According to the American College of Cardiology, Heart Failure (HF) Syndrome is defined as a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. The etiological agent of the clinical syndrome of HF may result from different causes, which impact the prognosis and impose the necessity for specific treatment strategies, underlining the relevance of specific data elements for emphasizing these differences in HF, including the time course evolution of HF. This view is similar to the current Brazilian guideline for HF. Despite improvement in HF treatment and management, with a reduction in overall mortality rate over time, the death number and economic costs are still high. In 2014 a deep revision including 197 countries showed that HF’s overall global economic cost in 2012 was estimated at $108 billion per annum. Importantly, HF spending was largely different in high-income, middle, and low-income countries. For example, between 2014-2020, the annual median total medical costs for heart failure care were estimated at $24,383 per patient in the United States of America, meanwhile in Brazil in 2015, the average cost per patient with HF was 1,569 US$, taking into account the exchange rate in 2015. The high cost per patient is probably related to the lack of effective therapies to improve human health during HF. Then unveiling the molecular basis of cardiac remodeling found in the disease is one of the main challenges in cardiovascular medicine.

In the last years, significant advances in understanding molecular mechanisms of adaptive and maladaptive hypertrophy and heart failure in response to stress signals have shown that many extracellular factors and signaling pathways are involved in the remodeling of cardiomyocytes, the working cells found in the heart tissue. Since the time course of HF is etiological-dependent, it is fundamental to understand how the HF syndrome develops. For example, the intracellular dynamics of Ca²are modified in the different etiologies of HF with reduced (HFrEF) or preserved (HFpEF) ejection fraction. In animal models of diabetic or hypertensive HFpEF and HFrEF, studies have shown that magnitude and kinetics of Ca²release remain unchanged in both HFpEF models but impaired in HFrEF. Although Sarco/endoplasmic reticulum Ca²adenosine triphosphatase-2a (SERCA) protein density was reduced in these HFrEF and HFpEF models, in the HFpEF model for hypertension, this is offset by increased PLB phosphorylation (Phospholamban is a protein able to modulate SERCA2A), but not in diabetic HFrEF and HFpEF resulting in delay intracellular Ca²reuptake by SERCA.

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