IJCS | Volume 31, Nº6, November / December 2018

658 Figure 3 - Phenocopies of heart failure with preserved ejection fraction. HF: heart failure; HFPEF: heart failure with preserved ejection fraction; HFmrEF: heart failure with mid-range ejection fraction; HFrEF: heart failure with reduced ejection fraction. Cardiac amyloidosis Hypertrophic cardiomyopathy Low-flow, low-gradient aortic stenosis Cardiac sarcoidosis Hemochromatosis HFPEF HFmrEF HFrEF HF Mesquita et al. HFPEF phenotypes Int J Cardiovasc Sci. 2018;31(6)652-661 Review Article hypertrophy, with late diagnosis due to its gradual progression. Nevertheless, it is worth pointing out that individuals withHFPEF usually have other comorbidities that independently contribute to diastolic dysfunction. 46-48 In addition to cardiac amyloidosis, “phenocopies” include other diseases such as hypertrophic cardiomyopathy, cirrhotic cardiomyopathy, 49 low-flow, low-gradient aortic stenosis, cardiac sarcoidosis and hemochromatosis (Figure 3). The identification of “phenocopies” in HFPEF may enable an individualized approach to molecular targets and functional abnormalities, such as the use of certain drugs in senile amyloidosis, and betablockers and/or calcium channel antagonists in hypertrophic cardiomyopathy. Besides, the chance of diagnostic errors may decrease and that of early diagnosis of other diseases may increase when the presence of diseases that mimic HFPEF is considered. The use of themachine learning technique for patients’ grouping by phenotypes allows the analysis of a wide variety of variables and relationship between them, and to classify them in mutually exclusive phenogroups. In addition to allowing a phenotype categorization and to contribute to a therapeutic revolution, the identification of possible “phenocopies” is crucial for the differential diagnosis of a HFPEF model (Figure 4). Conclusions HFPEF is a common syndrome, whose prevalence will increase in the community. However, classification of phenogroups and results of therapeutic approaches are still incipient. Today, the concept of adopting a phenotype network to explain HFPEF disrupts the Cartesian model in suggesting a complex approach of these patients, who may have many morphofunctional patterns. These distinct patterns may be related to abnormal signaling processes in the myocardium and associated with systemic inflammation, which is increased in patients with HFPEF and comorbidities. Phenotype mapping of heterogeneous clinical syndromes, such as HFPEF, enables the categorization of patients, and can serve as a basis for the development of clinical trials and identification of new therapeutic approaches. Author contributions Conception and design of the research: Mesquita ET, Grion DC, Kubrusly MC, Silva BBFF, Santos EAR. Acquisition of data: Mesquita ET, Grion DC, Kubrusly MC, Silva BBFF, Santos EAR. Analysis and