IJCS | Volume 33, Nº3, May / June 2020

DOI: https://doi.org/10.36660/ijcs.20190222 278 VIEWPOINT International Journal of Cardiovascular Sciences. 2020; 33(3):278-281 Mailing Address: José Francisco Kerr Saraiva Rua Oswaldo Oscar Barthelson, 1209 – Jardim Pauliceia. Postal Code: 13060-080, Campinas, SP – Brazil. E-mail: jfsaraiva@uol.com.br PARAGON-HF: Lessons Learned and Perspectives José Francisco Kerr Saraiva 1 a nd Isadora de Oliveira 2, 3 PUC-Campinas, 1 Campinas, SP – Brazil Novartis Brasil - Medical Affairs, 2 São Paulo, SP – Brazil Universidade de São Paulo, 3 São Paulo, SP – Brazil Manuscript received on December 09, 2019; reviewed on December 11, 2019; accepted on December 30, 2019. Heart Failure/physiopathology;Neprilysin/therapeutic use; Echocardiography/methods; Dysfunction Left Ventricular/abnormalities; Indicators of Morbidity and Mortality; Risk Factors; Valsartan/therapeutic use. Keywords An estimated 6.5 millionAmericans aged 20 and over have heart failure (HF) and projections show that the prevalence of HF will increase by 46% from 2012 to 2030, resulting in over 8 million people with HF. 1 Patients with HF can be stratified into different categories of left ventricular ejection fraction (LVEF), presentingdifferent phenotypes in terms of demographics, clinical presentation, etiology and outcomes. The current classification comprises HFwith reduced ejection fraction (EF) [EF ≤ 40% (HFrEF)], with intermediate EF [EF 40-50% (HFiEF), and preserved EF [EF ≥ 50% (HFpEF). 2,3 The diagnosis of HFpEF is challenging, startingwith its definition and classification. The definition of HFpEF has evolved over the past two decades, from a primary focus on an echocardiographic evidence of diastolic dysfunction in the LVEF ≥ 50%, moving towards a definition that includes (but is not limited to) cardiac structural abnormalities resulting from high filling pressures, diastolic abnormalities, high levels of biomarkers and high left ventricular (LV) filling pressures. 2,3 The risk of HFpEF increases with age. Additional risk factors for the development of HFpEF include hypertension, obesity, and coronary artery disease. HFpEF and atrial fibrillation (AF) are age-related conditions that commonly coexist and share clinical features. At least one third of patients with HFpEF have AF. Therefore, the prevalence of HfpEF has increased with increasing age and epidemics of obesity, hypertension and diabetes. 2,3 HFpEF is associated with high morbidity and mortality. 4 The survival of HFpEF is poor, particularly after hospitalization for HF. In a previous HFpEF epidemiology study, the survival of patients withHFpEF was 35% at 5 years after hospitalization for HF. 5 The prevalence of HFpEF ranges from 31% to 55%. Female gender is an important risk factor for the development of HfpEF, and the reason for this is not clear. However, women may have greater arterial and ventricular stiffness, which can be exacerbated with age. In addition, reproductive hormones may influence LV structure and function and on the response to overload changes. 6 Anotherpoint to stress is thatHFpEF isunderdiagnosed in the general population. Differently fromHFrEF where most of patients are diagnosed, in HFpEF there is a window of opportunities to improve clinical recognition and diagnosis. Recently, the H 2 FPEF, a score based on simple clinical and echocardiographic features to estimate the likelihood of HFpEF among patients with unexplained dyspnea, has been developed. This score includes the following variables: obesity (2 points), ≥ 2 antihypertensives (1 point), atrial fibrillation (3 points), pulmonary artery echocardiographic systolic pressure > 35 mm Hg (1 point), age ≥ 60 years (1 point) and echocardiogram E / e’ > 9 (1 point). 7 HFpEF, in addition to being a syndrome consisting of small left ventricle, significant concentric LVhypertrophy, normal EF, and diastolic dysfunction with reduced LV diastolic compliance, it is a multiorgan disease that involves not only the heart, but also the lungs, skeletal muscle, kidneys and adipose tissue. 8 The pathophysiology of HFpEF is associated with systemic inflammation with subsequent reductions in biological functions of NO (nitric oxide), cyclic guanosine