Potential systemic inflammatory reactions attributable to mechanical circulatory support in a patient with acute myocardial infarction complicating cardiogenic shock: a case report

Introduction

Background

Cardiogenic shock (CS) still presents a markedly high morbidity and mortality. Around 8% of patients with acute myocardial infarction (AMI) concomitantly presents CS. In particular, those with larger myocardial infarction, multi-vessel disease or the concomitance of mechanical complications are high-risk category who more likely exhibit hemodynamic instability. Despite current guideline-recommended primary percutaneous coronary intervention and medical therapies, their mortality rate is about 50% (1,2). Mechanical circulatory support (MCS) improves worsened hemodynamic condition in patients exhibiting CS. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides potent support for heart and lung perfusions, and microaxial continuous blood flow left ventricular assist device, Impella decompresses the left ventricle and delivers blood flow of up to 5.5 L/minutes (3-5). Despite their clinical efficacies, MCS-related complications affecting clinical outcomes occur. Several published studies showed that the use of VA-ECMO was associated with higher levels of interlukin-6, interlukin-8, interlukin-10, tumor necrosis factor α (TNF-α) (6). Mechanistically, the influx of blood into the membrane oxygenator of VA-ECMO has been considered to activate coagulation and inflammatory cascade. Similar to VA-ECMO, microaxial pump of Impella has been shown to elevate interlukin-6 and white blood cell counts (7). These findings suggest that the use of MCS might cause systemic inflammatory reactions, which could affect clinical outcomes in the setting of CS.

Rationale and knowledge gap

Whether the use of MCS induces the activation of inflammatory responses and then worsens clinical condition has not been fully characterized yet. While circulating inflammatory cytokines have been shown to increase after the use of MCS (6-10), there are no case reports and clinical studies that showed the use of MCS as a major cause for high fever and activated inflammatory reactions in vivo. In our case, serial imaging, multiple evaluation of blood cultures and autopsy were conducted to elucidate the association of MCS with continuing high fever.

Objective

Here, we report a case presenting ST-segment elevation myocardial infarction (STEMI) with CS who required VA-ECMO and Impella 5.5. By integrating multiple approaches, we sought to evaluate whether continuing high fever was driven by simply infectious diseases or the use of MCS. We present this case in accordance with the CARE reporting checklist (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-2025-20/rc).

Case presentation

A 60-year-old gentleman was hospitalized at the tertiary hospital due to acute anterior STEMI complicated by CS. He had a history of type 2 diabetes mellitus and chronic kidney disease. His initial Society for Cardiovascular Angiography and Interventions (SCAI)-shock stage was D. Following the commencement of circulatory support with VA-ECMO and intra-aortic balloon pump (IABP), primary percutaneous coronary intervention was successfully conducted to treat the occlusion of his left main trunk. Due to severe myocardial damage (creatine phosphokinase 9,825 U/L, creatine phosphokinase-myocardial band 1,146 U/L), his left ventricular ejection fraction on echocardiography was 10%. Moreover, he exhibited a continuing rise of lactate level (7.3 mmol/L) with low mixed venous oxygen blood saturation (SvO₂) (57%). He was transferred to National Cerebral & Cardiovascular Center for further therapeutic managements.

After hospitalization at National Cerebral & Cardiovascular Center, we decided to escalate MCS due to his refractory CS status under the use of both VA-ECMO and IABP (blood pressure =74/72 mmHg, heart rate =80 bpm/min, lactate =5.1 mmol/L, SvO₂ =55%). While VA-ECMO continued to be used, IABP was removed and then Impella 5.5 (Abiomed, Danvers, MA, USA) was surgically inserted from his right brachiocephalic artery by using vascular graft. Following the use of Impella 5.5, his lactate level decreased to 1.0 mmol/L with normal SvO₂ level (65%). Heat exchanger was used to maintain his body temperature with 37.0 ℃, and his C-reactive protein (CRP) level and systemic vascular resistance (SVR) calculated by Swan-Gantz catheter were 0.32 mg/dL and 3,150 dyne-sec/cm⁵, respectively (Table 1). Any infection was not identified by computed tomography (CT) on day 1 (Video 1). On day 4, shivering occurred and then his SVR decreased to 1,550 dyne-sec/cm⁵ with an elevated CRP level (24.9 mg/dL) (Table 1). Any abnormalities suggestive of infection were not observed, and his fever was 37.0 ℃ under the use of heat exchanger. Moreover, twice blood cultures were negative. Given that infectious signs were not evident, meropenem 3 g/day and vancomycin 2 g/day with deep sedation were empirically commenced. After these managements, his shivering had been dissolved and SVR was improved (1,950 dyne-sec/cm⁵). However, he continued to show high CRP level (Figure 1). Full-body CT scan on day 10 did not identify any abnormalities suggesting infection (Figure 2, Video 2).

Figure 1 Clinical course of this case. CRP, C-reactive protein; VA-ECMO, veno-arterial extracorporeal membrane oxygenation.

Figure 2 Serial full-body computed tomography scans. (A) Lung section. (B) Epigastric section. (C) Lower abdominal section. (D) Pelvic section.

On day 14, since his left ventricular ejection fraction improved (15%), VA-ECMO was surgically removed. Then, his body temperature gradually rose from 37.0 to 38.5 ℃ 2 hours after the removal of VA-ECMO. Furthermore, declines of SVR (1,380 dyne-sec/cm⁵), blood pressure (45/38 mmHg) and SvO₂ (53%) were observed, accompanied by an elevated lactate level (2.2 mmol/L) (Figure 1). He still exhibited an elevated CRP level on day 14 (19.4 mg/dL). Full-body CT scan on day 14 did not show any infectious causes and thromboembolic abnormalities (Figure 2, Video 3). Due to the potential association of medication with high fever, omeprazole, amiodarone, propofol, meropenem and vancomycin were discontinued. However, high fever continued. The blood transfusion was conducted 24 hours before the removal of VA-ECMO, and vital signs did not change during this transfusion. After the removal of VA-ECMO, the blood transfusion was not undertaken. Noradrenaline was commenced to maintain his blood pressure, and Swan-Ganz catheter was removed. Re-evaluation of blood cultures on day 16 showed the absence of any definitive bacteremia and any infectious signs on CT (Video 4). Antibiotic escalation with micafungin 100 mg/day and hydrocortisone 200 mg/day was conducted. However, his high fever still continued and we commenced vasopressin, but his shock status further worsened (Figure 1). He passed away on day 18 after hospitalization. An autopsy was performed 12 hours after his death. Macroscopic evaluation did not reveal any evidence causing his continuing high fever after the removal of VA-ECMO. With regard to his heart valves, macroscopically and microscopically, no vegetation associated with infective endocarditis was observed (Figure 3). Hematoma existed around the surgically anastomosed graft for the insertion of Impella 5.5. However, it did not show any infectious signs. On microscopic evaluation, there were no abnormalities suggesting infections around the anastomosed graft (Figure 3). While there were no inflammatory signs at lungs and kidneys, swelling of spleen and microthrombus at his mitral valve were observed.

Figure 3 Autopsy images. (A) Right ventricular outflow tract (white dotted rectangle indicates PV). (B) Left ventricular outflow tract (white dotted rectangle indicates AV). (C) Right ventricular inflow tract (white dotted rectangle indicates TV). (D) Left ventricular outflow tract (white dotted rectangle indicates MV). (E) Macroscopic evaluation of anastomosed vascular graft (white arrow indicates vascular graft; dotted white arrow indicates hematoma without any infections evidence). AV, aortic valve; LA, left atrium; LV, left ventricle; MV, mitral valve; PA, pulmonary artery; PV, pulmonary valve; RA, right atrium; RV, right ventricle; TV, tricuspid valve.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report, accompanying images and videos. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Key findings

In our case, continuing high fever and elevated CRP level after the removal of VA-ECMO was observed. Since serial CT (Video 1), multiple evaluation of blood cultures and autopsy did not detect any abnormality suggestive of infection, this case may reflect systemic inflammatory reaction syndrome driven by the insertion of MCS.

Strengths and limitations

The strength of this case report is that multiple evaluation was conducted to elucidate causes for continuing high fever after the removal of VA-ECMO. In addition to serial CT imaging and repeated evaluation of blood cultures, autopsy was undergone to further investigate infectious signs. These meticulous approaches enabled us to identify MCS-related systemic inflammatory reaction as a potential cause of high fever in our case. Given that there are no case reports and studies conducting autopsy to elucidate the association of MCS use with systemic inflammatory reactions, our case study provides clinical insights into activated inflammatory responses attributable to the use of MCS in patients presenting CS.

One of limitations in our case is that any inflammatory cytokines were not measured. Since elevated levels of interleukin-6, interlukin-8, interlukin-10 and TNF-α have been reported in patients who received MCS (6), serial measurement of inflammatory biomarkers may help to diagnose systemic inflammatory reactions driven by the use of MCS in our case (11,12). Another limitation is that the association of Impella 5.5 with continuing high fever remains unknown. Autopsy did not show any infectious signs around the surgically anastomosed graft for the use of Impella 5.5. Considering that the use of Impella has been reported to associate with an elevated level of interlukin-6 and procalcitonin, and white blood cell counts (7), this MCS might also affect systemic inflammatory reactions in our case. Diagnostic criteria of MCS-related systemic inflammatory reactions have not been established yet. There is no clinical evidence about appropriate timing and approach for the evaluation of MCS-related systemic inflammatory reactions. While measurements of biomarkers might be applicable to diagnose MCS-related systemic inflammatory reactions, whether biomarker-based approach clinically helps to identify activated inflammation driven by the use of MCS remains to be determined. Novel therapies modulating interleukin-6 has been recently developed. This agent significantly lowered circulating interleukin-6 levels (13). However, whether anti-inflammatory therapy is effective in patients with MCS-related systemic inflammatory reactions remains unknown.

Comparison with similar research

To date, there is no case reports and studies that demonstrated the occurrence of systemic inflammatory reactions attributable to the use of MCS. In our case, autopsy enabled us to evaluate infectious causes and inflammatory responses. More efforts and studies are needed to develop non-invasive approach such as molecular imaging and biomarkers for the diagnosis and management of MCS-related systemic inflammatory responses.

Explanations of findings

The use of VA-ECMO has been reported to associate with activation of inflammation. In vitro study using a neonatal extracorporeal life support system evaluated how roller pump of extracorporeal life support system could stimulate the secretion of inflammatory cytokines (6). In this study, elevated levels of TNF-α, interleukin-6 and interleukin-8 were observed in association with the use of roller pump. Furthermore, other in vivo studies reported the activation of the complement pathway after the insertion of VA-ECMO (14,15). These observations indicate VA-ECMO as a potential trigger to activate a variety of inflammatory responses through the exposure of patient’s blood to the VA-ECMO circuit. In our case, while we did not measure levels of inflammatory cytokines, a continuing high CRP level was observed after day 4. Considering that any features suggesting infection were not evident despite high fever and elevated CRP level (Table 1), it could be speculated that clinical course in our case may reflect MCS-related systemic inflammation.

The activation of the coagulation cascade has been considered as another response caused by VA-ECMO circuit. In particular, when patient’s blood contacts with VA-ECMO circuit, the activation of factor XII occurs, which leads to producing nitric oxide, TNF-α and interleukin-10 (6). As such, VA-ECMO-related progression of the coagulation cascade could also associate with responses of multiple inflammatory pathways. In our current case, how much the aforementioned coagulation cascade was activated remains unknown. However, both thrombin-antithrombin III (27.4 ng/mL) and D-dimer (15.2 µg/mL) levels on day 14 were elevated. These features might partly reflect the VA-ECMO-related effects on coagulation cascade.

Activated and prolonged inflammatory reaction caused by MCS could induce vascular endothelial damage, microcirculatory disorders and organ damage, which substantially affects clinical course (6). In our case, an elevated CRP level persisted to exist, although there were no evident signs associated with infections. Given that hemodynamic and clinical conditions worsened under continuing inflammatory reactions, our case might represent systemic inflammatory response syndrome (SIRS) due to the use of MCS.

Implications and actions needed

Several studies reported that the use of MCS was associated with elevated levels of inflammatory cytokines. For instance, the use of VA-ECMO has been shown to increase interleukin-6, interleukin-8, interleukin-10, TNF-α and white blood cells (6). Moreover, one mechanistic study using a porcine model revealed that the use of both VA-ECMO and Impella further increased circulating interleukin-6, interleukin-8, TNF-α, and serum amyloid A levels (16). These observations indicates that measurement of inflammatory biomarkers may help to identify the occurrence of MCS-related systemic inflammatory reactions. In the current study, while CRP level was elevated, other inflammatory biomarkers were not measured. Further investigation is required to elucidate whether evaluation of inflammatory biomarkers enable to differentiate sepsis from MCS-related inflammation.

One recent study reported that interlekin-6 levels increased after the insertion of Impella 5.5 (5). Additionally, one mechanistic study using a porcine model revealed that the use of both VA-ECMO and Impella further increased circulating interleukin-6 and interleukin-8, TNF-α, and serum amyloid A levels (16). These findings suggest the use of Impella 5.5 as another potential contributor to systematic inflammation in our case. To date, there is no study which has directly compared serial changes in inflammatory cytokines levels between these two devices. Future studies are warranted to investigate whether inflammatory reactions vary according to the type of MCS.

Our case highlights the importance of differential diagnosis of high fever after the use of MCS. Evaluation of infectious causes is a first step in the critical care settings. In parallel, it is important for physicians to consider MCS-related systemic inflammation as a potential another cause of high fever. Measurement of inflammatory biomarkers such as interleukin-6 might help to diagnosis it. The removal of VA-ECMO has to be considered to manage its systemic inflammatory reaction. Whether therapeutic approaches modulating inflammatory cytokines improves outcomes in patients with MCS-related systematic inflammatory reactions requires future clinical studies.

Conclusions

Our case exhibited continuing high fever and elevated CRP level. Given that serial CT scans and autopsy did not find any infectious signs, the use of MCS might cause systemic inflammatory responses, ultimately resulting in further deterioration of hemodynamic conditions. Combination of serial CT imaging, blood cultures and autopsy helped to diagnose MCS-related systemic inflammatory responses in our case. Since diagnostic criteria and appropriate diagnostic tools have not been established yet, diagnosis and management of MCS-related systemic inflammatory reactions are challenging. Further studies are required to develop diagnostic approach and effective therapeutic managements for activated inflammatory responses attributable to MCS use. Whether anti-inflammatory agents are effective for MCS-related systemic inflammatory reactions needs future dedicated studies.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-2025-20/rc

Peer Review File: Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-2025-20/prf

Funding: This work was supported by Taiju Life Social Welfare Foundation Research Grant (No. 2024) and Terumo Life Science Foundation Research Grant (No. 2024).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-2025-20/coif). Y.K. has received research support from Kowa, Nipro and Abbott, and honoraria from Nipro, Abbott, Kowa, Amgen, Sanofi, Astellas, Takeda, Novartis and Daiichi-Sankyo. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report, accompanying images and videos. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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