scholarly journals The Genetic Pathways Underlying Immunotherapy in Dilated Cardiomyopathy

2021 ◽  
Vol 8 ◽  
Author(s):  
Ayat Kadhi ◽  
Fathima Mohammed ◽  
Georges Nemer
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Genetic Basis ◽  
Systolic Dysfunction ◽  
Mortality Rates ◽  
The Novel ◽  
Global Public Health ◽  
Genetic Pathways ◽  
Recent Advancement ◽  
Secondary Causes

Heart failure (HF) is a global public health threat affecting 26 million individuals worldwide with an estimated prevalence increase of 46% by 2030. One of the main causes of HF and sudden death in children and adult is Dilated Cardiomyopathy (DCM). DCM is characterized by dilation and systolic dysfunction of one or both ventricles. It has an underlying genetic basis or can develop subsequent to various etiologies that cause myocardium inflammation (secondary causes). The morbidity and mortality rates of DCM remains high despite recent advancement to manage the disease. New insights have been dedicated to better understand the pathogenesis of DCM in respect to genetic and inflammatory basis by linking the two entities together. This cognizance in the field of cardiology might have an innovative approach to manage DCM through targeted treatment directed to the causative etiology. The following review summarizes the genetical and inflammatory causes underlying DCM and the pathways of the novel precision-medicine-based immunomodulatory strategies to salvage and prevent the associated heart failure linked to the disease.

scholarly journals Endocarditis de Libman-Sacks de válvulas nativas derechas en contexto de síndrome antifosfolípido y lupus eritematoso sistémico: ¡cuando el tratamiento marca la diferencia!

2020 ◽  
Vol 49 (4) ◽  
pp. 568-570
Author(s):  
Alma S. Arrioja Salazar ◽  
Luis Emiro Velazco C.
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Dilated Cardiomyopathy ◽  
Tricuspid Valve ◽  
Antiphospholipid Syndrome ◽  
Systolic Dysfunction ◽  
Transthoracic Echocardiogram ◽  
Exertional Dyspnea ◽  
Pulmonary Mass

We report the case of a 54 years old woman with antiphospholipid syndrome in irregular therapy, admitted due to exertional dyspnea and orthopnea. The transthoracic echocardiogram showed dilated cardiomyopathy with biventricular systolic dysfunction, pulmonary hypertension and masses related to the pulmonary and tricuspid valve without autonomic movement. The crops and white count were normal, with alteration of the SAF test, in addition, SLE was diagnosed. It was started therapy for heart failure, steroids, rituximab and anticoagulation, with improving of the symptoms. The echocardiographic control showed remission of the tricuspid masses and similar dimensions of the pulmonary mass.

scholarly journals THE PREVALENCE OF THROMBOTIC EVENTS IN CHILDREN WITH HEART FAILURE ON THE BACKGROUND OF THE DILATED CARDIOMYOPATHY PHENOTYPE

2019 ◽  
Vol 21 (2) ◽  
pp. 78-84
Author(s):  
Yuliya V. Derevnina ◽  
E. N. Basargina ◽  
K. V. Savostyanov ◽  
A. A. Pushkov ◽  
O. B. Gordeeva
Keyword(s):  
Heart Failure ◽  
Left Ventricle ◽  
Dilated Cardiomyopathy ◽  
Thrombus Formation ◽  
Superior Vena ◽  
Systolic Dysfunction ◽  
Vena Cava ◽  
Mthfr Gene ◽  
Functional Class ◽  
Class Iii

Thrombotic events seem to be one of the most common and severe complications having a direct impact on the course of the disease in patients with cardiomyopathy.There were examined 94 children with dilated cardiomyopathy (DCMP) phenotype [49 children with dilated cardiomyopathy (DCMP), including 45 patients with non-compaction cardiomyopathy (NCMP) and remodeling in dilated phenotype]. Thromboses were diagnosed in 9 patients, including 7 DCMP and 2 NCMP cases. In 4 DCMP children, the thrombus was localized in the cavity of the left ventricle, one in the left atrium, the right ventricle, and the inferior vena cava. In NCMP children, intracardiac thrombus formation was not determined, one patient was diagnosed with an acute ischemic disorder of the cerebral circulation; in the second one, the thrombus was detected in the superior vena cava. Thrombosis in DCMP patients was detected against a background of a severe systolic dysfunction of the left ventricle (LVEF of below 30%), and in NCMP children with a moderate dysfunction. Also, the greatest prevalence rate of thrombotic complications was noted in Functional Class III and IV heart failure cases. At the same time, there was no established any influence of polymorphic markers G1691A of gene F5, G20210A of gene F2, C677T of MTHFR gene on the prevalence of thrombotic events. The authors believe the formation of thrombi with the severe LV dysfunction in children with cMYP should be taken into account in the determination the tactics of the treatment of such patients, as it is necessary to make a decision about administering antithrombotic therapy.

Abstract 4188: Prognostic implications of Ischemic Myocardial Scar by Cardiac Magnetic Resonance in Patients with Normal Coronary Angiography and Dilated Cardiomyopathy

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Alfonso Valle ◽  
Miguel Corbi ◽  
Mercedes Nadal ◽  
Jordi Estornell ◽  
Elena Lucas ◽  
...  
Keyword(s):  
Heart Failure ◽  
Magnetic Resonance ◽  
Dilated Cardiomyopathy ◽  
Event Rate ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Cardiac Events ◽  
Prognostic Implications ◽  
Lge Cmr

Background . In patients (pts) with chronic heart failure, late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) is capable to distinguish left ventricular systolic dysfunction (LVSD) related or not to coronary artery disease (CAD). Moreover about 10% of pts with dilated cardiomyopathy (DCM) are actually «unrecognized » ischemic cardiomyopathy (ICM), possibly because of coronary recanalization after silent infarction. However, the prognostic implications of « unrecognized » ICM are not known. Methods. Three hundred consecutive pts with heart failure and LVSD underwent LGE-CMR and were followed prospectively during 833 days (12–2724). The primary endpoint was the composite of cardiac death or heart failure hospitalization. Pts were classified into 4 groups : DCM without LGE (N 149) ; DCM with midwall fibrosis (n 35) ; ICM : ischemic scar and CAD (n 81) ; « unrecognized » ICM : ischemic scar without CAD (n 30). Results. 111 pts (38%) experienced events during follow-up.. There were non significant differences in event rate in patients with « unrecognized » ICM and ICM (53% and 63% respectively). By contrast the event rate in ICM groups were significantly higher than in pts with DCM (29% in group 1 and 31% in group 2 ; p = 0.000001) (Figure ). By multivariate analysis LGE was the strongest predictor of cardiac events (HR 1,7 CI 95% 1.07–2.88). Conclusions . In our series, pts with « unrecognized » ICM detected by CMR had a high risk of cardiac events during follow up similar to those pts with ICM. These findings had potentially important implications for routine use of CMR as a diagnostic and prognostic tool in patients with heart failure and systolic dysfunction.

Abstract 156: Enalapril prevents Development of Dilated Cardiomyopathy in Lamin A/C Mutant Mice

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Abdelaziz Beqqali ◽  
Ingrid van Rijsingen ◽  
Inge van der Made ◽  
Stephanie van den Oever ◽  
Yigal Pinto
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Systolic Dysfunction ◽  
Treatment Strategies ◽  
Mutant Gene ◽  
Current Treatment ◽  
Response To Treatment ◽  
Lamin A

Dilated Cardiomyopathy (DCM) is one of the leading causes of heart failure due to systolic dysfunction. Mutations in the LMNA gene, which encodes the nuclear lamina proteins Lamin A and C, are the most common cause of familial DCM. Current treatment strategies to improve the prognosis are limited to implantable cardioverter-defibrillator and heart transplantation. Patients with LMNA-related DCM are treated in accordance with international guidelines for the management of heart failure with little consideration of the possible influence of the etiology on the response to treatment. Recent studies suggest that this might result in inappropriate therapy in some patients. The influence of genetic factors in determining the response (and timing) of drug therapy is largely unstudied in DCM. Therefore, our aim is to determine the efficacy of existing heart failure drugs in preventing or delaying LMNA-related DCM. We used a well-established mouse model of Lamin A/C mimicking human LMNA-related DCM. Mice heterozygous for the Lmna mutant gene (n=20 per group) were treated with Metoprolol (β-blocker) or Enalapril (ACE-inhibitor) before the onset of DCM and were functionally evaluated by serial echocardiography and ECG until 75 weeks of age. Hearts were harvested for histological analysis and molecular characterization. Interestingly, the experimental group treated with Enalapril had a preserved overall cardiac function comparable to wildtype mice. Mice treated with Metoprolol however, displayed progressive heart failure, and an aggravated cardiac function compared to untreated Lmna +/- mice. Both the beneficial effects of Enalapril in preventing development of systolic dysfunction as well as the detrimental effect of Metoprolol were confirmed by expression of molecular stress markers and degree of cardiac fibrosis. Our results suggest that Enalapril is effective in preventing Lmna+/- induced cardiomyopathy in mice. Strikingly, Metoprolol increases cardiac dysfunction and stress in Lmna+/- mice. Further studies will determine whether Enalapril is also effective in preventing LMNA-related DCM in patients, and whether omitting Metoprolol from the standard cocktail of prescribed heart failure medicine is beneficial for LMNA patients.

scholarly journals Modifications of Titin Contribute to the Progression of Cardiomyopathy and Represent a Therapeutic Target for Treatment of Heart Failure

2020 ◽  
Vol 9 (9) ◽  
pp. 2770 ◽  
Author(s):  
Charles Tharp ◽  
Luisa Mestroni ◽  
Matthew Taylor
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Diastolic Dysfunction ◽  
Therapeutic Target ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Post Translational Modifications ◽  
Left Ventricular Dilation ◽  
Molecular Springs

Titin is the largest human protein and an essential component of the cardiac sarcomere. With multiple immunoglobulin(Ig)-like domains that serve as molecular springs, titin contributes significantly to the passive tension, systolic function, and diastolic function of the heart. Mutations leading to early termination of titin are the most common genetic cause of dilated cardiomyopathy. Modifications of titin, which change protein length, and relative stiffness affect resting tension of the ventricle and are associated with acquired forms of heart failure. Transcriptional and post-translational changes that increase titin’s length and extensibility, making the sarcomere longer and softer, are associated with systolic dysfunction and left ventricular dilation. Modifications of titin that decrease its length and extensibility, making the sarcomere shorter and stiffer, are associated with diastolic dysfunction in animal models. There has been significant progress in understanding the mechanisms by which titin is modified. As molecular pathways that modify titin’s mechanical properties are elucidated, they represent therapeutic targets for treatment of both systolic and diastolic dysfunction. In this article, we review titin’s contribution to normal cardiac physiology, the pathophysiology of titin truncation variations leading to dilated cardiomyopathy, and transcriptional and post-translational modifications of titin. Emphasis is on how modification of titin can be utilized as a therapeutic target for treatment of heart failure.

scholarly journals P865 Ecstasy s use an unusual cause of dilated cardiomyopathy a case report

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
M Mouadili ◽  
M Elqadi ◽  
A Goulehcen ◽  
N Echarai ◽  
M Elhattaoui
Keyword(s):  
Heart Failure ◽  
Case Report ◽  
Dilated Cardiomyopathy ◽  
Systolic Dysfunction ◽  
Immunoglobulin M ◽  
Cardiac Complications ◽  
Barr Virus ◽  
History Of ◽  
Epstein Barr ◽  
Immunological Assays

Abstract Background 3,4-methylenedioxymethamphetamine is a stimulant used illegally around the world, including Morocco. Cardiomyopathy and heart failure may occur following chronic MDMA use and may cause many other acute cardiac complications. Case report A 30-year-old man, with a history of MDMA use, 2 tablets/week since 2 months, and 6 tablets the week before admission, presentedwith severe dyspnea at rest. The first evaluation shows a sinus tachycardia with tachypnea and signs of global heart failure, loud systolic murmur heard over the apex andcrackles at the base of the lungs were observed. The blood tests performed, including erythrocyte sedimentation rate, blood picture, liver function and kidney function tests, protein, iron, phosphocalcic balance, glucose, and thyroid hormones,were within normal range. Moreover, immunological assays [immunoglobulin M (IgM) and immunoglobulin G (IgG) anti-Epstein–Barr virus] and toxoplasmosis were negative. Cytomegalovirus IgM was also absent, and IgG titer value was also absent. Electrocardiogram (ECG) tracing showed a complete left bundle branch block (LBBB)with a regular sinus rhythm (100 bpm). Transthoracic echocardiography showed dilated cardiomyopathy with severe systolic dysfunction (12% by Simpson’s method) (Fig. 1). Additional evaluation in the hospital excluded other etiologies of the cardiomyopathy. Thus, his condition was referred to the MDMA use. The patient now is a heart transplant candidate. Conclusion There are several reports that show an increase in frequency of MDMA use, suggesting that cardiomyopathy and acute heart failure secondary to the Ecstasy use may be a new medical concern. Thus, proper history of illicit drug intake is crucial in the diagnosis of unexplained cardiomyopathies.

Identify cause of heart failure of unknown aetiology using cardiac magnetic resonance - a 10-year observational study

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
N Ojrzynska ◽  
M Marczak ◽  
Ł Mazurkiewicz ◽  
J Petryka-Mazurkiewicz ◽  
B Milosz-Wieczorek ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Ejection Fraction ◽  
Dilated Cardiomyopathy ◽  
Systolic Dysfunction ◽  
Clinical Signs ◽  
Clinical Syndrome ◽  
Valvular Disease ◽  
Unknown Aetiology

Abstract Funding Acknowledgements Type of funding sources: None. Background Heart failure (HF) is a clinical syndrome caused by structural or functional cardiac abnormality and is diagnosed on the basis of typical symptoms. It is associated with significant morbidity and mortality and affects more than 25 million people worldwide. HF of unknown aetiology is managed with symptomatic treatment. Patients with reduced (HFrEF) or mid-reduced ejection fraction (HFmrEF) and no clear cause of systolic dysfunction are usually classified as having DCM. In HFpEF group ejection fraction is preserved but diastolic dysfunction is present leading to HF symptoms. Purpose The aim of this study was to investigate the clinical significance of cardiac magnetic resonance (CMR) imaging to identify heart failure (HF) aetiology. Methods We retrospectively reviewed all medical charts of patients referred for CMR due to heart failure of unknown aetiology admitted to our hospital between 2008 and 2017. Only patients with no specific pre-CMR initial diagnosis were included. Patients with suspicion of any specific disease leading to HF were excluded. If a referring physician suspected myocarditis, cardiomyopathy, previous myocardial infarction or advanced stable coronary disease (based on clinical signs and symptoms, the patient’s and family history or all pre-CMR studies), these patients were omitted from our analysis. Thus, we included only patients whose diagnostic work-up did not reveal suspicion of any specific cardiac disease leading to HF. Results The study sample consisted of 243 patients (173 (71.2%) male, mean age 44.0 ± 14.2%). All patients underwent contrast-enhanced CMR. Late gadolinium enhancement (LGE) was detected in 74.9% cases. Cardiomyopathies comprised the main aetiology (174 cases, 71.6%), in particular dilated cardiomyopathy (143 patients, 58.8%). 17 patients (7.0%) were diagnosed with myocarditis and in 24 patients (9.9%) CMR-based diagnosis was ambiguous – pointing out myocarditis or dilated cardiomyopathy. In 23 cases (9.5%) CMR indicated the presence of prior infarction undetected by pre-CMR testing. In five patients (2.1%) valvular disease was revealed as the sole cause of HF. We analysed the change in patients’ management guided by the CMR results defined as change of treatment and/or necessity of further tests leading to therapeutic consequences. Change of pre-CMR diagnosis occurred in 94 patients (38.7%) and was judged crucial in 41 patients (16,9%). As crucial we adjudicated the diagnosis associated with a need immediately further investigation and treatment changing, as follows: newly diagnosed amyloidosis, ischaemic heart disease or complex advanced valvular disease and cardiomyopathies other than dilated, hypertrophic and restrictive. Conclusion Our study strongly suggests that cardiac magnetic resonance imaging is a valuable tool for determining the aetiology of heart failure and impacts patients" management. Abstract Figure.

Clinical Outcome and Reversibility of Systolic Dysfunction in Patients With Dilated Cardiomyopathy Due to Hypertension and Chronic Heart Failure

2004 ◽  
Vol 57 (9) ◽  
pp. 834-841 ◽  
Author(s):  
Manuel Anguita Sánchez ◽  
Marcos Rodríguez Esteban ◽  
Soledad Ojeda Pineda ◽  
Martín Ruiz Ortiz ◽  
Elías Romo Peña ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Clinical Outcome ◽  
Dilated Cardiomyopathy ◽  
Systolic Dysfunction

scholarly journals Design and rationale for a comparison study of Olmesartan and Valsartan On myocardial metabolism In patients with Dilated cardiomyopathy (OVOID) trial: study protocol for a randomized controlled trial

Trials ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Sua Jo ◽  
Hyeyeon Moon ◽  
Kyungil Park ◽  
Chang-Bae Sohn ◽  
Jeonghwan Kim ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Ventricular Remodeling ◽  
Myocardial Metabolism ◽  
Controlled Trial ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Comparison Study ◽  
Randomized Controlled ◽  
Link Type

Abstract Background Dilated cardiomyopathy (DCMP) is characterized by ventricular chamber enlargement and systolic dysfunction which may cause heart failure. Patients with DCMP have overactivation of the renin-angiotensin-aldosterone systems, which can also adversely affect myocardial metabolism in heart failure. The impairment of myocardial metabolism can contribute to the progression of left ventricular remodeling and contractile dysfunction in heart failure. Although angiotensin II receptor blockers (ARBs) have been used to treat patients with DCMP, there has been no direct comparison of the efficacy of these agents. The objective of this study is to compare the effects of olmesartan and valsartan on myocardial metabolism in patients with DCMP. Methods/design The OVOID study (a comparison study of Olmesartan and Valsartan On myocardial metabolism In patients with Dilated cardiomyopathy) is designed as a non-blinded, open-label, parallel-group, prospective, randomized, controlled, multicenter clinical trial. A total of 40 DCMP patients aged between 20 and 85 years will be randomly allocated into the olmesartan or the valsartan group. 18F-fluoro-2-deoxyglucose (FDG) cardiac positron emission tomography (PET) will be performed at baseline and six months after receiving the study agent. The primary endpoint is myocardial glucose consumption per square meter, measured using 18F-FDG PET 6 months after receiving the study agent. Discussion The purpose of this trial is to compare the efficacy between olmesartan and valsartan in improving myocardial metabolism in DCMP patients. This will be the first randomized comparative study investigating the differential effects of ARBs on heart failure. Trial registration ClinicalTrials.govNCT04174456. Registered on 18 November 2019

The heart in neuromuscular disease: Duchenne and limb girdle muscular dystrophies

ESC CardioMed ◽  
2018 ◽  
pp. 1535-1540
Author(s):  
Karim Wahbi
Keyword(s):  
Heart Failure ◽  
Muscular Dystrophy ◽  
Dilated Cardiomyopathy ◽  
Systolic Dysfunction ◽  
Genetic Diagnosis ◽  
Dystrophin Gene ◽  
Left Ventricular ◽  
Muscular Dystrophies ◽  
Circulatory Support ◽  
Converting Enzyme Inhibitors

Duchenne muscular dystrophy (DMD), the most common muscular disease, is caused by out-of-frame mutations in the dystrophin gene. Dilated cardiomyopathy is the most frequent cardiac presentation of the disease, with a prevalence increasing with age—it is uncommon before the age of 10 years and present in up to 80% after 18 years. Heart failure represents nowadays the leading cause of death in DMD. Electrocardiography and echocardiography are recommended at diagnosis and then every 2 years until 10 years of age and yearly after. Angiotensin-converting enzyme inhibitors are widely prescribed before left ventricular dysfunction is detected, generally before 10 years of age, with an indication supported by the results of a randomized trial showing a benefit in terms of prevention of systolic dysfunction and survival. Beta-adrenergic blockers and eplerenone are also promising medications for this indication, but additional studies are warranted to determine their benefit. Glucocorticoids, which are currently recommended in patients with DMD who are 5 years of age or older to protect muscular and pulmonary function, could also improve left ventricular function and long-term cardiac prognosis. An implantable cardioverter defibrillator and mechanical circulatory support can be indicated in selected patients. The term limb girdle muscular dystrophy encompasses a heterogeneous group of muscular dystrophies involving more than 30 genes and various prevalence and severity of cardiac disease, mostly dilated cardiomyopathy. Electrocardiography and echocardiography are recommended at diagnosis and thereafter according to initial findings and genetic diagnosis. Heart failure management should follow the same criteria as for the other forms of dilated cardiomyopathy.

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