scholarly journals Sarcomeric perturbations of myosin motors lead to dilated cardiomyopathy in genetically modified MYL2 mice

2018 ◽  
Vol 115 (10) ◽  
pp. E2338-E2347 ◽  
Author(s):  
Chen-Ching Yuan ◽  
Katarzyna Kazmierczak ◽  
Jingsheng Liang ◽  
Zhiqun Zhou ◽  
Sunil Yadav ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Novel Mutation ◽  
Systolic Dysfunction ◽  
Thick Filament ◽  
The United States ◽  
Left Ventricular ◽  
X Ray Diffraction ◽  
Gene Encoding ◽  
Underlying Mechanisms ◽  
Myosin Motors

Dilated cardiomyopathy (DCM) is a devastating heart disease that affects about 1 million people in the United States, but the underlying mechanisms remain poorly understood. In this study, we aimed to determine the biomechanical and structural causes of DCM in transgenic mice carrying a novel mutation in the MYL2 gene, encoding the cardiac myosin regulatory light chain. Transgenic D94A (aspartic acid-to-alanine) mice were created and investigated by echocardiography and invasive hemodynamic and molecular structural and functional assessments. Consistent with the DCM phenotype, a significant reduction of the ejection fraction (EF) was observed in ∼5- and ∼12-mo-old male and female D94A lines compared with respective WT controls. Younger male D94A mice showed a more pronounced left ventricular (LV) chamber dilation compared with female counterparts, but both sexes of D94A lines developed DCM by 12 mo of age. The hypocontractile activity of D94A myosin motors resulted in the rightward shift of the force–pCa dependence and decreased actin-activated myosin ATPase activity. Consistent with a decreased Ca2+ sensitivity of contractile force, a small-angle X-ray diffraction study, performed in D94A fibers at submaximal Ca2+ concentrations, revealed repositioning of the D94A cross-bridge mass toward the thick-filament backbone supporting the hypocontractile state of D94A myosin motors. Our data suggest that structural perturbations at the level of sarcomeres result in aberrant cardiomyocyte cytoarchitecture and lead to LV chamber dilation and decreased EF, manifesting in systolic dysfunction of D94A hearts. The D94A-induced development of DCM in mice closely follows the clinical phenotype and suggests that MYL2 may serve as a new therapeutic target for dilated cardiomyopathy.

scholarly journals Cardiomyopathies: An Overview

2021 ◽  
Vol 22 (14) ◽  
pp. 7722
Author(s):  
Tiziana Ciarambino ◽  
Giovanni Menna ◽  
Gennaro Sansone ◽  
Mauro Giordano
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Dilated Cardiomyopathy ◽  
Sudden Cardiac Arrest ◽  
Restrictive Cardiomyopathy ◽  
The United States ◽  
Abrupt Onset ◽  
Left Ventricular ◽  
Arrhythmogenic Cardiomyopathy ◽  
Athletic Field ◽  
Fibrofatty Tissue

Background: Cardiomyopathies are a heterogeneous group of pathologies characterized by structural and functional alterations of the heart. Aims: The purpose of this narrative review is to focus on the most important cardiomyopathies and their epidemiology, diagnosis, and management. Methods: Clinical trials were identified by Pubmed until 30 March 2021. The search keywords were “cardiomyopathies, sudden cardiac arrest, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy, arrhythmogenic cardiomyopathy (ARCV), takotsubo syndrome”. Results: Hypertrophic cardiomyopathy (HCM) is the most common primary cardiomyopathy, with a prevalence of 1:500 persons. Dilated cardiomyopathy (DCM) has a prevalence of 1:2500 and is the leading indication for heart transplantation. Restrictive cardiomyopathy (RCM) is the least common of the major cardiomyopathies, representing 2% to 5% of cases. Arrhythmogenic cardiomyopathy (ARCV) is a pathology characterized by the substitution of the myocardium by fibrofatty tissue. Takotsubo cardiomyopathy is defined as an abrupt onset of left ventricular dysfunction in response to severe emotional or physiologic stress. Conclusion: In particular, it has been reported that HCM is the most important cause of sudden death on the athletic field in the United States. It is needless to say how important it is to know which changes in the heart due to physical activity are normal, and when they are pathological.

scholarly journals Torsion Mechanics as an Indicator of More Advanced Left Ventricular Systolic Dysfunction in Secondary Mitral Regurgitation in Patients with Dilated Cardiomyopathy: A 2D Speckle-Tracking Analysis

Cardiology ◽  
2018 ◽  
Vol 139 (3) ◽  
pp. 187-196 ◽  
Author(s):  
Elena Kinova ◽  
Natalia Spasova ◽  
Angelina Borizanova ◽  
Assen Goudev
Keyword(s):  
Mitral Regurgitation ◽  
Dilated Cardiomyopathy ◽  
Speckle Tracking ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Functional Mitral Regurgitation ◽  
Compensatory Mechanism ◽  
Structural Wall ◽  
Group 2 ◽  
Group 1

Left ventricular (LV) twist serves as a compensatory mechanism in systolic dysfunction and its degree of reduction may reflect a more advanced stage of disease. Aim: The aim was to investigate twist alterations depending on the degree of functional mitral regurgitation (MR) by speckle-tracking echocardiography. Methods: Sixty-three patients with symptomatic dilated cardiomyopathy (DCM) were included. Patients were divided according to MR vena contracta width (VCW): group 1 with VCW <7 mm (mild/moderate MR) and group 2 with VCW ≥7 mm (severe MR). Results: There were no differences in LV geometry and function between groups. Group 2 showed lower endocardial basal rotation (BR) (–2.04° ± 1.83° vs. –3.23° ± 1.83°, p = 0.012); epicardial BR (–1.54° ± 1.18° vs. –2.31° ± 1.22°, p = 0.015); endocardial torsion (0.41°/cm ± 0.36°/cm vs. 0.63°/cm ± 0.44°/cm, p = 0.033) and mid-level circumferential strain (CSmid) (–6.12% ± 2.64% vs. –7.75% ± 2.90%, p = 0.028), when compared with group 1. Multivariable linear regression analysis identified endocardial BR, torsion and CSmid, as the best predictors of larger VCW. In the ROC curve analysis, endocardial BR and CSmid values greater than or equal to –3.63° and –9.35%, respectively, can differentiate patients with severe MR. Conclusions: In DCM patients, torsional profile was more altered in severe MR. Endocardial BR, endocardial torsion, and CSmid, can be used as indicators of advanced structural wall architecture damage.

Intersection of Heart Failure and Pregnancy: Beyond Peripartum Cardiomyopathy

2021 ◽  
Author(s):  
Ersilia M. DeFilippis ◽  
Jennifer H. Haythe ◽  
Mary Norine Walsh ◽  
Michelle M. Kittleson
Keyword(s):  
Heart Failure ◽  
Pregnant Women ◽  
De Novo ◽  
Systolic Dysfunction ◽  
The United States ◽  
Left Ventricular ◽  
Peripartum Cardiomyopathy ◽  
Ventricular Assist Devices ◽  
Left Ventricular Assist Devices ◽  
Common Diagnosis

Heart failure (HF) is a leading cause of morbidity and mortality in pregnant women in the United States. Although peripartum cardiomyopathy is the most common diagnosis for pregnant women with HF, women with preexisting cardiomyopathies and systolic dysfunction are also at risk as the hemodynamic demands of pregnancy can lead to decompensation, arrhythmia, and rarely death. The differential diagnosis of HF in pregnancy is broad and includes Takotsubo or stress cardiomyopathy, exacerbation of a preexisting cardiomyopathy, such as familial cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, or left ventricular noncompaction. This review will explore the implications of pregnancy in women with preexisting cardiomyopathies and de novo HF, risk assessment and preconception planning, decisions about contraception, the safety of HF medications and implantable cardioverter-defibrillators during pregnancy, pregnancy in women with left ventricular assist devices and following heart transplantation.

P595Characteristics of the right ventricle in patients with nonischemic dilated cardiomyopathy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Becker ◽  
C P Allaart ◽  
M Wubben ◽  
J H Cornel ◽  
A C Van Rossum ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Right Ventricular ◽  
Dilated Cardiomyopathy ◽  
Ventricular Function ◽  
Left Atrial ◽  
Systolic Dysfunction ◽  
Underlying Mechanism ◽  
Left Ventricular ◽  
End Diastolic Volume ◽  
Nonischemic Dilated Cardiomyopathy

Abstract Background In nonischemic dilated cardiomyopathy (DCM), diagnosis and prognosis is based on left ventricular function. Although concomitant right ventricular (RV) dysfunction is frequently observed, the underlying mechanism is currently not fully understood. Purpose We aimed to describe the characteristics of right ventricular function in DCM patients with cardiac magnetic resonance (CMR) imaging using cine and late-gadolinium enhancement (LGE) imaging. Methods Patients with DCM and left ventricular (LV) dysfunction (ejection fraction (EF) <50%) on LGE-CMR were included prospectively. LV and RV volumes and function were quantified and RV systolic dysfunction was defined as RV ejection fraction (RVEF)<45%. The presence and pattern of LGE were assessed visually and the extent was quantified using the full-width half maximum method. Septal midmyocardial LGE pattern was defined as midwall striae or hinge-point myocardial hyperenhancement. Moreover, left atrial (LA) volumes were calculated using the bi-plane area-length method. Results The study included 214 DCM patients (42% female, age 58±14 years) with a mean LVEF of 34±12% and RVEF of 46±12%. RV systolic dysfunction was present in 39% and was associated with the presence of septal midwall LGE (OR 1.96 (95% CI 1.09–3.54) p=0.026). In patients with RV dysfunction, LV dilation was more severe (LV end diastolic volume (EDV) 242±97mL vs. 212±58mL, p=0.011) and LVEF was lowere (26±12% vs. 39±8%, p<0.001) (figure A). There was a weak correlation between septal LGE amount and LVEDV and RVEDV (respectively r=0.36, p=0.003 and r=0.35, p=0.005) In patients with RV dysfunction, left atrial volumes were enlarged (56±23mL/m2 vs. 46±14mL/m2, p<0.001) and LA emptying fraction was moderately correlated to RVEF (figure B), also after exclusion of patients with a history of atrial fibrillation. RVEF in DCM patients Conclusion In DCM, reduced RVEF predominantly occurred in patients with a) LVEF lower than 30%, b) septal midwall enhancement, indicating progressive LV remodeling, c) LA dilation and d) LA dysfunction. This suggests that RV dysfunction in advanced DCM is drive by LV diastolic dysfunction resulting in increased afterload of the RV.

Sudden Cardiac Death and Heart Failure

2009 ◽  
Vol 20 (4) ◽  
pp. 356-365
Author(s):  
Brenda S. Thompson
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Left Ventricular Dysfunction ◽  
Cardiac Death ◽  
Ventricular Dysfunction ◽  
Treatment Guidelines ◽  
Systolic Dysfunction ◽  
The United States ◽  
Left Ventricular ◽  
Current Evidence

Ischemic heart disease and dilated cardiomyopathy are among the most common cardiovascular disease processes associated with heart failure that can lead to lethal arrhythmias and sudden cardiac death (SCD). With the increasing incidence of heart failure in the United States, many patients are now at risk for SCD. Nurses should understand the pathophysiology, current treatment guidelines, and the rationale for these therapies to effectively manage systolic dysfunction and to mitigate the risk of SCD. Nurses are more involved than ever with this patient population and play a key role as members of the heart failure disease management team. As a result, nurses are uniquely positioned to improve survival and reduce SCD in individuals diagnosed with left ventricular dysfunction. The purpose of this article is to increase the awareness of the risk of sudden death in patients with left ventricular dysfunction. Current evidence-based practice guidelines with rationale are reviewed.

Sign in / Sign up

Export Citation Format

Share Document