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Complement activation in patients undergoing mechanical circulatory support
1Department of Thoracic and Cardiovascular Surgery, Deutsches Herzzentrum Berlin, Germany.
Insights
Complement activation, indicated by C3a and C5a levels, predicts outcomes for patients with ventricular assist devices. High pre-implantation levels suggest BVAD support may be beneficial, while persistent elevation post-implantation signals a poor prognosis.
Area of Science:
- Cardiovascular Science
- Immunology
- Biomaterials Science
Background:
- Artificial surfaces in mechanical circulatory support trigger pro-inflammatory responses and complement activation.
- Understanding complement factor C3a and C5a is crucial for predicting patient outcomes after VAD implantation.
Purpose of the Study:
- To investigate the prognostic value of complement factors C3a and C5a in patients undergoing mechanical circulatory support.
- To assess the impact of ventricular assist device type (LVAD vs. BVAD) on complement activation.
Main Methods:
- Studied 66 patients with severe cardiogenic shock requiring pulsatile ventricular assist devices (VADs).
- Measured C3a and C5a levels before and 3 weeks after VAD implantation.
- Compared outcomes between left ventricular assist device (LVAD) and biventricular assist device (BVAD) groups.
Main Results:
- Pre-implantation C5a levels in the BVAD group predicted post-implantation course (p=0.02).
- Patients with higher pre-implantation C3a levels benefited more from BVAD support.
- Elevated C3a levels 3 weeks post-implantation correlated with poorer outcomes and not reaching transplantation (p=0.007).
Conclusions:
- Complement activation severity is primarily linked to cardiogenic shock severity, not the VAD type.
- C3a and C5a levels can predict patient outcomes and guide VAD selection.
- Complement activation serves as an indicator of shock severity and organ recovery during mechanical circulatory support.
Abstract:
Contact of blood with artificial surfaces activates pro-inflammatory responses and the complement cascade. This may have broad implications on the post implantation fate of patients needing mechanical circulatory support. Therefore, we investigated the course and prognostic value of complement factors C3a and C5a in 66 patients supported with pulsatile ventricular assist devices. All patients were in severe cardiogenic shock, i.e., catecholamine dependent and in the intensive care unit, before implementation of mechanical circulatory support. Isolated left ventricular support (Novacor [Oakland, CA] or Thermo Cardiosystems, Inc. [TCI; Woburn, MA]) was used in 28 patients, and biventricular support (Berlin Heart [Mediport, Berlin, Germany]) in 38 patients. Before initiation of mechanical circulatory support, no statistically significant differences in C3a or C5a between surviving and nonsurviving patients with left ventricular assist devices (LVADs) were found. Patients with biventricular assist devices (BVADs) had significantly higher C3a (804 +/- 364 ng/L) levels than patients with LVADs (536 +/- 204 ng/L, p = 0.02) before mechanical circulatory support. Only C5a, only in the BVAD group, was able to predict patients' post implantation course before implantation of a ventricular assist device (p = 0.02). Three weeks after initiation of mechanical circulatory support, complement factors remained increased in all groups. There was no difference, however, in complement activation between patients with LVADs and those with BVADs. Patients not reaching transplantation had significantly higher C3a levels at this point than those successfully supported (p = 0.007). The degree of complement activation mainly depends on the severity of cardiogenic shock before initiation of mechanical circulatory support, and not on the device used. Patients with extremely high levels of complement activation before implantation of the device could be saved with BVAD rather than LVAD support. Patients who continued to have highly elevated complement levels 3 weeks after initiation of mechanical circulatory support had unfavorable prognoses. Complement activation indicates the severity of cardiogenic shock before implementation of mechanical circulatory support and the degree of recovery from secondary organ dysfunction while on the device. It is fairly independent of the system used for mechanical circulatory support, and therefore can be applied to predict patients' post implantation course and outcome.