Heart failure and diabetes: metabolic alterations and therapeutic interventions: a state-of-the-art review from the Translational Research Committee of the Heart Failure Association–European Society of Cardiology

Maack, Christoph; Lehrke, Michael; Backs, Johannes; Heinzel, Frank R.; Hulot, Jean‐Sébastien; Marx, Nikolaus; Paulus, Walter; Rossignol, Patrick; Taegtmeyer, Heinrich; Bauersachs, Johann; Bayés‐Genís, Antoni; Brutsaert, Dirk L.; Bugger, Heiko; Clarke, Kieran; Cosentino, Francesco; Keulenaer, Gilles W. De; Dei, Alessandra; González, Arantxa; Huelsmann, M; Iaccarino, Guido; Lunde, Ida G.; Lyon, Alexander R.; Pollesello, Piero; Rena, Graham; Riksen, Niels P.; Rosano, Giuseppe; Staels, Bart; Laake, Linda W. van; Wanner, Christoph; Farmakis, Dimitrios; Filippatos, Gerasimos; Ruschitzka, Frank; Seferović, Petar; Boer, Rudolf A. de; Heymans, Stéphane

doi:10.1093/eurheartj/ehy596

Cited by 179 publications

(143 citation statements)

References 155 publications

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“…SGLT‐2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin) have a unique glucose‐lowering effect via inhibiting glucose reabsorption in the proximal renal tubule . Due to the favourable outcomes in recent trials, SGLT‐2 inhibitors are assumed to have cardioprotective properties, via several mechanisms, as reviewed . Beneficial effects of SGLT‐2 inhibition on CV outcomes have been shown in the recent landmark CVOTs with empagliflozin, canagliflozin and dapagliflozin ( Table ), while ertugliflozin is being assessed in an ongoing VERTIS trial (NCT01986881).…”

Section: Sodium–glucose Co‐transporter Type 2 Inhibitorsmentioning

confidence: 99%

“…Several haemodynamic and metabolic mechanisms (not mutually exclusive) have been proposed to explain the salutary CV effects of SGLT‐2 inhibitors ( Figure ), but they await confirmation from clinical trials. In a recent exploratory analysis of EMPA‐REG OUTCOME, changes in markers of plasma volume (haematocrit and haemoglobin) had the largest impact on relative risk reduction of CV death (51.8% and 48.9%, respectively) .…”

Section: Sodium–glucose Co‐transporter Type 2 Inhibitorsmentioning

confidence: 99%

“…dipeptidyl peptidase‐4 (DPP‐4) inhibitors, glucagon like peptide‐1 receptor agonists (GLP‐1 RA), and sodium–glucose co‐transporter type 2 (SGLT‐2) inhibitors] may have effects beyond glycaemic control pertinent to cardiovascular (CV) risk reduction in T2DM. Figure provides a summary of several proposed pleiotropic mechanisms that extend the benefits of new glucose‐lowering medications beyond glycaemic control to include positive metabolic, renal, vascular and haemodynamic effects . At present, the exact mechanism(s) underlying favourable CV effects of these medications in humans are unclear and are under assessment in several mechanistic studies.…”

Section: Introductionmentioning

confidence: 99%

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European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose‐lowering drugs in patients with heart failure

Seferović

Coats

Ponikowski

et al. 2019

European J of Heart Fail

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139

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Type 2 diabetes mellitus (T2DM) is common in patients with heart failure (HF) and associated with considerable morbidity and mortality. Significant advances have recently occurred in the treatment of T2DM, with evidence of several new glucose‐lowering medications showing either neutral or beneficial cardiovascular effects. However, some of these agents have safety characteristics with strong practical implications in HF [i.e. dipeptidyl peptidase‐4 (DPP‐4) inhibitors, glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA), and sodium–glucose co‐transporter type 2 (SGLT‐2) inhibitors]. Regarding safety of DPP‐4 inhibitors, saxagliptin is not recommended in HF because of a greater risk of HF hospitalisation. There is no compelling evidence of excess HF risk with the other DPP‐4 inhibitors. GLP‐1 RAs have an overall neutral effect on HF outcomes. However, a signal of harm suggested in two small trials of liraglutide in patients with reduced ejection fraction indicates that their role remains to be defined in established HF. SGLT‐2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) have shown a consistent reduction in the risk of HF hospitalisation regardless of baseline cardiovascular risk or history of HF. Accordingly, SGLT‐2 inhibitors could be recommended to prevent HF hospitalisation in patients with T2DM and established cardiovascular disease or with multiple risk factors. The recently completed trial with dapagliflozin has shown a significant reduction in cardiovascular mortality and HF events in patients with HF and reduced ejection fraction, with or without T2DM. Several ongoing trials will assess whether the results observed with dapagliflozin could be extended to other SGLT‐2 inhibitors in the treatment of HF, with either preserved or reduced ejection fraction, regardless of the presence of T2DM. This position paper aims to summarise relevant clinical trial evidence concerning the role and safety of new glucose‐lowering therapies in patients with HF.

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Section: Sodium–glucose Co‐transporter Type 2 Inhibitorsmentioning

confidence: 99%

Section: Sodium–glucose Co‐transporter Type 2 Inhibitorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose‐lowering drugs in patients with heart failure

Seferović

Coats

Ponikowski

et al. 2019

European J of Heart Fail

Self Cite

139

117

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show abstract

“…In individuals with high‐intensity resistance training or poor nutritional status, increased BCAAs intake may confer health benefits, although its indiscriminate or excessive use as health supplements may potentially cause harm . Dysregulation of energy metabolism due to excessive calorie intake and/or reduced energy expenditure can lead to obesity and type 2 diabetes (T2D), which are the leading causes of atherosclerotic cardiovascular disease (ASCVD) . With better control of cardiometabolic‐renal risk factors, use of cardioprotective drugs, and coronary interventions, we and others have witnessed declining trends of myocardial infarction and its complications, especially in high‐income countries .…”

Section: Introductionmentioning

confidence: 99%

“…Traditionally, HF is considered a consequence of long‐standing hypertension and coronary heart disease (CHD), although people with T2D may have subclinical cardiomyopathy for years due to predominantly metabolic causes . Given the high energy demand of myocardium, HF can be caused by abnormal utilization of energy substrate . In T2D and obesity, insulin resistance and beta‐cell dysfunction can lead to inefficient uptake of glucose for energy production and non‐suppression of lipolysis with increased release of free fatty acids (FFAs) .…”

Section: Introductionmentioning

confidence: 99%

Circulating branched‐chain amino acids and incident heart failure in type 2 diabetes: The Hong Kong Diabetes Register

Lim

Lau

Fung

et al. 2020

Diabetes Metabolism Res

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Aim Levels of branched‐chain amino acids (BCAAs, namely, isoleucine, leucine, and valine) are modulated by dietary intake and metabolic/genetic factors. BCAAs are associated with insulin resistance and increased risk of type 2 diabetes (T2D). Although insulin resistance predicts heart failure (HF), the relationship between BCAAs and HF in T2D remains unknown. Methods In this prospective observational study, we measured BCAAs in fasting serum samples collected at inception from 2139 T2D patients free of cardiovascular‐renal diseases. The study outcome was the first hospitalization for HF. Results During 29 103 person‐years of follow‐up, 115 primary events occurred (age: 54.8 ± 11.2 years, 48.2% men, median [interquartile range] diabetes duration: 5 years [1‐10]). Patients with incident HF had 5.6% higher serum BCAAs than those without HF (median 639.3 [561.3‐756.3] vs 605.2 [524.8‐708.7] μmol/L; P = .01). Serum BCAAs had a positive linear association with incident HF (per‐SD increase in logarithmically transformed BCAAs: hazard ratio [HR] 1.22 [95% CI 1.07‐1.39]), adjusting for age, sex, and diabetes duration. The HR remained significant after sequential adjustment of risk factors including incident coronary heart disease (1.24, 1.09‐1.41); blood pressure, low‐density lipoprotein cholesterol, and baseline use of related medications (1.31, 1.14‐1.50); HbA1c, waist circumference, triglyceride, and baseline use of related medications (1.28, 1.11‐1.48); albuminuria and estimated glomerular filtration rate (1.28, 1.11‐1.48). The competing risk of death analyses showed similar results. Conclusions Circulating levels of BCAAs are independently associated with incident HF in patients with T2D. Prospective cohort analysis and randomized trials are needed to evaluate the long‐term safety and efficacy of using different interventions to optimize BCAAs levels in these patients.

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Microvascular disease and heart failure with reduced and preserved ejection fraction in type 2 diabetes

et al. 2020

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Aims Identification of patients with type 2 diabetes (T2D) at increased risk of incident heart failure (HF) beyond traditional risk factors such as prior myocardial infarction (MI) might allow selection of patients who would benefit from preventative treatment. Microvascular disease (MiVD) is thought to play a pathophysiological role in the development of HF in T2D; however, its association with new-onset HF with reduced or preserved ejection fraction has not been specifically defined. Methods and results Patients in the Genetics of Diabetes Audit and Research Tayside Scotland study were linked to echocardiography, prescriptions, and clinical outcomes. In total, 9141 patients with T2D were identified for analysis. Clinical variables and the presence of retinopathy, nephropathy, and neuropathy were assessed. Cumulative incidence was calculated for the association of both individual and the total number of MiVD states and incident HF. Median follow-up was 9.3 years. In total, there were 900 HF events. The presence of any MiVD was independently associated with both HF with reduced ejection fraction (hazard ratio 1.40; 95% confidence interval 1.11-1.76, P = 0.004) and HF with preserved ejection fraction (hazard ratio 1.38; 95% confidence interval 1.10-1.72, P = 0.005), with a stepwise association between the number of MiVD states and risk of incident HF (P for trend <0.001). Similar associations were found in sensitivity analyses limited to patients without a prior MI, and using competing risks analysis. Conclusions Individuals with T2D and with MiVD are at risk of incident HF independent of a history of prior HF or MI. Patients with MiVD could benefit from screening for HF and individualized therapy with treatments that lower HF risk.

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Heart failure and diabetes: metabolic alterations and therapeutic interventions: a state-of-the-art review from the Translational Research Committee of the Heart Failure Association–European Society of Cardiology

Cited by 179 publications

References 155 publications

European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose‐lowering drugs in patients with heart failure

European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose‐lowering drugs in patients with heart failure

Circulating branched‐chain amino acids and incident heart failure in type 2 diabetes: The Hong Kong Diabetes Register

Microvascular disease and heart failure with reduced and preserved ejection fraction in type 2 diabetes

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