Dilated Cardiomyopathy
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2021 ◽  
Vol 11 (23) ◽  
pp. 11165
Pamela Franco ◽  
Julio Sotelo ◽  
Cristian Montalba ◽  
Bram Ruijsink ◽  
Eric Kerfoot ◽  

In this paper, we applied a method for quantifying several left intraventricular hemodynamic parameters from 4D Flow data and its application in a proof-of-concept study in dilated cardiomyopathy (DCM) patients. In total, 12 healthy volunteers and 13 DCM patients under treatment underwent short-axis cine b-SSFP and 4D Flow MRI. Following 3D segmentation of the left ventricular (LV) cavity and registration of both sequences, several hemodynamic parameters were calculated at peak systole, e-wave, and end-diastole using a finite element approach. Sensitivity, inter- and intra-observer reproducibility of hemodynamic parameters were evaluated by analyzing LV segmentation. A local analysis was performed by dividing the LV cavity into 16 regions. We found significant differences between volunteers and patients in velocity, vorticity, viscous dissipation, energy loss, and kinetic energy at peak systole and e-wave. Furthermore, although five patients showed a recovered ejection fraction after treatment, their hemodynamic parameters remained low. We obtained several hemodynamic parameters with high inter- and intra-observer reproducibility. The sensitivity study revealed that hemodynamic parameters showed a higher accuracy when the segmentation underestimates the LV volumes. Our approach was able to identify abnormal flow patterns in DCM patients compared to volunteers and can be applied to any other cardiovascular diseases.

2021 ◽  
pp. 1-3
Koichi Takamizawa ◽  
Ki-Sung Kim ◽  
Hideaki Ueda

Abstract Emery-Dreifuss muscular dystrophy is a slowly progressive skeletal muscle and joint disorder associated with cardiac complications. Dilated cardiomyopathy was the initial manifestation of Emery-Dreifuss muscular dystrophy in an 8-year-old girl. Despite normal muscle and myocardial biopsies, genetic testing revealed LMNA mutations. As Emery-Dreifuss muscular dystrophy is associated with minimal skeletal muscle weakness, cardiac complications can facilitate its diagnosis.

2021 ◽  
Ravi Shah ◽  
Babken Asatryan ◽  
Ghaith Sharaf Dabbagh ◽  
Nay Aung ◽  
Mohammed Y Khanji ◽  

Background: There is a paucity of data regarding the phenotype of dilated cardiomyopathy (DCM) gene variants in the general population. We aimed to determine the frequency and penetrance of DCM-associated putative pathogenic gene variants in a general, adult population, with a focus on the expression of clinical and subclinical phenotype, including structural, functional and arrhythmic disease features. Methods: UK Biobank participants who had undergone whole exome sequencing (WES), ECG and cardiovascular magnetic resonance (CMR) imaging were selected for study. Three different variant calling strategies (one primary and two secondary) were used to identify subjects with putative pathogenic variants in 44 DCM genes. The observed phenotype was graded to either 1) DCM (clinical or CMR diagnosis); 2) early DCM features, including arrhythmia and/or conduction disease, isolated ventricular dilation, and hypokinetic non-dilated cardiomyopathy; or 3) phenotype-negative. Results: Among 18,665 individuals included in the study, 1,463 (7.8%) subjects possessed ≥1 putative pathogenic variant in 44 DCM genes by the main variant calling strategy. A clinical diagnosis of DCM was present in 0.34% and early DCM features in 5.7% of individuals with putative pathogenic variants. ECG and CMR analysis revealed evidence of subclinical DCM in an additional 1.6% and early DCM features in 15.9% of individuals with putative pathogenic variants. Arrhythmias and/or conduction disease (15.2%) were the most common early DCM features, followed by hypokinetic non-dilated cardiomyopathy (4%). The combined clinical/subclinical penetrance was ≤30% with all three variant filtering strategies. Clinical DCM was slightly more prevalent among participants with putative pathogenic variants in definitive/strong evidence genes, as compared to those with variants in moderate/limited evidence genes. Conclusions: In the UK Biobank, approximately 1/6 of adults with putative pathogenic variants in DCM genes exhibited a subclinical phenotype based on ECG and/or CMR, most commonly manifesting with arrhythmias in the absence of substantial ventricular dilation/dysfunction.

2021 ◽  
Vol 26 (10) ◽  
pp. 4628
T. G. Vaikhanskaya ◽  
L. N. Sivitskaya ◽  
O. D. Levdansky ◽  
T. V. Kurushko ◽  
N. G. Danilenko

Aim. To study the diagnostic significance of genetic testing in patients with dilated cardiomyopathy (DCM), identify predictors of life-threatening ventricular tachyarrhythmias (VTAs) and assess adverse clinical outcomes in different genetic groups.Material and methods. The study included 126 unrelated patients with verified DCM as follows: 70 (55,6%) probands with criteria for familial DCM and 56 (44,4%) individuals with a probable hereditary component. All patients (age, 43,1±11,3 years; men, 92 (73%); left ventricular ejection fraction, 30,6±8,43%; left ventricular enddiastolic diameter, 68,3±8,36 mm; follow-up period — median, 49 months) receive a complex of diagnostic investigations, including genetic screening using nextgeneration sequencing, followed by verification of variants by the Sanger method.Results. Pathogenic and likely pathogenic genetic variants were found in 61 (48,4%) of 126 patients with DCM. The dominant mutations were titin-truncating variants (TTNtvs), identified in 16 individuals (12,7%), and variants of lamin A/C (LMNA), identified in 13 probands (10,3%). Mutations in the other 19 genes were found in 32 (25,4%) patients. The following primary endpoints were assessed: sudden cardiac death (SCD), episodes of VTA (sustained ventricular tachycardia/ventricular fibrillation) and appropriate shocks of implanted cardiac resynchronization therapy (CRT)/cardioverter defibrillators (CVD) devices. As a result of ROC analysis, the following independent risk factors for SCD were identified: mutations in the LMNA gene (AUC, 0,760; p=0,0001) and non-sustained ventricular tachycardia (cut-off heart rate ≥161 bpm: AUC, 0,788; p=0,0001). When comparing the phenotypes and genotypes of DCM, TTNtv genotype was associated with a lower prevalence of complete left bundle branch block (χ2=7,46; p=0,024), a lower need for CRT/CVD implantation (χ2=5,70; p=0,017) and more rare episodes of sustained ventricular tachycardia/ventricular fibrillation (χ2=30,1; p=0,0001) compared with LMNA carriers. Kaplan-Meier analysis showed the worst prognosis in carriers of LMNA mutations both in relation to life-threatening VTA (log rang χ2=88,5; p=0,0001) and in achieving all unfavorable outcomes (χ2=27,8; p=0,0001) compared with groups of genenegative individuals, carriers of TTNtv and other genotypes.Conclusion. The phenotypes of DCM with TTNtv did not significantly differ in the incidence of VTAs and adverse outcomes compared with the gene-negative group and other genotypes (with the exception of LMNA). The contribution of the associations of LMNA mutations with VTAs on prognosis was confirmed, which shows the important role of LMNA genotype diagnosis for SCD risk stratification in patients with DCM.

2021 ◽  

Reopening the chest in patients with left ventricular assist devices at the time of a heart transplant is challenging due to adhesions and the possibility of injury to vital structures. The sternal sparing bilateral thoracotomy approach utilized to implant a left ventricular assist device minimizes the chances of such injuries and offers a cosmetically better outcome. We demonstrate a procedure for implanting a left ventricular assist device in a 54-year-old man diagnosed with dilated cardiomyopathy who suffered rapid decompensation despite maximum medical therapy.

2021 ◽  
Vol 161 ◽  
pp. 122-123
Rajeev Gupta ◽  
Fady Gerges ◽  
Galal Eldin Nagib Elkilany ◽  
Neelesh Gupta

2021 ◽  
pp. 1-6
Mohammad Mahdavi ◽  
Neda Mohsen-Pour ◽  
Majid Maleki ◽  
Mahshid Hesami ◽  
Niloofar Naderi ◽  

Abstract Background: Salih myopathy, characterised by both congenital myopathy and fatal dilated cardiomyopathy, is an inherited muscle disorder that affects skeletal and cardiac muscles. TTN has been identified as the main cause of this myopathy, the enormous size of this gene poses a formidable challenge to molecular genetic diagnostics. Method: In the present study, whole-exome sequencing, cardiac MRI, and metabolic parameter assessment were performed to investigate the genetic causes of Salih myopathy in a consanguineous Iranian family who presented with titinopathy involving both skeletal and heart muscles in an autosomal recessive inheritance pattern. Results: Two missense variants of TTN gene (NM_001267550.2), namely c.61280A>C (p. Gln20427Pro) and c.54970G>A (p. Gly18324Ser), were detected and segregations were confirmed by polymerase chain reaction-based Sanger sequencing. Conclusions: The compound heterozygous variants, c.61280A>C, (p. Gln20427Pro) and c.54970G>A, (p. Gly18324Ser) in the TTN gene appear to be the cause of Salih myopathy and dilated cardiomyopathy in the family presented. Whole-exome sequencing is an effective molecular diagnostic tool to identify the causative genetic variants of large genes such as TTN.

2021 ◽  
Vol 8 ◽  
Tong Liu ◽  
Zhen Zhou ◽  
Kairui Bo ◽  
Yifeng Gao ◽  
Hui Wang ◽  

Purpose: Left ventricular global function index (LVGFI) assessed using cardiac magnetic resonance (CMR) seems promising in the prediction of clinical outcomes. However, the role of the LVGFI is uncertain in patients with heart failure (HF) with dilated cardiomyopathy (DCM). To describe the association of LVGFI and outcomes in patients with DCM, it was hypothesized that LVGFI is associated with decreased major adverse cardiac events (MACEs) in patients with DCM.Materials and Methods: This prospective cohort study was conducted from January 2015 to April 2020 in consecutive patients with DCM who underwent CMR. The association between outcomes and LVGFI was assessed using a multivariable model adjusted with confounders. LVGFI was the primary exposure variable. The long-term outcome was a composite endpoint, including death or heart transplantation.Results: A total of 334 patients (mean age: 55 years) were included in this study. The average of CMR-LVGFI was 16.53%. Over a median follow-up of 565 days, 43 patients reached the composite endpoint. Kaplan–Meier analysis revealed that patients with LVGFI lower than the cutoff values (15.73%) had a higher estimated cumulative incidence of the endpoint compared to those with LVGFI higher than the cutoff values (P = 0.0021). The hazard of MACEs decreased by 38% for each 1 SD increase in LVGFI (hazard ratio 0.62[95%CI 0.43–0.91]) and after adjustment by 46% (HR 0.54 [95%CI 0.32–0.89]). The association was consistent across subgroup analyses.Conclusion: In this study, an increase in CMR-LVGFI was associated with decreasing the long-term risk of MACEs with DCM after adjustment for traditional confounders.

2021 ◽  
Juan Qin ◽  
Jingfeng Zhang ◽  
Lianyun Lin ◽  
Omid Haji-Ghassemi ◽  
Zhi Lin ◽  

Several mutations identified in phospholamban (PLN) have been linked to familial dilated cardiomyopathy (DCM) and heart failure, yet the underlying molecular mechanism remains controversial. PLN interacts with sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and regulates calcium uptake, which is modulated by the protein kinase A (PKA)-dependent phosphorylation of PLN during the fight-or-flight response. Here, we present the crystal structures of the catalytic domain of PKA in complex with wild-type and DCM-mutant PLNs. Our structures, combined with the results from other biophysical and biochemical assays, reveal a common disease mechanism: the mutations in PLN reduce its phosphorylation level by changing its conformation and weakening its interactions with PKA. In addition, we demonstrate that another more ubiquitous SERCA-regulatory peptide, called another-regulin (ALN), shares a similar mechanism mediated by PKA in regulating SERCA activity.

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3180
Somy Yoon ◽  
Ulrich Gergs ◽  
Julie R. McMullen ◽  
Gwang Hyeon Eom

Heat shock protein (HSP) 70 is a molecular chaperone that regulates protein structure in response to thermal stress. In addition, HSP70 is involved in post-translational modification and is related to the severity of some diseases. Here, we tested the functional relevance of long-lasting HSP70 expression in a model of nonischemic heart failure using protein phosphatase 2 catalytic subunit A (PP2CA)-expressing transgenic mice. These transgenic mice, with cardiac-specific overexpression of PP2CA, abruptly died after 12 weeks of postnatal life. Serial echocardiograms to assess cardiac function revealed that the ejection fraction (EF) was gradually decreased in transgenic PP2CA (TgPP2CA) mice. In addition, PP2CA expression exacerbated systolic dysfunction and LV dilatation, with free wall thinning, which are indicators of fatal dilated cardiomyopathy. Interestingly, simultaneous expression of HSP70 in double transgenic mice (dTg) significantly improved the dilated cardiomyopathy phenotype of TgPP2CA mice. We observed better survival, preserved EF, reduced chamber enlargement, and suppression of free wall thinning. In the proposed molecular mechanism, HSP70 preferentially regulates the phosphorylation of AKT. Phosphorylation of AKT was significantly reduced in TgPP2CA mice but was not significantly lower in dTg mice. Signal crosstalk between AKT and its substrates, in association with HSP70, might be a useful intervention for patients with nonischemic heart failure to suppress cardiac remodeling and improve survival.

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