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.

scholarly journals Case Report: Dilated Cardiomyopathy in a Newborn, a Potential Association With SARS-COV-2

2021 ◽  
Vol 9 ◽  
Author(s):  
Estela Azeka ◽  
Adam Arshad ◽  
Cristiane Martins ◽  
Anna Claudia Dominguez ◽  
Adailson Siqueira ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Enzyme Inhibitors ◽  
Decompensated Heart Failure ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Orotracheal Intubation ◽  
Left Ventricular ◽  
Nasopharyngeal Swab ◽  
Converting Enzyme Inhibitors ◽  
Severe Left Ventricular Dysfunction

Objective: The objective of this study was to describe the clinical course of a newborn who developed dilated cardiomyopathy (DCM) after COVID-19 infection.Methods: We retrospectively assessed the clinical notes of a pediatric patient with decompensated heart failure and who was previously positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Results: A 23-day-old newborn presented with diarrhea, hypoactivity, tachypnea, and lethargy. The infant progressed to develop respiratory failure and required orotracheal intubation due to apnea. A nasopharyngeal swab tested positive for SARS-COV-2. An echocardiogram (ECHO) demonstrated severe left ventricular dysfunction. The patient was discharged after 18 days with furosemide and angiotensin-converting enzyme inhibitors. During the follow-up period, the infant had two episodes of decompensated heart failure, with evidence of DCM. Investigations for known causes of secondary DCM were negative. The infant was promptly referred for heart transplantation.Conclusion: Although rare, we have observed a case of DCM in a newborn following COVID-19 disease. DCM may be a complication following COVID-19 disease in newborns.

Abstract 468: Previously Unrecognized Intronic Variants in the Dystrophin Gene Identified as Possible Contributors to Dilated Cardiomyopathy

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Alex Gyftopoulos ◽  
Tamara Ashvetiya ◽  
Yi-Ju Chen ◽  
Libin Wang ◽  
Charles H Williams ◽  
...  
Keyword(s):  
Heart Failure ◽  
Muscular Dystrophy ◽  
Dilated Cardiomyopathy ◽  
Allele Frequency ◽  
Minor Allele Frequency ◽  
Mixed Model ◽  
Dystrophin Gene ◽  
Becker Muscular Dystrophy ◽  
Minor Allele ◽  
Intronic Variants

Nonischemic dilated cardiomyopathy (DCM) often has a genetic etiology, however, its prevalence and etiologies are not completely understood. The UK Biobank comprises clinical and genetic data for greater than 500,000 individuals with enrollees 40-69 years of age. Our group created a custom phenotype of heart failure using ICD-10 codes for several subtypes of heart failure diagnoses including DCM. We then compared the individuals included in the custom heart failure phenotype to control individuals in a 20-to-1 fashion to identify genetic differences. Data were compared using Mixed Model Analysis for Pedigrees/Populations (MMAP) mixed-model regression. We identified 8 unlinked intronic variants in the dystrophin gene ( DMD ) that, when separated by self-identified race, occurred with a combined minor allele frequency of 0.15 in individuals with heart failure who identified as being of African descent. The combined minor allele frequency of these variants was 0.05 in individuals who self-identified as being of European descent. One variant of DMD in particular (rs139029250), was identified with a minor allele frequency of 0.05 in African British with DCM. The unadjusted odds ratio of a diagnosis of heart failure in individuals with rs129029250 was 4.65. When separated by gender, the unadjusted odds ratios are 2.02 for females and 6.44 for males. DMD is most notably known for its role in Duchenne and Becker muscular dystrophy, both of which are known to cause dilated cardiomyopathy in affected individuals. However, none of the individuals (36 female and 43 male) identified in our analysis with rs129029250 have been diagnosed with Duchenne muscular dystrophy, Becker muscular dystrophy, or a primary disorder of muscle (ICD code G70). Additionally, these individuals have an intronic variant of DMD , while Duchene and Becker muscular dystrophy are both due to exonic mutations. These findings suggest a possible common variant in the DMD gene that may contribute to DCM in individuals of African descent.

scholarly journals Heart failure in dilated non-ischaemic cardiomyopathy

2019 ◽  
Vol 21 (Supplement_M) ◽  
pp. M40-M43 ◽  
Author(s):  
Petar M Seferović ◽  
Marija M Polovina ◽  
Andrew J S Coats
Keyword(s):  
Heart Failure ◽  
Alcohol Intoxication ◽  
Systolic Dysfunction ◽  
Clinical Status ◽  
Significant Coronary Artery Disease ◽  
Left Ventricular ◽  
Circulatory Support ◽  
Specific Information ◽  
Ischaemic Cardiomyopathy ◽  
System Disease

Abstract Heart failure (HF) is the prevailing cause of morbidity and mortality in patients with dilated non-ischaemic cardiomyopathy (DCM) and DCM is one of several causes of HF, with several distinct epidemiological and clinical features which may have important implications for its management and prognosis. This article reviews cardiovascular monitoring of specific characteristics of HF in DCM. DCM is defined as ventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or significant coronary artery disease, the predominant phenotypes of being HFmrEF or HFrEF. DCM accounts for ∼40% of all cardiomyopathies but its true prevalence among patients with HFrEF is difficult to ascertain with certainty. Compared with patients with other HF aetiologies, individuals with DCM tend to be younger, more likely male and less likely to have associated comorbidities. A genetic aetiology of DCM is deemed responsible for ∼40% of cases. Confirmation of a specific genetic background is clinically relevant (e.g. Duchene or Backer muscular dystrophies, lamin A/C mutation), because those patients may be at a high risk of progressive left ventricular dysfunction or conduction system disease and sudden death, prompting early prophylaxis with an implantable cardioverter defibrillator. However, in most instances, HF in DCM has a multifactorial aetiology, with multiple factors needing to be systematically evaluated and/or monitored, since correction of reversible causes or (e.g. tachycardia-induced cardiomyopathy, alcohol intoxication, iron-overload, cancer therapies etc.) or targeting specific pathophysiological causes could lead to an improvement in clinical status. The treatment of DCM encompasses HF-related pharmacological and device therapies, and aetiology-specific treatments. At present, options for aetiology-related therapies are limited, and their effectiveness mostly requires confirmation from larger scale randomized trials. Whether outcomes of patients with HF in DCM differ from those with other HF aetiologies is unresolved. DCM is attributable for >40% of patients receiving mechanical circulatory support for advanced HF and it is the leading indication for heart transplantation. More aetiology-specific information is needed both in the evaluation and treatment of dilated cardiomyopathy.

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.

scholarly journals Treatment of Heart Failure with Mid-Range Ejection Fraction: What Is the Evidence

2021 ◽  
Vol 10 (2) ◽  
pp. 203
Author(s):  
Eleni-Evangelia Koufou ◽  
Angelos Arfaras-Melainis ◽  
Sahil Rawal ◽  
Andreas P. Kalogeropoulos
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Current Knowledge ◽  
Systolic Function ◽  
Angiotensin Receptor Blockers ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Current Evidence ◽  
Converting Enzyme Inhibitors ◽  
Reduced Ejection Fraction

In this review, we briefly outline our current knowledge on the epidemiology, outcomes, and pathophysiology of heart failure (HF) with mid-range ejection fraction (HFmrEF), and discuss in more depth the evidence on current treatment options for this group of patients. In most studies, the clinical background of patients with HFmrEF is intermediate between that of patients with HF and reduced ejection fraction (HFrEF) and patients with HF and preserved ejection fraction (HFpEF) in terms of demographics and comorbid conditions. However, the current evidence, stemming from observational studies and post hoc analyses of randomized controlled trials, suggests that patients with HFmrEF benefit from medications that target the neurohormonal axes, a pathophysiological behavior that resembles that of HFrEF. Use of β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and sacubitril/valsartan is reasonable in patients with HFmrEF, whereas evidence is currently scarce for other therapies. In clinical practice, patients with HFmrEF are treated more like HFrEF patients, potentially because of history of systolic dysfunction that has partially recovered. Assessment of left ventricular systolic function with contemporary noninvasive modalities, e.g., echocardiographic strain imaging, is promising for the selection of patients with HFmrEF who will benefit from neurohormonal antagonists and other HFrEF-targeted therapies.

scholarly journals Cardiomyopathy secondary to Duchenne muscular dystrophy in children

2021 ◽  
Vol 64 (2) ◽  
pp. 70-78
Author(s):  
Iulia Rodoman ◽  
◽  
Ina Palii ◽  
Victoria Sacara ◽  
Sergiu Gladun ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Ventricular Dysfunction ◽  
Angiotensin Receptor Blockers ◽  
Systolic Dysfunction ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Left Ventricular ◽  
High Rate ◽  
Converting Enzyme Inhibitors ◽  
Lv Dysfunction

Background: Cardiomyopathy (CM) associated with Duchenne muscular dystrophy (DMD) is a commonly recognized appearance of this neuromuscular disease, significantly increased morbidity and mortality, as well as the necessity for cardiological management. CM in DMD is defined by left ventricular (LV) systolic dysfunction and both atrial and ventricular dysrhythmias and is associated with higher mortality than other cases of pediatric dilated CMs. Notwithstanding the high rate of cardiac involvement, patients are usually asymptomatic despite significant LV dysfunction, because of likely poor mobility that masks the usual heart failure (HF) symptoms. Also, imagistic predictors are provided to be very helpful in defining early LV dysfunction, especially electrocardiogram and cardiac imaging (transthoracic echocardiography, speckle-tracking, cardiac magnetic resonance) are used to detect the onset and progression of dilated cardiomyopathy (DCM) in DMD. Conclusions: As most DMD patients are asymptomatic for a long time of their life, so identifying predictors of HF is crucial to support these patients. Ventricular dysfunction based on the ejection fraction (EF) measurement helps to choose therapy. In the case of early DCM (LVEF≥50%) the great purpose is to prevent ventricular dysfunction incipience with first-line HF therapy with Angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARBs). Current guidelines recommend the use of conventional HF medication in case of disease progression and DCM with MidRange Reduction of LV EF (40-49%). The therapeutic approach for patients with DCM and severe ventricular dysfunction (<40%) has been studied less profoundly and contemporary guidelines recommend all drugs used for HF treatment

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