Rangaswami, Janani

The coronavirus disease 2019 (COVID-19) pandemic is associated with significant morbidity and mortality throughout the world, predominantly due to lung and cardiovascular injury. The virus responsible for COVID-19—severe acute respiratory syndrome coronavirus 2—gains entry into host cells via ACE2 (angiotensin-converting enzyme 2). ACE2 is a primary enzyme within the key counter-regulatory pathway of the renin-angiotensin system (RAS), which acts to oppose the actions of Ang (angiotensin) II by generating Ang-(1–7) to reduce inflammation and fibrosis and mitigate end organ damage. As COVID-19 spans multiple organ systems linked to the cardiovascular system, it is imperative to understand clearly how severe acute respiratory syndrome coronavirus 2 may affect the multifaceted RAS. In addition, recognition of the role of ACE2 and the RAS in COVID-19 has renewed interest in its role in the pathophysiology of cardiovascular disease in general. We provide researchers with a framework of best practices in basic and clinical research to interrogate the RAS using appropriate methodology, especially those who are relatively new to the field. This is crucial, as there are many limitations inherent in investigating the RAS in experimental models and in humans. We discuss sound methodological approaches to quantifying enzyme content and activity (ACE, ACE2), peptides (Ang II, Ang-[1–7]), and receptors (types 1 and 2 Ang II receptors, Mas receptor). Our goal is to ensure appropriate research methodology for investigations of the RAS in patients with severe acute respiratory syndrome coronavirus 2 and COVID-19 to ensure optimal rigor and reproducibility and appropriate interpretation of results from these investigations.

Hyponatremia is a very common electrolyte abnormality, associated with poor short- and long-term outcomes in patients with heart failure (HF). Two opposite processes can result in hyponatremia in this setting: Volume overload with dilutional hypervolemic hyponatremia from congestion, and hypovolemic hyponatremia from excessive use of natriuretics. These two conditions require different therapeutic approaches. While sodium in the form of normal saline can be lifesaving in the second case, the same treatment would exacerbate hyponatremia in the first case. Hypervolemic hyponatremia in HF patients is multifactorial and occurs mainly due to the persistent release of arginine vasopressin (AVP) in the setting of ineffective renal perfusion secondary to low cardiac output. Fluid restriction and loop diuretics remain mainstay treatments for hypervolemic/ dilutional hyponatremia in patients with HF. In recent years, a few strategies, such as AVP antagonists (Tolvaptan, Conivaptan, and Lixivaptan), and hypertonic saline in addition to loop diuretics, have been proposed as potentially promising treatment options for this condition. This review aimed to summarize the current literature on pathogenesis and management of hyponatremia in patients with HF.