Mechanisms of Post-critical Illness Cardiovascular Disease

Abstract

Prolonged critical care stays commonly follow trauma, severe burn injury, sepsis, ARDS, and complications of major surgery. Although patients leave critical care following homeostatic recovery, significant additional diseases affect these patients during and beyond the convalescent phase. New cardiovascular and renal disease is commonly seen and roughly one third of all deaths in the year following discharge from critical care may come from this cluster of diseases. During prolonged critical care stays, the immunometabolic, inflammatory and neurohumoral response to severe illness in conjunction with resuscitative treatments primes the immune system and parenchymal tissues to develop a long-lived pro-inflammatory and immunosenescent state. This state is perpetuated by persistent Toll-like receptor signaling, free radical mediated isolevuglandin protein adduct formation and presentation by antigen presenting cells, abnormal circulating HDL and LDL isoforms, redox and metabolite mediated epigenetic reprogramming of the innate immune arm (trained immunity), and the development of immunosenescence through T-cell exhaustion/anergy through epigenetic modification of the T-cell genome. Under this state, tissue remodeling in the vascular, cardiac, and renal parenchymal beds occurs through the activation of pro-fibrotic cellular signaling pathways, causing vascular dysfunction and atherosclerosis, adverse cardiac remodeling and dysfunction, and proteinuria and accelerated chronic kidney disease.

A random forest model using flow cytometry data identifies pulmonary infection after thoracic injury

“…During critical illness, the immune system and parenchymal tissues might develop a long-lived pro-inflammatory and immunosenescent state 28 . The clinical importance of prior and evolving immune experience in response to trauma has not been fully elucidated.…”

“…The most common thoracic injury pattern was rib fractures (52 of 70 [75.3%]), followed by pneumothorax (40 of 70 ). Median Injury Severity Score for the cohort was 27 (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) with no significant difference between subjects with and without PNA. Median Sequential (Sepsis-related) Organ Failure Assessment and APACHE scores were significantly higher in PNA patients (7 vs. 4 and 20.5 vs. 9.5, respectively; p < 0.01).…”

“…During critical illness, the immune system and parenchymal tissues might develop a long-lived pro-inflammatory and immunosenescent state. 28 The clinical importance of prior and evolving immune experience in response to trauma has not been fully elucidated. Thus, assessing immune phenotypes and their perturbations in young and otherwise immunologically balanced individuals is an ideal setting to understand human responses to trauma and predict clinical trajectories of recovery.…”

Cardiovascular Magnetic Resonance in Survivors of Critical Illness: Cardiac Abnormalities Are Associated With Acute Kidney Injury

“… 2 Immunometabolic changes, sustained inflammatory cascades, and activation of neurohormonal signaling pathways appear to contribute to fibrotic cardiac remodeling, atherosclerosis, and cardiac dysfunction. 3 Specifically, increased exposure to catecholamines, oxidative stress, and altered mitochondrial function were found to be involved in these changes. 3 , 4 In a previous study, biomarkers of cardiac failure were associated with reduced long‐term survival in patients after ICU treatment.…”

The authors reply

“…Alongside the increased prevalence of mechanical ventilation, the increased presence of chronic liver disease, higher inflammatory burden (6), and vasopressor dose (7) may also contribute to the higher use of RRT in HDLVEF cohorts.…”