Dilated Cardiomyopathy Left Ventricle Research Articles

Dissipative energy loss within the left ventricle detected by vector flow mapping in dilated cardiomyopathy patients

Objective To quantitatively analyze the energy loss (EL) of the left ventricle in dilated cardiomyopathy (DCM) by vector flow mapping (VFM). Methods Sixty-four DCM patients confirmed by clinical were enrolled and divided into three groups according to the level of left ventricular ejection fraction (LVEF): mild decreased LVEF group(group A, 40%≤LVEF<50%), moderate decreased LVEF group(group B, 30%≤LVEF<40%) and severe decreased LVEF group ( group C, LVEF<30%). Forty healthy volunteers were selected as control group (group D, 53%≤LVEF≤73%) for physical examination. The images of apical four-chamber and three-chamber in color Doppler echocardiography were acquired and EL was analyzed in different phases in a cardiac cycle. Results There was no significant difference of the EL in isovolumic systole and isovolumic diastole between DCM groups and the control group (P>0.05). In rapid and slow ejection period, the EL in group B and C were much lower than those in the control group (P<0.05). In rapid filling phase, the EL in DCM groups were much lower than that in the control group (P<0.05). While in slow filling period and atrial systole the EL in group C was lower than that in the control group (P<0.05). Conclusions VFM provides a new perspective for the cardiac function study of DCM patients. Key words: Echocardiography; Cardiomyopathy, dilated; Ventricular function, left; Vector flow mapping; Energy loss

Effects of Lower Limb Cycle Training on Echocardiographic Parameters of Left Ventricle in Dilated Cardiomyopathy Patients.

To determine the effect of lower limb ergometric training on echocardiographic parameters of left ventricle in dilated cardiomyopathy (DMC) patients. Randomized control trial. Rawalpindi Institute of Cardiology, Rawalpindi, Pakistan, from September 2016 to February 2017. Clinically stable patients with DCM (n=60), were randomly allocated into an interventional group with two-month interventional program and a non-trained control group (n=30 each). Treatment protocol for interventional group was lower limb ergometer exercise for 8 weeks, 4 days/week. Pre and post-treatment echocardiography was done in both groups at baseline and after 8 weeks. SPSS 21 was used for data analysis. The median (IQR) age of the patients was 51 (18) years in interventional group and 62 (11) years in control group. Male to female ratio was 18:9 in control group and 17:12 in Interventional group. Statistically significant results were detected within the groups regarding ejection fraction (EF), left ventricular internal dimension systole (LVIDS) and left ventricular internal diastolic dimension (LVIDD) (p <0.001). Exercise training with lower limb ergometer was effective in improving the ejection fraction and left ventricular dimensions in patients with dilated cardiomyopathies.

Modeling the Link between Left Ventricular Flow and Thromboembolic Risk Using Lagrangian Coherent Structures

A thrombus is a blood clot that forms on a surface, and can grow and detach, presenting a high risk for stroke and pulmonary embolism. This risk increases with blood-contacting medical devices, due to the immunological response to foreign surfaces and altered flow patterns that activate the blood and promote thromboembolism (TE). Abnormal blood transport, including vortex behavior and regional stasis, can be assessed from Lagrangian Coherent Structures (LCS). LCS are flow structures that bound transport within a flow field and divide the flow into regions with maximally attracting/repelling surfaces that maximize local shear. LCS can be identified from finite time Lyapunov exponent (FTLE) fields, which are computed from velocity field data. In this study, the goal was to use FTLE analysis to evaluate LCS in the left ventricle (LV) using velocity data obtained from flow visualization of a mock circulatory loop. A model of dilated cardiomyopathy (DCM) was used to investigate the effect of left ventricular assist device (LVAD) support on diastolic filling and transport in the LV. A small thrombus in the left ventricular outflow tract was also considered using data from a corresponding LV model. The DCM LV exhibited a direct flow of 0.8 L/cardiac cycle, which was tripled during LVAD support Delayed ejection flow was doubled, further illustrating the impact of LVAD support on blood transport. An examination of the attracting LCS ridges during diastolic filling showed that the increase is due primarily to augmentation of A wave inflow, which is associated with increased vortex circulation, kinetic energy and Forward FTLE. The introduction of a small thrombus in the left ventricular outflow tract (LVOT) of the LV had a minimal effect on diastolic inflow, but obstructed systolic outflow leading to decreased transport compared with the unobstructed LVOT geometry. Localized FTLE in the LVOT increased dramatically with the small thrombus model, which reflects greater recirculation distal to the thrombus location. The combination of the thrombus and the LVAD increased stasis distal to the thrombus, increasing the likelihood of recurring coagulation during Series flow conditions. The extension of the results of the previous studies with this analysis provides a more sensitive indicator of TE risk than the Eulerian velocity values do, and may provide an important tool for evaluating medical device design, surgical implantation, and treatment options.

Functional geometry of the left ventricle in dilated cardiomyopathy before and after resynchronization therapy

Aim. To analyse quantitative parameters of functional geometry of the left ventricle (LV) in patients with dilated cardiomyopathy (DCMP), to assess the changes in cardiac resynchronization therapy (CRT) and to reveal the relation of functional geometry of LV and its contractility. Material and methods. In DCMP patients group, who were directed to CRT according to the Guidelines of Russian Arhythmologists Society 2013, echocardiographic study was performed before and after CRT (at 5th day). Based on two-dimensional LV pictures the parameters were assessed in the cycle, as segmented kinetics of wall contraction, LV shape dynamics: sphericity index, Hibson, conicity of apical zone, Fourier shape complexity. Results. In DCMP patients the decrease of global ejection fraction <35% was followed with a decrease of systolic change of all sectoral squares of LV and enhancement of dimensional heterogeneity and asynchronicity of regional wall motion during cardiac cycle comparing to controls. There was negative correlation revealed between the proposed index of non-homogeneity and global ejection fraction. All shape indexes point to more spherical shape of LV in DCMP. However, opposite to controls, DCMP patients lack dynamical changes of shape indexes during cardiac cycle, that witnesses on significant disorders of wall motion coordination in cycle. After CRT there is significant re-coordination of LV wall motion, followed by restoration of non-homogeneity pattern of segmental kinetics, decrease of nonhomogeneity indexes and of asynchronicity and appearance of the dynamics of shape indexes changes during cardiac cycle. It was shown that end-systolic indexes of sphericity shape complexity of Fourier make it to separate patients who respond or does not on therapy, by clinical parameters. Changes of sphericity index between end diastole and end systole <3,5% selects patients with the highest prognostic significance comparing with other parameters. Conclusion. Disorders of functional geometry of the LV, particularly an increase of non-homogeneity and asynchronicity parameters of the regional motion of the wall, decrease of dynamical changes of LV sphericity indexes, might influence contractility and pumping function of the heart, and have diagnostic significance in selection of patients responding to CRT.

Regional mapping of myocardial hibernation phenotype in idiopathic end‐stage dilated cardiomyopathy

Myocardial hibernation (MH) is a well-known feature of human ischaemic cardiomyopathy (ICM), whereas its presence in human idiopathic dilated cardiomyopathy (DCM) is still controversial. We investigated the histological and molecular features of MH in left ventricle (LV) regions of failing DCM or ICM hearts. We examined failing hearts from DCM (n = 11; 41.9 ± 5.45 years; left ventricle-ejection fraction (LV-EF), 18 ± 3.16%) and ICM patients (n = 12; 58.08 ± 1.7 years; LVEF, 21.5 ± 6.08%) undergoing cardiac transplantation, and normal donor hearts (N, n = 8). LV inter-ventricular septum (IVS) and antero-lateral free wall (FW) were transmurally (i.e. sub-epicardial, mesocardial and sub-endocardial layers) analysed. LV glycogen content was shown to be increased in both DCM and ICM as compared with N hearts (P < 0.001), with a U-shaped transmural distribution (lower values in mesocardium). Capillary density was homogenously reduced in both DCM and ICM as compared with N (P < 0.05 versus N), with a lower decrease independent of the extent of fibrosis in sub-endocardial and sub-epicardial layers of DCM as compared with ICM. HIF1-α and nestin, recognized ischaemic molecular hallmarks, were similarly expressed in DCM-LV and ICM-LV myocardium. The proteomic profile was overlapping by ˜50% in DCM and ICM groups. Morphological and molecular features of MH were detected in end-stage ICM as well as in end-stage DCM LV, despite epicardial coronary artery patency and lower fibrosis in DCM hearts. Unravelling the presence of MH in the absence of coronary stenosis may be helpful to design a novel approach in the clinical management of DCM.

Thymidine kinase and mtDNA depletion in human cardiomyopathy: epigenetic and translational evidence for energy starvation

This study addresses how depletion of human cardiac left ventricle (LV) mitochondrial DNA (mtDNA) and epigenetic nuclear DNA methylation promote cardiac dysfunction in human dilated cardiomyopathy (DCM) through regulation of pyrimidine nucleotide kinases. Samples of DCM LV and right ventricle (n = 18) were obtained fresh at heart transplant surgery. Parallel samples from nonfailing (NF) controls (n = 12) were from donor hearts found unsuitable for clinical use. We analyzed abundance of mtDNA and nuclear DNA (nDNA) using qPCR. LV mtDNA was depleted in DCM (50%, P < 0.05 each) compared with NF. No detectable change in RV mtDNA abundance occurred. DNA methylation and gene expression were determined using microarray analysis (GEO accession number: GSE43435). Fifty-seven gene promoters exhibited DNA hypermethylation or hypomethylation in DCM LVs. Among those, cytosolic thymidine kinase 1 (TK1) was hypermethylated. Expression arrays revealed decreased abundance of the TK1 mRNA transcript with no change in transcripts for other relevant thymidine metabolism enzymes. Quantitative immunoblots confirmed decreased TK1 polypeptide steady state abundance. TK1 activity remained unchanged in DCM samples while mitochondrial thymidine kinase (TK2) activity was significantly reduced. Compensatory TK activity was found in cardiac myocytes in the DCM LV. Diminished TK2 activity is mechanistically important to reduced mtDNA abundance and identified in DCM LV samples here. Epigenetic and genetic changes result in changes in mtDNA and in nucleotide substrates for mtDNA replication and underpin energy starvation in DCM.

252 Cardiac β3-adrenoceptors as a new therapeutic target in dilated cardiomyopathy

Introduction β-adrenergic system is altered in heart failure (HF) due to non-ischemic dilated cardiomyopathy (DCM). There are few data concerning the relative contribution of β1- and β3-adrenoceptor subtypes (β1- and β3-AR) during DCM development. We evaluated the expression and the role of each β-AR subtype in this pathology. Methods DCM rat model is performed by doxorubicin injections (cumulative dose: 15 mg.kg-1) and validated by in vivo measurements with echocardiography-doppler. The variations of β1- and β3-AR transcript expression in left ventricle (LV) are evaluated by real-time RT-PCR. The ex vivo cardiac responses induced by selective β3-AR or non-selective β-AR stimulations are evaluated on isolated perfused heart. Results DCM rats present LV dilation, systolic and diastolic dysfunction (see table). Compared to controls, β1-AR transcripts and β3-AR transcripts are increased in DCM LV (+36%, n=8, p Table: Basal parameters and maximum values obtained by non-selective β1-AR stimulation (isoproterenol) or selective β3-AR stimulation (SR58611A). Results are expressed by mean ± SEM.*: p Control rats (n=9-31) DCM rats (n=10-31) Basal in vivo LV end-diastolic diameter (mm) 8.82±0.33 7.61±0.17 * LV ejection fraction (%) 83.0±1.9 71.2±2.8* LV Isovolumic relaxation time (ms) 21.41±1.13 32.39±1.10* Basal ex vivo DP/dt max (mmHg.s-1) 2035±365 2669±504* DP/dt min (mmHg.s-1) –1258±226 –1847±349* Isoproterenol ex vivo (1 μM) DP/dt max (mmHg.s-1) 5263±1754 4373±1383* DP/dt min (mmHg.s-1) –3815±1271 –3227±1020* SR58611A ex vivo (1 μM) DP/dt max (mmHg.s-1) 1722±497 1930±611£ DP/dt min (mmHg.s-1) –1027±297 –1138±360£ Conclusion DCM induces a β3-AR gene over-expression, associated to an increase of β3AR-induced negative inotropic and lusitropic effects. Those results could partly explain the alteration of isoproterenol response in our model, suggesting that β3-AR could be a new therapeutic target in DCM.

Role of Echocardiography in Assessing the Mechanism and Effect of Ramipril on Functional Mitral Regurgitation in Dilated Cardiomyopathy

The objectives of this article are to determine the possible mechanism of functional mitral regurgitation in patients with dilated cardiomyopathy (DCM) and to know the effect of ramipril on left ventricle (LV) and mitral regurgitation by ECHO. Several postulates are put forth for functional mitral regurgitation in DCM, and mitral annular dilatation is said to be the primary mechanism in the past, but the exact mechanism is not clear. Though angiotensin converting enzyme (ACE) inhibitors are known to remodel the LV, their beneficial effect in patients with DCM with functional mitral regurgitation is not known. Various cardiac dimensions and degree of mitral regurgitation were measured by echocardiography in 30 normal control group and in 30 patients with DCM of various etiologies except ischemic, before and after ramipril therapy. There was a significant difference in all parameters especially sphericity of left ventricle and position of papillary muscles (P < 0.0003) in DCM patients, but mitral valve annulus did not show significant change (P < 0.3) compared to control group. In 50% of the patients, the functional mitral regurgitation totally disappeared. In 30% of patients, it came down from grade II to I or became trivial. In 20% of patients, it remained unchanged. There was remarkable improvement in sphericity, LV dimension, volumes, and EF%, which increased from 31 +/- 9.81 to 39.3 +/- 8.3% (P < 0.0003). It is concluded that echocardiography clearly demonstrates the increased sphericity of LV in DCM. The lateral migration of papillary muscles possibly plays a major role in functional mitral regurgitation. Ramipril significantly reduces not only sphericity but also functional mitral regurgitation.

Ventricular remodeling and mitral valve modifications in dilated cardiomyopathy: New insights from anatomic study

Objective: The purpose of this study was to analyze the behavior of the mitral valve ring and the left ventricle in dilated cardiomyopathy. Methods: We analyzed 68 fixed adult human hearts, divided into 48 hearts with dilated cardiomyopathy of ischemic or idiopathic origin and 20 hearts free of pathologic heart conditions. Digital images of the mitral ring perimeter, attachment of the anterior and posterior leaflets, and fibrous and muscular portions were collected. We also measured the internal perimeter of the left ventricle, the distance from the septum to the anterior and posterior papillary muscles, the distance between the papillary muscles, and the extension of interventricular septum. Results: The analysis of the results showed proportional distribution of the ring's fibrous portion (r2 = 0.98) and muscular portion (r2 = 0.99) according to the degree of mitral valve dilation. Linear regression revealed that the perimeters of anterior and posterior leaflet attachments (r2 = 0.96 and r2 = 0.98, respectively) also had a proportional relation. We did not observe proportionality between the degree of dilation of the mitral ring and the left ventricle. It was observed that dilation of the left ventricle takes place globally in its segments. Conclusion: Differently from what was thought, in ischemic or idiopathic dilated cardiomyopathy, dilation of mitral ring is proportional and does not exclusively affect the posterior portion. The degree of left ventricular dilation does not determine the degree of dilation of the mitral ring because they are independent processes. These observations shed new light on the techniques used to correct mitral valve insufficiency in dilated cardiomyopathy.J Thorac Cardiovasc Surg 2002;124:1216-24

S-adenosylhomocysteine hydrolase activity in human myocardium.

Measurement of S-adenosylhomocysteine (SAH) accumulation in the heart reflects the concentration of free cytosolic adenosine and is thus a sensitive indicator of regional myocardial ischaemia. To evaluate the possibility of applying this method in combination with 11C-SAH positron emission tomography (PET) to patients with ischaemic heart disease the activity of SAH hydrolase in human heart muscle and its regional distribution were studied. Myocardium from patients with dilated cardiomyopathy (n = 4), hypertrophic obstructive cardiomyopathy (HOCM, n = 6), and mitral stenosis (n = 3) was analysed. Additional studies were performed in myocardium, isolated cardiomyocytes, and endothelial cells from dog and guinea pig hearts. Enzyme activity in synthetic and hydrolytic direction including kinetic data (Vmax, KM values, pH dependency) was measured in the cytosolic fraction of myocardial tissue and cell extracts, using high performance liquid chromatography and photometric methods, respectively. Rates of SAH synthesis (Vmax) in the left ventricle in dilated cardiomyopathy, mitral stenosis, and HOCM were 0.8 (SEM 0.1), 1.0(0.2), and 1.7(0.1) nmol.min-1.mg-1 protein respectively. KM values for DL-homocysteine, adenosine, and SAH in HOCM were 187, 2.2, and 3.4 microM, respectively. Enzyme activity was homogeneously distributed among right and left atria, right and left ventricles, and septum. Additional studies in homogenated muscle and isolated cardiomyocytes of guinea pig and canine hearts showed activities similar to man. (1) SAH hydrolase activity in the human heart is quantitatively comparable to that found in other mammals but certain myocardial diseases may go along with changes in SAH hydrolase activity; (2) the kinetic properties, absolute amounts, and homogeneous distribution of the enzyme may permit the non-invasive determination of free adenosine in the human heart by PET.

Theoretical Considerations in the Use of Dynamic Cardiomyoplasty to Treat Dilated Cardiomyopathy

Clinical data describing the hemodynamic benefits of cardiomyoplasty are inconclusive, and there has not been any study detailing the mechanisms by which dynamic cardiomyoplasty may improve the functional and mechanical impairments of the failing heart. The left ventricle in dilated cardiomyopathy is characterized by increased end-diastolic volume, inadequate systolic myocardial wall thickening, increased wall stress, and decreased stroke volume. Based on experimental and preliminary clinical data, we propose that cardiac assistance by dynamic cardiomyoplasty is the consequence of enhanced volume translocation rather than increased potential for pressure generation. A small augmentation of dimensional shortening results in a large increment of stroke volume because of the enlarged resting chamber volume. Key geometric effects are enhanced systolic chamber shortening and increased wall thickening, resulting in a net decrease of myocardial wall stress. The contractile skeletal muscle may improve myocardial mechanics, and normalization of the afterload mismatch may be an important mechanism by which dynamic cardiomyoplasty augments cardiac output.

Patterns of Flow Within the Dilated Cardiomyopathy Left Ventricle: Color Flow Doppler Observations

Study of the pathways of intraventricular flow by pulsed Doppler and color flow Doppler has shown that, in normal individuals, a broad strong stream flows into the left ventricular chamber from the mitral annulus to the apex during early rapid and late (atrial) ventricular filling phases; in systole, a broad rapid stream from the apex to the aortic orifice is dominant. In dilated cardiomyopathy, flow velocities are slower, and the typical pattern is a circular type of diastolic flow along the lateral left ventricular wall toward the apex and then from the apex to the aortic orifice along the septum. The systolic flow pattern is also different in dilated cardiomyopathy; in addition to the flow along the septum toward the aortic orifice, some blood flows in a circular manner back to the apex along the lateral wall. An important aspect of abnormal flow patterns in dilated dysfunctional left ventricular chambers is their association with a tendency to thrombus formation. Thus, the pathophysiology of abnormal intraventricular flow patterns may have academic but also therapeutic implications. (ECHOCARDIOGRAPHY, Volume 8, March 1991)

The clinical and prognostic significance of dipyridamole Tl-201 emission computed tomography in patients with dilated cardiomyopathy.

To clarify the clinical significance of regional myocardial perfusion abnormality of the left ventricle in dilated cardiomyopathy (DCM), 20 patients with DCM underwent dipyridamole Tl-201 emission computed tomography (ECT). The subjects were divided into 2 groups: group 1 had (n = 9) reversible defects and group 2 (n = 11) had persistent defects only. Group 2 patients significantly advanced heart failure and significantly poorer prognoses than group 1 (55% vs 11% in 2 years survival rate, p less than 0.05). The echocardiographic left ventricular end-diastolic dimension was larger in group 2 than group 1 (68.3 +/- 8.2 mm vs 61.9 +/- 4.0 mm, p less than 0.05) and % fractional shortening was smaller in group 2 than group 1 (18.0 +/- 4.5% vs 24.5 +/- 6.9%, p less than 0.05). Moreover, 12 of the 13 segments with reversible defect showed fairly well preserved left ventricular wall motion, whereas 35 of 58 segments with persistent defect had severely impaired wall motion (1/13 vs 35/58, p less than 0.01). Dipyridamole Tl-201 ECT demonstrated conclusively that the two types of defects (reversible and persistent) are useful to evaluate not only the abnormal myocardial perfusion but also myocardial damage and the prognosis in DCM.