ABC | Volume 113, Nº4, October 2019

Updated Updated Cardiovascular Prevention Guideline of the Brazilian Society Of Cardiology – 2019 Arq Bras Cardiol. 2019; 113(4):787-891 shown in the 2009 guidelines of the American Society of Echocardiography and the European Association of Cardiovascular Imaging (ASE/EACVI) and the Canberra Study Criteria (CSC). 44,45 Based on these recommendations, epidemiological studies and a meta-analysis 46,47 suggest that preclinical diastolic dysfunction (Stage B HF), defined as diastolic dysfunction with normal systolic function and without HF symptoms, is common in DM, and that its presence increases by 61 to 70% the risk for developing symptomatic HF (stages C and D). Despite being simple and non-invasive, 46,47 the echocardiographic diagnosis for patients at higher risk for HF does not seem to be as cost-effective as the measurement of BNP, 48,49 although these data are not specifically available for the Brazilian population. The diagnostic criteria became more specific and less sensitive in the 2016 ASE/EACVI guideline, 50,51 despite the simplification. With these criteria, the prevalence of diastolic dysfunction in the general population ranges from 1 to 7%. However, no studies have been designed to focus on primary prevention based on this diagnostic criterion. Risk scores for future HF – The HF risk in patients with DM and metabolic syndrome (MS) can be predicted with clinical scores. Although no scores have been developed specifically for patients with DM or MS, several studies have demonstrated good performance in these populations. Among the most used scores are the (i) Health ABC Heart Failure Score; 52 the (ii) The Framingham Heart Failure Risk Score; 53 and the (iii) And the Atherosclerosis Risk in Communities (ARIC) Heart Failure Risk Score. 54 The variables included in the Framingham Heart Failure Risk Score are age, gender, CAD, diabetes, left ventricular hypertrophy based on electrocardiogram (ECG), valvular disease, heart rate, and systolic blood pressure (SBP). The Health ABC Heart Failure Score includes the Framingham variables with the following differences: addition of serum albumin, serum creatinine, and smoking; replacement of glucose for diabetes; and exclusion of valvular disease. The ARIC Heart Failure Risk Score includes age, ethnicity, gender, CAD, diabetes, SBP, use of medicines for blood pressure (BP), heart rate, smoking, and body mass index (BMI). Designed for a community population of older adults, the Health ABC Heart Failure Score reached a positive and negative predictive power of 10 and 15% in comparison with the Framingham Heart Failure Risk Score 52 and 2 to 4% above the ARIC Heart Failure Risk. 54 The Health ABC Heart Failure Score is an instrument validated in observational and intervention studies and, thus, considered a reference for estimating the future HF risk in patients with DM and MS (detailed description in Figure 3.1). Although all scores are designed with only the variables listed above, the addition of BNP or NT-proBNP as linear variables would significantly increase the predictive power of all scores. 52,54 Based on the thresholds used in the studies PONTIAC 43 and STOP-HF, 42 we suggest reclassifying individuals with BNP ≥ 50 pg/mL or NT-proBNP ≥ 125 pg/mL into a higher risk category. 3.1.2. Preventive Therapies for Individuals at High and Very High Risk for Heart Failure in 5 Years and Secondary Prevention for Those with Clinical Heart Failure Drug Therapies for DM2 that impact HF – As stated previously, above 7%, the HF risk increases by 8% for each 1% increment in HbA1c, while a 1% reduction decreases the risk by 16%. Although, several clinical trials have investigated the effect of metformin on the CV system based on the pathophysiology of insulin resistance, the effect of this class directly on HF remains inconclusive. Studies with insulin and sulfonylureas showed a neutral effect on HF, and glucagon- like peptide-1 (GLP-1) agonists/analogs 55 and acarbose 56 proved to be neutral regarding the risk for HF hospitalizations and mortality. More recently, three large studies – EMPA-REG, CANVAS, and DECLARE – revealed that sodium-glucose 2 (SGLT2) cotransporter inhibitors reduced CV outcomes, including HF hospitalizations. 57,58 HF mortality among individuals who used empagliflozin was significantly lower than in those using a placebo. The studies EMPA-REG and DECLARE associated the risk of taking these drugs with a higher rate of genital infections in the group using empagliflozin and dapagliflozin, while the CANVAS study showed an increased risk of lower limb amputation. 57,58 Together, all three SGLT2 inhibitors available (empagliflozin, canagliflozin, and dapagliflozin) reduce the risk for HF hospitalization, even in asymptomatic patients at the start of treatment. Therefore, the use of these drugs is recommended for patients with DM or MS at high or very high risk for HF. Among the hypoglycemic agents that increase the chance of HF, we highlight the thiazolidinediones (RECORD study – rosiglitazone; and PROactive – pioglitazone) 59,60 and a dipeptidyl peptidase-4 inhibitor (DPP-4i) – the saxagliptin (SAVOR-TIMI 53). 61 In the studies RECORD and SAVOR- TIMI, patients with HF also had higher subsequent mortality rates. Thus, rosiglitazone, pioglitazone, and saxagliptin are contraindicated for patients with or at high risk for HF. 3.1.3. Therapies Focused on Cardiac Remodeling Although only two clinical trials substantiate these recommendations, patients with DM and MS at high and very high risk for HF seem to benefit from the early introduction of anti-remodeling therapies, such as RAAS inhibitors and beta- blockers. Based on these pharmacological strategies triggered by BNP or NT-proBNP levels above the risk threshold, the studies PONTIAC 43 and STOP-HF 42 suggested reducing the risk for HF hospitalization and mortality. In patients with clinical HF, clinical trials have demonstrated that the drug therapies tested were equally effective, regardless of the presence of DM and MS. Angiotensin blockers – The CHARM Trial (candesartan), 62 Val-HeFT (valsartan), 63 and ATLAS (lisinopril) 64 have demonstrated that the use of angiotensin-converting enzyme inhibitors (ACEI) or aldosterone-receptor blockers (ARB) favored the decrease in mortality and hospitalization among patients who had HF and reduced ejection fraction, regardless of the presence of DM2 or MS. 805