Expert Consensus Statement on the Evaluation, Treatment, and Transfer of Cardiogenic Shock Using a Delphi Method Approach　― A Report of the Japan Critical Care Cardiology Committee (J4CS) ―

Recent advances in pharmacological agents and mechanical circulatory support (MCS) have led to significant progress in the treatment of patients with cardiogenic shock (CS); however, mortality remains high. According to reports analyzing nationwide clinical data, CS-related in-hospital or 30-day mortality due to acute myocardial infarction remains high, at approximately 33–42% in Japan and 27–51% in Europe and North America.^1–3 Historically, CS treatment has largely depended on the individual experiences of facilities and clinicians. Recently, various countries have been making efforts to standardize CS treatment. A significant challenge in CS management in critical care cardiology practice is the rapid progression of the disease in a short period. We believe that a standardized approach in this area can improve survival rates through prompt decision-making and intervention. Therefore, this expert consensus aims to propose a management algorithm for CS focusing on the early phase. Given the limited evidence on CS and the small sample size of studies from Japan, this consensus refrains from addressing recommendation levels and presents the treatment algorithm as an expert consensus.

This consensus is intended for use by various professionals engaged in critical cardiology care, encouraging dialog, continuous revisions, and standardization of CS treatment.

Methods

This study aimed to develop an algorithm for the evaluation, treatment, and transfer of patients suspected of or with CS along the timeline from the point of suspicion to care in a cardiac intensive care unit (CICU) or cardiovascular intensive care unit (CVICU). To develop this consensus, a group of 9 expert panelists (T.N., T.K., J.N., K.S., S.K., M. Kuwabara, T.Y., M. Kikuchi, and N.S.) with specializations in emergency cardiovascular care and critical care recommended by the Emergency and Intensive Care Medicine Division of the Japanese Circulation Society (JCS) convened and established the Japan Critical Care Cardiology Committee (J4CS). The expert panelists were approved by the Emergency and Intensive Care Medicine Division on May 16, 2023, and by the JCS Board of Directors on June 9, 2023; a kickoff meeting was held on July 19, 2023. The workflow of discussions for the consensus decision is shown in Figure 1.

Figure 1.

Workflow for the expert consensus. CICU, cardiac intensive care unit; JCS, Japanese Circulation Society; JSICM, Japanese Society of Intensive Care Medicine.

Comprehensive Listing of Items for the CS Management Statement

The items for the CS management statement were listed comprehensively, referencing the treatment protocols of each facility, literature reviews, and panelist experience. Each item was divided into 3 phases along the management timeline for CS: Step 1, scene; Step 2, emergency department (ED); and Step 3, CICU. Additional measures to be considered at each phase included invasive testing/treatment and consultation/transfer to an advanced shock center.

Discussion and Determination of Consensus by the Delphi Method

The significance of each item in the statement list was evaluated using a modified Delphi method, which is particularly beneficial in fields where evidence is lacking and uncertainty prevails.^4,5 Each panelist scored the items on a 9-point scale, with 1 representing “inappropriate” and 9 representing “appropriate.” In the consensus conference after the first round of voting, the clinical significance of each item and the reasons for the wide variations in the scoring of items were discussed. After the consensus conference, the scores in the second round of voting were collected again and used as the final scores. Items were deemed inappropriate if the median score was ≤3.5, uncertain if the median score was 3.5–6.5, and appropriate if the median score ≥6.5.⁶ Items deemed appropriate were incorporated into the final algorithm.

This evaluation, while following the RAND method recommendation of including ≥7 participants, consists of a relatively small group, raising concerns regarding potential bias.⁷ However, when a relatively homogeneous group of field experts is gathered, a group of 9 can achieve an average group error of less than 0.6 and reliability coefficient close to 0.7.⁸ In the present study, to mitigate bias, panelists were selected from: (1) domestic and international institutions to avoid geographic concentration; (2) various institutions, including academic and community hospitals; and (3) a wide array of subspecialities, such as interventional cardiology, heart failure, clinical research, and public health. To ensure objectivity, the Delphi method was used for the evaluation, with each panelist submitting independent votes via email.

Consensus

We propose a management algorithm for CS along the timeline, consisting of 3 key steps: Step 1, first medical contact (FMC) at the scene; Step 2, initial response at the ED; and Step 3, management at the CICU. The proposed algorithm is structured to achieve specific goals at each step by executing the tasks and advancing through the steps along the timeline (Figure 2). If necessary, an Additional Step may be included: advanced assessment and treatment, and/or consultation with or transfer to an advanced shock center. Because CS is a severe condition necessitating early hemodynamic stabilization, it is not necessary to complete all items in each step if sufficient information or treatment is available to advance to the next step. The focus should be on advancing through the steps promptly without delay, keeping the overall timeline for management.

Figure 2.

Algorithm for cardiogenic shock. The left-hand side arrow from the top to the bottom represents target times for the general management of a patient with cardiogenic shock. The management timeline is divided into 3 stages: Step 1, first medical contact (FMC) at the scene; Step 2, initial response in the emergency department (ED); and Step 3, management at the cardiac intensive care unit (CICU). Consultations or patient transfers should be considered at any time point, if achieving the current or the next step’s goals will be challenging at the current facility. ¹The scene was assumed to involve both prehospital and in-hospital settings. ²The “ED boarding time” refers to the time interval from hospital arrival to discharge from the ED, corresponding to the door-in, door-out time. ³At any stage of shock management, transfer to a facility that can provide cardiovascular intensive care should be considered. ⁴The need to transfer a patient to the laboratory should be carefully evaluated, considering the associated risks. ⁵If ST-elevation myocardial infarction is suspected, the goal is to achieve FMC to device (FMC2D) time within 90 min. ⁶If the heart rate (HR) falls outside the presented range, HR may be considered as an indicator of potential shock or treatment responsiveness. However, this does not necessarily imply the need for intervention. In addition, if arrhythmia is detected, the potential effect of interventions during ongoing shock should be evaluated carefully. ⁷The target cardiac index (CI) and pulmonary capillary wedge pressure (PCWP) values correspond to the Forrester classification, except in cases where the patient’s medical history provides additional insights. Although pulmonary artery pressure (PAP) and right atrial pressure (RAP) are important indicators for understanding hemodynamics and pathophysiology, no target values were provided because achieving the goals of other parameters is prioritized during shock management. ABG, arterial blood gas; ACS, acute coronary syndrome; BNP, B-type natriuretic peptide; BP, blood pressure; CAG, coronary angiogram; CCL, cardiac catheterization laboratory; CPO, cardiac power output; Cr, creatine; CT, computed tomography; cTn, cardiac troponin; CVC, central venous catheter; ECG, electrocardiogram; ECMO, extracorporeal membrane oxygenation; FDP, fibrin degradation products; FM, fulminant myocarditis; HR, heart rate; IABP, intra-aortic balloon pump; LFTs; liver function tests; MBP, mean blood pressure; MCS, mechanical circulatory support; MV, mechanical ventilation; NIV, non-invasive ventilation; PAC, pulmonary artery catheter; PCI, percutaneous coronary intervention; PVAD, percutaneous left ventricular assisted device; RFTs, renal function tests; RR, respiratory rate; SBP, systolic blood pressure; SCAI, Society for Cardiovascular Angiography and Interventions; SvO₂, mixed venous oxygen saturation.

Definition of CS

CS is defined as “a life-threatening condition in which inadequate cardiac output due to cardiac dysfunction results in hypoperfusion and hypoxia in end organs and tissues, potentially leading to organ failure and death.” Historically, CS has been defined by classical signs alone; however, the importance of evaluating its severity has increased with advances in critical care. The CS classification proposed by the Society for Cardiovascular Angiography and Interventions (SCAI) is considered useful for evaluating the severity of shock.^9,10

Discussion of the Consensus

Eleven objective signs of suspected CS were reviewed, all of which were rated as appropriate in the final round (Table 1). Hypotension was consistently rated as the most important finding, with a score of 9; however, hypotension is not always necessary for diagnosing CS. Altered mental status and cold extremities were rated highly (scores of 8). Specific cut-off values for these signs were discussed. The consensus is consistent with previous guidelines, expert consensus statements, and randomized trials regarding the diagnostic and treatment indicators of CS, other forms of shock, and acute myocardial infarction.

Table 1.

Signs Suggestive of Cardiogenic Shock

Statement	Median score	IQR	Recommendation	Evidence (references)
Signs presumed to indicate hemodynamic instability
SBP <90 mmHg, or MAP <65 mmHg, or decrease ≥40 mmHg from baseline	9	8–9	Appropriate	45, 46
Heart rate <50 and ≥120 beats/min	8	7–8	Appropriate	47
Respiratory rate ≥22/min	8	7–8	Appropriate	48
SpO2 <90%	8	7.75–8	Appropriate
Physical findings
Acute alteration of mental status	8	7–9	Appropriate	47
Clammy skin	7	6–7.5	Appropriate	47
Cool extremities	8	7–8	Appropriate	47
Skin pallor	7	6.75–8.25	Appropriate
Delayed capillary refilling time (>2 s)	7	7–8.25	Appropriate	49
Mottled sign	7	7–8	Appropriate	50–52
Oliguria	7.5	7–8	Appropriate	47
Others
Presence of chest pain, dyspnea, or backache	7.5	6–8.25	Appropriate
Presence of cardiac arrest	8	7.75–9	Appropriate

IQR, interquartile range; MAP, mean arterial pressure; SBP, systolic blood pressure.

Step 1: FMC at the Scene

This step assumes the scenario of initial contact with a patient by emergency medical services in the case of out-of-hospital onset (Figure 2). It can also be applied to the initial situation when in-hospital onset is detected by medical staff as a result of a patient’s worsening condition. This step aims to: (1) recognize the possibility of CS early; and (2) implement initial management before arrival at the ED.

Recognition of the possibility of CS requires the assessment of CS signs based on vital signs and physical findings (including non-cardiogenic causes) and identification of more specific conditions, such as chest symptoms or cardiac arrest, which strongly indicate CS (Figure 2). If any one of these findings is observed, it should be considered a “suspected CS” situation. The key point of this step is to avoid undertriage, where CS is either not recognized or its recognition is delayed, leading to no or delayed treatment. If CS is suspected, selecting a hospital capable of managing CS is encouraged. In addition, performing and transmitting a prehospital 12-lead electrocardiogram (ECG) to the receiving hospital may allow for the early activation of the catheterization laboratory before the patient arrives, thus facilitating smoother progression through Step 2 and beyond.

Discussion of the Consensus

In this step, 4 points to be considered before arrival at hospital in cases of out-of-hospital onset, all of which were deemed appropriate, were primarily discussed (Table 2). First, the signs of suspected CS presented in Table 1 should be assessed. There was consensus that selecting an appropriate hospital for the transport of patients with CS could potentially improve patient outcomes. A multicenter observational study, which included patients transferred to percutaneous coronary intervention (PCI)-capable hospitals, reported that in ST-elevated acute coronary syndrome (ACS) with CS, a 10-min delay in PCI was associated with increased mortality.¹¹ Conversely, a randomized controlled trial (RCT) involving one-quarter of patients with CS across 35 facilities found no significant difference in 30-day all-cause mortality between direct routing to a cardiac arrest center and interhospital transfer via the nearest hospital with an ED in patients without ST elevation following return of spontaneous circulation.¹² Therefore, patients with CS secondary to ACS should preferably be transported to a PCI-capable hospital. The acquisition and transmission of a prehospital 12-lead ECG may improve short-term outcomes in acute myocardial infarction; however, because of insufficient evidence for CS, this statement was rated as appropriate with a lower score (7 points).¹³ Early activation of the catheterization laboratory was considered important; however, evidence is still awaited to determine whether direct patient transport to the catheterization laboratory, bypassing the ED, is more beneficial than transport through the ED.¹⁴

Table 2.

First Medical Contact at the Scene: Step 1

Statement	Median score	IQR	Recommendation	Evidence (references)
Assessment of signs of hemodynamic instability (see Table 1)	9	8–9	Appropriate
Hospital selection	8	7.75–8.25	Appropriate	1, 53–56
Prehospital 12-lead ECG	7	6.75–7.5	Appropriate	13
Early activation of the CCL	8	6.75–9	Appropriate	14

CCL, cardiac catheterization laboratory; ECG, electrocardiogram; IQR, interquartile range.

Step 2: Initial Response in the ED

This step assumes patient management in the ED (Figure 2). Depending on the facility’s protocol, it may also include direct transfer to the cardiac catheterization laboratory. In the case of in-hospital onset, this step corresponds to the next actions after recognizing a “suspected CS” situation in a ward. This step aims to: (1) diagnose CS; (2) assess the pathophysiology, cause, and severity of the CS; and (3) initiate initial CS treatment.

The items necessary for diagnosing CS include re-evaluating the shock signs in Step 1, taking a medical history, and performing various tests to identify the cause. Although CS is diagnosed comprehensively based on these items, until CS is ruled out patients should be managed as having a CS. The items used to diagnose CS also serve to assess its pathophysiology, cause, and severity. Based on these assessments, initial treatment consisting of inotropic/vasoactive agents, airway management, and respiratory support should be initiated as necessary. Upon confirmation of the signs of shock, a multidisciplinary shock team should be activated. The tasks in Step 2 must be completed within 30 min. Processes in certain cases advance directly from Step 2 to Step 3; however, if coronary angiography or MCS is thought to be required, management should proceed to the Additional Step.

Discussion of the Consensus

Of the 29 items considered for Step 2, 26 were deemed appropriate and the remaining were classified as uncertain (Table 3). The primary items for re-evaluating CS signs are outlined in Step 1 (Table 1); however, this focuses on more complex physical findings, such as skin pallor, delayed capillary refill time, and mottled sign. Among the tests, the 12-lead ECG received the highest score of 9 points, which an aim of obtaining it within 10 min of arrival in the ED, consistent with the recommendations of the acute myocardial infarction guidelines.¹⁵ Other tests necessary for assessing the severity and underlying causes of shock in Step 2 include cardiac ultrasound, chest X-ray imaging, blood gas analysis, and blood biochemistry. Lactate levels were highly valued for assessing organ dysfunction, scoring 9 points. Regarding the initial treatment, a previous consensus statement requires that endotracheal intubation should not be delayed in cases of increased work of breathing, decreased consciousness, or difficulty in maintaining or protecting the airway.¹⁶ However, in patients with CS, caution is required for the possibility of sudden hemodynamic changes after the procedure, and an environment equipped to manage these changes is preferred. Inotrope/vasoactive agents and respiratory support should be applied as needed. The insertion of an arterial line and central venous line was also considered; however, in this step, these procedures were not prioritized and were marked as uncertain. Fluid challenge was also discussed; although it may be effective in some conditions, many CS patients already have high left ventricular end-diastolic pressure, leading to a consensus of uncertainty. To rapidly achieve the goals of this step, the activation of a shock team to mobilize resources and the omission of unnecessary tests to prevent treatment delays were strongly recommended. The time frame for achieving the goals of Step 2 was discussed, with 30 min receiving the most agreement, aligning with the door-in to door-out time.¹⁷

Table 3.

Initial Response in the Emergency Department: Step 2

Statement	Median score	IQR	Recommendation	Evidence (references)
Reassessment of the signs of hemodynamic instability (see Table 1)	9	8–9	Appropriate
12-Lead ECG within 10 min after patient arrival to identify ACS	9	8.75–9	Appropriate	57
Echocardiography to assess the clinical phenotype and etiology	8	8–9	Appropriate	58
Chest X-ray imaging to assess the clinical phenotype and etiology	8	7–9	Appropriate
Arterial blood gas test
pH	8	7.75–8.25	Appropriate	59, 60
Lactate	9	8.75–9	Appropriate	40, 41, 60, 61
Biochemical markers
Cardiac troponin	8	7.75–9	Appropriate	62–64
BNP	7	3.75–8	Appropriate
Creatinine	8	6–8	Appropriate	65
Liver function test	7.5	6–8	Appropriate	66
D-dimer/FDP	6.5	5–8	Appropriate
Intervention
Endotracheal intubation should not be delayed if there is increased work of breathing, diminished consciousness, and inability to maintain or protect the airway	9	7–9	Appropriate	16
Oxygen supplementation, NIV, and MV in cases of low or inadequate oxygenation	9	7–9	Appropriate	67–70
Inotrope/vasopressor in cases of hemodynamic instability with a low or inadequate cardiac output	8	8–9	Appropriate	71
Fluid challenge in cases without remarkable hypovolemia or presumed RV dysfunction	6	2.5–8	Uncertain	72
Determine the need for arterial line insertion in the ED	6	3.75–8.25	Uncertain	73–77
Determine the need for central venous line insertion in the ED	6	4.75–7	Uncertain	78
Others
Taking a history of the present illness	9	7.75–9	Appropriate	–
Frequent reassessments of the shock status and response (e.g., SCAI SHOCK stage classification)	8	6.75–8.25	Appropriate	79
Assembling the shock team according to the institutional algorithm	9	7.75–9	Appropriate	80–83
Considering the omission of any examination, as appropriate, to minimize treatment delays	9	9–9	Appropriate	–

ACS, acute coronary syndrome; BNP, B-type natriuretic peptide; ECG, electrocardiogram; ED, emergency department; FDP, fibrin degradation products; IQR, interquartile range; MV, mechanical ventilation; NIV, non-invasive pressure ventilation; RV, right ventricular; SCAI, Society for Cardiovascular Angiography and Interventions.

Additional Step: Advanced Assessment/Treatment

The Additional Step refers to the management of patients requiring further disease-specific evaluation and treatment. This step can be proceeded to from any of Steps 1, 2, or 3. Patients who go through the Additional Step will proceed to either Step 3 or consultation/patient interhospital transfer.

Continuous consideration of differential diagnoses and therapeutic interventions is essential. If CS persists despite interventions in Step 2 or Step 3, or if right heart failure is suspected, a pulmonary artery catheter (PAC) use should be considered. MCS should be introduced without delay.^18,19 Evaluating the parameters obtained from the PAC can be useful in guiding MCS initiation and escalation.^20,21 In patients in whom the underlying disease is ACS, the first medical contact to first device passing time (FMC2D) target is ≤90 min for patients presenting directly to a PCI-capable center and ≤120 min for those requiring interhospital transfer.^22–25 If fulminant myocarditis is suspected as the underlying cause, a myocardial biopsy, which can aid in determining subsequent therapeutic interventions, is recommended.²⁶ If acute aortic syndrome or acute pulmonary embolism is suspected, computed tomography should be performed after hemodynamic stabilization.^27–31

Discussion of the Consensus

All 6 items considered in the Additional Step were deemed highly appropriate and scored accordingly (Table 4). In Japan, MCS devices are reimbursed for patients with CS, including the intra-aortic balloon pump, extracorporeal life support, and percutaneous left ventricular assist device. Early MCS initiation has been evaluated in RCTs for each device (IABP II SHOCK, ECLS-SHOCK, DanGer-SHOCK).^32–34 Currently, the DanGer-SHOCK trial is the only RCT that has demonstrated clinical efficacy in CS secondary to ACS, although it involved a selected cohort.³⁴ We reached a consensus that, in clinical practice, the choice of MCS should be based on multiple factors, such as patient characteristics, underlying pathophysiology, and institutional capabilities. The timing of MCS initiation was also discussed, and reports suggested that introducing percutaneous left ventricular assist device before PCI in ACS-related CS may reduce infarct size and improve outcomes. This received a score of 7.^18,35,36

Table 4.

Advanced Assessment / Treatment: Additional Step

Statement	Median score	IQR	Recommendation	Evidence (references)
Immediate implementation of MCS devices if patients were refractory to the initial treatment	9	7.75–9	Appropriate	34, 84–87
Immediate CAG/PCI in cases of presumed ACS (FMC2D ≤90 min for patients with direct routing to a PCI-capable center, and ≤120 min for those requiring interhospital transfer)	9	9–9	Appropriate	23, 88, 89
Implementation of an MCS device before PCI in patients with cardiogenic shock secondary to ACS	7	5.75–8	Appropriate	90–92
Early biopsy in cases of cardiogenic shock and presumed fulminant myocarditis	8	7.75–9	Appropriate	26
CT after achieving hemodynamic stability in cases of presumed vascular emergencies or acute pulmonary embolism	9	8.75–9	Appropriate	27–30
Placement of PAC in cases of refractory cardiogenic shock or presumed RV dysfunction	9	8–9	Appropriate	93–96

ACS, acute coronary syndrome; CAG, coronary angiography; CT, computed tomography; FMC2D, first medical contact to first device passing time; IQR, interquartile range; MCS, mechanical circulatory support; PAC, pulmonary artery catheter; PCI, percutaneous coronary intervention; RV, right ventricular.

Step 3: Management in the CICU

This step assumes management within the first 24 h after a patient with CS has been admitted to the CICU (Figure 2). Two potential pathways for the patient to enter the CICU are assumed: direct admission from the ED to the CICU (Step 2 → Step 3) or admission via the cardiac catheterization laboratory or operating room before entering the CICU (Additional Step → Step 3). Step 3 aims to stabilize and maintain a patient’s hemodynamics.

Treatment of the underlying cause of CS should be continued from Step 2. In addition to identifying the original cause of CS upon arrival at the ED, the patient must be carefully monitored for any new conditions that may arise over time (e.g., mechanical complications of acute myocardial infarction) and complications resulting from invasive procedures performed in the Additional Step.

Upon CICU admission, the hemodynamic parameters shown in Figure 2 should be promptly assessed. The response to the initial treatment started after ED arrival is assessed, and hemodynamic stability must be achieved within 60 min of CICU admission. The first step is to assess vital signs. In this consensus, unless there is pre-existing information on the patient, the following targets are recommended: systolic blood pressure ≥90 mmHg, mean arterial pressure ≥65 mmHg, heart rate 50–100 beats/min, respiratory rate <20 breaths/min, SpO₂ ≥90%, and urine output ≥0.5 mL/kg/h. In the CICU, invasive monitoring may be used depending on the condition to obtain a more precise understanding of a patient’s hemodynamic status. Such monitoring includes arterial pressure lines, PACs, and central venous catheters. Although the routine use of these tools is not recommended, they can aid in more detailed hemodynamic assessments and guide treatment decisions. In cases where hemodynamic stability cannot be achieved despite initial treatment, a worsening of hemodynamics is anticipated, or other modalities, such as echocardiography, are insufficient for accurate hemodynamic evaluation, the rapid insertion of a PAC after admission to the CICU is recommended.

In patients for whom previous hemodynamic data are unavailable, the following targets are suggested: cardiac index, ≥2.2 L/min/m²; cardiac power output, ≥0.6 W; pulmonary capillary wedge pressure <18 mmHg; and mixed venous oxygen saturation ≥60%. However, setting universal target values for pulmonary artery pressure or right atrial pressure in the CICU is challenging; therefore, no specific target values have been set. Because of the diverse hemodynamics of patients with CS, setting universal treatment targets for the parameters assessed by PACs is challenging. Instead, using multiple parameters obtained via the PAC is reasonable to accurately assess hemodynamics and determine the treatment targets in each case. Conversely, complications from catheter placement, such as infection, bleeding, arrhythmias, and pulmonary artery injury, should be considered, and unnecessary placement should be avoided.

If hemodynamic stabilization has not been achieved during Step 3, the underlying cause should be investigated, and treatment should be promptly intensified to stabilize the hemodynamics. This includes adjusting vasoactive agents, such as inotropes and vasopressors, and MCS initiation or escalation if necessary. Although patients may be transferred to the computed tomography or catheterization laboratory after CICU admission, imaging or performing catheter-based procedures on patients with unstable hemodynamics is associated with life-threatening events. Therefore, clinicians must thoroughly evaluate the need for such procedures and ensure an appropriate system is followed to manage potential hemodynamic deterioration during transport or testing.

Even after the initial evaluation upon CICU admission, the patient’s condition must be assessed continuously, regardless of whether hemodynamic stability has been achieved.³⁷ To confirm the appropriateness of the initial evaluation, the response to initial treatments should be assessed and new abnormal conditions identified, and the monitoring of hemodynamic parameters should be continued. The timing of each assessment is shown in Figure 3. Because CS-related multiple organ failure is closely associated with prognosis, renal and liver function tests should be performed.³⁸ The first checkpoint following the CICU admission assessment is set at 3 h after CICU entry. At this first checkpoint, if any hemodynamic parameters evaluated at the time of admission have not yet reached their targets, efforts to achieve those targets should be continued. The second checkpoint is set at 6 h after CICU entry. If the hemodynamic targets remain unmet, continued efforts to achieve these targets should be made. Serum lactate levels peaking at this point (within 6–8 h of CICU admission) were reported to correlate with prognosis. If the hemodynamic targets are achieved at this time, the third checkpoint is set at 24 h after CICU admission. However, if the targets are not met, the interval between checkpoints must be shortened, and the frequency of assessments must be increased as needed. The goal is to normalize serum lactate levels (<2 mmol/L) and ensure that serum creatinine and liver enzymes reach their peak within 24 h.^39–41 Furthermore, in cases of myocardial injury, the peak of troponin T and creatine kinase levels correlate with the size of the injury, and checking these markers is recommended in various national guidelines.^24,25,42,43

Figure 3.

Monitoring timeline after admission to the cardiac intensive care unit (CICU). The yellow dots represent typical checkpoints, and the green dots indicate additional checkpoints for patients with acute coronary syndrome (ACS). The number and timing of checkpoints should be adjusted based on a patient’s condition and cause of cardiogenic shock. ALT, alanine transaminase; AST, aspartate aminotransferase; CK, creatine kinase; cTn, cardiac troponin; ECG, electrocardiogram; LFTs, liver function tests; RNT, renal function tests.

If hemodynamic stabilization cannot or is unlikely to be achieved at the facility at any point in Step 3, there should be no hesitation in consulting with an advanced shock center and transferring the patient there.

Discussion of the Consensus

Of the 20 items considered for Step 3, 18 were deemed appropriate, 1 was deemed uncertain, and 1 was deemed inappropriate (Table 5). The ESCAPE trial showed that hemodynamic monitoring with a PAC did not contribute to improved survival days over 6 months in patients with severe heart failure, although patients with CS were excluded from the study.⁴⁴ However, recent reports suggest that PAC use in patients with CS is associated with better outcomes, and this consensus also concluded that invasive monitoring using a PAC is appropriate for patients with CS admitted to the CICU. Although serial evaluations using the PAC were given a high recommendation score (9 points), individual parameters mostly scored 7 or 8 points. This reflects the nature of CS, where it is difficult to evaluate treatment response or predict outcomes using a single parameter, and comprehensive assessment is recommended. The timing of the serial checkpoints was also discussed, with consensus on the assessments 3, 6, and 24 h after CICU admission. The number and timing of the checkpoints should be adjusted based on the patient’s condition and the cause of CS (Figure 3).

Table 5.

Management Upon Admission to the Cardiac Intensive Care Unit: Step 3

Statement	Median score	IQR	Recommendation	Evidence (references)
Achieving the following goals of treatment unless previous information is available
SBP ≥90 mmHg and MAP ≥65 mmHg	9	8–9	Appropriate	45, 46, 97–99
Heart rate 50–100 beats/min	7	7–7	Appropriate
Respiratory rate <20/min	7.5	7–8.25	Appropriate
SpO2 ≥90%	8.5	7.75–9	Appropriate
Urine output ≥0.5 mL/kg/h	7.5	7–8.25	Appropriate	100, 101
Sequential evaluation of hemodynamics if PAC is placed	9	8.75–9	Appropriate	37, 102
CI ≥2.2 L/min/m2	7	7–8.25	Appropriate	97, 103
CPO ≥0.6 W	7.5	7–8.25	Appropriate	97, 104, 105
PCWP ≤18 mmHg	7.5	7–8.25	Appropriate	97, 103
SvO2 ≥60%	8	7–8.25	Appropriate	105, 106
PAP	7	6.5–7	Appropriate	95
RAP	7	6.5–7	Appropriate	95
Evaluating hemodynamic status repeatedly at each checkpoint and continuing efforts to achieve the goals if not attained upon assessment at CICU admission	9	9–9	Appropriate	37, 102, 107
Serial measurements of the following biomarkers to assess response in the first 24 h after CICU admission
Lactate peaked out within 6–8 h	8	7–9	Appropriate	40, 41, 107
Complete lactate clearance <2 mmol within 24 h	8	7.75–9	Appropriate	41, 107
Creatinine peaked out within 24 h	7	6–8	Appropriate	38
LFT peaked out within 24 h	7	5.75–7	Appropriate	38
BNP peaked out within 24 h	3	1–7	Inappropriate
CK/CK-MB or cTn peaked out if patients were presumed to have myocardial injury	7.5	7–8.25	Appropriate	42, 43, 108
D-dimer/FDP peaked out	6	3.25–7	Uncertain

BNP, B-type natriuretic peptide; CI, cardiac index; CICU, cardiac intensive care unit; CK, creatine kinase; CPO, cardiac power output; IQR, interquartile range; LFT, liver function test; MAP, mean arterial pressure; PAC, pulmonary artery catheter; PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; RAP, right atrial pressure; SBP, systolic blood pressure; SvO₂, mixed venous oxygen saturation.

Consultation/ Interhospital Transfer

At any point during Steps 1–3 or the Additional Step, if achieving the current step’s goals is deemed difficult at the current facility, or if the goals of the next step will be challenging to achieve, consultation with and transfer to an advanced shock center should be considered.

Figure 2 outlines the requirements for a shock center receiving consultation or patient transfers, namely provision of uninterrupted (24 h/day, 7days/week) access to MCS and emergency PCI, the availability of a functioning multidisciplinary shock team, a fully equipped CICU, and sufficient experience with MCS cases. Based on these requirements, specialized facilities must be established, and collaboration systems that are tailored to the healthcare situation of each region are necessary. A key point is the early and appropriate sharing of information with the shock center to prevent CS from worsening in any step if necessary. Collaboration between facilities is essential to ensure the smooth progression of treatment. Facilities should also discuss and agree on safe transport methods, and the decision to transfer must consider the potential benefits of post-transfer treatment against the risks of transport.

Discussion of the Consensus

This section considered the necessity of consultation and transfer to an advanced shock center, as well as the desired requirements for shock centers, and all 6 items considered were deemed appropriate (Table 6). The requirement for the shock center to provide uninterrupted access to MCS and emergency PCI received a high score of 9 points.

Table 6.

Interhospital Consultation/Patient Transfer

Statement	Median score	IQR	Recommendation	Evidence (references)
Consultation with or transportation to an advanced cardiogenic shock center when evaluation or treatment cannot or is unlikely to be performed adequately or when treatment goals cannot be achieved	9	9–9	Appropriate	109, 110
Advanced cardiogenic shock centers accepting consultations or patient transfer from referral hospitals ideally meet the following requirements:
• 24/7 availability of MCS (IABP, PVAD, and ECMO) initiation	9	9–9	Appropriate	2, 111, 112
• 24/7 availability of evaluation and treatment in a catheterization laboratory	9	9–9	Appropriate	2, 53, 111, 112
• Sufficient number of annual cases with an MCS	7	6.5–8.25	Appropriate	54–56, 113
• Multidisciplinary shock team	8.5	7.75–9	Appropriate	80–83
• Management with cardiology or intensive care specialists in the CICU	8.5	7–9	Appropriate	80–83, 112, 114

CICU, cardiac intensive care unit; ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; IQR, interquartile range; MCS, mechanical circulatory support; PVAD, percutaneous ventricular assisted device.

Future Directions

This consensus focused on the rapidly progressing nature of CS over time, and an expert consensus was developed on the rapid management of CS with an emphasis on the timeline. During the development of this expert consensus, we encountered the following evidence gaps: (1) the effectiveness of obtaining and transmitting a prehospital 12-lead ECG in CS; (2) the effectiveness of the direct transfer of patients with CS to the cardiac catheterization laboratory vs. indirect transfer via the ED; (3) the decision to admit patients with abnormal vital signs predictive of progression to shock to the CICU; (4) appropriate selection of inotrope/vasoactive agents; (5) appropriate timing for introducing MCS; (6) the advantage of a CICU vs. a mixed ICU; and (7) hemodynamic target values in the management of patients with CS (noting slight variations in target values among international protocols). These issues must be addressed through further research.

In addition, the smooth implementation of this CS management algorithm, which focuses on the timeline, faces challenges in clinical practice in Japan. The most significant barrier, and a critical issue to resolve, is establishing a smooth system of collaboration among non-cardiology specialists, other healthcare professionals, different departments, prehospital emergency personnel, and even other facilities associated with each step. The concept of the hub-spoke medical collaboration system and shock teams, which have become important in the CS field, aligns with this concept, and it is essential to establish similar systems in Japan. Despite the need for further detailed algorithms and checklists to build an effective collaborative system, this consensus focuses on providing an overall view of time-sensitive CS treatment. Moving forward, it is essential to develop a specific CS registry for Japan to validate and update these consensus guidelines. We hope that this consensus will serve as a collaborative platform for various professionals in critical care cardiology, promoting its application across various disciplines, encouraging the exchange of diverse perspectives, and allowing for continuous revisions over time. By promoting collaboration between this consensus and various academic organizations, including the Japan Resuscitation Council resuscitation guidelines, we seek to advance the standardization of CS treatment and ultimately improve patient outcomes.

Acknowledgments

The authors express their sincere gratitude to the staff, members of the Japanese Circulation Society, and all organizations and institutes involved in this study for their valuable contributions and support.

Sources of Funding

This study did not receive any specific funding.

Disclosures

The authors have declared relationships that may be perceived as actual or reasonably perceived conflicts of interest on the Disclosure Questionnaire, which all authors are required to complete and submit (Appendix 2). The conflicts of interest described in the Disclosure Questionnaire include those related to the declarant himself/herself, his/her spouse, first-degree relatives, and persons living and making a living together. The period of the conflict is from April 2023 to December 2024, which covers the development of the guidelines to publication.

Appendix 1. Details of Members

• Takahiro Nakashima, MD, PhD, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

• Toru Kondo, MD, PhD, Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

• Jun Nakata, MD, PhD, Division of Cardiovascular Intensive Care, Nippon Medical School Hospital, Tokyo, Japan

• Keita Saku, MD, PhD, Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan

• Shoji Kawakami, MD, PhD, Department of Cardiology, Aso Iizuka Hospital, Fukuoka, Japan

• Masanari Kuwabara, MD, PhD, FJCS, Division of Public Health, Center for Community Medicine; and Division of Cardiovascular Medicine, Jichi Medical University, Tochigi, Japan

• Takeshi Yamamoto, MD, PhD, FJCS, Division of Cardiovascular Intensive Care, Nippon Medical School Hospital, Tokyo, Japan

• Migaku Kikuchi, MD, PhD, Emergency and Critical Care Center, Dokkyo Medical University, Tochigi, Japan

• Ichiro Takeuchi, MD, PhD, Department of Emergency Medicine, Yokohama City University, Yokohama, Japan

• Kuniya Asai, MD, PhD, FJCS, Division of Cardiovascular Intensive Care, Nippon Medical School Hospital, Tokyo, Japan

• Naoki Sato, MD, PhD, Department of Cardiovascular Medicine, Kawaguchi Cardiovascular and Respiratory Hospital, Saitama, Japan

Appendix 2. Disclosure of Potential Conflicts of Interest (COI) (2023/1/1–2024/12/31)

Author	Member’s own declaration items									COI of the marital partner, first-degree family members, or those who share income and property			COI of the head of the organization/department to which the member belongs (if the member is in a position to collaborate with the head of the organization/department)
	Employer/ leadership position (private company)	Stakeholder	Patent royalty	Honorarium	Payment for manuscripts	Research grant	Scholarship (educational) grant	Endowed chair	Other rewards	Employer/ leadership position (private company)	Stakeholder	Patent royalty	Research grant	Scholarship (educational) grant
Takahiro Nakashima						A Grant- in- Aid for Young Scientists (A) (20K17914) of the Japan Society for the Promotion of Science
Toru Kondo				Abbott Japan LLC AstraZeneca K.K. Boehringer Ingelheim Ono Pharmaceutical Co. Ltd. Kowa Company Ltd Kyowa Kirin Co.Ltd. Novartis Pharma K.K
Keita Saku				Abiomed Japan K.K. Mallinckrodt Pharma K.K. ONO PHARMACEUTICAL CO. LTD.		Abiomed Inc. NTT Research Asahi Kasei ZOLL Medical Corporation Neuroceuticals Inc. Zeon Medical Inc.
Ichiro Takeuchi						Nihon Kohden Corporation TERUMO CORPORATION
Kuniya Asai				AstraZeneca K.K. Boehringer Ingelheim Kyowa Kirin Co.Ltd. Novartis Pharma K.K Otsuka				Medtronic Japan Co. Ltd Boston Scientific FUKUDA DENSHI CO. LTD Japan Lifeline Co. Ltd
Naoki Sato				Otsuka Novartis BMS Bayer Terumo Boehringer-Ingelheim Daiichi-Sankyo Ono Roche AstraZeneca Taisho Kowa Heartorgnaization

Notation of corporation is omitted.

 

The following persons have no conflict of interest to declare:

Jun Nakata

Shoji Kawakami

Masanari Kuwabara

Takeshi Yamamoto

Migaku Kikuchi

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