Cardiovascular events complicate condition of sepsis patients

Cardiovascular events (CVEs) pose more problems in half of critically ill patients with sepsis, with nearly four in five developing CVEs within the first week of hospitalization, leading to longer intensive care unit (ICU) and hospital length of stay (LOS), a Singapore study has shown.

“The number of critically ill patients is expected to rise with an ageing population and cause a further strain on healthcare resources,” the researchers said. “Awareness of the association between sepsis and CVEs presents a potential opportunity for earlier recognition of CVEs.”

In this retrospective cohort study led by Sharlene Ho, critically ill patients admitted to the medical ICU between July 2015 and October 2016 were analysed. Intra-hospital CVEs were the primary outcomes, while in-hospital mortality, ICU and hospital LOS were secondary.

CVEs occurred more frequently among patients with sepsis (n=662) than those without (52.9 percent vs 23.0 percent; p<0.001). [Ann Acad Med Singap 2022;51:272-282]

Of the sepsis patients, 350 (52.9 percent) had one or more CVEs: 59 (8.9 percent) acute coronary syndrome, 198 (29.9 percent) type 2 myocardial infarction (MI), 124 (18.7 percent) incident atrial fibrillation (AF), 76 (11.5 percent) new or worsening heart failure (HF), 32 (4.8 percent) cerebrovascular accident, and 33 (5.0 percent) cardiovascular death.

The following factors correlated with a higher risk of CVEs: age (adjusted relative risk [aRR], 1.013, 95 percent confidence interval [CI], 1.007‒1.019), ethnicity (Malay: aRR, 1.214, 95 percent CI, 1.005‒1.465) and Indian: aRR, 1.240, 95 percnet CI, 1.030‒1.494, when compared to Chinese), and comorbidity of ischaemic heart disease (aRR, 1.317, 95 percent CI, 1.137‒1.527).

A total of 278 patients (79.4 percent) developed CVEs within the first week of hospitalization. These patients had a longer median LOS in the ICU (6 vs 4 days; p<0.001) and in the hospital (21 vs 15 days; p<0.001) compared to those without CVEs. However, no difference was noted in in-hospital mortality between the two groups (46.9 percent vs 45. Percent; p=0.792).

“The majority of CVEs occurred early during hospitalization,” the researchers said. “This temporal pattern of cardiovascular risk being the highest immediately after the onset of respiratory infection was observed previously.” [Circulation 2012;125:773-781; N Engl J Med 2019;380:171-176]

With regard to the types of CVEs, type 2 MI was the most common, followed by AF and HF. About one in five (20.4 percent) patients with sepsis had two or more types of CVEs. This was consistent with previous studies where 20‒40 percent of patients developed at least two cardiac complications. [Circulation 2012;125:773-781; Lancet 2013;381:496-505]

“Several other mechanisms have been proposed to explain the pathogenesis of CVEs in sepsis,” according to the researchers.

For instance, sepsis causes systemic inflammation and cytokine release, resulting in micro- and macro-circulatory changes, as well as direct impact on cardiomyocytes. [Lancet 2013;381:496-505; Am J Respir Crit Care Med 2020;202:361-370]

In addition, sepsis triggers myocardial dysfunction with reduction in stroke volume, which further complicates shock. Cardiac arrhythmias, particularly AF, also potentially exacerbates demand ischaemia, causes HF, and contributes to cardioembolic stroke. [J Intensive Care 2016;4:22; JAMA 2011;306:2248-2254]

“Other factors that have been implicated in the development of CVEs include excessive neurohormonal activation, direct cytotoxic effect of microorganism, and modulating effect of treatments (eg, water and sodium balance and arrhythmogenic potential of certain medications),” the researchers said. [Clin Respir J 2018;12:2212-2219; Circulation 2007;116:793-802]

“Future research is needed to develop preventive strategies and effective therapeutics to improve the outcomes of these patients,” they noted.