were similar compared with control subjects (PINP, 45.9±22.9 versus 53.4±25.9 μg/L; P=0.21; PIIINP, 4.8±1.7 versus 4.4±1.1 μg/L; P=0.26). No significant net positive transcardiac concentration gradient was detected for either biomarker of collagen synthesis. The cardiac contribution to peripheral levels of byproducts of collagen synthesis in patients with HCM is insignificant. Furthermore, peripheral levels of these biomarkers do not accurately reflect myocardial collagen content in these patients.

Myocardial fibrosis in patients with myotonic dystrophy type 1: a cardiovascular magnetic resonance study

BackgroundMyotonic dystrophy type 1 (DM1) is associated with increased cardiac morbidity and mortality. Therefore, assessment of cardiac involvement and risk stratification for sudden cardiac death is crucial. Nevertheless, optimal screening-procedures are not clearly defined. ECG, echocardiography and Holter-monitoring are useful but insufficient. Cardiovascular magnetic resonance (CMR) can provide additional information of which myocardial fibrosis may be relevant.The purpose of this study was to describe the prevalence of myocardial fibrosis in patients with DM1 assessed by CMR, and the association between myocardial fibrosis and abnormal findings on ECG, Holter-monitoring and echocardiography.MethodsWe selected 30 unrelated patients with DM1: 18 patients (10 men, mean age 51 years) with, and 12 patients (7 men, mean age 41 years) without abnormal findings on ECG and Holter-monitoring.Patients were evaluated with medical history, physical examination, ECG, Holter-monitoring, echocardiography and CMR.ResultsMyocardial fibrosis was found in 12/30 (40%, 9 men). The presence of myocardial fibrosis was associated with the following CMR-parameters: increased left ventricular mass (median (range) 55 g/m2 (43–83) vs. 46 g/m2 (36–64), p = 0.02), increased left atrial volume (median (range) 52 ml/m2 (36–87) vs. 46 ml/m2 (35–69), p = 0.04) and a trend toward lower LVEF (median (range) 63% (38–71) vs. 66% (60–80), p = 0.06). Overall, we found no association between the presence of myocardial fibrosis and abnormal findings on: ECG (p = 0.71), Holter-monitoring (p = 0.27) or echocardiographic measurements of left ventricular volumes, ejection fraction or global longitudinal strain (p = 0.18).ConclusionPatients with DM1 had a high prevalence of myocardial fibrosis which was not predicted by ECG, Holter-monitoring or echocardiography. CMR add additional information to current standard cardiac assessment and may prove to be a clinically valuable tool for risk stratification in DM1.

Diffuse myocardial fibrosis is associated with impaired myocardial strain and disease activity in rheumatoid arthritis: a cardiovascular magnetic resonance study

Background Rheumatoid arthritis (RA) is a chronic autoimmune disease of the joints, with frequent extra-articular complications including cardiovascular disease and cardiac fibrosis from multiple causes. Diffuse myocardial fibrosis can be detected non-invasively by extracellular volume (ECV) mapping based on preand postcontrast T1 measurements using cardiovascular magnetic resonance (CMR). We therefore hypothesized that CMR T1 mapping can detect subclinical diffuse myocardial fibrosis in patients with RA.

Quantitative comparison of 2D and 3D late gadolinium enhancement MR imaging for cardiomyopathies

Background LGE is widely used as a means to quantify scar or fibrotic tissue in patients suffering from cardiomyopathies. In clinical routine 2D data acquisition is most commonly practiced, albeit having the drawback of multiple breath-holds and long acquisition times. 3D acquisition can significantly reduce acquisition time. This leads to shortened scan time and a more efficient use of available MRI resources. So our purpose was to determine whether the quantification of myocardial fibrosis in patients with Fabry disease and hypertrophic cardiomyopathy (HCM) using a late gadolinium enhancement (LGE) single-breath-hold threedimensional (3D) inversion recovery magnetic resonance (MR) imaging sequence is comparable with a clinically established two-dimensional (2D) multi-breath-hold sequence.

Left ventricle morphological and functional characteristics associated to the presence and magnitude of myocardial fibrosis by CMR in hypertrophy cardiomiopathy

Background Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease present in one in 500 of the general population, and it is main cause of sudden death in young people. The presence of myocardial fibrosis in HCM is very common (more than 2/3 of patients), and its identification by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) helps the diagnosis and it is associated with ventricular arrhythmias and worse prognosis. The aim of our study was to find CMR characteristics that are related to the presence and burden of myocardial fibrosis by CMR in HCM. Methods We evaluated 115 consecutive HCM patients who underwent cardiac MRI and analyzed both the presence/ absence of myocardial fibrosis (LGE) and also its magnitude (estimated as absolute mass of myocardial fibrosis in grams and normalized to LV mass as percentage of LV myocardial mass) with other morphological and functional factors as well as population characteristics. Patients with a history of acute myocardial infarction as well as other cardiomyopathies that could present late enhancement were excluded. Results The mean age was 46.6 ± 16.1 yo, 77% male. Eighty patients (70%) had myocardial fibrosis in cardiac MRI. Patients with myocardial fibrosis had lower ejection fraction of the left ventricle (68.8 vs. 74.6 ± 0.1%, p = 0.011), higher end-systolic volume (45 ± 24 [23 ± 11] vs. 33 ± 12 [18 ± 5] ml [ml/m2], p = 0.027 [p = 0.041]), greater maximum thickness of the ventricular wall (21.9 ± 5.2 vs. 16.4 ± 2.8 mm, p < 0.001) and increased left ventricular mass (192.8 ± 58.1 [98.5 ± 27.0] vs. 157.5 ± 50.4 [82.8 ± 21.5] g[g/m2], p < 0.001 [p = 0.001]). In a logistic regression analysis, only ejection fraction (p = 0.034) and maximum wall thickness (p < 0.001) were independently associated with the presence of fibrosis. Among those with myocardial fibrosis, a greater mass of fibrosis correlated with a lower ejection fraction (r = -0.42, p = 0.003), lower end-systolic volumes (r = 0.56, p < 0.001), greater maximum thickness wall (r = 0.28, p = 0.024) and increased left ventricular mass (r = 0.35, p = 0.017). On the multivariate analysis, only the stroke volume (p < 0.001) and maximum thickness (p = 0.020) were correlated with the mass of myocardial fibrosis. However, when we analyzed the burden of fibrosis in relation to left ventricular mass (percentage of fibrosis) only greater end-systolic volume was independently associated with a higher percentage of fibrosis (r = 0.48, p < 0.001). Conclusions The presence of myocardial fibrosis in patients with HCM is independently related to lower ejection fraction and higher maximum thickness of the ventricular wall. The burden of fibrosis correlated independently with a higher maximum wall thickness (mass of fibrosis) and lower end-systolic volume (mass and percentage of fibrosis).

Quantification of diffuse myocardial fibrosis in patients with resistant hypertension undergoing renal denervation versus hypertensive controls - preliminary results

Background Renal Denervation (RDN) is a novel therapy for patients with resistant hypertension. Its cardiac effects at followup are currently unknown. On the other hand, T1 mapping permits the assessment of myocardial extracellular volume (ECV), a parameter proposed to quantify diffuse myocardial fibrosis and independently associated with mortality and hard cardiovascular events. Our aim was to study the effects of RDN on ECV at 6-month follow-up. Methods 14 patients with resistant hypertension undergoing RD (RD group) and 4 resistant hypertensive patients not undergoing RD (control group) were prospectively included. A 1.5T cardiac MR including T1 mapping preand post-contrast was performed before the RD procedure and at 6-month follow-up in both groups. Blood hematocrit was determined at both time points. Images were post-processed using commercial software (Qmass, Medis

Noninvasive assessment of myocardial fibrosis in patients with obstructive hypertrophic cardiomyopathy

ObjectiveLate gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the reference standard for non-invasive assessment of fibrosis. In hypertrophic cardiomyopathy (HCM) patients the histological substrate for LGE is still unknown....

Abstract 18189: Focal Fibrosis and Diffuse Fibrosis Are Predictors of Positive Left Ventricular Remodeling in Patients With Non-Ischemic Cardiomyopathy

Background: Prognostic value of myocardial fibrosis in patients with non-ischemic idiopathic cardiomyopathy (NICM) is not well-defined. We sought to assess the association of focal and diffuse myocardial fibrosis to left ventricular reversed remodeling. Methods: Patients with NICM who underwent cardiac MRI and baseline and subsequent follow-up echocardiographic were included in the study. Post-contrast T1 times were measured using Look-Locker gradient echo, and was adjusted for renal function, body size, gadolinium dose and delayed time after Gadolinium injection. Patients were followed over a median time of 29 months (20,37) to evaluate changes of left ventricular end-systolic volume index (LVESVi) over time. Linear Mixed Model was used to assess the relationship between the LVESVi during follow-up,T1 value, and delayed hyperenhancement (DHE). Results: A total of 103 patients (mean age 51±15 years, 62% male) were included in the analysis. Mean LVEF 32±10%, LVESVi 62±39 ml/m2, and T1 time 415+98. DHE was identified in 45 patients (44%). Age, LVEF and LVESVi in patients with DHE are not statistically different compared to patients without DHE. Patient with DHE were more likely to be male (32 vs 11, p=0.024) and had lower T1 time (381±104 Vs 440±87, p=0.003). Patients with focal DHE (n=45) had higher LVESVi at baseline and during follow-up, compared to the patients with no DHE (Δ= 11.3 ml/m2 SE 8.8 ml/2, p= 0.024) (Figure A). However, post T1 values of the myocardium without DHE were not associated with differences in LVESVi. In patients without DHE (n=58), T1 value &gt; 450 was associated with further reduction in LVESVi at the follow-up (Δ= 24.6 ml/m2 SE 14.6 ml/2, p= 0.048)(Figure B.) Conclusion: Presence of myocardial DHE, but not T1 value, is a marker of LV reversed remodeling in NICM patients. However, diffuse fibrosis predicts LV reversed remodling in patients without DHE.

Myocardial Tissue Characterization By Cardiac MR Imaging In Myelodysplastic Syndromes

IntroductionMagnetic Resonance Imaging (MRI) provides unique insight regarding tissue characterization in the heart. We reported the baseline MRI findings at the end of the recruitment in the MIOMED (Myocardial Iron Overload in MyElodysplastic Diseases) study. In particular, we evaluated the distribution of iron overload in the whole left ventricle (LV) and he presence of myocardial fibrosis in patients with myelodysplastic syndromes (MDS); the association with LV function was also investigated. No data are available in the literature about this issue. MethodsMIOMED is an observational, MRI multicentre study in low and intermediate-1 risk MDS patients who have not received regular iron chelation therapy. Out of the 51 MDS patients enrolled, 48 underwent the baseline MRI exam. Mean age was 71.7±8.5 years and 17 patients were females. MIO was assessed using a multislice multiecho T2* approach. Biventricular function parameters were quantified by cine sequences. Myocardial fibrosis was evaluated by late gadolinium enhancement acquisitions. ResultsWe found 27 (56.3%) patients with no MIO (all 16 segmental T2* values >20 ms). The remaining patients showed an heterogeneous MIO (some segments with T2* values >20 ms and other segments with T2* values <20 ms) and of them 2 (9.5%) showed a global T2* value <20 ms, indicating significant MIO. A reduced LV ejection fraction (EF) was found in the 29.5% of cases and a reduced RV EF in the 23.3%. There was not a significant association between heart T2* values and LV EF.Myocardial fibrosis was detected in the 35.9% of the patients. Three patients showed an ischemic pattern and one of them had a transmural fibrosis in the LV apical region. Out of the 3 patients with an ischemic pattern, only one patient had a positive history for a previous myocardial infarction. The majority of the patients had two or more foci of myocardial fibrosis, involving more frequently the septal segments. Patients with myocardial fibrosis were significantly older (75.4±7.9 vs 68.9±7.6 yrs; P=0.019). Global heart T2* and LV volumes were not significantly different between patients with and without fibrosis. The LV EF was lower in fibrotic patients but the statistical significance was not reached (58.4±11.7 vs 64.8±8.9 %; P=0.067). ConclusionsAlthough a significant heart iron was found only in two cases, nearly half the patients had abnormal T2* values in at least one myocardial segment. This finding underlines the importance to use a multislice approach in order to perform an early diagnosis and prevent a more diffuse iron distribution by chelation therapy. This goal could be critical in patients with myocardial fibrosis that seems to be a relative common findings in the old MDS patients. In fact, an underlying heart damage as represented by fibrosis could make the hearts of the old MDS patients more sensitive to lower levels of accumulated iron. Disclosures:No relevant conflicts of interest to declare.

Magnetic Resonance Assessment of Prevalence and Correlates of Right Ventricular Abnormalities in Isolated Left Ventricular Noncompaction

The aim of the present study was to evaluate the prevalence and correlates of right ventricular (RV) noncompaction (RVNC), RV systolic dysfunction, and RV myocardial fibrosis in patients with isolated left ventricular (LV) noncompaction (LVNC). For this purpose, cine and contrast-enhanced cardiac magnetic resonance imaging (MRI) was used. A total of 56 consecutive patients with isolated LVNC were included in the study. The diagnosis of isolated LVNC was based on the presence of standard cardiac MRI and clinical criteria. For each patient, cine and contrast-enhanced cardiac MR images were analyzed to evaluate the prevalence and correlates of RVNC, RV dysfunction, and late gadolinium enhancement (a surrogate of myocardial fibrosis) involving the RV. Mean age of the patient population was 45 ± 19 years; 35 patients (63%) were men. RVNC was observed in 5 patients (9%). Impaired RV systolic function was observed in 9 patients (16%). Late gadolinium enhancement was not observed in any RV segment. No association was found between wall motion abnormalities and noncompaction at RV segmental level (φ coefficient 0.041, p = 0.26). At multivariate analysis, LV ejection fraction was the only variable independently related to RV ejection fraction (β = 0.62, p <0.001). In conclusion, RV systolic dysfunction is present in a non-negligible proportion of patients with isolated LVNC; LV systolic function is the only variable independently related to RV systolic function.

The Incidence, Pattern, and Prognostic Value of Left Ventricular Myocardial Scar by Late Gadolinium Enhancement in Patients With Atrial Fibrillation

This study sought to identify the frequency, pattern, and prognostic significance of left ventricular (LV) late gadolinium enhancement (LGE) in patients with atrial fibrillation (AF). There are limited data on the presence, pattern, and prognostic significance of LV myocardial fibrosis in patients with AF. LGE during cardiac magnetic resonance imaging is a marker for myocardial fibrosis. A group of 664 consecutive patients without known prior myocardial infarction who were referred for radiofrequency ablation of AF were studied. Cardiac magnetic resonance imaging was requested to assess pulmonary venous anatomy. Overall, 73% were men, with a mean age of 56 years and a mean LV ejection fraction of 56 ± 10%. LV LGE was found in 88 patients (13%). The endpoint was all-cause mortality, and in this cohort, 68 deaths were observed over a median follow-up period of 42 months. On univariate analysis, age (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 1.03 to 1.08; chi-square likelihood ratio [LRχ(2)]: 15.2; p = 0.0001), diabetes (HR: 2.39; 95% CI: 1.41 to 4.09; LRχ(2): 10.3; p = 0.001), a history of heart failure (HR: 1.78; 95% CI: 1.09 to 2.91; LRχ(2): 5.37; p = 0.02), left atrial dimension (HR: 1.04; 95% CI: 1.01 to 1.08; LRχ(2): 6.47; p = 0.01), presence of LGE (HR: 5.08; 95% CI: 3.08 to 8.36; LRχ(2): 28.8; p < 0.0001), and LGE extent (HR: 1.15; 95% CI: 1.10 to 1.21; LRχ(2): 35.6; p < 0.0001) provided the strongest associations with mortality. The mortality rate was 8.1% per patient-year in patients with LGE compared with 2.3% patients without LGE. In the best overall multivariate model for mortality, age and the extent of LGE were independent predictors of mortality. Indeed, each 1% increase in the extent of LGE was associated with a 15% increased risk for death. In patients with AF, LV LGE is a frequent finding and is a powerful predictor of mortality.

Aldosterone induced galectin-3 secretion via MR/PI3K/Akt/NF-kB signaling in THP-1 cell: a possible mediator of myocardial fibrosis in patients with primary aldosteronism

Purpose: Patients with primary aldosteronism (PA) are associated with increased myocardial fibrosis. Galectin-3 is one of the most important mediators between macrophage activation and myocardial fibrosis. Our objective was to investigate aldosterone induced galectin-3 secretion and the association between galectin-3 and myocardial fibrosis in cell and human study. Methods: We investigated the possible molecular mechanism of aldosterone to induce galectin-3 secretion in THP-1 cell and the possible effect on fibroblast. Further, we conducted a prospective clinical study to evaluate the relation between plasma galectin-3 level and myocardial fibrosis (measured by cyclic variation of integrated backscatter (CVIBS)) in patients with aldosterone producing adenoma (APA) and patients with essential hypertension (EH). Repeated measurement was performed in APA patents one year after adrenalectomy. Result: Aldosterone induced gelactin-3 secretion in the THP-1 cell and the pathway was through the mineralocorticoid receptor. The induced secretion occurs via the PI3K/Akt pathway, and through the NF-κB transcription pathway. Furthermore, aldosterone induced galectin-3 expression enhanced fibrosis related factor expression in fibroblast.Patients with APA had a significant higher plasma galectin-3 level and lower CVIBS data than EH. The plasma galectin-3 level is significantly reversely correlated with CVIBS data. One year after adrenalectomy, the plasma galectin-3 level decreased and CVIBS data increased significantly in APA patients. Conclusion: Aldosterone induced galectin-3 formation in THP-1 cell and further increased myocardial fibrosis. These findings suggest galectin-3 plays an important role on the pathogenesis of aldosterone-induced myocardial fibrosis.

Influence of serum adiponectin level and SNP +45 polymorphism of adiponectin gene on myocardial fibrosis

Adiponectin plays an important role in the development of hypertension, atherosclerosis, and cardiomyocyte hypertrophy, but very little was known about the influence of serum adiponectin or the adiponectin gene polymorphism on myocardial fibrosis. Our study investigates the influence of the SNP +45 polymorphism of the adiponectin gene and serum levels of adiponectin on myocardial fibrosis in patients with essential hypertension. A case-control study was conducted on 165 hypertensive patients and 126 normotensive healthy controls. The genotypes of adiponectin gene polymorphisms were detected by the polymerase chain reaction (PCR) method. Serum concentrations of procollagen were measured by a double antibody sandwich enzyme-linked immunosorbent assay (ELISA) in all subjects. The integrated backscatter score (IBS) was measured in the left ventricular myocardium using echocardiography. The serum levels of adiponectin in hypertensive patients were significantly lower than those in the normal control group ((2.69±1.0) μg/ml vs. (4.21±2.89) μg/ml, respectively, P<0.001). The serum levels of type-I procollagen carboxyl end peptide (PICP) and type-III procollagen ammonia cardinal extremity peptide (PIIINP) in the hypertension group were significantly higher than those in the control group. In the hypertension group, serum levels of adiponectin were significantly and negatively related to the average acoustic intensity and corrected acoustic intensity of the myocardium (r=0.46 and 0.61, respectively, P<0.05 for both). The serum levels of PICP and PIIINP were significantly different among the three genotypes of SNP +45 (P<0.01). Logistic regression analyses showed that sex and genotype (GG+GT) were the major risk factors of myocardial fibrosis in hypertensive patients (OR=5.343 and 3.278, respectively, P<0.05). These data suggest that lower levels of adiponectin and SNP +45 polymorphism of the adiponectin gene are likely to play an important role in myocardial fibrosis in hypertensive patients.

Usefulness of High-Sensitivity Cardiac Troponin T and Brain Natriuretic Peptide as Biomarkers of Myocardial Fibrosis in Patients With Hypertrophic Cardiomyopathy

Myocardial fibrosis assessed by late gadolinium enhancement cardiac magnetic resonance imaging is associated with cardiovascular events in patients with hypertrophic cardiomyopathy (HC), but few data are available regarding the utility of biomarkers for detecting late gadolinium enhancement. The aim of this study was to examine serum levels of myoglobin, cardiac myosin light chain I, high-sensitivity cardiac troponin T (hs-cTnT), and creatine kinase-MB isoenzyme and plasma levels of brain natriuretic peptide (BNP) in relation to late gadolinium enhancement in 53 patients with HC. Levels of hs-cTnT and BNP were higher in 23 patients with late gadolinium enhancement than in 30 patients without it (p <0.01 for both). An hs-cTnT level ≥0.007 ng/ml or a BNP level ≥70 pg/ml had good diagnostic value for detecting late gadolinium enhancement, with sensitivity of 96% or specificity of 90% with the combination of these 2 biomarkers. The extent of late gadolinium enhancement was correlated with BNP level (p <0.01) but not with hs-cTnT level in 23 patients with HC with late gadolinium enhancement. The increase in the extent of late gadolinium enhancement was related to hs-cTnT level in 8 patients during 22 months of follow-up (p = 0.02). In conclusion, the combination of hs-cTnT and BNP is useful in detecting myocardial fibrosis in patients with HC. The findings of this study indicate that hs-cTnT is a direct marker of ongoing myocardial fibrosis and that BNP is a marker of left ventricular overload partially associated with myocardial fibrosis.