scholarly journals Regulation of energy metabolism by combination therapy attenuates cardiac metabolic remodeling in heart failure

2020 ◽  
Vol 16 (16) ◽  
pp. 3133-3148
Author(s):  
Yuting Huang ◽  
Kai Zhang ◽  
Miaomiao Jiang ◽  
Jingyu Ni ◽  
Jingrui Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Combination Therapy ◽  
Metabolic Remodeling

scholarly journals Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in heart failure patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takashi Yokota ◽  
Shintaro Kinugawa ◽  
Kagami Hirabayashi ◽  
Mayumi Yamato ◽  
Shingo Takada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Aerobic Capacity ◽  
Plantar Flexion ◽  
Exercise Intolerance ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Systemic Oxidative Stress

AbstractOxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p < 0.01) and the serum activities of superoxide dismutase (SOD), an antioxidant, were significantly lower (9.2 ± 7.1 vs. 29.4 ± 9.7 units/L, p < 0.01) in the CHF cohort versus the controls. The oxygen uptake (VO2) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by 31phosphorus- and 1proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients.

Energy Metabolism in Cardiac Remodeling and Heart Failure

2013 ◽  
Vol 21 (3) ◽  
pp. 135-140 ◽  
Author(s):  
Paula S. Azevedo ◽  
Marcos F. Minicucci ◽  
Priscila P. Santos ◽  
Sergio A. R. Paiva ◽  
Leonardo A. M. Zornoff
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Cardiac Remodeling

Effect of Sacubitril/Valsartan Combined with Dapagliflozin on Long-Term Cardiac Mortality in Heart Failure with Reduced Ejection Fraction

Angiology ◽  
2021 ◽  
pp. 000331972110473
Author(s):  
Umut Karabulut ◽  
Kudret Keskin ◽  
Dilay Karabulut ◽  
Ece Yiğit ◽  
Zerrin Yiğit
Keyword(s):  
Heart Failure ◽  
Combination Therapy ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Mortality ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Neprilysin Inhibitor

The angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan and sodium-glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin have been shown to reduce rehospitalization and cardiac mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We aimed to compare the long-term cardiac and all-cause mortality of ARNI and dapagliflozin combination therapy against ARNI monotherapy in patients with HFrEF. This retrospective study involved 244 patients with HF with New York Heart Association (NYHA) class II–IV symptoms and ejection fraction ≤40%. The patients were divided into 2 groups: ARNI monotherapy and ARNI+dapagliflozin. Median follow-up was 2.5 (.16–3.72) years. One hundred and seventy-five (71.7%) patients were male, and the mean age was 65.9 (SD, 10.2) years. Long-term cardiac mortality rates were significantly lower in the ARNI+dapagliflozin group (7.4%) than in the ARNI monotherapy group (19.5%) ( P = .01). Dapagliflozin [Hazard Ratio (HR) [95% Confidence Interval (CI)] = .29 [.10–.77]; P = .014] and left ventricular ejection fraction (LVEF) [HR (95% CI) = .89 (.85–.93); P < .001] were found to be independent predictors of cardiac mortality. Our study showed a significant reduction in cardiac mortality with ARNI and dapagliflozin combination therapy compared with ARNI monotherapy.

Using A 21-Year Real-World Database from a Private Cardiologist's Practice to Test the Hypothesis that Combining Pharmacological Therapies (Carvedilol, Spironolactone and Statins) with Weight Loss May Benefit Patients with HFpEF

2020 ◽  
pp. 1-9
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Weight Loss ◽  
Clinical Trials ◽  
Endothelial Dysfunction ◽  
Combination Therapy ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Left Ventricular ◽  
Lv Diastolic Dysfunction

Heart Failure with preserved Ejection Fraction (HFpEF) is a clinical syndrome in which patients have symptoms of Heart Failure (HF), such as dyspnea and fatigue, a Left Ventricular Ejection Fraction (LVEF) ≥ 50% and evidence of cardiac dysfunction as a cause of symptoms, such as abnormal Left Ventricular (LV) diastolic dysfunction with elevated filling pressures. Besides LV diastolic dysfunction, recent investigations suggest a more complex and heterogeneous pathophysiology, including systolic reserve abnormalities, chronotropic incompetence, stiffening of ventricular tissue, atrial dysfunction, secondary Pulmonary Arterial Hypertension (PAH), impaired vasodilatation and endothelial dysfunction. Unlike Heart Failure with Reduced Ejection Fraction (HFrEF), clinical trials over the years have not yet identified effective treatments that reduce mortality in patients with HFpEF. A database on use of carvedilol in a private cardiologist's practice was begun in 1997 and concluded at the end of 2018. We used this database to test the hypothesis that combining pharmacological interventions to address diastolic dysfunction (carvedilol), volume overload (spironolactone/eplerenone) and endothelial dysfunction (statins) with weight loss may benefit patients with HFpEF. We report analysis of 335 patients with HFpEF comprised of 61% female (mean age 74 ± 8) and 39% males (mean age 72 ± 7). Initial EF ranged between 50 and 77% with mean EF of 57 ± 6%. Only 15 patients were changed to metoprolol succinate, verapamil or diltiazem because of adverse side effects. Two hundred and twenty of the patients were in normal sinus rhythm when started on carvedilol, spironolactone/eplerenone and statin therapy with weight loss counseling. After 5 years, 191 patients were still on combination therapy, and only 31 (17%) had developed Atrial Fibrillation (AF). Compared to previous HFpEF trials reporting a 32% risk of developing atrial fibrillation after 4 years, our combination therapy significantly (p < 0.05) reduced the risk of developing AF over 5 years. Thus, irrespective of age and sex with comorbidities of type 2 Diabetes Mellitus (DM) and Chronic Kidney Disease (CKD), patients with HFpEF can be managed successfully with carvedilol, spironolactone/eplerenone and statins with a clinical benefit being a reduced risk of developing AF. We consider these data hypothesis-generating and hope these results will be tested further in database analyses and clinical trials.

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