Echocardiography 2020: Toward deciphering the “Rosetta stone” of left ventricular diastolic function

Saha, Samir K.; Kiotsekoglou, Anatoli; Nanda, Navin C.

doi:10.1111/echo.14830

Cited by 7 publications

(6 citation statements)

References 29 publications

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“…Similarly, to our previous data, these results were sex independent (Figure 6A). In live mice, treatment rescued diastolic dysfunction in db/db hearts to control-like levels, measured as E/A ratio through Doppler echocardiography [42] (Figure 5B). Despite these encouraging results, we still need to ascertain the extent to which the GR-KLF15 axis activation mediates the functional rescue we observed in diabetic hearts.…”

Section: Resultsmentioning

confidence: 99%

Glucocorticoid chrono-pharmacology unveils novel targets for the cardiomyocyte-specific GR-KLF15 axis in cardiac glucose metabolism

El Abdellaoui-Soussi,

Durumutla,

Latimer

et al. 2023

Preprint

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Circadian time of intake determines the cardioprotective outcome of glucocorticoids in normal and infarcted hearts. The cardiomyocyte-specific glucocorticoid receptor (GR) is genetically required to preserve normal heart function in the long-term. The GR co-factor KLF15 is a pleiotropic regulator of cardiac metabolism. However, the cardiomyocyte-autonomous metabolic targets of the GR-KLF15 concerted epigenetic action remain undefined. Here we report that circadian time of intake determines the activation of a transcriptional and functional glucose oxidation program in heart by the glucocorticoid prednisone with comparable magnitude between sexes. We overlayed transcriptomics, epigenomics and cardiomyocyte-specific inducible ablation of either GR or KLF15. Downstream of a light-phase prednisone stimulation in mice, we found that both factors are non-redundantly required in heart to transactivate the adiponectin receptor expression (Adipor1)and promote insulin-stimulated glucose uptake, as well as transactivate the mitochondrial pyruvate complex expression(Mpc1/2)and promote pyruvate oxidation. We then challenged this time-specific drug effect in obese diabeticdb/dbmice, where the heart shows insulin resistance and defective glucose oxidation. Opposite to dark-phase dosing, light-phase prednisone rescued glucose oxidation indb/dbcardiomyocytes and diastolic function indb/dbhearts towards control-like levels with sex-independent magnitude of effect. In summary, our study identifies novel cardiomyocyte-autonomous metabolic targets of the GR-KLF15 concerted program mediating the time-specific cardioprotective effects of glucocorticoids on cardiomyocyte glucose utilization.

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Section: Resultsmentioning

confidence: 99%

Glucocorticoid chrono-pharmacology unveils novel targets for the cardiomyocyte-specific GR-KLF15 axis in cardiac glucose metabolism

El Abdellaoui-Soussi,

Durumutla,

Latimer

et al. 2023

Preprint

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“…The parameters for assessing diastolic function were shown to predict mortality in three major HFpEF clinical trials [89,90]. Using existing guidelines alone to interpret resting echocardiographic data can only identify 34% to 60% of patients with invasively confirmed HFpEF [91].…”

Section: Heart Failure With Preserved Ejection Fractionmentioning

confidence: 99%

Interpreting Diastolic Dynamics and Evaluation Through Echocardiography

Zhang,

Li,

Cardoso

et al. 2024

Preprint

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In patients with heart failure, the evaluation of left ventricular (LV) diastolic function is vital, offering crucial insights into hemodynamic impact and prognostic accuracy. Echocardiography stands as the primary imaging modality for diastolic function assessment, and using it effectively requires a profound understanding of the underlying pathology. This review covers four main topics: first, the fundamental driving forces behind each phase of normal diastolic dynamics, along with the physiological basis of two widely used echocardiographic assessment parameters, E/e' and mitral annulus early diastolic velocity (e'); second, the intricate functional relationship between the left atrium and LV in patients with varying degrees of LV diastolic dysfunction (LVDD); third, the role of stress echocardiography in diagnosing LVDD and the significance of parameter changes in this context; and fourth, the clinical utility of evaluating diastolic function from echocardiography images across diverse cardiovascular care areas.

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“…There may be a decline in the left ventricular systolic long-axis at earlier stages, followed by evidence of more greater, subtle defects. On physical training, with decreased augmentation of function in the long-axis, impairment in systolic twist, decreased global strain, and electromechanical dys-synchrony will reduce the myocardial systolic reserve [ 16 , 17 , 18 ]. The twist function may alter during oxidative myocardial dysfunction, which may be an early marker of HF.…”

Section: Left Ventricular Twist As Function Of the Heartmentioning

confidence: 99%

“…However, in the normal heart, the base of the heart has clockwise rotation during systole and the apex of the heart has counterclockwise rotation, causing a wringing movement. The cardiologists are not able to understand the utility of the twist function in clinical practice, which may be due to the problems in the measurement of cardiac rotation and torsion in the clinic [ 3 , 18 ]. It seems that three-dimensional STE may be an alternative method to assess the twist function, during plane motion.…”

Section: Left Ventricular Twist As Function Of the Heartmentioning

confidence: 99%

“…However, it seems that the measurement of the twist function would enhance our knowledge of physiological mechanics of the heart, such as the early diagnosis of abnormality in the rotation, indicating sub-endocardial dysfunction, the second stage of the six stages of HF, that may occur due to behavioral risk factors such as tobacco and Western diet. These risk factors may be also helpful in exploring the secrets of the diastole (a Rosetta stone), which could be a new concept in diastolic function and diastolic HF, via STE, in the light of neuro-humoral dysfunction [ 3 , 12 , 18 , 19 , 20 ]. It seems that the physician needs to have a closer look to understand the physio-pathogenesis of oxidative myocardial function and cardiac dysfunction, in particular, the LV twist and decline in myocardial strain [ 8 ].…”

Section: Left Ventricular Twist As Function Of the Heartmentioning

confidence: 99%

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High Exogenous Antioxidant, Restorative Treatment (Heart) for Prevention of the Six Stages of Heart Failure: The Heart Diet

Singh¹,

Fedačko

Pella

et al. 2022

Antioxidants

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The exact pathophysiology of heart failure (HF) is not yet known. Western diet, characterized by highly sweetened foods, as well as being rich in fat, fried foods, red meat and processed meat, eggs, and sweet beverages, may cause inflammation, leading to oxidative dysfunction in the cardiac ultra-structure. Oxidative function of the myocardium and how oxidative dysfunction causes physio-pathological remodeling, leading to HF, is not well known. Antioxidants, such as polyphenolics and flavonoids, omega-3 fatty acids, and other micronutrients that are rich in Indo-Mediterranean-type diets, could be protective in sustaining the oxidative functions of the heart. The cardiomyocytes use glucose and fatty acids for the physiological functions depending upon the metabolic requirements of the heart. Apart from toxicity due to glucose, lipotoxicity also adversely affects the cardiomyocytes, which worsen in the presence of deficiency of endogenous antioxidants and deficiency of exogenous antioxidant nutrients in the diet. The high-sugar-and-high-fat-induced production of ceramide, advanced glycation end products (AGE) and triamino-methyl-N-oxide (TMAO) can predispose individuals to oxidative dysfunction and Ca-overloading. The alteration in the biology may start with normal cardiac cell remodeling to biological remodeling due to inflammation. An increase in the fat content of a diet in combination with inducible nitric oxide synthase (NOSi) via N-arginine methyl ester has been found to preserve the ejection fraction in HF. It is proposed that a greater intake of high exogenous antioxidant restorative treatment (HEART) diet, polyphenolics and flavonoids, as well as cessation of red meat intake and egg, can cause improvement in the oxidative function of the heart, by inhibiting oxidative damage to lipids, proteins and DNA in the cell, resulting in beneficial effects in the early stage of the Six Stages of HF. There is an unmet need to conduct cohort studies and randomized, controlled studies to demonstrate the role of the HEART diet in the treatment of HF.

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Echocardiography 2020: Toward deciphering the “Rosetta stone” of left ventricular diastolic function

Cited by 7 publications

References 29 publications

Glucocorticoid chrono-pharmacology unveils novel targets for the cardiomyocyte-specific GR-KLF15 axis in cardiac glucose metabolism

Glucocorticoid chrono-pharmacology unveils novel targets for the cardiomyocyte-specific GR-KLF15 axis in cardiac glucose metabolism

Interpreting Diastolic Dynamics and Evaluation Through Echocardiography

High Exogenous Antioxidant, Restorative Treatment (Heart) for Prevention of the Six Stages of Heart Failure: The Heart Diet

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