scholarly journals An Adult Mouse Model of Dilated Cardiomyopathy Caused by Inducible Cardiac-Specific Bis Deletion

2021 ◽  
Vol 22 (3) ◽  
pp. 1343
Author(s):  
Hye Hyeon Yun ◽  
Soon Young Jung ◽  
Bong Woo Park ◽  
Ji Seung Ko ◽  
Kyunghyun Yoo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Late Onset ◽  
Small Heat Shock Protein ◽  
Left Ventricular ◽  
Therapeutic Interventions ◽  
Ventricular Contractility ◽  
Knock Out ◽  
Multifunctional Protein ◽  
Cell Death Suppressor

BCL-2 interacting cell death suppressor (BIS) is a multifunctional protein that has been implicated in cancer and myopathy. Various mutations of the BIS gene have been identified as causative of cardiac dysfunction in some dilated cardiomyopathy (DCM) patients. This was recently verified in cardiac-specific knock-out (KO) mice. In this study, we developed tamoxifen-inducible cardiomyocyte-specific BIS-KO (Bis-iCKO) mice to assess the role of BIS in the adult heart using the Cre-loxP strategy. The disruption of the Bis gene led to impaired ventricular function and subsequent heart failure due to DCM, characterized by reduced left ventricular contractility and dilatation that were observed using serial echocardiography and histology. The development of DCM was confirmed by alterations in Z-disk integrity and increased expression of several mRNAs associated with heart failure and remodeling. Furthermore, aggregation of desmin was correlated with loss of small heat shock protein in the Bis-iCKO mice, indicating that BIS plays an essential role in the quality control of cardiac proteins, as has been suggested in constitutive cardiac-specific KO mice. Our cardiac-specific BIS-KO mice may be a useful model for developing therapeutic interventions for DCM, especially late-onset DCM, based on the distinct phenotypes and rapid progressions.

scholarly journals Temporal trends in outcome and patient characteristics in dilated cardiomyopathy, data from the Swedish Heart Failure Registry 2003–2015

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Helen Sjöland ◽  
Jonas Silverdal ◽  
Entela Bollano ◽  
Aldina Pivodic ◽  
Ulf Dahlström ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Temporal Trends ◽  
Physical Symptoms ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Continuous Change ◽  
Ventricular Ejection Fraction ◽  
Increased Risk ◽  
Over Time

Abstract Background Temporal trends in clinical composition and outcome in dilated cardiomyopathy (DCM) are largely unknown, despite considerable advances in heart failure management. We set out to study clinical characteristics and prognosis over time in DCM in Sweden during 2003–2015. Methods DCM patients (n = 7873) from the Swedish Heart Failure Registry were divided into three calendar periods of inclusion, 2003–2007 (Period 1, n = 2029), 2008–2011 (Period 2, n = 3363), 2012–2015 (Period 3, n = 2481). The primary outcome was the composite of all-cause death, transplantation and hospitalization during 1 year after inclusion into the registry. Results Over the three calendar periods patients were older (p = 0.022), the proportion of females increased (mean 22.5%, 26.4%, 27.6%, p = 0.0001), left ventricular ejection fraction was higher (p = 0.0014), and symptoms by New York Heart Association less severe (p < 0.0001). Device (implantable cardioverter defibrillator and/or cardiac resynchronization) therapy increased by 30% over time (mean 11.6%, 12.3%, 15.1%, p < 0.0001). The event rates for mortality, and hospitalization were consistently decreasing over calendar periods (p < 0.0001 for all), whereas transplantation rate was stable. More advanced physical symptoms correlated with an increased risk of a composite outcome over time (p = 0.0043). Conclusions From 2003 until 2015, we observed declining mortality and hospitalizations in DCM, paralleled by a continuous change in both demographic profile and therapy in the DCM population in Sweden, towards a less affected phenotype.

scholarly journals Myocardial work index: a marker of left ventricular contractility in pressure‐induced or volume overload‐induced heart failure

2021 ◽  
Author(s):  
Bálint Károly Lakatos ◽  
Mihály Ruppert ◽  
Márton Tokodi ◽  
Attila Oláh ◽  
Szilveszter Braun ◽  
...  
Keyword(s):  
Heart Failure ◽  
Volume Overload ◽  
Left Ventricular ◽  
Ventricular Contractility ◽  
Left Ventricular Contractility ◽  
Work Index

Role of angiotensin-signalling in anthracycline-induced cardiotoxicity

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Findlay ◽  
J.H Gill ◽  
R Plummer ◽  
C.J Plummer
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Angiotensin Ii ◽  
Late Onset ◽  
Left Ventricular Systolic Dysfunction ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Funding Source ◽  
Study Results

Abstract   Anthracycline chemotherapy remains a key component of cancer treatment regimens in both paediatric and adult patients. A significant issue with their use is the development of anthracycline-induced cardiotoxicity (AIC), with subclinical AIC and clinical heart failure observed in 13.8% and 3.1% of patients, respectively. The major clinical complication of AIC is the development of late-onset cardiotoxicity, occurring several years after drug administration, presenting as life-threatening heart failure (HF). Determining the relationship between subclinical AIC and late-onset HF, strategies for mitigation of AIC, and impacts upon the cancer survivor population remains a complex challenge. Administration of drugs targeting the angiotensin system, specifically angiotensin converting enzyme inhibitors (ACEi), have been reported to reduce AIC in the clinic. Whilst the therapeutic effect of ACEi in management of left ventricular systolic dysfunction and consequent HF is principally through optimisation of cardiac haemodynamics, the mechanism involved with mitigation of late-onset AIC several years after anthracycline exposure are currently unknown. Using a variety of human cardiomyocyte in vitro models we have previously demonstrated induction of cardiomyocyte hypertrophy by angiotensin II and anthracyclines. Importantly, selective blockade of the angiotensin II receptor 1 (ATR1) on cardiomyocytes mitigated the anthracycline-induced hypertrophic response, implicating synergism between AIC and angiotensin signalling in cardiomyocytes. Adult human ventricular cardiac myocyte AC10 cell-line were treated in vitro with a range of clinically relevant doxorubicin doses for clinically appropriate durations, with AT1 receptor gene expression evaluated using semi-quantitative PCR. Our results confirm a positive correlation between clinically-relevant concentration of doxorubicin and induction of genetic expression of ATR1 in AC10 cells, with up to 200% increases in ATR1 expression observed. Maximal doxorubicin-induced gene expression being observed at 8 and 24-hours, respectively. These preliminary results agreeing with clinical exposure parameters for this drug with protein expression studies being optimised to support these gene expression study results. Our preliminary studies also imply patients developing AIC carry a deleted polymorphism within intron 16 of the ACE gene and increased systemic levels of the ACE product angiotensin II, both with a known association to hypertrophic cardiomyopathy. Taken together, these data support our mechanistic hypothesis that a relationship exists between AIC and modulation of the angiotensin signalling pathway in cardiomyocytes, involving structural cellular changes and asymptomatic cardiac hypertrophy. An elevation in angiotensin II levels, potentially through polymorphisms in ACE, could thereby exacerbate anthracycline-induced hypertrophy and promote the development of late-onset anthracycline-induced HF. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Cancer Research UK funded PhD

Abstract P135: Hyperpolarized Carbon-13 Magnetic Resonance Reveals Early- and Late-Onset Changes to Metabolism in the Failing Heart

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Marie Schroeder ◽  
Angus Z Lau ◽  
Albert P Chen ◽  
Jennifer Barry ◽  
Damian J Tyler ◽  
...  
Keyword(s):  
Heart Failure ◽  
Magnetic Resonance ◽  
Late Onset ◽  
Krebs Cycle ◽  
Left Ventricular ◽  
Cine Mri ◽  
Cardiac Structure ◽  
End Diastolic Volume ◽  
Myocardial Energetics ◽  
And Function

Disordered metabolic substrate utilisation has been implicated in the pathogenesis of heart failure (HF). Hyperpolarised (HYP) 13C magnetic resonance, a technique in which the fate of 13C-labelled metabolites can be followed using MR imaging or spectroscopy, has enabled non-invasive assessment of metabolism. The aim of this study was to monitor carbohydrate metabolism alongside cardiac structure, function, and energetics, throughout HF progression. HF was induced in pigs (n=5) by right ventricular pacing at 188 bpm for 5 weeks. Pigs were examined at weekly time points: cine MRI assessed cardiac structure and function, HYP 13C2-pyruvate was administered intravenously and 13C MRS was used to assess 13C-glutamate production via Krebs cycle, 31P MRS assessed myocardial energetics, and HYP 13C1-pyruvate was administered to enable MRI of H13CO3- production from pyruvate dehydrogenase (PDH). At baseline, pigs had a normal left ventricular (LV) cardiac index (CI) and end diastolic volume (EDVi). The PCr/ATP was 2.3 ± 0.2. The 13C-glutamate/13C2-pyruvate was 4.3 ± 0.9%, and the H13CO3-/13C1-pyruvate ratio was 1.6 ± 0.2%. After 1–2 weeks of pacing, CI decreased to 3.3 ± 0.5 l/min/m2, PCr/ATP decreased to 1.7 ± 0.1, and 13C-glutamate/13C2-pyruvate decreased to 2.1 ± 0.6%. With the onset of HF, EDVi increased to 140.3 ± 14.1 ml/m2 and H13CO3-/13C1-pyruvate decreased to 0.5 ± 0.2%. In conclusion, we observed an early defect in Krebs' cycle that occurred alongside impaired cardiac energetics and function. Carbohydrate oxidation via PDH was maintained until the onset of HF. These results encourage use of metabolic therapies to delay/prevent the onset of heart failure in patients.

Nghiên cứu đánh giá chức năng tâm trương thất trái theo khuyến cáo ASE/EACVI 2016 ở bệnh nhân bệnh cơ tim giãn

2021 ◽  
Author(s):  
Quang Tuan Pham
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Left Ventricular Diastolic Function ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Ventricular Diastolic Function ◽  
Ventricular Diastolic Dysfunction ◽  
The Mean

TÓM TẮT Mục tiêu: Khảo sát chức năng tâm trương thất trái theo khuyến cáo ASE/EACVI 2016 ở bệnh nhân bệnh cơ tim giãn bằng siêu âm tim. Tìm hiểu mối liên quan giữa chức năng tâm trương thất trái với tình trạng giãn thất trái, độ suy tim NYHA, phân suất tống máu thất trái, phân suất co cơ thất trái. Đối tượng và phương pháp nghiên cứu: Nghiên cứu mô tả cắt ngang trên 56 bệnh nhân bệnh cơ tim giãn nguyên phát được nhập viện và điều trị tại bệnh viện Trung ương Huế từ tháng 4/2018 đến tháng 8/2020. Kết quả: Đường kính thất trái cuối tâm trương và cuối tâm thu trung bình là 66,11 ± 7,3 mm và 57,7 ± 8,02 mm. Đường kính nhĩ trái trung bình là 40,61 ± 7,65 mm. Phân suất tống máu thất trái trung bình là 24,68 ± 5,97 %. Phân suất co cơ thất trái trung bình là 12,91 ± 4,55 %. Tất cả các bệnh nhân nhóm nghiên cứu đều có rối loạn chức năng tâm trương thất trái. Chiếm tỷ lệ cao nhất là rối loạn chức năng tâm trương độ II (44,6%), tiếp sau là rối loạn chức năng tâm trương độ III (35,8%) và rối loạn chức năng tâm trương độ I là 19,6%. Không có sự liên quan có ý nghĩa thống kê giữa mức độ rối loạn tâm trương thất trái với đường kính thất trái cuối thì tâm thu và tâm trương (p > 0,05). Có mối liên quan giữa rối loạn chức năng tâm trương thất trái với các thông số phân suất tống máu EF và phân suất co cơ FS (p < 0,005). Có sự tương quan thuận mức độ vừa giữa phân độ rối loạn chức năng tâm trương thất trái với phân độ suy tim theo NYHA với r = 0,445, sự tương quan đó có ý nghĩa thống kê (p < 0,001). Kết luận: Tất cả các bệnh nhân bệnh cơ tim giãn trong nhóm nghiên cứu đều có rối loạn chức năng tâm trương thất trái, chủ yếu là rối loạn chức năng tâm trương nặng độ II - III. Sự rối loạn này thể hiện rõ qua sự biến đổi các thông số đánh giá chức năng tâm trương thất trái trên siêu âm tim theo khuyến cáo ASE/ EACVI 2016, một khuyến cáo mới đưa ra nhằm tiếp cận đánh giá chức năng tâm trương một cách thuận tiện và dễ dàng hơn. Từ khóa: Bệnh cơ tim giãn, rối loạn chức năng tâm trương thất trái, khuyến cáo ASE/EACVI 2016 ABSTRACT EVALUATION OF LEFT DYSTOLIC FUNCTION ACCORDING TO THE RECOMMENDATION ASE/EACVI 2016 INPATIENTS WITH DILATED CARDIOMYPAHTIES Background: Dilated cardiomyopathy is a disease of the heart muscle, characterized by dilatation of the heart chamber and a dysfunction of the left or both ventricles. It often leads to progressive heart failure, and is the leading cause of heart transplant among all cardiomyopathy. The annual rate of sudden cardiac death in dilated cardiomyopathy is 2 - 4%, with sudden death accounting for half of all deaths [9]. Echocardiography is an evaluation of a patient with dilated cardiomyopathy. There have been many studies on dilated cardiomyopathy in the world. However, there are still few studies evaluating diastolic function in patients with dilated cardiomyopathy using cardiac Doppler echocardiography. Experts around the world have made many recommendations in assessing left ventricular diastolic function, most recently is the recommendation ASE/EACVI 2016. Comparing with the 2009 EAE/ASE recommendation, the recommendation ASE/EACVI 2016 for assessment of left ventricular diastolic function has fewer parameters, so it is easier to implement and more convenient in clinical practice. Objective: Surveying left ventricular diastolic function according to the recommendation ASE/EACVI 2016 in patients with dilated cardiomyopathy by echocardiography and investigating the relationship between left ventricular diastolic function with left ventricular dilatation, heart failure NYHA, left ventricular ejection fraction, left ventricle fractional shortening. Methods: Research was designed as a cross - sectional descriptive study. Studied on 56 patients with primary dilated cardiomyopathy were hospitalized and treated at Hue Central Hospital. Results: The results showed: The mean end - diastolic and end - systolic left ventricular diameters were 66,11 ± 7,3 mm and 57,7 ± 8,02 mm. The mean left atrial diameter was 40,61 ± 7,65 mm. The mean left ventricular ejection fraction was 24,68 ± 5,97%. The mean fractional shortening of left ventricular contraction was 12,91 ± 4,55%. All patients in the study group had left ventricular diastolic dysfunction. The highest proportion is diastolic dysfunction grade II (44,6%), followed by diastolic dysfunction grade III (35,8%) and diastolic dysfunction grade I is 19,6%. There was no statistically significant relationship between the classification of left ventricular diastolic dysfunction and left ventricular systolic and diastolic diameter (p > 0.05). There is a relationship between left ventricular diastolic dysfunction and parameters of ejection fraction EF and contraction fraction FS (p < 0.005). There is a moderate positive correlation between the classification of left ventricular diastolic dysfunction and the heart failure rating according to NYHA (r = 0,445, p < 0,001). Conclusion: All patients in the study group had left ventricular diastolic dysfunction, mostly grade II and grade III diastolic dysfunction. This disorder is clearly demonstrated by the change in the parameters of the left ventricular diastolic function assessment on echocardiography according to the 2016 ASE/ EACVI recommendations, a new recommendation introduced to approach the assessment of diastolic functionmore convenient and easier way. Key words: Dilated cardiomyopathy, left ventricular diastolic dysfunction, the recommendation ASE / EACVI 2016.

scholarly journals Hyperuricemia and the Risk of Heart Failure: Pathophysiology and Therapeutic Implications

2021 ◽  
Vol 12 ◽  
Author(s):  
Ke Si ◽  
Chijing Wei ◽  
Lili Xu ◽  
Yue Zhou ◽  
Wenshan Lv ◽  
...  
Keyword(s):  
Heart Failure ◽  
Vascular Inflammation ◽  
Cardiovascular Effects ◽  
Daily Practice ◽  
Left Ventricular ◽  
Therapeutic Interventions ◽  
Current Evidence ◽  
Free Oxygen Radical ◽  
Positive Role ◽  
Therapeutic Implications

The association between hyperuricemia and cardiovascular disease (CVD) has been reported and studied in the past two decades. Xanthine oxidase (XO) induced uric acid (UA) serves as a risk factor and has the independent prognostic and functional impact of heart failure (HF), but whether it plays a positive role in the pathogenesis of HF has remained unclear. Growing evidence suggest the up-regulated XO avtivity and increased production of free oxygen radical (ROS) correspondingly are the core pathogenesis of HF with hyperuricemia, which results in a whole cluster of pathophysiologic cardiovascular effects such as oxidative stress, endothelial dysfunction, vascular inflammation, left ventricular (LV) dysfunction as well as insulin resistance (IR). The use of XO inhibition represents a promising therapeutic choice in patients with HF due to its dual effect of lowering serum UA levels as well as reducing ROS production. This review will discuss the pathophysiologic mechanisms of hyperuricemia with HF, the targeted therapeutic interventions of UA lowering therapies (ULT) with XO inhibition and mechanism underlying beneficial effects of ULT. In addition, the review also summarizes current evidence on the role of ULT in HF and compares CV risk between allopurinol and febuxostat for practical and clinical purposes. Guidelines and implementation of CV risk management in daily practice will be discussed as well.

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.

scholarly journals An Echocardiographic Evaluation of Dilated Cardiomyopathy in a Tertiary Care Hospital

2019 ◽  
Vol 57 (215) ◽  
Author(s):  
Raj Kumar Thapa ◽  
Kanchan K.C ◽  
Rishi Khatri ◽  
Devendra Khatri ◽  
Rajeeb Kumar Deo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Left Ventricle ◽  
Ejection Fraction ◽  
Dilated Cardiomyopathy ◽  
Tertiary Care ◽  
Left Ventricular ◽  
Care Hospital ◽  
Echocardiographic Evaluation ◽  
Significant Difference

Introduction: Cardiomyopathies are diseases of heart muscle that may originate from genetic defects, cardiac myocyte injury or infiltration of myocardial tissues. Dilated cardiomyopathy is the most common phenotype and is often a final common pathway of numerous cardiac insults. Mostly it remains unknown in the absence of echocardiography, histopathology and genetic evaluation. Though common it is underdiagnosed with not much of data available in our setup.Methods: This study was analytical cross-sectional study of hospital data on Echocardiographic findings in 65 patients of DCM visiting cardiology unit for Echocardiographic evaluation from 1st of February to 31st July 2018 for the period of six months in Shree Birendra Hospital, a tertiary care military hospital at Chhauni, Kathmandu. Pediatric age group patients and those who refused to give consent were excluded. Data obtained were entered in Microsoft Excel 2010 and analyzed by IBM SPSS 21.Results: Among 65 patients enrolled 40 (61%) were male and 25 (39%) female with male to female ratio of 1.6:1. Elderly people (61-75 years) with an average age of 65 were commonly involved and they presented mostly with congestive heart failure, 32 (49%). Echocardiographic evaluation showed 36 (55%) with mildly dilated Left Ventricle (5.6-6.0cm). Majority had reduced Left ventricular systolic function with an average Ejection fraction (EF) of 39.6%. No significant difference between male and female with the average EF% (P=0.990) and there was no significant relation between age and average EF% (P=0.091).Conclusions: Dilated Cardiomyopathy is the commonest cardiomyopathy phenotype mostly presenting with congestive heart failure. It is often underdiagnosed in our part of the world, however echocardiography will easily detect the condition. Keywords: dilated cardiomyopathy; echocardiography; ejection fraction; left ventricle.

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