Pilot Italian Cardiogenic Shock Initiative

Background and rationale Acute myocardial infarction complicated by cardiogenic shock (AMICS) is the leading cause of inhospital mortality in acute myocardial infarctions (AMI), occurs in up to 10% of cases, and is increasingly frequent 2,3. Primary percutaneous coronary intervention (pPCI) is the cornerstone of treatment for AMI complicated by CS (AMICS), and its routine use is associated with a long-term survival benefit4. However, despite innovations in pharmacologic and device-based therapies and systems of care, in-hospital and 30-day mortality in AMICS remain high (50 to 70%) 5. To address this survival plateau, percutaneous mechanical circulatory support devices (pMCS) have been introduced in this clinical setting 6-8. Unfortunately, these technologies are restricted to tertiary hub centres with specific expertise, selection, and management. As a result, shock centres have developed internal protocols to timely manage cardiogenic shock patients. Nevertheless, spoke centres frequently lack dedicated shock protocols for correct and timely management and refer AMICS patients to hub centres, especially in the early phase of the acute presentation. On the other side, a standardized approach to cardiogenic shock performed by a shock team has been demonstrated to have a significant impact on in-hospital and 1-month mortality. The Hub-and-Spoke model is based on the current model for STEMI, trauma, and stroke referral systems9. Studies including patients receiving ECMO and LVADs 10,11 have all demonstrated better outcomes in higher volume facilities. This model can potentially contribute to concentrating resources in each region. The key to the success of the hub and spoke model is the close collaboration between the hub and the spoke centres to develop common protocols and provide training for their effective implementation 12. Recent experiences in the US demonstrated how correct management among Hub and Spoke centres may improve the outcomes of the AMICS patients admitted at Emergency Departments of the spoke centres.

The Spoke and Hub network is a consolidated reality in the Italian sanitary system since the primary PCI networkintroduction for STEMI patients at the end of the 1990s. This approach has been proposed in the last few years also for more complex clinical scenarios, such as cardiogenic shock.

The implementation of a hub and spoke network for the management of cardiogenic shock offers significant advantages as the opportunity to benefit from a specialized shock team and the maximize the implementation of mechanical circulatory support. Having a dedicated multidisciplinary cardiogenic shock team within a referral centre (hub) is crucial. Clinical studies have demonstrated that the timely activation of a multidisciplinary team, including interventional cardiologists, cardiothoracic surgeons, and intensivists, can dramatically reduce mortality associated with this critical condition13. The speed of intervention and the team and expertise in performing life-saving procedures such as pPCI or the implantation and management of ventricular assist devices are determining factors to improve patient survival.

The hub and spoke network also offer the possibility to use more advanced medical therapy and/or mechanical circulatory support and to serve as bridge to recovery or bridge to permanent ventricular assist device or heart transplantation. In fact, patients with cardiogenic shock might benefit from temporary and or permanent ventricular assist devices (VAD). The availability of these devices in hub centres allows for more effective management and continuous monitoring of critically ill patients14.

Timely access to these technologies can significantly increase the chances of hemodynamic stabilization and recovery.

In conclusion, a hub and spoke network for cardiogenic shock offers an integrated and specialized approach that can significantly improve the clinical outcome of patients, both through the presence of an expert team and through the optimization of mechanical circulatory support.

However, although an informal agreement already exists among hub and spoke centres, a consolidated network it is not standardized in term of patient stratification and communication between physicians of different hospitals.

Therefore, the aim of the spoke-hub cardiogenic shock protocol is to test whether in a real-world setting the use of a prespecified shock management protocol improving communication and collaboration among centres to timely refer AMICS patients from spoke to hub centres can reduce the incidence of in hospital and 30-day mortality. A correct transfer protocol of selected patients will extend the implementation of dedicated and complex cardiogenic shock treatments to patients initially admitted to spoke centres; this protocol must be adapted according to the local health care organization and economic availability in each area or country. This will help to provide an equal access to care for CS patients in the metropolitan area and is expected to improve their outcomes. This study will evaluate the impact on in-hospital or 30-day mortality of the use of a prespecified shock management protocol improving communication and collaboration among centres in the same area to timely refer CS patients from spoke to hub centres in hospital networks in Turin and Milan metropolitan Area.

2.1. Hub and spoke network: literature review The creation of hub and spoke networks has demonstrated a significant benefit on mortality in various cardiovascular acute care settings, greatly improving the management of complex patients. In both STEMI and stroke, the presence of hub and spoke networks has enabled easier communication between referral centres and the periphery to improve clinical management of the patient. Preliminary data regarding the impact of the hub and spoke-integrated protocols regarding CS have been published by several groups.

Daniel Lu et al 13 compared the outcomes of CS patients among three cohorts: (A) direct admissions to spokes, (B) direct admissions to hubs, and (C) interhospital transfer to hubs. The authors stratified all consecutive patients enrolled in their CS registry (Nationwide Readmissions Database 2010 - 2014). A total of 130 656 (31.7%) patients with CS were directly admitted to spokes, 253 234 (61.4%) were directly admitted to hubs, and 28 777 (7.0%) were transferred to hubs. Similarly, to the Italian health care organization, most of the included centres were spoke centres in sub-urban regions with limited access to mechanical support devices and low volume for PCI, while hub centres were about 30% and mainly in metropolitan areas. CS mortality was 47.8% at spoke hospitals and was lower at hub hospitals, both for direct admissions (39.3%) and transferred (33.4%) patients. On multivariable analysis, direct admission to CS hubs \[odds ratio (OR) 0.86, 95% confidence interval (CI) 0.84-0.89, \] and transfer to hubs (OR 0.72, 95% CI 0.69-0.76,) were both associated with lower mortality. The authors conclude that treatment of CS at transfer hubs was associated with significantly lower mortality within this large real-world sample. Another experience has been reported by WellStar Medical Center15 and consists of the implementation of the hub-and-spoke model, with a cardiogenic shock algorithm. Well-Star Kennestone Regional Medical Centre served as the hub; it is a highvolume centre for of cardiogenic shock, with 250 STEMIs per year and 24-hour cardiology critical care expertise, cardiac surgery, and advanced heart failure therapies for patients in need of more advanced care. When WellStar implemented its hub-and-spoke model, the survival rate for AMI-CS was at about 50 percent, consistent with national averages. Within a few months, survival rates raised to 60% and up to 70%.

A further example of the effectiveness of optimal protocols applications in the care of patients presenting with CS comes from the experience described in the Japanese registry by Dr. Ako et al., who analysed 593 consecutive AMICS patients from the J-PVAD registry and their cumulative 30-day survival and safety profiles. The overall 30-day survival was 80.9% when microaxial flow pumps were used. These results were obtained with a strict application of the enrolment protocol.16 Tehrani et al 14 compared the outcomes of CS patients initially admitted to spoke versus hub hospitals within a regional care network (The Inova Health System Regionalized Care Network for Cardiogenic Shock). The authors stratified all consecutive patients enrolled in their CS registry (January 2017 to December 2019) by first admission to a spoke versus hub hospitals. Of 520 CS patients, more than half initially presented to spoke hospitals. In their analysis, patients first admitted to hub centres were more often supported with pVAD (44% vs 11%; P \< 0.01) and veno-arterial extracorporeal membrane oxygenation (13% vs 0%; P \< 0.01). Initial presentation to a spoke was not associated with increased risk-adjusted 30-day mortality, bleeding, or stroke. The authors conclude that spoke and hub patients experienced similar short-term outcomes within a regionalized CS network.

In all these experiences the applied protocol was promoting a prompt stratification and diagnosis of SCAI shock class, recognition of right ventricular failure, use of pVADs when indicated - as soon as possible, down titration of inotropic agents, prompt upscale of mechanical cardiac support, if needed, bridge to recovery and /or permanent VAD and /or heart transplantation. Recently, it was published by Lombardy region a local guideline (DGR N° XII / 1117 meeting date 16/10/2023) about acute heart failure/cardiogenic shock network identifying in Milano area two hub centres (IRCCS San Raffaele ASST Grande Ospedale Metropolitano Niguarda) whom the spoke centre should refer to. Nevertheless, this network system is not nowadays applied in our country, and the Italian healthcare system is still lacking a CS Network. The optimal strategy to promote standardized care and improved outcomes across regional CS networks deserve further investigation. 2.2. Creation of hub and spoke network A hub and spoke network in cardiogenic shock facilitates the rapid transfer of patients to specialized tertiary care centres. When a patient presents with cardiogenic shock at a spoke hospital, immediate hemodynamic stabilization is the priority. The network communication channels enable rapid consultation with the hub, where specialised cardiac teams evaluate the patient condition remotely and provide expert recommendations. If advanced interventions, such as pPCI or mechanical circulatory support, are required, the patient is promptly transferred to the hub. This expedited transfer process ensures that patients receive timely access to specialized care, reducing treatment delays and improving the chances of a favourable outcome.

A hub and spoke network establishes regional centres of excellence in the management of cardiogenic shock. The hub acts as the central facility equipped with advanced cardiac interventions, highly skilled healthcare professionals, and state-of-the-art infrastructure. This concentration of expertise allows for specialised care that may not be available at smaller spoke hospitals. By designating specific hubs, patients have improved access to specialized resources, including cardiac catheterization laboratories, advanced imaging technologies, and multidisciplinary CS teams trained in managing complex cases of cardiogenic shock. These regional centres of excellence ensure that patients are directed to facilities with the highest level of expertise, increasing the likelihood of successful treatment and improved patient outcomes.

Cardiogenic shock patients often face geographic disparities when accessing specialized care, especially in rural or remote areas. A hub and spoke network addresses this challenge by bringing s

• Stroke, (fatal or non-fatal) or TIA [Срок оценки: 30-days]
• Bleedings (BARC classification ≥3), [Срок оценки: 30-days]
• Renal replacement therapy [Срок оценки: 30-days]
• Vascular complications [Срок оценки: 30-days]
• Non-fatal myocardial infarction [Срок оценки: 30-days]
• Door-to-support time [Срок оценки: 30-days]
• Onset of symptoms to support time [Срок оценки: 30-days]