In patients with durable LVAD support, infections are an adverse event frequently contributing to significant morbidity and mortality. According to the International Society for Heart and Lung Transplantation, infections in these patients can be classified as:

• Non-LVAD-related infections: Infections not promoted by the presence of the device and unlikely to be associated with it, such as respiratory and urinary tract infections.
• LVAD-related infections: Infections that can also occur in patients without an LVAD; however, unique considerations arise due to the LVAD system, including endocarditis, mediastinitis, and bacteremia.
• LVAD-specific infections: Infections unique to LVAD carriers, linked to the device’s physical components and unlikely to occur in non-LVAD patients, such as driveline infections and infections involving any of the device’s components or the implantation space.

The study’s objective was to investigate the possible association between infections and thromboembolic events, particularly cerebrovascular accidents (CVAs), in long-term LVAD-supported patients.

The data analyzed were obtained from the European Registry for Patients Assisted with Mechanical Circulatory Support (EUROMACS). A Kaplan-Meier survival analysis was conducted to assess the risk of CVA in patients who developed infectious processes while supported by an LVAD, alongside a multivariable Cox regression model.

A total of 3282 patients were included, of whom 1262 (38%) experienced some form of infection, and 457 (14%) suffered a CVA episode. Cox regression analysis revealed that a history of infection nearly doubled the risk of CVA (HR 1.9; 95% CI: 1.5–2.3; p < 0.001). When infections were categorized as previously mentioned, only LVAD-related and LVAD-specific infections reached statistical significance, increasing the risk of CVA by 50% (HR 1.5; 95% CI: 1.1–2.0; p = 0.002) and almost doubling it (HR 1.9; 95% CI: 1.4–2.8; p < 0.001), respectively.

COMMENTARY:

This study indicates that infections in LVAD patients constitute a significant risk factor for the development of both ischemic and hemorrhagic CVAs, either synchronously or metachronously. Several insights emerge from this research:

1. The clinical temporal association between infections leading to CVAs is often unclear in the literature. Kaplan-Meier follow-up analysis suggests that some embolic episodes likely arise from a hypercoagulable state during active infection, while others may occur later due to biofilms and microthrombi formation on the system, following previous bacteremia episodes.
2. Continuous-flow LVADs also contribute to endothelial dysfunction, which can exacerbate existing acquired von Willebrand disease and thus increase hemorrhagic events. The septic nature of some emboli and the hemorrhagic tendency in the context of anticoagulation predispose to hemorrhagic transformation of initially asymptomatic microemboli, leading to secondary hemorrhagic CVA.
3. Although infection and CVA association may be primarily linked to previous bacteremia episodes, intriguingly, the analysis suggests an equal or greater influence of LVAD-specific infections compared to LVAD-related infections regarding CVA risk. This may be due to a higher-than-expected rate of subclinical bacteremia episodes.

Therefore, prompt and aggressive treatment of infections in LVAD patients is essential, coupled with proactive anticoagulation management. Radical infection treatment remains challenging, and to date, there are no evidence-based antimicrobial guidelines for these patients. Further studies are needed to develop a standardized diagnostic and therapeutic approach, targeting both infection treatment and CVA risk reduction, as these events are more interconnected than initially presumed.

REFERENCE:

Zijderhand CF, Antonides CFJ, Veen KM, Verkaik NJ, Schoenrath F, Gummert J, et al. Left ventricular assist device-related infections and the risk of cerebrovascular accidents: a EUROMACS study. Eur J Cardiothorac Surg. 2022 Oct 4;62(5). doi: 10.1093/ejcts/ezac421.