The following are key points to remember from the 2023 European Society of Cardiology (ESC) guidelines for the management of cardiovascular disease (CVD) in patients with diabetes, part 2 of 2:

1. Heart failure (HF) and diabetes:
   • HF is one of the most common initial manifestations of CVD in patients with type 2 diabetes mellitus (T2DM), and may present as HF with preserved ejection fraction (HFpEF) with left ventricular EF (LVEF) ≥50%, HF with mildly reduced EF (HFmrEF) with LVEF 41-49%, and HF with reduced EF (HFrEF) with LVEF ≤40%.
   • Major causes of HF in diabetes are ischemic heart disease, hypertension, direct or indirect effects of hyperglycemia, and obesity and related factors on the myocardium.
   • Coronary heart disease is often accelerated, severe, diffuse, and silent, and increases the risk of myocardial infarction (MI) and ischemic MI. Given that the prognosis of patients with both comorbidities is worse, it is of utmost importance to screen all patients with diabetes for HF to allow early implementation of life-saving therapies.
   • To predict the HF risk among outpatients with T2DM, the risk score was developed. WATCH-DM includes Weight [BMI], Age, Hypertension, Creatinine, HDL-C, Diabetes control [fasting plasma glucose], QRS duration, MI, and CABG). Each increment of 1 unit in the risk score is associated with a 24% higher HF risk within 5 years. The WATCH-DM risk score is available at: Diabetes Care 2019;42:2298-306; https://doi.org/10.2337/dc19-0587.
   • Biomarker-based risk score including high-sensitivity cardiac troponin T ≥6 ng/L, N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥125 pg/mL, high-sensitivity C-reactive protein ≥3 mg/L, and LV hypertrophy by electrocardiogram (ECG) (with one point for each abnormal parameter) demonstrated good discrimination and calibration for predicting 5-and 10-year HF risk among patients with diabetes. The highest 5-year risk of HF was noted among those with scores ≥3.481. This score is available at: Eur J Heart Fail 2022;24:1162-70; https://doi.org/10.1002/ejhf.2575.
2. Approach to patients with diabetes at risk for HF:
   • Repeat evaluation regularly including symptoms and/or signs for HF and/or abnormal ECG. If yes, screen HF biomarkers and if NT-proBNP ≥125 pg/mL or BNP ≥35 pg/mL. Note natriuretic peptide concentrations may be disproportionately low in patients with obesity or in women, and disproportionately high in patients with advanced chronic kidney disease (CKD), advanced age, or atrial fibrillation (AF). Still, elevated concentrations support the diagnosis of HF and may guide further cardiac investigation.
   • Obtain echocardiography to assess for structural and/or functional cardiac abnormality. If HF is confirmed, define phenotype based on LVEF. And perform chest x-ray to assess for pulmonary congestion, pleural effusions, and pulmonary diseases.
   • Determine etiology and commence therapy.
3. Recommendations for treatment of HF in patients with HFrEF and diabetes:
   • Sodium–glucose co-transporter-2 (SGLT2) inhibitors (dapagliflozin, empagliflozin, or sotagliflozin) are recommended in all patients with HFrEF and T2DM to reduce the risk of HF hospitalization and CV death.
   • Sacubitril/valsartan or an angiotensin-converting enzyme inhibitor (ACE-I) is recommended in all patients with HFrEF and diabetes to reduce the risk of HF hospitalization and death.
   • Beta-blockers are recommended in patients with HFrEF and diabetes to reduce the risk of HF hospitalization and death.
   • Mineralocorticoid receptor antagonists (MRAs) are recommended in patients with HFrEF and diabetes to reduce the risk of HF hospitalization and death.
   • An intensive strategy of early initiation of evidence-based treatment (SGLT2 inhibitors, angiotensin receptor–neprilysin inhibitor (ARNI)/ACE-Is, beta-blockers, and MRAs), with rapid up-titration to trial-defined target doses starting before discharge and with frequent follow-up visits in the first 6 weeks following a HF hospitalization is recommended to reduce re-admissions or mortality.
4. Recommendations for other treatments indicated in select patients with HFrEF (NYHA class II-IV) and diabetes:
   • Device therapy with an implantable cardioverter-defibrillator (ICD), cardiac resynchronization therapy-pacemaker (CRT-P), or CRT wit an implantable defibrillator (CRT-D) is recommended in patients with diabetes, as in the general population with HFrEF.
   • ARBs are recommended in symptomatic patients with HFrEF and diabetes who do not tolerate sacubitril/valsartan or ACE-Is, to reduce the risk of HF hospitalization and CV death.
   • Diuretics are recommended in patients with HFrEF, HFmrEF, and HFpEF and diabetes with signs and/or symptoms of fluid congestion to improve symptoms, exercise capacity, and reduce HF hospitalization.
   • Ivabradine should be considered to reduce the risk of HF hospitalization and CV death in patients with HFrEF and diabetes in sinus rhythm, with a resting heart rate ≥70 bpm, who remain symptomatic despite treatment with beta-blockers (maximum tolerated dose), ACE-Is/ARBs, and MRAs.
   • Hydralazine and isosorbide dinitrate should be considered in self-identified Black patients with diabetes and LVEF ≤35% or with LVEF <45% combined with a dilated left ventricle in NYHA class II–IV despite treatment with an ACE-I (or ARNI), a beta-blocker, and an MRA, to reduce the risk of HF hospitalization and death.
   • Digoxin may be considered in patients with symptomatic HFrEF in sinus rhythm despite treatment with sacubitril/valsartan or an ACE-I, a beta-blocker, and an MRA, to reduce the risk of hospitalization.
5. Recommendations for glucose-lowering medication in patients with T2DM with and without heart failure:
   • SGLT2 inhibitors empagliflozin, canagliflozin, dapagliflozin, ertugliflozin, or sotagliflozin are recommended in patients with T2DM with multiple atherosclerotic CVD (ASCVD) risk factors or established ASCVD to reduce the risk of HF hospitalization.
   • SGLT2 inhibitors epagliflozin or dapagliflozin are recommended in patients with T2DM and LVEF >40% (HFmrEF and HFpEF) to reduce the risk of HF hospitalization or CV death.
   • SGLT2 inhibitors dapagliflozin, empagliflozin, or sotagliflozin are recommended in patients with T2DM and HFrEF to reduce the risk of HF hospitalization and CV death.
6. Recommendations for additional glucose-lowering agents with safety demonstrated for HF hospitalization in patients with T2DM if additional glucose control is needed:
   • Metformin should be considered for glucose-lowering treatment in patients with T2DM and HF.
   • Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (liraglutide, semaglutide, exenatide extended release, dulaglutide) have a neutral effect on the risk of HF hospitalization, and should be considered for glucose-lowering treatment in patients with T2DM at risk of or with HF.
   • Dipeptidyl peptidase-4 (DPP-4) inhibitors (sitagliptin and linagliptin) have a neutral effect on the risk of HF hospitalization, and should be considered for glucose-lowering treatment in patients with T2DM at risk of or with HF.
   • Basal insulins (glargine and degludec) have a neutral effect on the risk of HF hospitalization and should be considered for glucose-lowering treatment in patients with T2DM at risk of or with HF.
7. Glucose-lowering medications with an increased risk of HF hospitalization in patients with diabetes:
   • Pioglitazone is associated with an increased risk of incident HF in patients with diabetes and is not recommended for glucose-lowering treatment in patients at risk of HF (or with previous HF).
   • The DPP-4 inhibitor saxagliptin is associated with an increased risk of HF hospitalization in patients with diabetes and is not recommended for glucose-lowering treatment in patients at risk of HF (or with previous HF).
8. Recommendations for AF in patients with diabetes:
   • Screening for AF by pulse taking or ECG is recommended in patients ≥65 years of age.
   • Screening for AF by pulse taking or ECG is recommended in patients with diabetes <65 years of age (particularly when other risk factors are present).
   • Systematic ECG screening should be considered to detect AF in patients aged ≥75 years, or those at high risk of stroke.
9. Recommendation for anticoagulation for AF in patients with diabetes:
   • Oral anticoagulation is recommended for preventing stroke in patients with AF and diabetes and with at least one additional (CHA₂DS₂-VASc) risk factor for stroke.
   • For preventing stroke in AF, nonvitamin K antagonist oral anticoagulants (NOACs) are recommended in preference to vitamin K antagonists, with the exception of patients with mechanical valve prostheses or moderate to severe mitral stenosis.
   • Oral anticoagulation should be considered for preventing stroke in patients with AF and diabetes but no other CHA₂DS₂-VASc risk factor for stroke. This includes patients with T1DM or T2DM <65 years old.
   • Use of a formal, structured, bleeding risk score (HAS-BLED score) should be considered to identify modifiable and nonmodifiable risk factors for bleeding in patients with diabetes and AF, and to identify patients in need of closer follow-up.
10. Ventricular arrhythmias and risk of sudden cardiac death (SCD) and diabetes: 
    • Compared with the general population, patients with diabetes have an increased risk of both SCD and non-SCD. The risk of SCD was two-fold higher in diabetes compared to those without diabetes. However, patients with diabetes also exhibited a nearly three-fold greater risk of non-SCD than patients without diabetes.
    • Both hyperglycemia and hypoglycemia are independently associated with increased risk of ventricular arrhythmias. Insulin-induced hypoglycemia has been associated with nocturnal death (also called 'dead-in-bed syndrome') in T1DM, and arrhythmic deaths were reported in several T2DM trials. Diabetic kidney disease might also play a role in the arrhythmia-associated mechanism of sudden death in this setting.
    • Patients with diabetes and frequent premature ventricular beats, episodes of nonsustained ventricular tachycardia, or symptoms suggestive of HF should be examined for the presence of an underlying structural heart disease and their eligibility for an ICD should be assessed; this is a general principle in managing patients with HF, irrespective of diabetes status.
    • In case of sustained ventricular arrhythmias, diagnosing underlying structural heart disease with imaging techniques and coronary angiography is usually needed if no obvious trigger factors, such as electrolyte imbalance, can be identified.
11. Recommendations for patients with CKD and diabetes:
    • Patients with diabetes should be routinely screened for kidney disease by assessing estimated glomerular filtration rate (eGFR) defined by CKD-EPI and urine albumin-to-creatinine ratio (UACR).
    • Treatment with intensive medical or an initial invasive strategy is recommended in people with CKD, diabetes, and stable moderate or severe coronary artery disease (CAD), due to similar outcomes.
    • Kidney specialist advice may be considered for managing a raised serum phosphate, other evidence of CKD with mineral bone disease, and renal anemia.
    • Intensive low-density lipoprotein cholesterol (LDL-C) lowering with statins or a statin/ezetimibe combination is recommended.
    • A blood pressure (BP) target of ≤130/80 mm Hg is recommended to reduce risk of CVD and albuminuria.
    • Personalized glycated hemoglobin (HbA1c) targets (6.5–8.0%) are recommended, with a target <7.0% to reduce microvascular complications, wherever possible.
    • The maximum tolerated dose of an ACE-I or angiotensin-receptor blocker (ARB) is recommended.
    • A SGLT2 inhibitor (canagliflozin, empagliflozin, or dapagliflozin) is recommended in patients with T2DM and CKD with an eGFR ≥20 mL/min/1.73 m² to reduce the risk of CVD and kidney failure.
    • Finerenone, a nonsteroidal selective MRA, is recommended in addition to an ACE-I or ARB in patients with T2DM and eGFR >60 mL/min/1.73 m² with a UACR ≥300 mg/g, or eGFR 25–60 mL/min/1.73 m² and UACR ≥30 mg/g, to reduce CV events and kidney failure.
    • A GLP-1 RA is recommended at eGFR >15 mL/min/1.73 m² to achieve adequate glycemic control, due to low risk of hypoglycemia and beneficial effects on weight, CV risk, and albuminuria.
    • Low-dose aspirin (ASA) is recommended in patients with CKD and ASCVD.
    • Combined use of an ARB with an ACE-I is not recommended.
12. Recommendations for peripheral arterial disease and aortic disease in patients with diabetes:
    • Screening for lower extremity arterial disease (LEAD) in diabetes is recommended on a regular basis, with clinical assessment and/or ankle-brachial index (ABI) measurement.
    • In diabetes and symptomatic LEAD, antiplatelet therapy is recommended.
    • In diabetes and chronic limb-threatening ischemia (CLTI), assess the risk of amputation; the WIfI score containing three main factors (wound, ischemia, foot infection) is useful for this purpose.
    • As diabetes and LEAD are at very high CV risk, an LDL-C target of <55 mg/dL and an LDL-C reduction of ≥50% is recommended.
    • Patient education about foot care is recommended in patients with diabetes, and especially those with LEAD, even if asymptomatic. Early recognition of tissue loss and/or infection, and referral to a multidisciplinary team, is mandatory to improve limb salvage.
    • An ABI ≤0.90 is diagnostic of LEAD, irrespective of symptoms. In symptomatic cases, further assessment including duplex ultrasound is recommended.
    • When ABI is elevated (>1.40), other noninvasive tests, including toe-brachial index or duplex ultrasound, are recommended.
    • Duplex ultrasound is recommended as the first-line imaging method to assess the anatomy and hemodynamic status of lower-extremity arteries. In case of CLTI, revascularization is recommended whenever feasible for limb salvage.
    • In patients with chronic, symptomatic LEAD without high bleeding risk, a combination of low-dose rivaroxaban (2.5 mg BID) and low-dose ASA should be considered.
    • In patients with diabetes and carotid artery disease, it is recommended to implement the same diagnostic workup and therapeutic strategies (medical, surgical, or endovascular) as in patients without diabetes.
    • In patients with diabetes and aortic aneurysm, it is recommended to implement the same diagnostic workup and therapeutic strategies (medical, surgical, or endovascular) as in patients without diabetes.

Note: Click the link under Related Content (top right) for Part 1 of this Journal Scan.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism, Nonstatins, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound, Exercise

Keywords: Anticoagulants, Antihypertensive Agents, Arrhythmias, Cardiac, Atherosclerosis, Atrial Fibrillation, Biomarkers, Blood Pressure, Cholesterol, LDL, Cardiac Resynchronization Therapy, Death, Sudden, Cardiac, Diabetes Mellitus, Type 2, Diagnostic Imaging, Electrocardiography, Echocardiography, ESC Congress, ESC23, Exercise, Glucose, Glycated Hemoglobin A, Heart Failure, Hyperglycemia, Hypoglycemia, Kidney Diseases, Natriuretic Peptides, Obesity, Peripheral Arterial Disease, Pharmaceutical Preparations, Primary Prevention, Risk Assessment, Risk Factors, Renal Insufficiency, Chronic, Secondary Prevention, Stroke, Vascular Diseases

< Back to Listings