ABC | Volume 112, Nº6, June 2019

Review Article Mesquita et al HFmrEF - state of the art Arq Bras Cardiol. 2019; 112(6):784-790 CHARACTERISTICS* PROGNOSIS Age Sexo gender CAD DM HBP AF HOSP † HOSP - HF ‡ DEATH † CV DEATH ‡ +++ +++ +++ +++ +++ +++ ? ? ? +++ +++ +++ +++ +++ +++ +++ ++ + + + + ++ ++ ++ ++ ++ ++ ++ ++ ++ HEpEF HFmrEF HFrEF Figure 2 – Comparisons of the clinical characteristics among the different phenotypes of HF; ? : presence of conflict between studies; CAD: coronary artery disease; DM: diabetes mellitus; HBP: high blood pressure (hypertension);AF: atrial fibrillation; HOSP: hospitalization; HOSP-HF: hospitalization for HF; DEATH: death from all causes; CV-DEATH: cardiovascular death; * Data for constructing the characteristics were taken from references; 7,22-27,32 † Data taken from references; 27,32 ‡ Data taken from reference. 32 HFmrEF than in those with HFrEF (p < 0.001), but less frequent than in patients with HFpEF (p < 0.001). Diabetes mellitus (DM) was significantly less frequent in patients with HFmrEF and HFrEF (p = 0.17) than in those with HFpEF (p = 0.021). AF was more frequent among patients withHFmrEF than among those with HFrEF (p < 0.001), but less frequent than in patients with HFpEF (p < 0.001). The prevalence of COPD was lower in individuals with HFmrEF than in HFpEF (p < 0.001), but higher when compared to patients with HFrEF (p = 0.001). Patients with HFmrEF had significantly better renal function than patients with HFpEF (p < 0.001) but worse than patients with HFrEF (p = 0.001). In the RICA 26 registry, patients with HFmrEF showed mixed characteristics in relation to the other groups. Patients with HFmrEF were similar to patients with HFrEF regarding hypertension rates, and chronic kidney disease (CKD) history, as well as in relation to the presence of higher systolic pressure, higher blood pressure, lower frequency of New York Association (NYHA) classes III-IV, higher prevalence of AF and previous HF. The study by Bhambhani et al., 22 which analyzed 28,829 without HF participants for an average of 12 years, found that 48% of the patients who developed HFmrEF were females. In addition, participants with HFmrEF shared some similarities with the HFrEF group, including lower body mass index (BMI) in relation to patients with HFpEF, with a lower obesity prevalence, a higher coronary artery disease (CAD) prevalence and lower levels of high density lipoproteins (HDL). Other clinical characteristics of participants with HFmrEF were intermediate between those with HFpEF and HFrEF. The CHARM 27 study found that patients with HFmrEF were similar to HFpEF for most of the characteristics, including age, systolic blood pressure, percentage of women, previous myocardial infarction and AF. HFmrEF was intermediate between HFrEF and HFpEF regarding the history of hypertension, NYHA and BMI class distribution. Some characteristics, such as DM, were simultaneously prevalent in all three categories. 27,28 In addition, the study by Wang et al. 23 showed no significant differences in gender between HFmrEF, HFpEF and HFrEF. The HFmrEF group was intermediate compared to the other groups regarding characteristics such as age, smoking history, DM and CKD. In contrast, the HFmrEF group was similar to HFpEF regarding the history of ischemic heart disease, with both groups showing significantly higher rates than HFpEF. In the Swedish Heart Failure 24 registry, HFmrEF was intermediate in terms of age, gender, hypertension, AF, valvular and renal disease. However, the presence of ischemic disease was more common in HFrEF and HFmrEF when compared to HFpEF, and the prevalence of DM did not differ between the three groups. The BMI was lower and fewer patients had anemia in HFmrEF. A summary of the clinical-epidemiological HFmrEF characteristics is shown in figure 2. Biomarkers Regarding biomarkers, HFmrEF has an intermediate profile, with inflammatory biomarkers being more common in HFpEF and heart distension biomarkers in HFrEF. 13 In the study by Bhambhani et al. 22 was found that the predictors of HFmrEF were similar to the predictors of other types of HF. However, a higher BMI was a predictor of HFpEF, but not of HFmrEF, and natriuretic peptides were more robust predictors of HFpEF than of HFmrEF. The Swedish Heart Failure registry 24 concluded the median value of NT-pro BNP in HFmrEF was 1,540 pg / mL with an interquartile range of 652-3,317. This value was minimally and not significantly higher than in HFpEF but was significantly higher than in HFrEF (p < 0.001). The study by Moliner et al. 29 also concluded that NT-ProBNP levels in HFmrEF were significantly lower than in HFrEF (p = 0.02), but similar to 786