We studied 3,180 patients diagnosed with TTS in Sweden between 2015 and 2022 from the SCAAR registry, applying a gradient-boosting machine learning algorithm to uncover significant predictors of 30-day mortality. Our study recognizes the pivotal role of the treating hospital in predicting 30-day mortality among TTS patients. Previous research mainly focused on variables centered on the patient, whereas our study identified a prominent role of the treating hospital.
The impact of hospital resources on the outcomes of TTS patients is multifaceted and significantly influenced by various factors. One critical aspect is the role of certain hospitals in admitting high-risk TTS cases transferred from smaller facilities. This, along with the number of TTS patients diagnosed and treated, the availability and implementation of coronary angiography, and access to advanced treatments, crucially affects patient prognosis. A critical aspect of advanced treatment for TTS is the timely use of Extracorporeal Membrane Oxygenation (ECMO), especially for patients facing severe hemodynamic instability17. However, it's important to note that ECMO is not available in all hospitals, highlighting disparities in treatment capabilities across different healthcare settings. It's crucial to acknowledge that hospitals may vary in their proficiency and readiness to diagnose and treat not only TTS but also other severe conditions that can trigger TTS, such as stroke, internal bleeding, sepsis, trauma, respiratory insufficiency, or complications from malignancies. We have illustrated these hospital-level determinants by three real-world cases with fatal outcomes (see the supplement).
The hospitals may differ in the proficiency of healthcare teams and the accessibility of essential resources for TTS management. Consequently, efforts to improve outcomes should aim at augmenting institutional capabilities, including education and judicious distribution of resources. Specifically, the pharmacological management of TTS can vary widely and may have significant implications for patient outcomes3,18. One potential area of variability is using vasoactive agents, including positive and negative inotropes and diuretics. In TTS, these treatments can be detrimental19. The main challenge in the pharmacological management of TTS lies in our limited understanding of the syndrome's pathophysiology. TTS is a complex condition with multifaceted pathophysiology that is not yet fully understood. The myocardial stunning seen in TTS is thought to result from an acute surge in catecholamines in response to stress, but other factors are likely at play. Given these complexities, potent vasoactive agents in TTS should be cautiously approached until we better understand the syndrome's underlying mechanisms. Our study identified the treating hospital as the most critical predictor of 30-day mortality in TTS patients, which underscores the need for further research to elucidate the optimal pharmacological management strategies for this condition. This could involve multicenter randomized controlled trials comparing different treatment strategies and further studies exploring the pathophysiology of TTS to guide the development of more targeted therapies19. Currently, there is only one study of this kind, initiated by our group and utilizing the Swedish national registry platform — BROKEN SWEDEHEART (NCT04666454)20.
An additional aspect that merits attention is the role of timely and accurate diagnosis and adequate risk estimation in TTS patients. The ability to promptly recognize and accurately diagnose TTS and an informed and precise estimation of the risks involved can be decisive for patient outcomes. This implies that not only does proficiency in management matter but also the acuteness in the initial approach to TTS. Strengthening diagnostic capabilities and improving risk assessment protocols could be vital to improving patient outcomes. The importance of clinical presentation in angiography is consistent with existing literature, indicating that more severe presentations are associated with worse outcomes21,22. Likewise, the significance of creatinine level and Killip class, both markers of disease severity, aligns with previous research highlighting their predictive value in heart failure syndromes23.
There are limitations to this study. First, the registry data used in this study did not include all potential confounding factors that might influence the results. These consist of comorbidities not included in Table 1. Second, there is an increase in missing data during the study period, which can differ between hospitals. The hospitals that document the lowest number of cases may exclude low-risk cases, whereas hospitals with the greatest number of instances report many low-risk cases. Third, the analysis was based on data from a single country, which might limit the generalizability of our findings. However, the main goal was to provide reliable data that could lead to the generation of hypotheses for further investigation.
In conclusion, our findings highlight the importance of hospital and clinical factors in predicting 30-day mortality in TTS patients. Future research should focus on improving the management of TTS in hospitals with higher mortality rates and further refining risk stratification tools for TTS to provide personalized care.