Cardiogenic shock (CS) associated with acute myocardial infarction (AMI) remains a condition with high mortality despite therapeutic advances. Until the publication of the DanGer Shock clinical trial, recently reviewed in this blog, no study had demonstrated a significant reduction in mortality through the systematic use of mechanical circulatory support (MCS) devices. This trial marks a turning point, showing lower 180-day mortality with the systematic use of Impella CP® in patients with CS secondary to AMI. Similarly, observational studies, such as that by Buda KG et al., suggest that early MCS use may improve survival, gradually consolidating the evidence supporting its systematic implementation despite previous less encouraging results. 

Acute kidney injury (AKI) is a common complication in patients with CS related to AMI and is associated with increased mortality. This substudy evaluated the incidence of AKI and the need for renal replacement therapy (RRT) in patients treated with microaxial flow pumps (mAFP) versus standard management. 

The clinical trial included 355 patients with CS secondary to AMI, randomly assigned to two groups: mAFP with the Impella CP® device (n=179) and standard treatment (n=176). Acute kidney injury (AKI) was defined using the RIFLE criteria, specifically category RIFLE I (Injury) or higher, characterized by a doubling of baseline serum creatinine and/or a reduction in urine output to less than 0.5 mL/kg/h for at least 12 hours. For the analysis of RRT requirements, the competitive risk of mortality was considered. Results showed an AKI incidence of 61% in the Impella CP® group versus 45% in the control group (p<.01), while RRT was required in 42% and 27%, respectively (p<.01). Although both events increased 180-day mortality, the use of Impella CP® demonstrated consistent survival benefits, regardless of AKI occurrence or RRT requirements. 

The authors conclude that the severity of CS, the use of Impella CP®, and device-associated complications increase the risk of AKI. However, mechanical support demonstrated significant survival advantages, highlighting the need to develop strategies to minimize adverse renal effects. 

COMMENTARY 

The DanGer Shock substudy provides crucial insights into the interactions between mechanical support and renal outcomes in CS management. While the 180-day survival benefits reinforce the value of Impella CP®, the high rates of AKI and RRT underscore the need to optimize its use. 

From the analysis, three key reflections stand out: 

1. Incidence of AKI and RRT. Elevated levels of plasma-free hemoglobin (derived from hemolysis) were associated with a higher risk of AKI. The greater incidence of AKI and RRT in the Impella CP® group could be attributed to events such as suction, high device speeds, and prolonged support durations—all associated with increased hemolysis. Therefore, meticulous device management is essential to minimize these events. 

1. Clinical predictors of AKI. Factors such as baseline renal function, positive fluid balance, and hemorrhagic events were identified as significant predictors of AKI. These findings emphasize the importance of rigorous and continuous monitoring during mechanical support to prevent and promptly manage this adverse outcome. 

1. Survival despite renal complications. Although AKI incidence was higher, Impella CP® consistently demonstrated survival benefits, suggesting that renal complications do not negate its overall hemodynamic advantages. 

The incidence of AKI and the need for RRT in this population exceeded what has been reported in previous studies, likely due to differences in definitions and criteria used. Among notable limitations, the heterogeneity in RRT initiation criteria across participating centers may have influenced the results. Furthermore, the lack of data on hemolysis biomarkers and other AKI indicators limits deeper analysis. Pulmonary artery catheter-derived data were also unavailable, complicating the distinction between cardiogenic and vasodilatory components of CS, which could have influenced both AKI incidence and outcomes. Lastly, the prolonged recruitment period, exceeding 10 years, during which advances in shock management, revascularization, and mechanical support occurred, could limit the current applicability of the findings. 

Based on these findings, the following strategies can be proposed to reduce the incidence of renal failure in patients treated with Impella CP®: 

1. Strict management protocols: Establish clear guidelines to prevent suction events and other device-associated complications. This includes early detection of suction indicators through pressure monitoring, proper inflow cannula positioning confirmed via echocardiography, optimization of intravascular volume, and adjustments to the lowest feasible support levels. 

1. Periodic biomarker monitoring: Conduct regular evaluations of hemolysis biomarkers such as plasma-free hemoglobin, bilirubin, haptoglobin consumption, and lactate dehydrogenase levels. Additionally, frequent monitoring of creatinine levels and fluid balance is recommended to identify early signs of AKI. 

1. Innovation in mAFP devices: Promote the development of improved microaxial flow pump devices with lower hemolysis risk and greater hemodynamic compatibility to minimize renal complications. 

This comprehensive strategy could not only optimize clinical outcomes and minimize complications in patients undergoing circulatory support with Impella CP® but also encourage the adoption of uniform criteria for RRT initiation, significantly improving the comparability and robustness of future studies. 

REFERENCE 

Zweck E, Hassager C, Beske RP, et al. Microaxial Flow Pump Use and Renal Outcomes in Infarct-Related Cardiogenic Shock: A Secondary Analysis of the DanGer Shock Trial. Circulation. 2024;150:1990–2003. doi:10.1161/CIRCULATIONAHA.124.072370.