Dilated cardiomyopathy: a review

Luk, Adriana; Ahn, Eric; Soor, Gursharan S.; Butany, Jagdish

doi:10.1136/jcp.2008.060731

Cited by 143 publications

(94 citation statements)

References 41 publications

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“…There is also a subset of patients that develop DCM in later life following earlier presentation with congenital heart defects, such as incomplete septation and failed myocardial compaction (23,39). This is comparable with the known embryonic phenotype of Prox1 mutant hearts (7) and suggests that future studies to investigate PROX1 as a candidate disease gene, causative for contractile protein misregulation, may be of significant prognostic value for DCM patients.…”

Section: Discussionmentioning

confidence: 51%

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Loss ofProx1in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy

Petchey¹,

Risebro²,

Vieira

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance How cardiac and skeletal muscle function is maintained and regulated is important in terms of understanding normal muscle physiology and muscle-based disease (myopathy). The two striated muscle types are structurally and functionally divergent, suggesting alternate molecular regulation. However, our discovery that the transcription factor Prox1 controls the same fast skeletal muscle gene program in both cardiac and slow skeletal muscle is significant in assigning a common genetic mechanism to striated muscle development. These studies establish a novel model of human dilated cardiomyopathy and reveal how loss of a single factor underpins conversion of slow to fast skeletal muscle, with implications for the molecular specification of endurance (stamina) versus rapidly contractile muscle function (speed).

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Section: Discussionmentioning

confidence: 51%

“…Postnatal mutants were further associated with the development of large intra-atrial (7/8) and intraventricular (4/8) thrombi at 12 wk (Fig. 2C), indicative of hemostasis associated with poor systolic function (23). To confirm the extent of impaired cardiac function, mutant hearts were analyzed by magnetic resonance imaging (MRI).…”

Section: Resultsmentioning

confidence: 99%

Loss ofProx1in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy

Petchey¹,

Risebro²,

Vieira

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…2B, cf. panels i and iii), indicating that reactive fibrosis, a common feature of cardiac remodeling found in DCM (de Leeuw et al 2001;Luk et al 2009), took place in CKO hearts. Additionally, immunostaining with anti-HSPG2 (also known as Perlecan) shows increased interstitial HSPG2 staining (Fig.…”

Section: Cko Hearts Exhibit Similar Cardiac Remodeling Observed In DCmentioning

confidence: 99%

DOT1L regulates dystrophin expression and is critical for cardiac function

Nguyen¹,

Xiao²,

Neppl³

et al. 2011

Genes Dev.

135

114

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Histone methylation plays an important role in regulating gene expression. One such methylation occurs at Lys 79 of histone H3 (H3K79) and is catalyzed by the yeast DOT1 (disruptor of telomeric silencing) and its mammalian homolog, DOT1L. Previous studies have demonstrated that germline disruption of Dot1L in mice resulted in embryonic lethality. Here we report that cardiac-specific knockout of Dot1L results in increased mortality rate with chamber dilation, increased cardiomyocyte cell death, systolic dysfunction, and conduction abnormalities. These phenotypes mimic those exhibited in patients with dilated cardiomyopathy (DCM). Mechanistic studies reveal that DOT1L performs its function in cardiomyocytes through regulating Dystrophin (Dmd) transcription and, consequently, stability of the Dystrophin-glycoprotein complex important for cardiomyocyte viability. Importantly, expression of a miniDmd can largely rescue the DCM phenotypes, indicating that Dmd is a major target mediating DOT1L function in cardiomyocytes. Interestingly, analysis of available gene expression data sets indicates that DOT1L is down-regulated in idiopathic DCM patient samples compared with normal controls. Therefore, our study not only establishes a critical role for DOT1L-mediated H3K79 methylation in cardiomyocyte function, but also reveals the mechanism underlying the role of DOT1L in DCM. In addition, our study may open new avenues for the diagnosis and treatment of human heart disease.

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“…Dilated cardiomyopathy is a disease of the myocardium characterized by chamber dilation and reduced left ventricular systolic function in the absence of abnormal cardiovascular loading conditions [5,6]. Although in many cases no cause is identified, DCMP can be attributed to etiologies such as infectious disease, chemotherapy side effects, alcohol abuse, pregnancy, and endocrine diseases including hyperthyroidism and hypothyroidism [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…Although in many cases no cause is identified, DCMP can be attributed to etiologies such as infectious disease, chemotherapy side effects, alcohol abuse, pregnancy, and endocrine diseases including hyperthyroidism and hypothyroidism [6,7].…”

Section: Introductionmentioning

confidence: 99%

Differential reversibility in heart failure due to hypothyroidism: A series of contrasting cases with review of literature

Roberto¹,

Aung²,

Agarwal³

et al. 2016

IJCRI

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International Journal of Case Reports and Images (IJCRI) is an international, peer reviewed, monthly, open access, online journal, publishing high-quality, articles in all areas of basic medical sciences and clinical specialties.Aim of IJCRI is to encourage the publication of new information by providing a platform for reporting of unique, unusual and rare cases which enhance understanding of disease process, its diagnosis, management and clinico-pathologic correlations.IJCRI publishes Review Articles, Case Series, Case Reports, Case in Images, Clinical Images and Letters to Editor. Website: www.ijcasereportsandimages.comDifferential reversibility in heart failure due to hypothyroidism:A series of contrasting cases with review of literature E. Samuel Roberto, Thein Aung, Ajay Agarwal, Roberto J. Colón ABSTRACT Introduction: Ranking third as a leading cause of heart failure in the United States, dilated cardiomyopathy (DCMP) affects 5 in 100,00 adults with an eight-year mortality rate between 70-80%. In the setting of hypothyroidism, DCMP is unique due to its potential reversibility with medical therapy. Thyroid hormone affects cardiac physiology and intracellular calcium regulation via SERCA2 and phospholamban, with concentrations of phospholamban most numerous in the ventricles. Administration of thyroid hormone can restore contractile function. However, the relationship between disease timeline and reversibility in DCMP due to hypothyroidism has not been previously described. Case Series: A 65-year-old Caucasian male presented with new onset severe dyspnea and fatigue. Thyroid-stimulating hormone was markedly elevated. Following levothyroxine therapy, his dilated cardiomyopathy reversed and returned to normal within six months. LVEF improved from 15-45% with decreased chamber dilation. A 60-year-old Caucasian female presented minimally responsive in overt heart failure due to myxedema coma. History revealed chronically uncontrolled hypothyroidism. TSH was significantly elevated. Following prolonged hospitalization and intravenous levothyroxine therapy, her clinical status began to reverse. LVEF improved from 10-25%, with decreased chamber dilation. Conclusion:Once the underlying mechanism of heart failure was addressed, the cases displayed varying recovery of contractility following thyroid hormone replacement. This may suggest that with longer duration of uncontrolled disease and consequent cardiac structural remodeling, the reversibility diminishes into irreversibility. These cases underscore the need to identify and treat early any contributing hypothyroidism in the setting of new onset dilated cardiomyopathy, as reversibility may be at stake.

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Dilated cardiomyopathy: a review

Cited by 143 publications

References 41 publications

Loss ofProx1in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy

Loss ofProx1in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy

DOT1L regulates dystrophin expression and is critical for cardiac function

Differential reversibility in heart failure due to hypothyroidism: A series of contrasting cases with review of literature

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