Abstract 15315: SGLT2 Inhibitor Ertugliflozin Decreases Elevated Intracellular Sodium, Improves Myocardial Energetics and Enhances Function in Metabolic Heart Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Dominique Croteau ◽  
Tomas Baka ◽  
Sara Young ◽  
Huamei He ◽  
David R Pimentel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Disease ◽  
Contractile Function ◽  
Control Diet ◽  
Sglt2 Inhibitor ◽  
Atp Synthesis ◽  
Intracellular Sodium ◽  
Contractile Reserve ◽  
Isolated Hearts ◽  
Metabolic Heart Disease

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are antidiabetic drugs of great interest in cardiology due to their improvement of heart failure outcomes independent of diabetes. As SGLT2 is not expressed in cardiomyocytes, the mechanism of such benefit remains unclear. Elevated myocardial intracellular sodium [Na + ] i has been found in heart failure and SGLT2 inhibition lowers [Na + ] i in isolated cardiomyocytes. Elevated [Na + ] i was shown to decrease mitochondrial calcium via mitochondrial Na/Ca exchanger (NCx MITO ), resulting in decreased mitochondrial ATP synthesis. We have previously shown that mice fed a diet high in fat and sugar (HFHS) develop metabolic heart disease (MHD) characterized by decreased mitochondrial ATP synthesis with decreased phosphocreatine (PCr), worsened diastolic function and contractile reserve. We hypothesize that the SGLT2 inhibitor ertugliflozin (ERTU) decreases the elevated [Na + ] i to improve energetics and contractile function in MHD. Methods and Results: Isolated hearts from mice after 6 months of HFHS vs. control diet (CD), +/- ERTU in the last month, were studied using 31 P and 23 Na NMR spectroscopy to measure PCr/ATP ratio and [Na + ] i , respectively. As expected, HFHS hearts showed lower PCr/ATP, diastolic dysfunction (↑LVEDP) and lack of contractile reserve (↓RPP) during high work protocol compared to CD hearts. Myocardial [Na + ] i was elevated more than 2-fold in HFHS compared to CD. One month of ERTU treatment decreased [Na + ] i and improved energetics and contractile function in HFHS to levels similar to or better than CD. Perfusion with CGP 37157, which inhibits NCx MITO , improved PCr/ATP in HFHS hearts. Conclusion: Lowering of myocardial [Na + ] i by ertugliflozin contributes to improved energetics and function in MHD. These results suggest targeting [Na + ] i as an effective strategy to improve cardiac dysfunction in MHD and other forms of heart disease associated with elevated myocardial [Na + ] i.

scholarly journals Increasing mitochondrial ATP synthesis with butyrate normalizes ADP and contractile function in metabolic heart disease

2020 ◽  
Vol 33 (5) ◽  
Author(s):  
Marcello Panagia ◽  
Huamei He ◽  
Tomas Baka ◽  
David R. Pimentel ◽  
Dominique Croteau ◽  
...  
Keyword(s):  
Heart Disease ◽  
Contractile Function ◽  
Atp Synthesis ◽  
Metabolic Heart Disease

scholarly journals Impaired Myocardial Energetics Causes Mechanical Dysfunction in Decompensated Failing Hearts

Function ◽  
2020 ◽  
Vol 1 (2) ◽  
Author(s):  
Rachel Lopez ◽  
Bahador Marzban ◽  
Xin Gao ◽  
Ellen Lauinger ◽  
Françoise Van den Bergh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Free Energy ◽  
Inorganic Phosphate ◽  
Contractile Function ◽  
Adenine Nucleotides ◽  
Pressure Overload ◽  
Atp Synthesis ◽  
Whole Body ◽  
Metabolic Dysfunction ◽  
Mechanical Function

Abstract Cardiac mechanical function is supported by ATP hydrolysis, which provides the chemical-free energy to drive the molecular processes underlying cardiac pumping. Physiological rates of myocardial ATP consumption require the heart to resynthesize its entire ATP pool several times per minute. In the failing heart, cardiomyocyte metabolic dysfunction leads to a reduction in the capacity for ATP synthesis and associated free energy to drive cellular processes. Yet it remains unclear if and how metabolic/energetic dysfunction that occurs during heart failure affects mechanical function of the heart. We hypothesize that changes in phosphate metabolite concentrations (ATP, ADP, inorganic phosphate) that are associated with decompensation and failure have direct roles in impeding contractile function of the myocardium in heart failure, contributing to the whole-body phenotype. To test this hypothesis, a transverse aortic constriction (TAC) rat model of pressure overload, hypertrophy, and decompensation was used to assess relationships between metrics of whole-organ pump function and myocardial energetic state. A multiscale computational model of cardiac mechanoenergetic coupling was used to identify and quantify the contribution of metabolic dysfunction to observed mechanical dysfunction. Results show an overall reduction in capacity for oxidative ATP synthesis fueled by either fatty acid or carbohydrate substrates as well as a reduction in total levels of adenine nucleotides and creatine in myocardium from TAC animals compared to sham-operated controls. Changes in phosphate metabolite levels in the TAC rats are correlated with impaired mechanical function, consistent with the overall hypothesis. Furthermore, computational analysis of myocardial metabolism and contractile dynamics predicts that increased levels of inorganic phosphate in TAC compared to control animals kinetically impair the myosin ATPase crossbridge cycle in decompensated hypertrophy/heart failure.

scholarly journals Decreased ATP production and myocardial contractile reserve in metabolic heart disease

2018 ◽  
Vol 116 ◽  
pp. 106-114 ◽  
Author(s):  
Ivan Luptak ◽  
Aaron L. Sverdlov ◽  
Marcello Panagia ◽  
Fuzhong Qin ◽  
David R. Pimentel ◽  
...  
Keyword(s):  
Heart Disease ◽  
Contractile Reserve ◽  
Atp Production ◽  
Myocardial Contractile ◽  
Myocardial Contractile Reserve ◽  
Metabolic Heart Disease

Abstract 16817: Correlation of Right Heart Echocardiographic Quantitation With Cpet Parameters to Predict Clinical Outcomes in Patients With Congenital Right Heart Disease

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Asaad A Khan ◽  
Ami B Bhatt ◽  
Romain Capoulade ◽  
Ada Stefanescu ◽  
Aaron Eisman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Disease ◽  
Contractile Function ◽  
Cardiopulmonary Exercise Testing ◽  
Tissue Doppler ◽  
Doppler Imaging ◽  
Major Adverse Cardiovascular Events ◽  
Healthy Population ◽  
Right Heart ◽  
Peak Vo2

Background: Adults with congenital right heart disease (ACHD) patients have a diminished exercise tolerance compared to healthy population, and abnormal peak VO2 as assessed by cardiopulmonary exercise testing (CPET)significantly predicts outcomes of heart failure and death in this population. Despite this, CPET is not as widely available as echocardiography. Aim: We aim to correlate resting echocardiographic patterns of regional RV contractile function among ACHD patients with peak VO2 and major adverse cardiovascular events (MACE). Methods: We retrospectively recruited 160 ACHD patients who underwent CPET at our hospital . Out of these, 94 patients had complete echocardiographic data for analysis, in studies performed within 1 year of their CPET.RV quantitative parameters measured included: Tricuspid Annular Plane Systolic Excursion (TAPSE), Tissue doppler imaging TDI (S’), RA area, RV dimensions and RV fractional area change % (FAC).These variables were correlated with peak VO2,exercise RV function by ventriculography(RV score) and MACE(heart failure, arrhythmia,death or transplantation)after CPET. Results: The most frequent congenital pathology was Tetralogy of Fallot (35%).14% (n=13) patients had systemic right ventricles.There were 28 MACE during a median follow up of 1.3 years. FAC, TAPSE and S’ significantly correlated with peak VO2 in multivariate analysis.FAC also correlated with RV score. Decrease in FAC was associated with MACE in a continuous fashion while a cutoff value of S’< 9.5 cm/sec was also significantly associated with MACE (p=0.04,HR 2.48)(table) Conclusion: This is a heterogenous group of ACHD lesions and routinely acquired echo RV assessment was able to broadly correlate with exercise and outcome. This differentiates us from other papers which are all lesion specific or based on strain measurements (difficult to peform and reproduce).These findings can also help prioritize patients for more sophisticated testing like CPET.

scholarly journals Light Emitting Diodes Photobiomodulation Improves Cardiac Function by Promoting ATP Synthesis in Mice With Heart Failure

2021 ◽  
Vol 8 ◽  
Author(s):  
Wenwen Zhang ◽  
Xinlu Gao ◽  
Xiuxiu Wang ◽  
Desheng Li ◽  
Yiming Zhao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Light Emitting Diodes ◽  
Contractile Function ◽  
Atp Synthesis ◽  
High Morbidity ◽  
Effective Wavelength ◽  
Light Emitting ◽  
Beneficial Effects ◽  
The Common

Heart failure (HF) is the common consequences of various cardiovascular diseases, often leading to severe cardiac output deficits with a high morbidity and mortality. In recent years, light emitting diodes-based therapy (LEDT) has been widely used in multiple cardiac diseases, while its modulatory effects on cardiac function with HF still remain unclear. Therefore, the objective of this study was to investigate the effects of LED-Red irradiation on cardiac function in mice with HF and to reveal its mechanisms. In this study, we constructed a mouse model of HF. We found that LED-Red (630 nm) was an effective wavelength for the treatment of HF. Meanwhile, the application of LED-Red therapy to treat HF mice improved cardiac function, ameliorate heart morphology, reduced pulmonary edema, as well as inhibited collagen deposition. Moreover, LED-Red therapy attenuated the extent of perivascular fibrosis. Besides, LED-Red irradiation promoted calcium transients in cardiomyocytes as well as upregulated ATP synthesis, which may have positive implications for contractile function in mice with HF. Collectively, we identified that LED-Red exerts beneficial effects on cardiac function in HF mice possibly by promoting the synthesis of ATP.

Ultrasound in cardiology —state of the art

2011 ◽  
Author(s):  
Fausto J. Pinto
Keyword(s):  
Heart Failure ◽  
Heart Disease ◽  
Diagnostic Tool ◽  
Objective Assessment ◽  
Myocardial Revascularization ◽  
Disease Process ◽  
Lv Function ◽  
Contractile Reserve ◽  
Artery Disease ◽  
Systolic And Diastolic Function

Echocardiography represents the most widely used diagnostic tool in cardiology. From its beginnings, in 1953, when Professor Inge Edler first used it in Lund, Sweden, there always was a clinical question underlying its use and development. This might be one of the main reasons why echocardiography has always been one of the most popular diagnostic methods to be used clinically and several authors have named it as the fastest growing technique in cardiology. In fact, there are a variety of areas where echocardiography has proven to be fundamental not only for clinical orientation but also for significantly increasing the understanding of the underlying pathophysiology of the disease process. The other important aspect is the fact that, at the same time, significant technological developments have occurred that have made it possible to develop adequate transducers able to accompany the clinical questions. Some of the main features and contributions of echocardiography in different clinical conditions can be summarized as follows. Heart failure remains one of the main killers in the developed world with its prevalence increasing worldwide mainly as the result of coronary artery disease (CAD), responsible for almost two-thirds of cases of left ventricular (LV) dysfunction. Echocardiography has played a major role in the understanding of the different mechanisms involved in the development of the different types of heart failure. In addition, it has helped to monitor and develop new therapeutic targets and strategies in heart failure. LV function represents the most important prognostic indicator in patients with heart disease regardless of their aetiology. Echocardiography has been the main diagnostic tool to assess how much systolic and diastolic function are involved in the mechanism of heart failure in a particular patient. Regarding systolic function, echocardiography can provide different measurements that contribute to a more objective assessment of function, including: global and regional function, degree of ventricular remodelling, contractile reserve, presence of ischaemia and/or viability, particularly in patients post-acute coronary syndromes or post-myocardial revascularization, and the concomitant presence of valvular heart disease, which may significantly impact on the assessment of LV function (particularly the presence of significant volume overload, such as in mitral and/or aortic regurgitation).

Estimation of the Safety of Intraoperative Fluid Therapy during Great Abdominal Surgery in Patients with Coronary Heart Disease

2020 ◽  
Vol 5 (5) ◽  
pp. 158-163
Author(s):  
V. I. Lysenko ◽  
◽  
E. A. Karpenko ◽  
Ya. V. Morozova
Keyword(s):  
Heart Failure ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Fluid Therapy ◽  
Troponin I ◽  
Significant Proportion ◽  
Myocardial Damage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cardiac Complications ◽  
Fluid Regimen

The study of intraoperative fluid therapy tactics has been of great interest over the past few years, especially in people with concomitant coronary heart disease, as they make up a significant proportion of all surgical patients. The purpose of our study was to assess the risk of intraoperative myocardial damage in patients with concomitant coronary heart disease depending on the fluid regimen used based on monitoring of hemodynamic parameters, electrocardiogram and biomarkers of myocardial damage. Material and methods. The study involved 89 patients, who were divided into two groups depending on the tactics of intraoperative fluid therapy – restrictive and liberal. In order to detect cardiac complications at different stages, we assessed biomarkers of myocardial damage Troponin I, NT-proBNP by solid-phase enzyme-linked immunosorbent assay (ELISA). Results and discussion. Analysis of the obtained data showed that MINS (myocardial injury in noncardiac surgery) incidents were diagnosed in 5 patients (11.1%) in the first group and in 6 patients (13.6%) in the second. In patients of both groups there was an increase in NT-proBNP in the dynamics at all stages, and in the 2nd group, with a liberal regimen of intraoperative fluid therapy, it was more pronounced. It should be noted that the obtained values of NT-proBNP in all patients did not differ significantly from those allowed for this age group; such dynamics of NT-proBNP may indicate a relative risk of complications of liberal fluid therapy in patients with baseline heart failure. One of the important points when choosing the mode of fluid therapy in patients with high cardiac risk is the assessment of the initial volemic status and careful monitoring of water balance in the perioperative period with the desire for "zero" balance. The obtained dynamics of laboratory markers of myocardial damage indicates that in patients with a significant reduction in cardiac reserves compensated for heart failure, a restrictive fluid regimen is preferable, which is also confirmed by slight changes in the concentration of biomarkers. Conclusion. Thus, the study demonstrated the relative safety of selected fluid regimens in patients with concomitant coronary heart disease without signs of congestive heart failure

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