ABC | Volume 112, Nº6, June 2019

Review Article Mesquita et al HFmrEF - state of the art Arq Bras Cardiol. 2019; 112(6):784-790 HFmrEF was diagnosed Patients with LVEF improvement and history of HFrEF Persistent LVEF between 40% to 50% by dilated cardiomyopathy* HFmrEF with worsening of LVEF (LVEF was > 50%) † Maintain therapeutic optimization for HFrEF Beta-blocker, ACEI or ARB (if ACE inhibitors are not tolerated) Figure 3 – Algorithm for treatment of HFmrEF according to the Brazilian Guideline for Chronic and Acute Heart Failure of 2018; 5 ACEi: angiotensin-converting-enzyme inhibitor;ARB: angiotensin II receptor blockers; * In the absence of deposit cardiomyopathies, hypertrophic, inflammatory or infectious diseases; † Particularly for coronary heart disease and/or acute myocardial infarction. However, the CHARM study showed that the candesartan use improved outcomes for HFmrEF to a degree comparable to improvement for HFrEF. For the HFmrEF group, the incidence rates for the primary outcome (cardiovascular death or HF hospitalization) of candesartan vs. placebo were 7.4 vs. 9.7 per 100 patients per year (HR 0.76, 95% CI, 0.61-0.96, p = 0.02), and the incidence rate of recurrent hospitalization for HF was 0.48 (95 % CI, 0.33-0.70, p <0.001). 27,36 The study by Cleland JGF et al., 37 which included 18,637 patients, found that for patients with HF with sinus rhythm and LVEF between 40% and 49%, beta-blockers showed a reduction in cardiovascular death when compared to placebo (HR 0.048, 95% CI, 0.24-0, 97, p = 0.04) and improvement in LV systolic function. 37 In the study by Gwag et al., 38 maintenance therapy with β -blocker was seen to be associated with LVEF improvement in patients with HFmrEF (HR 2.021; 95% HF 1.033-3.033; p = 0.04). In addition, maintenance therapy with renin- angiotensin system blockers or aldosterone antagonists were significantly associated with improved survival (HR 0,309; CI 95% 0,162–0,588; p < 0,001; and HR 0,240; CI 95% 0,085 – 0,673; p = 0,01, respectively). Digoxin use was evaluated in the study by Abdul-Rahim AH et al., 39 which included 7788 patients, with 1995 patients being classified as HFmrEF. Digoxin reduced cardiovascular death or HF hospitalization (HR: 0.83; 95% CI, 0.66-1.05). 39 The study Chang et al. 9 showed the comorbidities observed in patients with HFmrEF were more similar to the ones observed in patients with HFpEF, and CAD was associated with greater declines in LVEF in patients with HFpEF. 40 Therefore, the management of CAD can help prevent LV systolic dysfunction progression in individuals with HFmrEF. 21 Non-cardiac comorbidities, such as hypertension, DM and COPD, are highly prevalent in the HF population and contribute to the general morbidity of these patients. 41 In patients with HFmrEF, uncontrolled hypertension was the main precipitant factor of hospitalization for HF compared to the other HF groups. 7 In patients with HFmrEF and hypertension, therapy with angiotensin II receptor blockers (ARB) or aldosterone antagonists has shown a reduction in hospitalizations, which suggests that such drugs can be used to control hypertension and reduce the risk of LVEF decline in patients with HFmrEF. 7 Regarding the patients with HF undergoing treatment for DM sodium-glucose cotransporter-2 (SGLT2) inhibitors use in patients at high cardiovascular risk showed improvements in the primary outcome, consisting of death from cardiovascular causes, infarction and non‑fatal stroke. (HR 0.86; 95% CI, 0.74-0.99; p < 0.001 for noninferiority and p = 0.04 for superiority). In addition, empagliflozin use showed a reduction in cardiovascular death and death from all causes (HR 0.62, 95% CI 0.49-0.77, p < 0.001 and HR 0.68, 95% CI, 0.57-0.82, p < 0.001, respectively), in addition to the reduction in hospitalization for HF (HR 0.65, 95% CI, 0.50-0.85, p = 0.002). 42 The current BSC HF guideline 5 proposes that initially, the specific treatment of the etiology and comorbidities should be addressed, when possible. Patients with a history of HFrEF who show an improvement of LVEF, which reclassifies them as HFmrEF patients, should be treated by maintaining the therapeutic optimization for HFrEF. For patients with previous HFpEF who show worsening of LVEF and also those with persistent HFmrEF, the use of beta-blocker and angiotensin- convertingenzyme inhibitor (ACEi) or ARB (if ACEi is not tolerated) is recommended. The treatment scheme proposed by the SBC is shown in figure 3. 788