Timing and treatment strategies according to SCAI classification in cardiogenic shock

Abstract

In patients with cardiogenic shock (CS), particularly those with acute myocardial infarction (AMI), evidence suggests that timely diagnosis and treatment interventions are critical in the prevention of haemo-metabolic compromise. Temporary mechanical circulatory support (tMCS) has shown potential in facilitating revascularization and recovery of patients with acute myocardial infarction cardiogenic shock (AMI-CS). Timing of treatment strategies for CS patients needs to be optimized for use of tMCS devices that are applicable to this heterogeneous patient population. Here, the latest evidence as well as the gaps in knowledge surrounding the role of time in the management of patients with CS is summarized.

Introduction

In cardiogenic shock (CS), a loss of myocardial contractility, as seen in patients with acute myocardial infarction (AMI), triggers a vicious circle of tissue hypoperfusion, inflammation, and other detrimental compensatory mechanisms, ultimately leading to end-organ failure and death.¹ Temporary mechanical circulatory support (tMCS) may, in theory, slow down this deadly cascade by restoring oxygen delivery to the body, reducing myocardial workload and oxygen consumption, facilitating revascularization, and recovery of the patient. However, robust evidence on their efficacy and safety is currently lacking, and these devices are themselves associated with an increased risk of complications and significant costs for health care systems.^2,3 Although the benefit has yet to be confirmed by randomized trials, a timely diagnosis and treatment of acute myocardial infarction cardiogenic shock (AMI-CS) patients seems to be a critical element for success in preventing the downward spiral of hemo-metabolic compromise. Therefore, we critically appraise current evidence and gaps in knowledge on the role of time in the management of AMI-CS, proposing best practices and future research goals.

Shock phenotyping and device selection

An early diagnosis and accurate assessment of CS likely contributes to optimization of the use of these devices, as it can help to identify patients in whom the risk from the disease outweighs the risk from the device. To achieve this, clinicians should speak the ‘same language’ when assessing patients with CS. Since its first publication in 2019, the Society for Cardiovascular Angiography and Interventions (SCAI) CS classification has provided a frame for assessment of CS and has repeatedly shown that it is applicable to a heterogeneous patient population.^4–7 This classification system can then be further enhanced by the application of specific risk scores, which provide additional granularity in terms of individual risk assessment.^8,9 Additionally, factoring in phenotypic clusters of CS, e.g. patients presenting with predominantly non-congested vs. cardiorenal vs. cardiometabolic phenotypes, might provide further information about the risk of disease progression.¹⁰ The use of haemodynamic assessments is debated for patients with CS, especially in terms of diagnosis. However, the identification of hypoperfusion due to inadequate cardiac output is most likely of central value to guide the use of tMCS, as indicated by a recent retrospective analysis and future outcome data from an ongoing randomized controlled trial [Pulmonary Artery Catheter in Cardiogenic Shock Trial (PACCS) NCT05485376], is likely to provide clearer evidence on this soon.¹¹ An accurate assessment of a patient presenting with CS is important to assess the eligibility for different tMCS including evaluation of the vascular anatomy for the feasibility of implantation, as well as for the bleeding and ischaemic risk. Also as important is the assessment of the overall treatment options and goals for a given patient due to other life-limiting diseases, diseases impacting the candidacy status for durable assist devices, and/or candidacy for heart transplantation should be factored into the decision process.

Treatment options: focus on timing and devices

Timely goals for the treatment of AMI-CS include supporting the systemic circulation (door-to-support, DTS), unloading the left ventricle (LV) (door-to-unloading, DTU), improving myocardial perfusion and coronary revascularization (door-to-balloon, DTB). In translational studies, LV unloading with Impella during coronary occlusion, even when prolonging ischaemia time, has been associated with reduced myocardial oxygen demand, reduced LV end-systolic wall stress, and reduction in infarct size compared with immediate revascularization.^12–14 Several registry-based studies and meta-analyses of these studies suggest higher survival rates in AMI-CS when Impella is placed before revascularization, rather than in patients where Impella is placed after percutaneous coronary intervention (PCI)^15–20 although not all.²¹ However, the level of evidence is low as the data are subject to significant selection bias. As such, patients who might stabilize rapidly by opening the culprit vessel, and thereby have a better prognosis, will appear in the pre-PCI group and not in the post-PCI group where only patients who remain in shock after revascularization may appear. In patients with AMI and no shock, pre-PCI Impella has been shown to be feasible²² and the ongoing Door to Unloading trial (NCT03947619) will provide insight into the potential benefit of pre-PCI Impella in patients at early AMI-CS stages (SCAI class A and B, Figure 1). The same potential benefit of pre-PCI Impella has not been demonstrated for intra-aorta balloon pump (IABP) where pre-PCI IABP has failed to reduce infarct size in the CRISP AMI trial.²³ Moreover, the registry data and a post hoc analysis of the IABP-SHOCK 2 trial failed to demonstrate survival benefit of pre-PCI placement of the device in AMI-CS.^24,25 Data on pre-PCI venous-arterial extracorporeal membrane oxygenation (V-A ECMO) is limited but bias prone registry data has also indicated lower risk of death with early placement.²⁶

Figure 1.

Understanding the interplay between the time of tMCS implantation and outcomes in AMI-CS. AMI, acute myocardial infarction; CS, cardiogenic shock; DTB, door-to-balloon; DTS, door-to-support; DTU, door-to-unload; ECMO, ExtraCorporeal Membrane Oxygenation; ECLS, Extra Corporeal Life Support; tMCS, temporary mechanical cardiac support; NSTEMI, non-ST elevation myocardial infarction; PCI, percutaneous coronary intervention; PPCI, primary percutaneous coronary intervention; R, Randomization; SOC, standard of care; STEMI, ST elevation myocardial infarction. *overall CS aetiology.

Until results of ongoing randomized trials are available, timing and choice of tMCS should consider the severity of haemodynamic decay, comorbidity, and complexity of coronary lesions but also the potential delay in coronary revascularization, the only treatment proven to benefit in AMI-CS. Thus, in the SCAI C and SCAI D conditions and in patients with ongoing chest compression, tMCS should be considered when hypoperfusion is identified and before PCI when feasible. In the SCAI E situation with overt multi-organ failure, the benefit of tMCS is low and initiation of tMCS has to be evaluated on case by case by a shock team. Likewise, patients resuscitated for out-of-hospital cardiac arrest are not ideal candidates for tMCS. The arrest will create a haemodynamic state that is undisguisable from SCAI C shock but may rapidly recover after the return of circulation.²⁷ In these patients an initial wait-and-see strategy may be advisable with a preliminary attempt to stabilize with fluid and vasopressor therapy before initiating tMCS. Further questions remain open like the possible escalation or combination therapies in patients without prompt recovery of haemodynamic conditions.

Prognosis and SCAI class modifiers

Despite shock aetiology, phenotype, and actual SCAI shock stage several risk modifiers have been proposed that may affect mortality. Several factors such as age, sex, aetiology of CS, heart rate, systolic blood pressure, glucose and lactate levels, pH, and cardiac arrest have been identified.⁸ Particular attention to co-morbidities that are non-modifiable risk factors (i.e. patient age and sex) must be considered in device selection.²⁸ Especially presentation after cardiac arrest with a high-risk of hypoxic brain injury and coma as two of the strongest negative risk modifiers, especially in patients presenting in higher SCAI shock stages.^7,29 Extensive therapy escalation should be undertaken with caution in these cases. However, some of the cardiac arrest patients may recover quickly with conservative treatment of CS once the malignant arrhythmia and/or hypotension is resolved.²⁷ Thus, cardiac arrest per se is not a good predictor of mortality and confounds the selection of tMCS.³⁰

The presence or development of organ failure leads to further deterioration of shock patients.^31,32 Some of these may be affected positively and organ failure may be treated successfully over the course of the patient’s hospital stay with subsequent change of the SCAI shock stage and risk of mortality.

In addition, the development of systemic inflammatory response (SIRS) may affect prognosis negatively since the incidence is increasing from SCAI stage A to E, which affects in-hospital survival negatively in SCAI stages A, C, and D.³³ Patient frailty and susceptibility to complications may lead to a poor prognosis of shock patients too. It is of note that most of the risk modifiers might affect each other and promote worse outcomes. Knowledge and utilization of the risk modifier system helps to mimic the dynamic course of CS and helps to estimate the mortality risk of the presenting patient. Some of the prognostic modifiers are still not well studied or validated, with the number and relevance changing over time with the use of targeted management and treatment strategies.

Strategies (shock networks, transportation)

The CS network is a complex model based on a hub-and-spoke system (out-of-hospital network) and shock team (in-hospital network) with the main objective to provide the best care possible to patients (Figure 2). This is especially true for those who live in suburban or rural areas and aim to centralize expertise and technology, reduce healthcare cost, and improve outcomes.³⁴ The multidisciplinary team is composed of intensive care cardiologists, interventional cardiologists, cardiac surgeons, cardio-anesthesiologists, dedicated nurses, and a perfusionist to properly treat patients admitted for CS. Observational data suggest that the presence of a dedicated multidisciplinary shock team has a beneficial impact on in-hospital- and 1-month mortality in patients admitted for CS.³⁵ Furthermore, patients receiving short-term and durable left-ventricle assist devices³⁶ in the facilities with the highest volumes have been reported to have better outcomes. As such, the dedicated and standardized regionalized network of care for CS patient’s, centralized in tertiary centres has been demonstrated to improve short-term outcomes.³⁷ The Hub-and-Spoke model based on the current model for ST-elevation MI, trauma, and stroke referral systems, does not always fit the CS scenario and specific protocols according to each region's capabilities should be developed and implemented. Key to the hub and spoke model’s success is the close collaboration between the hub and the spoke sites to develop joint protocols and provide training for the effective implementation of these protocols at each site.³⁸ The first important step is an appropriate diagnosis of CS SCAI stage with guidelines-directed therapies and prompt identification of patients with a high likelihood of rapid deterioration in order to be ready for patient transfer. A complementary approach is identifying three distinct CS phenotypes upon presentation: non-congested, cardiorenal, and cardiometabolic among patients with AMI-CS and acute heart failure CS.¹⁰ These classifications represent important steps toward guiding early therapeutic interventions and selecting patients for the transferral. After the case discussion and bilateral agreement, a key point for a successful network is the patient's transport, which is associated with high mortality.^39,40 In such cases, the patients should be transferred from the spoke to the hub centre according to the local protocol by a dedicated ambulance system with an intensivist cardiologist and/or cardio-anesthesiologist onboard. In selected cases, due to the haemodynamic instability of the patients making the transfer at a really high risk of mortality, a dedicated hub centre’s team may place a percutaneous tMCS at the spoke centre for a protected transfer.⁴¹

Figure 2.

Time issues in AMI-CS. DTB, door-to-balloon; DTS, door-to-support; DTU, door-to-unload; LV, left ventricular; tMCS, temporary mechanical circulating support; MVD, multi-vessel disease; PCI, percutaneous coronary intervention; RV, right ventricle.

Conclusions

The time to interventions (i.e. DTB), DTU (when unloading is considered), or DTS (for V-A ECMO) remains of utmost important to interrupt the vicious cycle of ischaemia and prevent severe haemodynamic decay and metabolic derangement of patients with CS. Thus a ‘4 early step’ approach (Figure 2) including detection, interventions, with defined and prompt therapeutic escalation, activation of protocols, and recognition of prognosis modifiers, seems, at the current stage of knowledge, the most warranted approach to this complex subset of patients. Upcoming trials will shed more light on the required therapeutic options in AMI CS (Figure 1).

Funding

This work has been supported by Abiomed Europe GmbH to cover publication costs as well as professional language editing of each manuscript. No individual fees were paid to the authors in the generation of this publication. This paper was published as part of a supplement financially supported by Abiomed GmbH.

Data availability

No new data were generated or analysed in support of this research.