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Massachusetts General Hospital | MGH · Cardiovascular Research Center

Background: Myocardial infarction (MI) is a major risk factor for the development of heart failure with reduce ejection fraction (HFrEF). While previous studies have focused on HFrEF, the cardiovascular effects of ketone bodies in acute MI are unclear. We examined the effects of oral ketone supplementation as a potential treatment strategy in a sw...

Background: Obesity is associated with derangement of cardiac metabolism and the development of subclinical cardiovascular disease. This prospective study examined the impact of bariatric surgery on cardiac function and metabolism. Methods: Subjects with obesity underwent cardiac magnetic resonance imaging (CMR) at Massachusetts General Hospital...

Background Late gadolinium enhancement cardiac magnetic resonance imaging is an effective and reproducible method for characterizing myocardial infarction. However, gadolinium‐based contrast agents are contraindicated in patients with acute and chronic renal insufficiency. In addition, several recent studies have noted tissue deposition of free gad...

Background: Exercise promotes cardioprotective benefits for the adult heart; however, the exercise-induced molecular and microstructural remodeling processes have yet to be fully characterized. This study sought to define the spatial interactions between molecular and microstructural remodeling that are induced by exercise and might result in cardi...

Introduction: Myocardial infarction (MI) is a major risk factor for the development of heart failure with reduce ejection fraction (HFrEF). While previous studies have focused on HFrEF, the role of ketone bodies in MI is unclear. Hypothesis: K etone may exert some cardioprotective effects following MI. Methods: Male Yorkshire pigs underwent percuta...

Preclinical models of aortic stenosis can induce left ventricular pressure overload and coarsely control the severity of aortic constriction. However, they do not recapitulate the haemodynamics and flow patterns associated with the disease. Here we report the development of a customizable soft robotic aortic sleeve that can mimic the haemodynamics...

Purpose of Review We review the clinical benefits of altering myocardial substrate metabolism in heart failure. Recent Findings Modulation of cardiac substrates (fatty acid, glucose, or ketone metabolism) offers a wide range of therapeutic possibilities which may be applicable to heart failure. Augmenting ketone oxidation seems to offer great prom...

As one of the highest energy consumer organs in the body, the heart requires tremendous amount of adenosine triphosphate (ATP) to maintain its continuous mechanical work. Fatty acids, glucose, and ketone bodies are the primary fuel source of the heart to generate ATP with perturbations in ATP generation possibly leading to contractile dysfunction....

Both exercise-induced molecular mechanisms and physiological cardiac remodeling have been previously studied on a whole heart level. However, the regional microstructural tissue effects of these molecular mechanisms in the heart have yet to be spatially linked and further elucidated. We show in exercised mice that the expression of CITED4, a transc...

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as powerful drugs that can be used to treat heart failure (HF) patients, both with preserved and reduced ejection fraction and in the presence or absence of type 2 diabetes. While the mechanisms underlying the salutary effects of SGLT2 inhibitors have not been fully elucidated, there is...

Background Heart failure (HF) is considered to be a prothrombotic condition and it has been suggested that coagulation factors contribute to maladaptive cardiac remodelling via activation of the protease-activated receptor 1 (PAR1). We tested the hypothesis that anticoagulation with the factor Xa (FXa) inhibitor apixaban would ameliorate cardiac re...

Accumulating evidence suggests that the failing heart reverts energy metabolism toward increased utilization of ketone bodies. Despite many discrepancies in the literature, evidence from both bench and clinical research demonstrates beneficial effects of ketone bodies in heart failure. Ketone bodies are readily oxidized by cardiomyocytes and can pr...

Erythropoietin (EPO) is a haematopoietic hormone that regulates erythropoiesis, but the EPO-receptor (EpoR) is also expressed in non-haematopoietic tissues. Stimulation of the EpoR in cardiac and skeletal muscle provides protection from various forms of pathological stress, but its relevance for normal muscle physiology remains unclear. We aimed to...

ATPase inhibitory factor-1 (IF1) preserves cellular ATP under conditions of respiratory collapse, yet the function of IF1 under normal respiring conditions is unresolved. We tested the hypothesis that IF1 promotes mitochondrial dysfunction and pathological cardiomyocyte hypertrophy in the context of heart failure (HF). Methods and results: Cardiac...

MI surgery increased the myocardial expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and increased the relative expression of foetal (β-MHC) compared to with that of adult (α-MHC) myosin heavy-chain isoform (i.e. β-MHC/α-MHC ratio).

Background : ATPase inhibitor factor-1 (IF1) preserves cellular ATP under conditions of respiratory collapse, yet the function of IF1 under normal respiring conditions is unresolved. We tested the hypothesis that IF1 promotes mitochondrial dysfunction and pathological cardiomyocyte hypertrophy in the context of heart failure (HF). Methods and resul...

Metabolic perturbations underlie a variety of cardiovascular disease states; yet, metabolic interventions to prevent or treat these disorders are sparse. Ketones carry a negative clinical stigma as they are involved in diabetic ketoacidosis. However, evidence from both experimental and clinical research has uncovered a protective role for ketones i...

Background Accumulating evidence suggests that the failing heart reprograms fuel metabolism toward increased utilization of ketone bodies and that increasing cardiac ketone delivery ameliorates cardiac dysfunction. As an initial step toward development of ketone therapies, we investigated the effect of chronic oral ketone ester (KE) supplementation...

While patients with type 2 diabetes mellitus (T2DM) are at increased risk to develop atrial fibrillation (AF), the mechanistic link between T2DM and AF-susceptibility remains unclear. Common co-morbidities of T2DM, particularly hypertension, may drive AF in the setting of T2DM. But direct mechanisms may also explain this relation, at least in part....

Background The use of sodium–glucose co-transporter 2 inhibitors (SGLT2i) is currently expanding to cardiovascular risk reduction in non-diabetic subjects, but renal (side-)effects are less well studied in this setting.Methods Male non-diabetic Sprague Dawley rats underwent permanent coronary artery ligation to induce MI, or sham surgery. Rats rece...

The mechanism of action of empagliflozin in heart failure with reduced ejection fraction (HFrEF) was deciphered using deep learning in silico analyses together with in vivo validation. The most robust mechanism of action involved the sodium-hydrogen exchanger (NHE)-1 co-transporter with 94.7% accuracy, which was similar for diabetics and nondiabeti...

Purpose: Sodium glucose co-transporter-2 (SGLT-2) inhibition reduces heart failure(HF) hospitalizations in patients with diabetes, irrespective of glycemic control. We examined the effect of SGLT-2 inhibition with Empagliflozin (EMPA) on cardiac function in non-diabetic rats with HF after myocardial infarction (MI). Methods: Male non-diabetic Spra...

Aims Sodium–glucose co‐transporter 2 (SGLT2) inhibition reduces heart failure hospitalizations in patients with diabetes, irrespective of glycaemic control. We examined the effect of SGLT2 inhibition with empagliflozin (EMPA) on cardiac function in non‐diabetic rats with left ventricular (LV) dysfunction after myocardial infarction (MI). Methods a...