Annually, more than 250,000 patients in the United States suffering from advanced heart failure may potentially benefit from treatment with durable left ventricular assist device (LVAD) therapy as a bridge to cardiac transplantation or as permanent therapy.1 However, the broader application of durable LVAD therapy, particularly for permanent use, has been hindered by the overall burden of adverse events and the need for frequent hospital readmission.2 Although significant improvements in device technology have reduced the risks of stroke, pump malfunction, need for pump exchange, and nonsurgical bleeding, infection remains a significant problem and is now a leading cause of morbidity and mortality in patients supported with durable LVADs.3,4 Device-specific infections, those directly related to infection of the LVAD, have been shown to significantly increase mortality risk and are associated with a hazard of death of 2.92 (95% confidence interval [CI]: 2.57–3.32).5 Additional studies have recently found that rates of infection in patients receiving durable LVAD support (risk adjusted by patient characteristics) vary by hospital and contribute to a significant increase in medical costs.6

Patients supported with durable LVADs are at increased risk for device-related and nondevice-related infection despite highly protocolized perioperative and postoperative care. Current durable LVAD technology requires an uninterrupted external power source connected to the patient through a percutaneous lead or driveline to provide power and control to the implantable pump. This device design is a major limitation of the current LVAD technology and serves as a potential source for the development of infection given its connectivity between the patient and the external environment.5 In addition, LVAD therapy is frequently associated with other infections that are nondevice-related, including pneumonia and surgical site or bloodstream infections.7 LVAD patients are at a unique risk for infections given: 1) the burden of multiple preoperative comorbid conditions; 2) the invasive nature of durable LVAD implantation; 3) hemodynamic instability and systemic inflammation that often occurs at the time of device implantation; 4) the presence of the percutaneous lead; 5) extended intensive care unit stays; and (6) concurrent need for invasive monitoring.

Recent reviews of the literature examining nonpatient-related factors and patient factors associated with infection in LVAD recipients have identified that the majority of studies investigating infection in the setting of durable LVAD therapy are single-center, observational studies.6,8,9 These literature reviews have identified only two nonpatient factors consistently associated with a lower risk of infection in patients receiving durable LVAD implant: 1) increasing center experience and 2) establishing a silicone-skin interface at the driveline exit site.8 With regard to patient factors, patient race, and sex did not correlate with infection risk. Additionally, no consistent association has been noted between obesity, diabetes, or psychosocial/socio-economic factors and infections in patients supported with durable LVADs.9 Only two observational studies have reported a significant association between malnutrition and hypoalbuminemia and postimplant infections in LVAD recipients.9 Patient-related comorbidities, especially body composition and diabetes, were the most common comorbidities evaluated but were not shown to be consistently associated with infections following durable LVAD implantation.

Despite the heightened concern regarding the risk of infection and efforts to identify factors contributing to infection and methods for prevention, infection in patients supported with durable LVADs, particularly device-related infections, remains on ongoing problem with durable LVAD support. In this issue, of the Journal, Lumish et al.10 investigated the impact of standardized driveline care initiatives, specific pathogens, and chronic antibiotic suppression on rates of driveline infections and outcomes in patients receiving durable LVAD therapy. In a retrospective, single-center, observational study of 591 LVAD recipients, patients were retrospectively categorized based on driveline care initiatives implemented at their institution from 2009 through 2019. The categories of the era included: 1) Era (E)1: nonstandardized care; 2) E2: implementation of a standardized driveline care protocol; 3) E3: addition of preoperative marking the driveline exit site; and 4) E4: addition of a “no shower” policy. During the study period, 87 (15%) patients developed a driveline infection at a median time (IQR) of 403 (520) days following device implantation. Of the causative organisms, Staphylococcus aureus and Pseudomonas aeruginosa were the most common pathogens. With respect to treatment, 31 (36%) of patients experiencing a driveline infection required incision and drainage and 5 (5.7%) patients required device exchange. Of the infecting organisms, Pseudomonas aeruginosa was associated with a significantly increased risk for initial incision and drainage (Hazard ratio: 2.7; 95% CI: 1.1–6.3) and recurrent need for incision and drainage or death (Hazard ratio: 4.2; 95% CI: 1.4–12.5). Initial treatment with incision and drainage was associated with a significant increased risk of death (Hazard ratio: 2.92 95% CI: 1.33–6.44); P = 0.008) when compared with patients who did not develop a driveline infection. Importantly, implementation of standardized driveline care protocol (E2) was associated with increased 2-year freedom from driveline infection compared with non-standardized care (Hazard ratio: 0.36; 95% CI: 0.2–0.6; P < 0.01). Additional preventive strategies including preoperative marking of the driveline exit site and prohibiting patient showers demonstrated no further reduction in rates of driveline infections. Of the patients with a driveline infection, 57 (65%) received chronic antibiotic suppression and 44% of patients required escalation to intravenous antibiotics and/or treatment with incision and drainage. The presence of infection with Pseudomonas aeruginosa markedly increased the risk of the need for incision and drainage and for death.

The study by Lumish et al.10 is notable and significant for several reasons. First, the study reaffirms the morbidity and mortality of device-related infection in patients supported with durable LVAD therapy. Despite notions to the contrary, driveline infections are not benign events and significantly impact the quality of life and survival for patients supported with durable LVADs. In their study, approximately 43% of patients with a driveline infection received heart transplantation. Thus, the long-term risks of driveline infection were likely mitigated in the study by Lumish et al.10 and underestimated the adverse impact of these infections on patients receiving durable LVAD therapy for permanent use. Second, infection with Pseudomonas aeruginosa portends a significant progression of infection that is unlikely to be controlled with local therapy, either antibiotic suppression or local incision and drainage. Local control methods using incision and drainage with vacuum-assisted wound closure were not uniformly successful and nearly 40% of patients in the study undergoing an incision and drainage procedure for any infection required recurrent incision and drainage. This observation highlights a strategy of prevention as the best principal approach to driveline infection and makes the last major point of the study so impactful. During the course of the study, the authors noted that implementation of a standardized driveline care protocol was associated with increased 2-year freedom from driveline infection.

There are a number of important limitations to the study reported by Lumish et al.10 First, this is a single-center, retrospective, observational study and likely has issues of confounding that cloud some of the inferences of the study. As noted by Shore et al.8 and Pienta et al.,9 the overwhelming number of studies reported in the literature on this topic are retrospective and observational in nature. Prospective, randomized studies to assess interventions to prevent or treat infection in this population are importantly needed but lacking. The methods for local surgical intervention likely varied over the course of the study and by surgeon and details of the approaches are limited in the description. Few patients underwent device exchange, so the effectiveness of this strategy is not assessable. Finally, the study largely consisted of a population of transplant-eligible patients that is significantly different than patients currently receiving durable LVAD therapy in the United States who receive durable LVAD support for destination therapy.

Care processes and care protocols do matter and the work by Lumish et al.10 should be highlighted to emphasize this point. Prevention is a viable and effective strategy to limit the adverse impact of driveline infections. Until such time improvements in durable LVAD technology remove the need for a driveline and introduce totally implantable devices, our focus of care should highlight effective strategies on infection prevention in this population.

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