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Coronary microvascular function in patients with sepsis and myocardial injury: an invasive coronary physiology study
Samantha Lörstad1, Per Åstrand2, Patrik Gille-Johnson3
1Department of Clinical Sciences, Division of Internal Medicine, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden. samantha.rutherford.lorstad@ki.se.
Background:
Myocardial injury is common in sepsis and associated with increased mortality, but its underlying mechanisms remain incompletely understood. Coronary microvascular dysfunction (CMD) has been proposed as a contributor, although in vivo evidence is limited. We characterised coronary microvascular function in patients with sepsis and myocardial injury and its relationship with cardiac troponin release.
Methods:
Consecutive adults with sepsis (Sepsis-3 criteria) and myocardial injury (hs-cTnT ≥ 15 ng/L) were prospectively enrolled between June 2019 and December 2024. Patients underwent coronary angiography, invasive thermodilution-based assessment of coronary microvascular function, and transthoracic echocardiography after clinical stabilisation. CMD was defined as an index of microcirculatory resistance (IMR) > 25 and/or microvascular resistance reserve (MRR) ≤ 3. Associations between hs-cTnT concentrations and coronary microvascular indices, obstructive coronary artery disease (CAD), and echocardiographic variables were assessed using regression analyses. Coronary microvascular indices were compared with those of age-, sex-, and CAD-matched patients with chronic coronary syndrome (CCS) using mixed-effects models.
Results:
Fifty-five patients underwent coronary angiography and 49 completed invasive coronary microvascular assessment. Obstructive CAD was identified in 12/55 (22%). CMD was present in 30/49 (61%). Among these, 8/49 (16%) had elevated IMR only, 9/49 (18%) had functional CMD (MRR ≤ 3 and IMR ≤ 25), and 13/49 (27%) had structural CMD (MRR ≤ 3 and IMR > 25). Restricted cubic spline analyses demonstrated no evidence of associations between hs-cTnT and IMR (overall P = 0.899; non-linearity P = 0.687) or MRR (overall P = 0.987; non-linearity P = 0.954). CMD was associated with a higher prevalence of ventriculo-arterial uncoupling, right ventricular systolic dysfunction, and impaired right ventricular-pulmonary arterial coupling. Patients with sepsis demonstrated reduced coronary microvascular vasodilatory capacity compared with matched CCS controls (MRR 3.2 [IQR 2.4-4.5] vs. 4.0 [2.7-6.2]). IMR was similar between groups.
Conclusions:
CMD was common and heterogeneous and exhibited distinct phenotypes in patients with sepsis and myocardial injury. Measures of coronary microvascular function were not associated with troponin release. Previously unrecognised obstructive CAD was identified in 22% of patients, supporting consideration of underlying CAD in patients with sepsis and myocardial injury.
Trial Registration:
ClinicalTrials.gov identifier NCT06294730.
Insights
Coronary microvascular dysfunction (CMD) is common in sepsis patients with myocardial injury, presenting diverse phenotypes. However, CMD measures did not correlate with troponin levels, suggesting other injury mechanisms.
Area of Science:
- Cardiology
- Intensive Care Medicine
- Pathophysiology
Background:
- Myocardial injury in sepsis is linked to higher mortality, with unclear mechanisms.
- Coronary microvascular dysfunction (CMD) is a suspected contributor, but in vivo data is limited.
- This study investigates coronary microvascular function in sepsis patients with myocardial injury.
Purpose of the Study:
- To characterize coronary microvascular function in sepsis patients with myocardial injury.
- To explore the relationship between CMD, cardiac troponin release, and obstructive coronary artery disease (CAD).
- To compare coronary microvascular function in sepsis patients versus those with chronic coronary syndrome (CCS).
Main Methods:
- Prospective enrollment of adult sepsis patients with myocardial injury (hs-cTnT ≥ 15 ng/L).
- Invasive assessment of coronary microvascular function using thermodilution (IMR, MRR) via coronary angiography.
- Echocardiography and regression analyses to assess associations between hs-cTnT, microvascular indices, CAD, and cardiac function.
Main Results:
- Coronary microvascular dysfunction (CMD) was present in 61% of patients, showing heterogeneous phenotypes (elevated IMR, functional, or structural CMD).
- No association was found between hs-cTnT levels and index of microcirculatory resistance (IMR) or microvascular resistance reserve (MRR).
- Sepsis patients exhibited reduced coronary microvascular vasodilatory capacity compared to CCS controls, with similar IMR.
Conclusions:
- Coronary microvascular dysfunction (CMD) is prevalent and heterogeneous in sepsis with myocardial injury.
- Coronary microvascular function measures were not associated with troponin release.
- A significant proportion (22%) had previously unrecognized obstructive CAD, highlighting its importance in sepsis-induced myocardial injury.
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