scholarly journals A Novel ALDH2 Activator AD-9308 Improves Diastolic and Systolic Myocardial Functions in Streptozotocin-Induced Diabetic Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 450
Author(s):  
Hsiao-Lin Lee ◽  
Siow-Wey Hee ◽  
Chin-Feng Hsuan ◽  
Wenjin Yang ◽  
Jing-Yong Huang ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Cardiac Tissue ◽  
Therapeutic Potential ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Water Soluble ◽  
Cellular Damage ◽  
Diabetic Mice ◽  
Mitochondrial Functions ◽  
Lv Diastolic Dysfunction

Diabetes mellitus has reached epidemic proportion worldwide. One of the diabetic complications is cardiomyopathy, characterized by early left ventricular (LV) diastolic dysfunction, followed by development of systolic dysfunction and ventricular dilation at a late stage. The pathogenesis is multifactorial, and there is no effective treatment yet. In recent years, 4-hydroxy-2-nonenal (4-HNE), a toxic aldehyde generated from lipid peroxidation, is implicated in the pathogenesis of cardiovascular diseases. Its high bioreactivity toward proteins results in cellular damage. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that detoxifies 4-HNE. The development of small-molecule ALDH2 activator provides an opportunity for treating diabetic cardiomyopathy. This study found that AD-9308, a water-soluble andhighly selective ALDH2 activator, can improve LV diastolic and systolic functions, and wall remodeling in streptozotocin-induced diabetic mice. AD-9308 treatment dose-dependently lowered serum 4-HNE levels and 4-HNE protein adducts in cardiac tissue from diabetic mice, accompanied with ameliorated myocardial fibrosis, inflammation, and apoptosis. Improvements of mitochondrial functions, sarco/endoplasmic reticulumcalcium handling and autophagy regulation were also observed in diabetic mice with AD-9308 treatment. In conclusion, ADLH2 activation effectively ameliorated diabetic cardiomyopathy, which may be mediated through detoxification of 4-HNE. Our findings highlighted the therapeutic potential of ALDH2 activation for treating diabetic cardiomyopathy.

scholarly journals AB0422 LEFT VENTRICULAR ABNORMALITIES IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS FOLLOWED BY SEQUENTIAL ECHOCARDIOGRAPHY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1510.1-1511
Author(s):  
T. Kuga ◽  
M. Matsushita ◽  
K. Tada ◽  
K. Yamaji ◽  
N. Tamura
Keyword(s):  
Lupus Erythematosus ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Monocyte Count ◽  
Lv Dysfunction ◽  
Group A ◽  
Group B ◽  
Lv Diastolic Dysfunction ◽  
Group D

Background:Cardiovascular disease (CVD) is detected in up to 50% of systemic lupus erythematosus (SLE) patients1and major cause of death2. Even clinically silent SLE patients can develop left ventricular (LV) diastolic dysfunction3. Proper echocardiographic follow up of SLE patients is required.Objectives:To clarify how the prevalence of LV abnormalities changes over follow-up period and identify the associated clinical factors, useful in suspecting LV abnormalities.Methods:29 SLE patients (24 females and 5 men, mean age 52.8±16.3 years, mean disease duration 17.6±14.5 years) were enrolled. All of them underwent echocardiography as the baseline examination and reexamined over more than a year of follow-up period(mean 1075±480 days) from Jan 2014 to Sep 2019. Patients complicated with pulmonary artery hypertension, deep venous thrombosis or pulmonary embolism and underwent cardiac surgery during the follow-up period were excluded. Left ventricular(LV) systolic dysfunction was defined as ejection fraction (EF) < 50%. LV diastolic dysfunction was defined according to ASE/EACVI guideline4. LV dysfunction (LVD) includes one or both of LV systolic dysfunction and LV diastolic function. Monocyte to HDL ratio (MHR) was calculated by dividing monocyte count with HDL-C level.Prevalence of left ventricular abnormalities was analysed at baseline and follow-up examination. Clinical characteristics and laboratory data were compared among patient groups as follows; patients with LV dysfunction (Group A) and without LV dysfunction (Group B) at the follow-up echocardiography, patients with LV asynergy at any point of examination (Group C) and patients free of LV abnormalities during the follow-up period (Group D).Results:At the baseline examination, LV dysfunction (5/29 cases, 13.8%), LV asynergy (6/29 cases, 21.7%) were detected. Pericarditis was detected in 7 patients (24.1%, LVD in 3 patients, LV asynergy in 2 patients) and 2 of them with subacute onset had progressive LV dysfunction, while 5 patients were normal in echocardiography after remission induction therapy for SLE. At the follow-up examination, LV dysfunction (9/29 cases, 31.0%, 5 new-onset and 1 improved case), LV asynergy (6/29 cases, 21.7%, 2 new-onset and 2 improved cases) were detected. Though any significant differences were observed between Group A and Group B at the baseline, platelet count (156.0 vs 207.0, p=0.049) were significantly lower in LV dysfunction group (Group A) at the follow-up examination. Group C patients had significantly higher uric acid (p=0.004), monocyte count (p=0.009), and MHR (p=0.003) than Group D(results in table).Conclusion:LV dysfunction is progressive in most of patients and requires regular follow-up once they developed. Uric acid, monocyte count and MHR are elevated in SLE patients with LV asynergy. Since MHR elevation was reported as useful marker of endothelial dysfunction5, our future goal is to analyse involvement of monocyte activation and endothelial dysfunction in LV asynergy of SLE patients.References:[1]Doria A et al. Lupus. 2005;14(9):683-6.[2]Manger K et al. Ann Rheum Dis. 2002 Dec;61(12):1065-70.[3]Leone P et al. Clin Exp Med. 2019 Dec 17.[4]Nagueh SF et al. J Am Soc Echocardiogr. 2016 Apr;29(4):277-314.[5]Acikgoz N et al. Angiology. 2018 Jan;69(1):65-70.Numbers are median (interquartile range), Mann-Whitney u test were performed, p value less than 0.05 was considered statistically significant.Disclosure of Interests: :None declared

Abstract 16485: The Nitroxyl Donor 1-Nitrosocyclohexyl Acetate Limits Cardiac Superoxide Upregulation and Diastolic Dysfunction in a Mouse Model of Diabetic Cardiomyopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Rebecca H Ritchie ◽  
Nga Cao ◽  
Yung George Wong ◽  
Sarah Rosli ◽  
Helen Kiriazis ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mouse Model ◽  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Ex Vivo ◽  
Systolic Function ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Lv Diastolic Dysfunction ◽  
The Impact

Nitroxyl (HNO), a redox congener of NO•, is a novel regulator of cardiovascular function combining vasodilator and positive inotropic properties. Our previous studies have demonstrated these properties occur concomitantly in the intact heart; HNO moreover also exhibits antihypertrophic and superoxide-suppressing actions. HNO donors may thus offer favorable actions in heart failure. The impact of chronic HNO donor administration has however yet to be reported in this context. We tested the hypothesis that the HNO donor 1-nitrosocyclohexyl acetate (1-NCA) limits cardiomyocyte hypertrophy and left ventricular (LV) diastolic dysfunction in a mouse model of diabetic cardiomyopathy in vivo. Male 6 week-old FVB/N mice received either streptozotocin (55 mg/kg/day i.p. for 5 days, n=17), to induce type 1 diabetes, or citrate vehicle (n=16). After 4 weeks of hyperglycemia, mice were allocated to 1-NCA therapy (83mg/kg/day i.p.) or vehicle, and followed for a further 4 weeks. As shown in the table, blood glucose was unaffected by 1-NCA. LV diastolic dysfunction was evident in diabetic mice, measured as echocardiography-derived A wave velocity, deceleration time and E:A ratio; LV systolic function was preserved. Diabetes-induced diastolic dysfunction was accompanied by increased LV cardiomyocyte size, hypertrophic and pro-fibrotic gene expression, and upregulation of LV superoxide. These characteristics of diabetic cardiomyopathy were largely prevented by 1-NCA treatment. Selectivity of 1-NCA as a donor of HNO versus NO• was demonstrated by the sensitivity of the coronary vasodilation response of 1-NCA to the HNO scavenger L-cysteine (4mM), but not to the NO• scavenger hydroxocobalamin (50μM), in the normal rat heart ex vivo (n=3-7). Collectively, our studies provide the first evidence that HNO donors may represent a promising new strategy for the treatment of diabetic cardiomyopathy, and implies their therapeutic efficacy in settings of chronic heart failure.

scholarly journals Progression of Left Ventricular Myocardial Dysfunction in Systemic Sclerosis: A Speckle-tracking Strain Echocardiography Study

2019 ◽  
Vol 46 (4) ◽  
pp. 405-415 ◽  
Author(s):  
Suzanne E. van Wijngaarden ◽  
Samira Ben Said-Bouyeri ◽  
Maarten K. Ninaber ◽  
Tom W.J. Huizinga ◽  
Martin J. Schalij ◽  
...  
Keyword(s):  
Muscle Weakness ◽  
Speckle Tracking ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Lv Ejection Fraction ◽  
Lv Diastolic Dysfunction ◽  
Echocardiographic Speckle Tracking

Objective.Cardiac involvement is a main cause of mortality in systemic sclerosis (SSc). Its detection remains challenging using conventional echocardiography and little is known about its potential progression. This study assessed changes in cardiac performance over time in a prospective cohort of patients with SSc, including echocardiographic speckle-tracking strain analysis.Methods.The study included 234 patients with SSc [196 women, age 52 ± 14 yrs, 165 limited SSc, time since diagnosis 5.2 yrs, interquartile range (IQR) 2.9–11.3]. Clinical variables, laboratory tests, pulmonary function tests, and echocardiographic measures were recorded at baseline and followup (median 2.3 yrs, IQR 1.3–3.9). Additionally, left ventricular (LV) systolic function was assessed with global longitudinal strain (GLS) by echocardiographic speckle-tracking analysis.Results.At followup, GLS had significantly worsened (−21% ± 2 vs −19% ± 2, p < 0.001) while LV ejection fraction had not changed (62% ± 7 vs 61% ± 8, p = 0.124). In particular, 39 patients showed a significant deterioration of GLS as defined by a ≥ 15% decrease, which was accompanied by a concomitant worsening of proximal muscle weakness, lung fibrosis, renal function, LV diastolic function, and right ventricular systolic function. Baseline variables associated with ≥ 15% deterioration in GLS were proximal muscle weakness (OR 3.437, 95% CI 1.13–10.43, p = 0.020), decreased DLCO (OR 3.621, 95% CI 1.25–10.51, p = 0.049), and LV diastolic dysfunction (OR 2.378, 95% CI 1.07–5.27, p = 0.033).Conclusion.In patients with SSc, progression of LV systolic dysfunction was demonstrated by GLS but not by LV ejection fraction. Proximal muscle weakness, DLCO, and LV diastolic dysfunction may identify patients at risk for progressive LV systolic dysfunction and in need of closer cardiac monitoring.

scholarly journals Diabetic cardiomyopathy: acute and reversible left ventricular systolic dysfunction due to cardiotoxicity of hyperglycaemic hyperosmolar state—a case report†

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Umut Kocabaş ◽  
Özgür Yılmaz ◽  
Volkan Kurtoğlu
Keyword(s):  
Blood Glucose ◽  
Diabetic Cardiomyopathy ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Blood Glucose Control ◽  
Left Ventricular ◽  
Pathophysiological Mechanism ◽  
Ventricular Systolic Dysfunction ◽  
Arterial Blood

Abstract Background Diabetic cardiomyopathy (DC) is defined as a ventricular diastolic and/or systolic dysfunction, which is directly related to diabetes mellitus (DM) in the absence of coronary artery disease, valvular, congenital or hypertensive heart disease, and alcoholism. In this report, we present an unusual case of a patient with DC and reversible, acute left ventricular systolic dysfunction due to cardiotoxicity of hyperosmolar hyperglycaemic state (HHS). Case summary A 20-year-old male patient presented with weakness and polyuria. Physical examination and electrocardiogram were normal. Laboratory results and arterial blood gas analysis were consistent with HHS. Baseline echocardiography showed global left ventricular hypokinesis with an ejection fraction (EF) of 36%. The patient’s clinical condition improved after blood glucose level normalization and echocardiography revealed progressive improvement in the left ventricular systolic function with an EF of 54% at the 5-day follow-up and an EF of 69% at the 15-day follow-up. Discussion Uncontrolled DM and hyperglycaemic crisis may result in cardiotoxicity, acute left ventricular systolic dysfunction, and DC. The pathophysiological mechanism of this phenomenon is still unclear. Blood glucose control is the most important strategy for the prevention of DC.

scholarly journals Peripartum Cardiomyopathy Presenting with Predominant Left Ventricular Diastolic Dysfunction: Efficacy of Bromocriptine

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Piercarlo Ballo ◽  
Irene Betti ◽  
Giuseppe Mangialavori ◽  
Leandro Chiodi ◽  
Gherardo Rapisardi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Peripartum Cardiomyopathy ◽  
Lv Function ◽  
Lv Diastolic Dysfunction ◽  
Lv Diastolic Function

Management of patients with peripartum cardiomyopathy (PPCM) is still a major clinical problem, as only half of them or slightly more show complete recovery of left ventricular (LV) function despite conventional evidence-based treatment for heart failure. Recent observations suggested that bromocriptine might favor recovery of LV systolic function in patients with PPCM. However, no evidence exists regarding its effect on LV diastolic dysfunction, which is commonly observed in these patients. Tissue Doppler (TD) is an echocardiographic technique that provides unique information on LV diastolic performance. We report the case of a 37-year-old white woman with heart failure (NYHA class II), moderate LV systolic dysfunction (ejection fraction 35%), and severe LV diastolic dysfunction secondary to PPCM, who showed no improvement after 2 weeks of treatment with ramipril, bisoprolol, and furosemide. At 6-week followup after addition of bromocriptine, despite persistence of LV systolic dysfunction, normalization of LV diastolic function was shown by TD, together with improvement in functional status (NYHA I). At 18-month followup, the improvement in LV diastolic function was maintained, and normalization of systolic function was observed. This paper might support the clinical utility of bromocriptine in patients with PPCM by suggesting a potential benefit on LV diastolic dysfunction.

scholarly journals NAD+ Redox Imbalance in the Heart Exacerbates Diabetic Cardiomyopathy

2020 ◽  
Author(s):  
Ying Ann Chiao ◽  
Akash Deep Chakraborty ◽  
Christine M. Light ◽  
Rong Tian ◽  
Junichi Sadoshima ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Troponin I ◽  
Therapeutic Potential ◽  
Redox Balance ◽  
Diabetic Mice ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Redox Imbalance ◽  
Nadh Ratio ◽  
Regulate Protein

AbstractBackgroundDiabetes is a risk factor of heart failure and promotes cardiac dysfunction. Diabetic tissues are associated with NAD+ redox imbalance; however, the hypothesis that NAD+ redox imbalance leads to dysfunction of diabetic hearts has not been tested. In this study, we employed mouse models with altered NAD+ redox balance to test the hypothesis.Methods and ResultsDiabetes was induced in C57BL/6 mice by streptozotocin injections, and diabetic cardiomyopathy (DCM) was allowed to develop for 16 weeks. Diabetic stress led to cardiac dysfunction and lowered NAD+/NADH ratio. This diabetogenic regimen was administered to cardiac-specific knockout mice of complex I subunit Ndufs4 (cKO), a model with lowered cardiac NAD+/NADH ratio without baseline dysfunction. Cardiac NAD+ redox imbalance in cKO hearts exacerbated systolic and diastolic dysfunction of diabetic mice in both sexes. Collagen levels and transcript analyses of fibrosis and extracellular matrix-dependent pathways did not show change in diabetic cKO hearts, suggesting that the exacerbated cardiac dysfunction was likely due to cardiomyocyte dysfunction. We found that cardiac NAD+ redox imbalance promoted superoxide dismutase 2 (SOD2) acetylation, protein oxidation, induced troponin I S150 phosphorylation and impaired energetics in diabetic cKO hearts. Importantly, elevation of cardiac NAD+ levels by nicotinamide phosphoribosyltransferase (NAMPT) normalized NAD+ redox balance, over-expression alleviated cardiac dysfunction and reversed pathogenic mechanisms in diabetic mice.ConclusionOur results show that NAD+ redox imbalance to regulate protein acetylation and phosphorylation is a critical mediator of the progression of DCM, and suggest the therapeutic potential of harnessing NAD+ metabolism in DCM.

scholarly journals Right ventricular dysfunction and remodeling in diabetic cardiomyopathy

2019 ◽  
Vol 316 (1) ◽  
pp. H113-H122 ◽  
Author(s):  
Yin Kang ◽  
Sheng Wang ◽  
Jiapeng Huang ◽  
Lu Cai ◽  
Bradley B. Keller
Keyword(s):  
Early Detection ◽  
Right Ventricular ◽  
Diabetic Cardiomyopathy ◽  
Clinical Symptoms ◽  
Systolic Dysfunction ◽  
Right Ventricular Dysfunction ◽  
Biomechanical Properties ◽  
Left Ventricular ◽  
Structure And Function ◽  
And Function

The increasing prevalence of diabetic cardiomyopathy (DCM) is an important threat to health worldwide. While left ventricular (LV) dysfunction in DCM is well recognized, the accurate detection, diagnosis, and treatment of changes in right ventricular (RV) structure and function have not been well characterized. The pathophysiology of RV dysfunction in DCM may share features with LV diastolic and systolic dysfunction, including pathways related to insulin resistance and oxidant injury, although the RV has a unique cellular origin and composition and unique biomechanical properties and is coupled to the lower-impedance pulmonary vascular bed. In this review, we discuss potential mechanisms responsible for RV dysfunction in DCM and review the imaging approaches useful for early detection, protection, and intervention strategies. Additional data are required from animal models and clinical trials to better identify the onset and features of altered RV and pulmonary vascular structure and function during the onset and progression of DCM and to determine the efficacy of early detection and treatment of RV dysfunction on clinical symptoms and outcomes.

scholarly journals Plasma indoxyl sulfate levels predict cardiovascular events in patients with mild chronic heart failure

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Miki Imazu ◽  
Hiroki Fukuda ◽  
Hideaki Kanzaki ◽  
Makoto Amaki ◽  
Takuya Hasegawa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiovascular Events ◽  
Systolic Dysfunction ◽  
Cardiorenal Syndrome ◽  
High Plasma ◽  
Cardiovascular Death ◽  
Left Ventricular ◽  
Indoxyl Sulfate ◽  
Lv Diastolic Dysfunction

Abstract Indoxyl sulfate (IS) is associated with either chronic kidney disease or renal failure, which may predict cardiovascular events via cardiorenal syndrome. The present study aimed to elucidate whether the plasma levels of IS can predict the occurrence of cardiovascular events in patients with chronic heart failure (CHF) and investigate which causes of CHF leading to cardiovascular events are highly influenced by plasma IS levels. We measured the plasma IS levels in 165 patients with CHF [valvular disease: 78, dilated cardiomyopathy: 29, hypertrophic cardiomyopathy (HCM): 25 and others: 33] admitted to our hospital in 2012, and we followed up these patients for more than 5 years (the median follow-up period: 5.3 years). We measured the plasma IS level in 165 patients with CHF, and Kaplan–Meier analyses showed that high plasma IS levels (≥ 0.79 µg/mL, the median value) could predict the occurrence of cardiovascular events, i.e., cardiovascular death or rehospitalization due to the worsening of CHF. The sub-analyses showed that the high IS level could predict cardiovascular events in patients with CHF due to HCM and that the plasma IS levels were closely associated with left ventricular (LV) dimension, LV systolic dysfunction, and plasma B-type natriuretic peptide levels, rather than LV diastolic dysfunction. Plasma IS level predicts cardiovascular events in patients with CHF, especially those with HCM along with cardiac dysfunction. Besides, IS may become a proper biomarker to predict cardiovascular events in patients with CHF.

The Prognostic Value of Echocardiographic Findings in Prediction of In-Hospital Mortality of COVID-19 Patients

2021 ◽  
Author(s):  
Roxana Sadeghi ◽  
Amirmohammad Toloui ◽  
Asma Pourhoseingholi ◽  
Niloufar Taherpour ◽  
Mohammad Sistanizad ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Hospital Mortality ◽  
Diastolic Dysfunction ◽  
Systolic Dysfunction ◽  
Mitral Valve Regurgitation ◽  
Left Ventricular ◽  
Pulmonary Valve Insufficiency ◽  
Valve Insufficiency ◽  
Lv Diastolic Dysfunction ◽  
Echocardiographic Findings

Introduction: The correlation between echocardiographic findings and the outcome of COVID-19 patients is still under debate. Objective: In the present study it has been endeavored to evaluate the cardiovascular condition of COVID-19 patients using echocardiography and to assess the association of these findings with in-hospital mortality. Methods: In this retrospective cohort study, hospitalized COVID-19 patients from February to July 2020 with at least one echocardiogram were included. Data were extracted from patients’ medical records and the association between echocardiographic findings and in-hospital mortality was assessed using a multivariate model. The findings were reported as relative risk (RR) and 95% confidence interval (95% CI). Results: Data from 102 COVID-19 hospitalized patients were encompassed in the present study (63.7±15.7 mean age; 60.8% male). Thirty patients (29.4%) died during hospitalization. Tricuspid regurgitation (89.2%), mitral valve regurgitation (89.2%), left ventricular (LV) diastolic dysfunction (67.6%), pulmonary valve insufficiency (PI) (45.1%) and LV systolic dysfunction (41.2%) were the most common findings on patients’ echocardiogram. The analyses of data showed that LV systolic (p=0.242) and diastolic (p=0.085) dysfunction was not associated with in-hospital mortality of COVID-19 patients, while the presence of PI (RR=1.85; 95% CI: 1.02 to 3.33; p=0.042) and patients’ age (RR=1.03; 95% CI: 1.01 to 1.08; p=0.009) were the two independent prognostic factors of in-hospital mortality. Conclusions: It seems that LV systolic and diastolic dysfunction was not associated with in-hospital mortality of COVID-19 patients. However, presence and PI and old age are possible prognostic factors of COVID-19 in-hospital mortality. Therefore, using echocardiography might be useful in management of COVID-19.

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