Cardiovascular Subphenotypes in ARDS: Diagnostic and Therapeutic Implications and Overlap with Other ARDS Subphenotypes

Abstract

Acute respiratory distress syndrome (ARDS) is a highly heterogeneous clinical condition. Shock is a poor prognostic sign in ARDS, and heterogeneity in its pathophysiology may be a barrier to its effective treatment. Although right ventricular dysfunction is commonly implicated, there is no consensus definition for its diagnosis, and left ventricular function is neglected. There is a need to identify the homogenous subgroups within ARDS, that have a similar pathobiology, which can then be treated with targeted therapies. Haemodynamic clustering analyses in patients with ARDS have identified two subphenotypes of increasingly severe right ventricular injury, and a further subphenotype of hyperdynamic left ventricular function. In this review, we discuss how phenotyping the cardiovascular system in ARDS may align with haemodynamic pathophysiology, can aid in optimally defining right ventricular dysfunction and can identify tailored therapeutic targets for shock in ARDS. Additionally, clustering analyses of inflammatory, clinical and radiographic data describe other subphenotypes in ARDS. We detail the potential overlap between these and the cardiovascular phenotypes.

Keywords: acute respiratory distress syndrome; latent class analysis; right ventricular dysfunction; right ventricular failure; subphenotypes; transthoracic echocardiography.

Figure 1

Pathophysiology of cardiovascular subphenotypes in ARDS. Numbers indicate step-wise transition from baseline (1) to deranged physiology (2,3,4). PHTN = pulmonary hypertension; RV = right ventricular; Ees = end-systolic elastance; Ea = arterial elastance; LV = left ventricular; CO = cardiac output; PEEP = positive end-expiratory pressure; MV = mechanical ventilation; iNO = inhaled nitric oxide; regurg = regurgitation; circ = circulation; BF = blood flow; anti-inf = anti-inflammatory; SVR = systemic vascular resistance; IL = interleukin; TNF = tumour necrosis factor. Created with Biorender.com (accessed on 27 November 2022).

Figure 2

Potential overlap between ARDS subphenotypes/subgroups. Four different domains of subphenotypes/subgroups are identified (1. systemic inflammation, 2. cause or risk factor for ARDS, 3. cardiovascular and 4. lung morphology/respiratory). The high risk of mortality subphenotypes from these domains, identified in red shading, overlap in some aspects: systemic/endothelial inflammation (inflam), diffuse lung injury (inj), shock/vasopressor requirement (VP req), metabolic acidosis/low bicarbonate (bicarb) levels, extrapulmonary (extrapulm) sepsis, acute kidney injury (AKI) or renal replacement therapy (RRT) and multiorgan dysfunction syndrome (MODS). Created with Biorender.com (accessed on 28 November 2022).