Function In Dilated Cardiomyopathy Research Articles

Insulin-like growth factor binding protein 2: a core biomarker of left ventricular dysfunction in dilated cardiomyopathy

BackgroundRNA modifications, especially N6-methyladenosine, N1-methyladenosine and 5–methylcytosine, play an important role in the progression of cardiovascular disease. However, its regulatory function in dilated cardiomyopathy (DCM) remains to be undefined.MethodsIn the study, key RNA modification regulators (RMRs) were screened by three machine learning models. Subsequently, a risk prediction model for DCM was developed and validated based on these important genes, and the diagnostic efficiency of these genes was assessed. Meanwhile, the relevance of these genes to clinical traits was explored. In both animal models and human subjects, the gene with the strongest connection was confirmed. The expression patterns of important genes were investigated using single-cell analysis.ResultsA total of 4 key RMRs were identified. The risk prediction models were constructed basing on these genes which showed a good accuracy and sensitivity in both the training and test set. Correlation analysis showed that insulin-like growth factor binding protein 2 (IGFBP2) had the highest correlation with left ventricular ejection fraction (LVEF) (R = -0.49, P = 0.00039). Further validation expression level of IGFBP2 indicated that this gene was significantly upregulated in DCM animal models and patients, and correlation analysis validation showed a significant negative correlation between IGFBP2 and LVEF (R = -0.87; P = 6*10–5). Single-cell analysis revealed that this gene was mainly expressed in endothelial cells.ConclusionIn conclusion, IGFBP2 is an important biomarker of left ventricular dysfunction in DCM. Future clinical applications could possibly use it as a possible therapeutic target.

CMR-derived left ventricular intraventricular pressure gradients identify different patterns associated with prognosis in dilated cardiomyopathy.

Left ventricular (LV) blood flow is determined by intraventricular pressure gradients (IVPG). Changes in blood flow initiate remodelling and precede functional decline. Novel cardiac magnetic resonance (CMR) post-processing LV-IVPG analysis might provide a sensitive marker of LV function in dilated cardiomyopathy (DCM). Therefore, the aim of our study was to evaluate LV-IVPG patterns and their prognostic value in DCM. LV-IVPGs between apex and base were measured on standard CMR cine images in DCM patients (n = 447) from the Maastricht Cardiomyopathy registry. Major adverse cardiovascular events, including heart failure hospitalisations, life-threatening arrhythmias, and sudden/cardiac death, occurred in 66 DCM patients (15%). A temporary LV-IVPG reversal during systolic-diastolic transition, leading to a prolonged transition period or slower filling, was present in 168 patients (38%). In 14%, this led to a reversal of blood flow, which predicted outcome corrected for univariable predictors [hazard ratio (HR) = 2.57, 95% confidence interval (1.01-6.51), P = 0.047]. In patients without pressure reversal (n = 279), impaired overall LV-IVPG [HR = 0.91 (0.83-0.99), P = 0.033], systolic ejection force [HR = 0.91 (0.86-0.96), P < 0.001], and E-wave decelerative force [HR = 0.83 (0.73-0.94), P = 0.003] predicted outcome, independent of known predictors (age, sex, New York Heart Association class ≥ 3, LV ejection fraction, late gadolinium enhancement, LV-longitudinal strain, left atrium (LA) volume-index, and LA-conduit strain). Pressure reversal during systolic-diastolic transition was observed in one-third of DCM patients, and reversal of blood flow direction predicted worse outcome. In the absence of pressure reversal, lower systolic ejection force, E-wave decelerative force (end of passive LV filling), and overall LV-IVPG are powerful predictors of outcome, independent of clinical and imaging parameters.

Prognostic significance of right ventricle size and function in dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Dilated cardiomyopathy (DCM) is diagnosed based on systolic dysfunction and dilatation of the left ventricle (LV). Although the right ventricle (RV) can be also affected, the significance of concomitant RV pathology in DCM is less studied. Aim To analyse the prognostic significance of RV dilatation (RVD) and RV systolic dysfunction (RVSD) in DCM. Methods Between 2010 and 2020 we retrospectively analysed out- and in-hospital records of 545 DCM patients (age 53 ± 13 years, 89% male, NYHA 2.4 ± 0.9, LV end-diastolic diameter 65 ± 10mm, LV ejection fraction - LVEF 27 ± 11%, RV outflow tract diameter - RVOT 33 ± 7mm, tricuspid annular plane systolic excursion - TAPSE 19 ± 5mm). The RVD was diagnosed as RVOT from parasternal long-axis view &amp;gt;35mm, and RVSD - as TAPSE &amp;lt;17mm. Results There were 284 (52%) patients with RV pathology: 192 (35%) PTS with RVD, 175 (32%) patients with RVSD, 83 (15%) patients had both RVD and RVSD (RVD + RVSD). During 47 ± 31months 83 (15%) patients died: 20 (24%) patients with RVD (p = 0.007), 32 (18%) patients with RVSD (p = 0.08), 39 (11%) patients with both RVD and RVSD (p = 0.002). All RV pathologies were found to be significant prognostic factors in DCM (RVD: HR 0.41 [95%CI 0.27-0.65]; RVSD: HR 0.59 [95%CI 0.38-0.93]; RVD + RVSD: HR 0.40 [95%CI 0.24-0.67]) (Fig. 1). However, only RVD was found to be significant prognostic factor irrespectively of LVEF (multivariate: LVEF – HR 0.97 [95%CI 0.94-0.99]; RVD – HR 0.50 [95%CI 0.31-0.79]; RVSD – HR 0.82 [9%CI 0.51-1.32]). Conclusion Half of DCM patients had RV pathology: dilatation or systolic dysfunction, however, only 15% had both RVD and RVSD. RVD and RVSD were associated with survival, however, only RV dilatation was found to be a prognostic factor irrespectively of LVEF. Abstract Figure 1. RVSD and RVD in DCM.

Altered Aortic Hemodynamics and Relative Pressure in Patients with Dilated Cardiomyopathy

Ventricular-vascular interaction is central in the adaptation to cardiovascular disease. However, cardiomyopathy patients are predominantly monitored using cardiac biomarkers. The aim of this study is therefore to explore aortic function in dilated cardiomyopathy (DCM). Fourteen idiopathic DCM patients and 16 controls underwent cardiac magnetic resonance imaging, with aortic relative pressure derived using physics-based image processing and a virtual cohort utilized to assess the impact of cardiovascular properties on aortic behaviour. Subjects with reduced left ventricular systolic function had significantly reduced aortic relative pressure, increased aortic stiffness, and significantly delayed time-to-pressure peak duration. From the virtual cohort, aortic stiffness and aortic volumetric size were identified as key determinants of aortic relative pressure. As such, this study shows how advanced flow imaging and aortic hemodynamic evaluation could provide novel insights into the manifestation of DCM, with signs of both altered aortic structure and function derived in DCM using our proposed imaging protocol.Graphic r

Relationship Between Myocardial Perfusion and Myocardial Function in Dilated Cardiomyopathy by Shown Ultrasonography.

Myocardial contrast echocardiography (MCE) and two-dimensional speckle tracking echocardiography (2D-STE) were used to detect left ventricular myocardial microcirculation perfusion and myocardial systolic function in dilated cardiomyopathy (DCM) and to explore the relationship between the two.Conventional ultrasound, MCE, and 2D-STE examinations were performed on 30 patients and 30 controls. Left ventricular microcirculation perfusion, left ventricular longitudinal strain (GLS), and circumferential strain (GCS) were analyzed to further compare the correlation between left ventricular perfusion and myocardial strain parameters.Regional myocardial perfusion was reduced in patients with DCM, manifesting as a decrease in the rising slope (A) of the mid-segment of the posterior septum, the peak intensity (PI) of the mid-segment of the anterior septum and the posterior septum, the apical segment of the lateral wall, the area under the curve (AUC) of the posterior septum, the basal segment of the posterior wall, the anterior septum, posterior septum, posterior wall, mid-segment of the lateral wall, and apical segment of the lateral wall and the overall average PI and AUC of the mid-segment, compared with that in the controls (P < 0.05). The left ventricular systolic function and the strain parameters GLS and GCS of DCM patients were lower than those of the controls (P < 0.001). Correlation analysis revealed a positive correlation between the A of the mitral valve and GCS (r = 0.372, P = 0.043), and MV-E/e' had a positive correlation with the AUC of the basal and intermediate segments (r = 0.379, P = 0.039; r = 0.404, P = 0.027).In patients with DCM, regional myocardial microcirculation perfusion is reduced, and myocardial strain is impaired. Myocardial perfusion has a good positive correlation with myocardial mechanics.

Apelin improves cardiac function mainly through peripheral vasodilation in a mouse model of dilated cardiomyopathy

There is growing evidence that apelin plays a role in the regulation of the cardiovascular system by increasing myocardial contractility and acting as a vasodilator. However, it remains unclear whether apelin improves cardiac contractility in a load-dependent or independent manner in pathological conditions. For this purpose we investigated the cardiovascular effects of apelin in α-actin transgenic mice (mActin-Tg mice), a model of cardiomyopathy. [Pyr1]apelin-13 was administered by continuous infusion at 2 mg/kg/d for 3 weeks. Effects on cardiac function were determined by echocardiography and a Pressure-Volume (PV) analysis. mActin-Tg mice showed a dilated cardiomyopathy (DCM) phenotype similar to that encountered in patients expressing the same mutation. Compared to WT animals, mActin-Tg mice displayed cardiac systolic impairment [significant decrease in ejection fraction (EF), cardiac output (CO), and stroke volume (SV)] associated with cardiac ventricular dilation and diastolic dysfunction, characterized by an impairment in mitral flow velocity (E/A) and in deceleration time (DT). Load-independent myocardial contractility was strongly decreased in mActin-Tg mice while total peripheral vascular resistance (TPR) was significantly increased. As compared to vehicle-treated animals, a 3-week treatment with [Pyr1]apelin-13 significantly improved EF%, SV, E/A, DT and corrected TPR, with no significant effect on load-independent indices of myocardial contractility, blood pressure and heart rate. In conclusion [Pyr1]apelin-13 displayed no intrinsic contractile effect but improved cardiac function in dilated cardiomyopathy mainly by reducing peripheral vascular resistance, with no change in blood pressure.

Differential Expression Profiles and Functional Analysis of Long Non-coding RNAs in Children With Dilated Cardiomyopathy.

Aim: To evaluate the expression profile of long non-coding RNAs (lncRNAs) in different left ventricular function of dilated cardiomyopathy (DCM) in children and explore their possible functions.Methods: The lncRNA microarray experiment was used to determine the differential expression profile of lncRNA in three children with DCM and three healthy volunteers. The functional analysis and the construction of the lncRNA-mRNA interaction network were carried out to study the biological functions. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to verify the microarray data.Results: There were 369 up-regulated lncRNAs identified in the DCM patients (fold change >2, P < 0.05), and 505 down-regulated lncRNAs. Based on target gene prediction and co-expression network construction, 9 differentially expressed lncRNAs were selected for the PCR to verify the accuracy of the microarray data, of which 5 were up-regulated and 4 were down-regulated, and finally proved that 7 of them were consistent with the trend of microarray data results. Four of these lncRNAs had significant differences between the patients with poor cardiac function and patients with improved left ventricle function.Conclusion: LncRNAs may play an important role in pediatric DCM and may provide a new perspective for the pathogenesis, diagnosis, and treatment of this disease.

Partial recovery of left ventricular function in dilated cardiomyopathy as a result of tuberculosis treatment (RCD code: III-1B.9.o)

We present the case of a young patient with dilated cardiomyopathy (DCM) and concomitant pulmonary tuberculosis (TB), emphasising the need for an interdisciplinary approach when considering underlying aetiology. A 36‐year‐old male was admitted to the hospital due to signs of acute heart failure (HF). After diagnostic work‐up, which included laboratory examination, echocardiography, and coronary angiography, a diagnosis of DCM was established and therapy was initiated. Despite optimal medical therapy for HF, the patient’s condition did not improve. During further diagnostic workup, pulmonary tuberculosis was identified. A significant reduction in HF signs and symptoms and improvement in left ventricular ejection fraction occurred only after TB was treated with 6 months of therapy. The presented case study illustrates the necessity to perform a complete diagnostic workup to identify reversible causes of DCM. JRCD 2019; 4 (2): 56-58.

Effect of Shenqi Yangxin decoction on high mobility group box 1 and inflammatory signal pathway in a rat model of dilated cardiomyopathy

OBJECTIVETo investigate the effects of Shenqi Yangxin decoction (SQYXD) on heart function in a rat model of dilated cardiomyopathy (DCM) and its potential mechanisms. METHODSSprague-Dawley rats were randomly divided into normal (10 rats) and DCM (150 rats) groups. DCM was induced by an intraperitoneal injection of adriamycin. Then, DCM baseline group was randomly selected sixteen DCM rats. The remaining DCM rats were randomly divided into DCM control, perindopril, metoprolol, and SQYXD groups. Cardiac function and histological analysis plus biochemical measurement of serum levels of brain natriuretic peptide (BNP), and inflammatory factors were measured. The mRNA and protein expression levels of high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR-4), receptor for advanced glycation end products (RAGE), and nuclear factor-κB (NF-κB) were determined. Myocardial metabolism imaging was performed on the normal, SQYXD and DCM control groups to evaluate the effectiveness of treatments. RESULTSRats in the DCM control group exhibited dilated left ventricular diameter, impaired cardiac function, disorganized sarcomere, impaired glucose metabolism, increased heart weight index, and increased levels of BNP, which were improved by treatment with SQYXD. In addition, hearts from rats in the DCM baseline group exhibited significantly higher levels of HMGB1, TLR-4, RAGE, NF-κB, tumor necrosis factor-α, interleukin-1, interleukin-6, interleukin-10, compared with the normal group. Interestingly, the mRNA level of HMGB1 in the DCM baseline group was positively correlated with that of TLR-4, RAGE, NF-κB, BNP, and LVEDD, but negatively correlated with LVEF. SQYXD inhibited the upregulation of HMGB1 expression and its downstream inflammatory factors. CONCLUSIONShenqi Yangxin decoction effectively reduced the dilated left ventricular diameter and improved heart function in dilated cardiomyopathy. The mechanisms underlying the action on DCM involve regulating the gene and protein expression of HMGB1 and its inflammatory signal pathways in the DCM rat model.

Serelaxin attenuates renal inflammation and fibrosis in a mouse model of dilated cardiomyopathy.

What is the central question of this study? The aim was to determine the renoprotective effects of serelaxin in the setting of chronic heart failure. What are the main findings and its importance? Our data indicate that serelaxin can reduce renal fibrosis and inflammation in experimental heart failure. Currently, there are no effective treatments to rescue renal function in heart failure patients, and our data suggest that serelaxin might have the potential to reduce renal fibrosis and inflammation in heart failure. Serelaxin has been demonstrated to attenuate renal fibrosis and inflammation in cardiorenal disease. In the present study, we tested the hypothesis that serelaxin can prevent the decline in renal function in dilated cardiomyopathy (DCM) by targeting renal fibrosis and inflammation. Male transgenic mice with DCM (n=16) and their wild-type littermates (WT; n=20) were administered either vehicle or serelaxin (500μgkg-1 day-1 ; subcutaneous minipumps; 8weeks). Cardiac function was assessed via echocardiography before and during the eighth week of serelaxin treatment. Renal function and inflammation as well as cardiac and renal fibrosis were assessed at the end of the study. Serelaxin had minimal effect on cardiac function (P≥0.99). Tubulointerstitial and glomerular fibrosis were ∼3-fold greater in vehicle-treated DCM mice compared with vehicle-treated WT mice (P≤0.001). Renal mRNA expression of Tnfα and Il1α were ∼4- and ∼3-fold greater, respectively, in vehicle-treated DCM mice compared with vehicle-treated WT mice (P≤0.05). Tubulointerstitial and glomerular fibrosis were 46 and 45% less, respectively, in serelaxin-treated DCM mice than in vehicle-treated DCM mice (P≤0.01). Renal cortical mRNA expression of Tnfα and Il1α were 56 and 58% less, respectively, in the former group compared with the latter (P≤0.05). The urinary albumin:creatinine ratio was ∼3-fold greater in vehicle-treated DCM mice compared with vehicle-treated WT mice (P=0.02). The urinary albumin:creatinine ratio was not significantly different between vehicle-treated DCM mice and serelaxin-treated DCM mice (P=0.38). These data suggest that serelaxin can attenuate renal fibrosis and inflammation and has the potential to exert renoprotective effects in DCM.

Right ventricular function in dilated cardiomyopathy: women are the stronger sex!

Heart failure is mostly caused by disease of the left ventricle, but the right ventricle may play a more important role in functional capacity and prognosis of heart failure patients than is often realised. Thus, right ventricular (RV) function has been well established to be a better marker for exercise capacity than left ventricular (LV) function in both ischaemic and dilated cardiomyopathy (DCM) [1], and is correlated with clinical status and outcome in patients with ischaemic LV dysfunction [2]. Interestingly, for a comparable degree of LV dysfunction, RV function is even worse in patients with idiopathic DCM as compared with patients with ischaemic cardiomyopathy [3, 4] and, also in this patient group, is a predictor for outcome [5]. It is increasingly recognised that development, progression, prognosis and potentially also treatment of cardiovascular disease are not only dependent on the severity of disease, but are also influenced by age and gender. A potential explanation for the effect of gender on cardiovascular morbidity may be that RV function differs between men and women, with women generally having a smaller right ventricle with a higher ejection fraction (EF) [6]. Indeed, it is shown that, although the incidence of pulmonary hypertension is higher in females than males, in patients with established disease the prognosis is better in female than male patients, and that this is caused by a better preservation of RV function and a better response of the RV function to therapy, despite similar changes in the pulmonary vasculature [7]. In the present issue of the Netherlands Heart Journal, Martinez-Selles and co-workers investigated whether differences in RV function between male and female patients could explain, at least in part, why women with DCM have a better prognosis than men. They found that RV dysfunction was only present in patients with more severe LV dysfunction (LVEF < 35) and that particularly in the group of patients with the worst LV function (LVEF < 25 %), RVEF was higher in women than men [8]. Although larger studies are required to establish causality between the effect of gender, better RV function and decreased mortality, this is a provocative study that further suggests that, also in DCM, the right ventricle plays an important role. Future studies should address whether improved RV function is correlated with improved exercise capacity, and try to identify the mechanism behind the improvement in RV function. Interestingly, in rats with pulmonary hypertension, improved outcome in female rats as compared with their male counterparts was associated with reduced RV fibrosis. As the degree of fibrosis in the left ventricle has been shown to be of predictive value for worsening of LV dysfunction in DCM [9], it would be very interesting to measure late gadolinium enhancement in magnetic resonance imaging to show a potential predictive value of RV fibrosis.

Multicentre, randomized, double-blind trial of intracoronary autologous mononuclear bone marrow cell injection in non-ischaemic dilated cardiomyopathy (the dilated cardiomyopathy arm of the MiHeart study).

Pre-clinical and few clinical studies suggest that transplantation of autologous bone marrow mononuclear cells (BMNC) improves heart function in dilated cardiomyopathies. Our objective was to determine if intracoronary injection of autologous BMNC improves the left ventricular ejection fraction (LVEF) of patients with non-ischaemic dilated cardiomyopathy (NIDCM). This study was a multicentre, randomized, double-blind, placebo controlled trial with a follow-up of 12 months. Patients with NIDCM and LVEF <35% were recruited at heart failure ambulatories in specialized hospitals around Brazil. One hundred and sixty subjects were randomized to intracoronary injection of BMNC or placebo (1:1). The primary endpoint was the difference in change of LVEF between BMNC and placebo groups as determined by echocardiography. One hundred and fifteen patients completed the study. Left ventricular ejection fraction decreased from 24.0% (21.6-26.3) to 19.9% (15.4-24.4) in the BMNC group and from 24.3% (22.1-26.5) to 22.1% (17.4-26.8) in the placebo group. There were no significant differences in changes between cell and placebo groups for left ventricular systolic and diastolic volumes and ejection fraction. Mortality rate was 20.37% in placebo and 21.31% in BMNC. Intracoronary injection of autologous BMNC does not improve left ventricular function in patients with NIDCM. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00333827.

Right ventricular function in dilated cardiomyopathy and ischemic heart disease: assessment with non-invasive imaging.

BackgroundDilated cardiomyopathy and ischaemic heart disease can both lead to right ventricular (RV) dysfunction. Direct comparisons of the two entities regarding RV size and function using state-of-the-art imaging techniques have not yet been performed. We aimed to determine RV function and volume in dilated cardiomyopathy and ischaemic heart disease in relation to left ventricular (LV) systolic and diastolic function and systolic pulmonary artery pressure.Methods and resultsA well-characterised group (cardiac magnetic resonance imaging, echocardiography, coronary angiography and endomyocardial biopsy) of 46 patients with dilated cardiomyopathy was compared with LV ejection fraction (EF)-matched patients (n = 23) with ischaemic heart disease. Volumes and EF were determined with magnetic resonance imaging, diastolic LV function and pulmonary artery pressure with echocardiography.After multivariable linear regression, four factors independently influenced RVEF (R2 = 0.51, p < 0.001): LVEF (r = 0.54, p < 0.001), ratio of peak early and peak atrial transmitral Doppler flow velocity as measure of LV filling pressure (r = − 0.52, p < 0.001) and tricuspid regurgitation flow velocity as measure of pulmonary artery pressure (r = − 0.38, p = 0.001). RVEF was significantly worse in patients with dilated cardiomyopathy compared with ischaemic heart disease: median 48 % (interquartile range (IQR) 37–55 %) versus 56 % (IQR 48–63 %), p < 0.05.ConclusionsIn patients with dilated cardiomyopathy and ischaemic heart disease, RV function is determined by LV systolic and diastolic function, the underlying cause of LV dysfunction, and pulmonary artery pressure. It was demonstrated that RV function is more impaired in dilated cardiomyopathy.

Evaluation of nonscarred myocardial T1 value using contrast-enhanced look-locker cardiac MRI and its relationship to cardiac function in dilated cardiomyopathy: Comparison of 1.5 and 3.0 Tesla MRI

To assess relationship between nonscarred myocardial T1 value measured using contrast-enhanced Look-Locker MRI and cardiac function in dilated cardiomyopathy (DCM) at 1.5 Tesla (T) and 3.0T MRI. Contrast-enhanced Look-Locker MRI was performed in 35 DCM patients. Nonscarred myocardial and blood T1 values were calculated from the signal intensity values and the delay time obtained on Look-Locker MRI. We assessed the correlation between the myocardial T1 value or myocardial T1 minus blood T1 value and cardiac function estimated using cine MRI (e.g., end-diastolic volume: EDV, left ventricular ejection fraction: LVEF) or brain natriuretic peptide (BNP). With 1.5T MRI (n = 16), the myocardial T1 value correlated negatively with the EDV(r = -0.66) and end-systolic volume (ESV; r = -0.68), and positively with the LVEF (r = 0.51); the myocardial T1 minus blood T1 value correlated inversely with EDV (r = -0.70), ESV (r = -0.62), and brain natriuretic peptide (BNP; r = -0.56). With 3.0T MRI (n = 17), the myocardial T1 value correlated negatively with ESV (r = -0.44), septal thickness (r = -0.60), and BNP (r = -0.51), and positively with LVEF (r = 0.61); the myocardial T1 minus blood T1 value negatively correlated with BNP (r = -0.50) and positively with LVEF (r = 0.54). The nonscarred myocardial T1 value measured with either 1.5T or 3.0T contrast-enhanced Look-Locker MRI is significantly related to cardiac dysfunction in DCM.

Right ventricular function in dilated cardiomyopathy: relation to location of focal myocardial fibrosis

Background Severe right ventricular dysfunction (RVD) is an important prognostic parameter in dilated cardiomyopathy (DCM). The relationship between myocardial fibrosis of the left ventricle (LV) and particularly the septum and right ventricular (RV) function remains poorly understood. We sought to investigate this relationship in a large cohort of DCM patients using cardiovascular magnetic resonance (CMR). Methods We studied 257 patients (52±15ys,193men) with known DCM using a clinical 1.5 T CMR scanner (Philips Achieva). Short axis slices covering entirely both ventricles were acquired using standard SSFP-sequences for measurement of LV and RV volumes and ejection fraction (EF). Focal myocardial fibrosis was assessed in late gadolinium enhancement (LGE) CMR images acquired 10 minutes after i.v. injection of 0.2mmol/kg Gd-DTPA (Magnevist). SSFP and LGE CMR images were assessed by different observers who were blinded to measurement results and clinical data. Severe RVD was defined as RVEF<35%. In a subgroup of patients (n=96) invasive measurement of pulmonary artery pressure was performed. Results Mean LVEF was 35±14% while mean RVEF was 42 ±13%. Focal myocardial fibrosis was present in 92 (36%) patients and was located a) intra-murally within the inter-ventricular septum in 29 patients (LGE -septum) or b) sub-epicardially/diffuse in 63 patients (any-LGE). None of the patients had sub-endocardial LGE. LGEseptum patients exhibited a significantly higher RVEF (49±12%; vs. 40±14%;p=0.006), a higher RV EDV index (115±43 ml/m2; vs. 99±23 ml/m2 ;p=0.05) and a higher RV ESV index (73±45 ml/m2; vs. 52±22 ml/m2 ;p=0.01)

The Study on The Mechanism of Cardiac Function Improvement of Dilated Myopathy in Rats By Transplantation of Bone Marrow Stroma Stem Cell

Bone marrow stroma stem cells(BMSSCs) have shown promising future in repairing injured myocardium.However,few studies have explored the potential mechanism of BMSSCs transplantation for dilated cardiomyopathy(DCM).In this study we aimed to examine whether BMSSCs transplantation can improves the cardiac function of dilated cardiomyopathy of rats and investigate the possible mechanism of BMSSCs transplantation improving the cardiac function of dilated cardiomyopathy according to investigate the collagen fiber deposition,capillary density,VEGF and its receptor expression.Global heart failure in Wistar rats was induced by means of adriamycin administration,after labeled with DAPI,BMSSCs were transplanted into the myocardium of rats which were divided into transplantation group and control group.At 1w,2w,3w,4w after transplantation,heart function was measured by hemodynamic,the deposition of collagen fiber,expressions of VEGF and its receptor and capillary density were checked by immunochemistry and RT-PCR.Immunofluorescence microscopy revealed that the transplanted BMSSCs were visible at four weeks after transplantation.Compared with the control group,the transplantation group had a significantly higher maximum rate of rise and decline(±dp/dt) of left ventricular pressure and left ventricular systolic pressure(P 0.05),as well as a significantly lower rate of left ventricular diastolic pressure(P 0.05).The deposition of collagen fibers in the myocardium of transplantation group was reduced,according to A value in transplant group is less than control group(P 0.05).The expression of VEGF and its receptor were significantly higher than those of control group,and the upregulation of VEGF and its receptors was unsynchronized,the capillary density is higher in transplantation group than control group after four weeks.Taken together,our results suggest that BMSSCs transplantation can improve dilated cardiomyopathy's heart function of rats,we found that BMSSCs transplantation prevented the fusion of collagen fibers to some extent,decrease the deposition of collagen fiber and maintained the orderly structural arrangement of myocardial tissue.BMSSCs transplantation can also promote the angiogenesis,in our study we found that capillary density increased,BMSSCs transplantation not only upregulated the expression of VEGF,but also upregulated the expression of VEGF receptors.Unsynchronized upregulation of VEGF and its receptors was observed which may promote angiogenesis continuously and steadily.

Myocardial alterations and clinical implications associated with recovery of cardiac function in dilated cardiomyopathy with obesity

BackgroundObesity is associated with an increased risk of heart failure (HF) but the relationship between changes in cardiac function and the specific pathological features of dilated cardiomyopathy (DCM) with obesity, remains unknown. MethodsEndomyocardial biopsies from the left ventricle (LV) were obtained from 50 patients with DCM, at the first-onset of decompensated HF. Thirty patients were obese (obese-group: body mass index >30kg/m2) and 20 were non-obese (lean-group). Clinical data were acquired at the admission, after one month and one year. ResultsThe obese-group had higher systolic blood pressure (142.8±33.9 vs 113.6±18.7mmHg; p<0.001) and serum troponin-T level (0.049±0.07 vs 0.020±0.03ng/mL; p=0.022) than the lean-group. LV ejection fraction (LVEF) was not significantly different between groups, but after one year the obese-group had an improved LVEF (57.0±11.4 vs 44.3±17.1; p=0.003). Light microscopy revealed that the obese-group had larger cardiomyocytes (17.2±1.7 vs 16.4±1.4μm; p=0.033) and less myofilament lysis (37 vs 75%; p=0.008) with a higher density of lipid droplets (1.93±0.8 vs 0.94±0.7 /μm2; p<0.001). Multivariate regression analysis revealed that independent predictors of LVEF improvement after 12months were diuretics use, nuclear diameter, and absence of myofilament lysis (p=0.024, 0.012 and 0.028, respectively). ConclusionsCardiac function in most patients with DCM with obesity is reversible and myocardial structural changes are trivial even at the ultrastructural level.

Evaluation of diffuse myocardial fibrosis using contrast-enhanced look-locker cardiac MRI and its relation with cardiac function in dilated cardiomyopathy: comparison between 1.5T and 3T

The purpose of this study was to evaluate diffuse myocardial fibrosis by measuring myocardial and blood T1-values using contrast-enhanced Look-Locker cardiac MRI and comparing these values with left cardiac function in dilated cardiomyopathy (DCM). We also sought to assess the relation between the diffuse myocardial fibrosis and cardiac function on 1.5T and 3.0T.

Association between right ventricular two-dimensional strain and exercise capacity in patients with either idiopathic or ischemic dilated cardiomyopathy

To detect right ventricular myocardial function in dilated cardiomyopathy (DCM) using two-dimensional strain echocardiography (2DSE) and to evaluate the relationship between right ventricular dysfunction and response to cardiopulmonary exercise test (CPET). Seventy-five DCM patients (44 idiopathic and 31 ischemic) without clinical signs of right ventricular failure underwent standard echo, 2DSE analysis of right ventricle and bicycle CPET. The two groups were comparable for clinical and standard two-dimensional echocardiographic and Doppler variables, except for right ventricular diameters that were mildly increased in patients with idiopathic DCM. Right ventricular global longitudinal strain (RV GLS) and regional peak myocardial right ventricular strain were significantly impaired in patients with idiopathic DCM compared with ischemic DCM (both P<0.001). A significant correlation was detectable among RV GLS and VO2 peak percentage (r= -0.65, P<0.0001), VE/VCO2 slope (r=0.35, P<0.01), maximum work rate percentage (r= -0.55, P<0.001) and peak circulatory power (r=0.53, P<0.001). These correlations with RV GLS remained significant even in multivariate analysis. 2DSE represents a promising noninvasive technique to assess right ventricular myocardial function in patients with DCM. Reduced right ventricular myocardial deformation is related to decreased ability to perform aerobic exercise and work rate, and to impaired ventilatory response.

Is atrial function in Chagas dilated cardiomyopathy more impaired than in idiopathic dilated cardiomyopathy?

Atrial function is an important component in overall cardiovascular performance. However, information on atrial function in dilated cardiomyopathy is limited. This study aimed to assess atrial function in dilated cardiomyopathy and to investigate if parameters of atrial function are more impaired in Chagas dilated cardiomyopathy (CDC) than in idiopathic dilated cardiomyopathy (IDC). Seventy-two patients with dilated cardiomyopathy (36 with CDC and 36 with IDC) and 32 healthy controls were evaluated by tissue Doppler, Doppler-based strain and strain rate (SR) imaging of the left atrium (LA) and right atrium (RA). Peak atrial strain during systole and SR during systole, early and late diastolic SR, were measured at the interatrial septum, LA inferior wall and at the lateral wall of the RA. The clinical characteristics and the parameters of LV function were similar between patients with CDC and IDC. Myocardial deformation indices during the reservoir phase of both RA and LA were lower in patients with dilated cardiomyopathy than in controls, suggesting atrial dysfunction in cardiomyopathies. However, LA and RA deformation parameters did not differ between CDC and IDC patients (interatrial septal strain during the reservoir phase: -25.2 ± 14.8 vs. -24.9 ± 16.0%, P = NS; strain rate during the reservoir phase: -1.3 ± 0.7 vs. -1.5 ± 0.9/s, P = NS). Atrial myocardial deformation properties are abnormal in patients with dilated cardiomyopathy. CDC does not seem to have more atrial involvement than IDC.