Heart transplantation in patients with dystrophinopathic cardiomyopathy: Review of the literature and personal series

Papa, Andrea Antonio; D’Ambrosio, Paola; Petillo, Roberta; Palladino, Alberto; Politano, Luisa

doi:10.5582/irdr.2017.01024

Cited by 37 publications

(44 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Dilated cardiomyopathy, ultimately leading to heart failure, is the most common outcome in patients with dystrophin mutations (Kamdar and Garry, 2016;Papa et al, 2017), and it develops in DMD patients due to muscle wasting, but remains mostly unexplained in its dynamics. The DMD (mdx) mouse model has critical limitations since it develops only mild symptoms of heart failure with slow progression and unaffected lifespan compared to control mice (Carnwath and Shotton, 1987;Coulton et al, 1988;Shirokova and Niggli, 2013).…”

Section: Discussionmentioning

confidence: 99%

DMD Pluripotent Stem Cell Derived Cardiac Cells Recapitulate in vitro Human Cardiac Pathophysiology

Jelínková

Vilotić

Přibyl

et al. 2020

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Duchenne muscular dystrophy (DMD) is associated with progressive dilated cardiomyopathy eventually leading to heart failure as the main cause of death in DMD patients. A human cardiomyocyte (CM) model was developed from several independent dystrophin-deficient human pluripotent stem cell (hPSC) lines from DMD patients and hESC line with deletion of DMD gene generated by CRISPR/Cas9 technology. DMD hPSC were differentiated into CMs. DMD mutation-carrying cells are less prone to differentiate into CMs. DMD CMs further demonstrate an enhanced cell death rate. Ion channel expression was altered in terms of potassium (Kir2.1 overexpression) and calcium handling (DHPR overexpression). DMD-CMs exhibited mishandling of calcium demonstrated by increased time of calcium release. Further mechanical impairment (hypocontractility), bradycardia, increased beat rate variability, and blunted β-adrenergic response connected with remodeling of β-adrenergic receptors' expression was found in DMD-CMs (LTCC L-type calcium channel, cTnT-cardiac troponin T, Kir2.1-potassium channel).

show abstract

Section: Discussionmentioning

confidence: 99%

DMD Pluripotent Stem Cell Derived Cardiac Cells Recapitulate in vitro Human Cardiac Pathophysiology

Jelínková

Vilotić

Přibyl

et al. 2020

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

show abstract

“…15 Heart protection of DH2-R19 mini-dystrophin was studied in 21-month-old male mdx mice that showed moderate cardiomyopathy. [15][16][17][18] In contrast to what was seen in skeletal muscle, 12,14 expression of DH2-R19 minidystrophin in the heart only partially corrected electrocardiogram (ECG) and cardiac hemodynamic deficiencies. 15 This unexpected result suggests that DH2-R19 mini-dystrophin may lack domain(s) important for heart function.…”

Section: Introductionmentioning

confidence: 92%

Cardiac-Specific Expression of ΔH2-R15 Mini-Dystrophin Normalized All Electrocardiogram Abnormalities and the End-Diastolic Volume in a 23-Month-Old Mouse Model of Duchenne Dilated Cardiomyopathy

et al. 2018

View full text Add to dashboard Cite

Heart disease is a major health threat for Duchenne/Becker muscular dystrophy patients and carriers. Expression of a 6-8 kb mini-dystrophin gene in the heart holds promise to change the disease course dramatically. However, the mini-dystrophin gene cannot be easily studied with adeno-associated virus (AAV) gene delivery because the size of the minigene exceeds AAV packaging capacity. Cardiac protection of the ΔH2-R19 minigene was previously studied using the cardiac-specific transgenic approach. Although this minigene fully normalized skeletal muscle force, it only partially corrected electrocardiogram and heart hemodynamics in dystrophin-null mdx mice that had moderate cardiomyopathy. This study evaluated the ΔH2-R15 minigene using the same transgenic approach in mdx mice that had more severe cardiomyopathy. In contrast to the ΔH2-R19 minigene, the ΔH2-R15 minigene carries dystrophin spectrin-like repeats 16 to 19 (R16-19), a region that has been suggested to protect the heart in clinical studies. Cardiac expression of the ΔH2-R15 minigene normalized all aberrant electrocardiogram changes and improved hemodynamics. Importantly, it corrected the end-diastolic volume, an important diastolic parameter not rescued by ΔH2-R19 mini-dystrophin. It is concluded that that ΔH2-R15 mini-dystrophin is a superior candidate gene for heart protection. This finding has important implications in the design of the mini/micro-dystrophin gene for Duchenne cardiomyopathy therapy.

show abstract

“… 7 Individuals with DMD are unable to qualify for transplant surgery, due to skeletal-muscle impairment, rejection, and low levels of pulmonary function. 33 A recent review of the literature indicates individuals with BMD who are eligible for cardiac transplant will tolerate the procedure on par with individuals with other forms of heart failure. 33 …”

Section: Clinical Presentation In Adolescencementioning

confidence: 99%

“… 33 A recent review of the literature indicates individuals with BMD who are eligible for cardiac transplant will tolerate the procedure on par with individuals with other forms of heart failure. 33 …”

Section: Clinical Presentation In Adolescencementioning

confidence: 99%

Duchenne and Becker muscular dystrophy in adolescents: current perspectives

Andrews¹,

Wahl²

2018

AHMT

View full text Add to dashboard Cite

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are life-limiting and progressive neuromuscular conditions with significant comorbidities, many of which manifest during adolescence. BMD is a milder presentation of the condition and much less prevalent than DMD, making it less represented in the literature, or more severely affected individuals with BMD may be subsumed into the DMD population using clinical cutoffs. Numerous consensus documents have been published on the clinical management of DMD, the most recent of which was released in 2010. The advent of these clinical management consensus papers, particularly respiratory care, has significantly increased the life span for these individuals, and the adolescent years are now a point of transition into adult lives, rather than a period of end of life. This review outlines the literature on DMD and BMD during adolescence, focusing on clinical presentation during adolescence, impact of living with a chronic illness on adolescents, and the effect that adolescents have on their chronic illness. In addition, we describe the role that palliative-care specialists could have in improving outcomes for these individuals. The increasing proportion of individuals with DMD and BMD living into adulthood underscores the need for more research into interventions and intracacies of adolescence that can improve the social aspects of their lives.

show abstract

Heart transplantation in patients with dystrophinopathic cardiomyopathy: Review of the literature and personal series

Cited by 37 publications

References 44 publications

DMD Pluripotent Stem Cell Derived Cardiac Cells Recapitulate in vitro Human Cardiac Pathophysiology

DMD Pluripotent Stem Cell Derived Cardiac Cells Recapitulate in vitro Human Cardiac Pathophysiology

Cardiac-Specific Expression of ΔH2-R15 Mini-Dystrophin Normalized All Electrocardiogram Abnormalities and the End-Diastolic Volume in a 23-Month-Old Mouse Model of Duchenne Dilated Cardiomyopathy

Duchenne and Becker muscular dystrophy in adolescents: current perspectives

Contact Info

Product

Resources

About