Short- and mid-term prognosis of non-ischemic cardiogenic shock patients: insights from an international study

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Abstract Background Non-ischemic cardiogenic shock (NICS) represents an increasingly prevalent clinical challenge, characterized by significant heterogeneity and high mortality. Unlike cardiogenic shock (CS) due to acute coronary syndrome (AMI-CS), NICS remains poorly characterized, and evidence-based management strategies are still limited, leaving a critical gap in risk stratification and therapeutic optimization. Purpose This study aimed to evaluate the clinical trajectory of NICS patients, identifying clinical, biochemical, and therapeutic markers dictating in-hospital and one-year outcomes. Primary endpoint was in-hospital mortality; secondary endpoints included in-hospital complications, 1-year mortality, and a composite of 1-year mortality, heart transplantation or left ventricular assist device implantation. Methods We performed an international, multicenter, retrospective study including 98 patients (aged 18-85) admitted to Cardiac Intensive Care Unit for NICS between 2021 and 2024. To ensure a specific NICS focus, patients presenting with cardiac arrest, AMI-CS, post-surgical, obstructive, or non-cardiac shock were excluded. Multivariable logistic regression and Cox proportional hazards models were utilized to identify independent drivers of short- and mid-term outcomes. Results The cohort (median age 61.4 years, 68% male) predominantly presented with acute-on-chronic CS (67%). The underlying heart disease was mainly represented by dilated cardiomyopathy (38%), followed by chronic ischemic heart disease (20%) and valvular heart disease (18%). In-hospital complications occurred in 89.8% of cases, primarily acute kidney injury and supraventricular arrhythmias. In-hospital mortality was high (33.3%) and independently predicted by advanced age (OR 1.10, p=0.036), active malignancy (OR 19.17, p=0.028), acute liver injury (OR 16.97, p=0.039), and lower BMI (OR 0.69, p=0.015). At 1 year, mortality was significantly higher in acute-on-chronic presentations (aHR 7.84, p=0.034) and those with lower discharge left ventricular ejection fraction (LVEF; aHR 0.90, p=0.005). Conversely, early implementation of temporary mechanical circulatory support (t-MCS; aHR 0.07, p=0.017) and angiotensin receptor neprilysin inhibitors (ARNIs) prescription at discharge (aHR 0.06, p=0.01) were predictors of survival. Regarding the composite endpoint, older age, female sex, acute-on-chronic CS, and higher admission creatinine were independent predictors of adverse outcomes (all p<0.05). Conclusions Although limited by its retrospective design, our study underscores that NICS carries a severe prognosis, mainly dictated by systemic vulnerability and chronicity of the cardiac substrate. Furthermore, our findings highlight a critical "window of opportunity": aggressive intervention with t-MCS and early optimization of neurohormonal blockade—specifically with ARNIs—can significantly pivot the clinical trajectory of NICS patients toward improved mid-term survival.Population main featuresFor image description, please refer to the figure legend and surrounding text.In-hospital complicationsFor image description, please refer to the figure legend and surrounding text.

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