Left ventricular assist device (LVAD)-related infections present a significant risk to patients undergoing continuous flow LVAD implantation with mortality rates up to 50%.1 The percutaneous driveline (DL) is the most common site of infection and if progressive, may predispose to ascending infection of the tissues surrounding the DL tract and deeper infection of the device itself and pump pocket.1 Driveline infections (DLI) occur in approximately 19% of recipients by 12 months after implant and negatively affect morbidity and mortality.2
It is now well recognized that trauma of the skin region surrounding the DL percutaneous exit site promotes the onset and maintenance of an inflammatory process and local infection.3 A number of patient related and unrelated factors have been proposed to increase the risk of DLI. Those include young age,2 diabetes,4 BMI extremes (overweight and underweight),4 low serum albumin,5 and blood product administration.6 Several measures including smaller DL size and use of the silicone portion of the HMII DL at the DL exit side7 have reduced incidence of DLI, whereas prophylactic antibiotics have not been proven to be beneficial.8 Because DL trauma is a major contributor to DLI, the placement of a temporary external anchoring suture (EAS; Figure 1) compromises skin integrity and increase risks of early cutaneous trauma when removed. In a survey from 2012, 78% of the 38 participating US institutions were using some form of EAS.9 Evidence for the use of EAS does not exist. We assessed whether the intraoperative placement of an EAS influenced the rate of DLI after index device implantation and evaluated preoperative and operative factors that may predict DLI. We further addressed the impact of pump type on incidence of DLI.
This research has been approved by the institutional review board of Vanderbilt University IRB 131978. From 2009 to 2014, we retrospectively analyzed patients undergoing HeartMate II (HMII, Thoratec Cooperation, Pleasanton, CA) or HeartWare ventricular assist device (HVAD, HeartWare Corporation, Framingham, MA) implantation at Vanderbilt University Medical Center for bridge to transplant (BTT) or destination therapy (DT) indications. We analyzed two consecutive patient cohorts according to placement of EAS or not. Exclusion criteria included continuous-flow LVAD (CF-LVADs) of a different type than HMII or HVAD, pulsatile flow LVAD recipients, right ventricular assist device, total artificial heart, and patients with preimplantation temporary support VAD support.
Both groups in this study had an internal anchoring suture placed within the mediastinum at the time of the LVAD procedure before sternum closure; a heavy 2.0 Prolene was uniformly used for to anchor the internal part of the DL to the diaphragmatic portion of the pericardium. For patients with an EAS, a chest tube-like 2.0 silk suture was added outside at the skin near the DL to further secure it. This silk suture was removed 4–6 weeks after device implantation according to surgeon’ recommendation. For patients with NO EAS, the DL was anchored internally to the rectus fascia without the use of the external anchoring silk suture. Both groups had subcutaneous tissue and skin closed around the DL using a 4.0 Monocryl suture. The velour portion of the DL was buried at least 2 cm away from the cutaneous exit site for all patients.
Perioperative and Outpatient LVAD Management Protocol
Patients were evaluated for CF-LVAD by our multidisciplinary LVAD selection committee based on current guidelines.10,11 All CF-LVADs were implanted by a single surgeon (S.M). Prophylactic antibiotics (vancomycin 1.5 mg/kg, cefepime 2 g, or levaquin 500 mg if penicillin allergy) were given before index surgery and continued postoperatively for 48 hours or until chest tubes were removed. All patients were initiated on guideline-based anticoagulation with aspirin, coumadin (with heparin bridging starting postoperative day 2), and heart failure medications after LVAD implantation as tolerated.12 Driveline site dressing changes were performed daily after index implant if drainage was present, however upon discharge, all DL dressing changes were performed with sterile technique utilizing a standard dressing supply kit (Centurion Medical Products, Williamston, MI) every 3–5 days. All patients were counseled on wearing an abdominal binder. Outpatient follow-up was mandatory and clinic visits are staffed by an advanced heart failure cardiologist weekly for the first month, bi-weekly for the second month, then monthly thereafter. Driveline infections were assessed at each clinic visit, regardless of specific patient complaints. All patients were also seen by the implanting LVAD surgeon in follow up, who made the decision to remove external fixation (average 4–6 weeks after implant when DL was completely incorporated). All patients and caregivers were required to attend CF-LVAD education sessions and DL management care proficiency before discharge.10,11 If DL trauma or infection was suspected or confirmed, patients were treated empirically with oral ciprofloxacin 500 mg by mouth twice a day and doxycycline 100 mg by mouth twice a day for 7–10 days.
Definition of Suspected and Confirmed DLI
Confirmed DLI was defined by clinical signs of infection, pain, fever, drainage, laboratory signs of infection, radiological examination and a positive bacterial culture taken from the DL exit site. Suspected DLI was defined by the previously mentioned clinical signs without a positive culture result (or if no culture was available).13 Suspected DLI also included mechanical trauma to the DL, which resulted in new drainage, even without classical evidence of infection. All instances of suspected DLI resulted in prophylactic treatment with doxycycline and ciprofloxacin for 7 days.
The primary end-point of this study was a diagnosis of confirmed or suspected DLI based on presence or absence of an EAS. Unadjusted time to infection as estimated by Kaplan–Meier analysis was performed for confirmed and suspected DLI and based on device type (HMII or HVAD). Infection rates were calculated in events per patient year. A covariate adjusted Cox proportional hazards model was used to assess the effect of EAS on infection. Prespecified covariates included age, BMI, blood product utilization, LVAD type (HMII or HVAD), and diabetes. Total blood products used was modeled with a cube root transformation because of its high skewness. These analyses were done using the R statistical package, version 3.1.1 (2014).14
A total of 161 patients (HMII 82, 51%; HW 79, 49%) were included in the final analysis. Eighty-five patients were included in the EAS group (HMII 49, HW 36) and 76 patients (HMII 33, HW 43) were in the NO EAS group. Baseline characteristics (age, gender, diabetes, BMI, CF-LVAD type) were comparable between groups (Table 1) except blood product utilization was higher in the EAS group compared with the NO EAS group (p = 0.005). Follow up ranged from 0.04 to 5.42 years with a mean of 0.93 years.
Driveline Infection Analysis
A total of 18 (11.1%) patients developed confirmed culture positive DLI, with a “first infection” rate of 0.13 events per patient year. Mean time to confirmed DLI was 0.69 years. A total of 73 patients (45%) developed suspected DLI with a “first infection” rate of 0.68 events per patient year. Mean time to suspected DLI was 0.46 years. Freedom from confirmed (p = 0.05) and suspected (p = 0.085) DLI is depicted in Figures 2 and 3, respectively. Confirmed DLI was less likely (hazard ratio [HR] = 0.28, 0.95 confidence interval [CI] = 0.06–1.25, p = 0.056) to occur in the NO EAS (2/18) group then in EAS (16/18) group. Suspected DLI was more likely (HR = 1.56, 0.95 CI = 0.94–2.57; p = 0.085) to occur in the NO EAS group (42/73) versus the EAS group (31/73). Confirmed and suspected DLI was comparable between device types (p = 0.30; Figures 4 and 5).
Covariate-Adjusted Analyses of Time to Infection
After adjusting for age, BMI, blood product use, device type and diabetes, multivariable Cox regression showed equivocal effects of EAS with current follow-up (HR = 3.05, 0.95 CI = 0.65–14.31, p = 0.12); and the direction of the EAS effect seemed harmful. None of the preselected covariates was predictive of confirmed DLI (Table 2) or suspected DLI (Table 3).
Main Findings of the Study
This is the first clinical study to analyze the value of temporary EAS placement for the prevention of DLI. We found that an EAS does not decrease risk for DLI and actually may potentially increase the risk of confirmed DLI after device implantation. Unfortunately, we were unable to find predictors of DLI from perioperative variables, such as age, BMI, diabetes, or total perioperative blood product use. These findings have important clinical implications because recent trends in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry indicate CF-LVADs continue to be heavily used as a BTT/DT strategy.15 As duration of device support continues to increase, patients will be exposed to a greater burden of DLI, highlighting the importance of this topic in future studies attempting to systematically explore ways to reduce DLI. These results have changed our current practice and should prompt the LVAD community to consider a standardized approach for DL fixation eliminating the use of an EAS. Because of the current findings, we now avoid utilization of an EAS for all patients implanted with long-term device in our institution.
Driveline Infections After Device Implantation
Driveline infections are a common complication of VAD support often leading to increased complexity of medical care, decreased patients’ quality of life, and increased costs for LVAD patients and the health care system.16,17 Furthermore, patients who develop DLI experience overall lower rates of cardiac transplantation18 and a trend toward decreased survival.6 Most DLI occur at the exit site and have been found to be related to local trauma within the first several months.19,20 The effectiveness of current therapies of DLI is unknown and includes antibiotic therapy and surgical interventions like debridement or VAD exchange. Thus, the prevention of DLI has become one of the primary focuses of perioperative management of VAD therapy. Some of the measures commonly applied are temporary EAS, continuous abdominal binders and other devices for immobilization of the DL like a drain tube attachment device (Hollister Incorporated, Libertyville, IL) or a Foley anchor (Centurion Medical Products, Williamston, MI). The only studied intervention is the StatLock (Bard Medical, Covington, GA) device used to immobilize the DL after VAD implantation. Although its use has been reported to be successful at DL immobilization, outcomes were only studied in a case series of six patients.21 Our finding that the widely applied EAS do not decrease the risk for confirmed DLI but might be even associated with a higher risk could be explained by the additional introduction of a foreign material into the DL exit area, which serves as an entry point for pathogens. Furthermore, the removal of the suture material approximately 1 month after its placement might represent an additional hazard for trauma and local infection.
Risk Factors for DLI
There is uncertainty in the literature as to which patient related and unrelated factors are associated with the development of DLI. Variables such as younger age, high BMI, and diabetes1,19,22 have been rebutted in various studies.5,23 Imamura et al5 assessed 57 patients who were supported with heterogeneous continuous flow devices for perioperative predictors of DLI and derived an equation using serum albumin and BMI that was able to predict DLI with an AUC of 0.81. In our study, we did not find a relationship among the covariates (age, BMI, device type, blood product use, diabetes, and EAS use) and DLI. Discrepancies between various studies could be explained by study populations, number of patients included in the study sites, DL dressing protocols, and definition of DLI. We choose to study DLI based on a conservative definition of confirmed DLI. Clinically, it is not realistic to obtain DL cultures (and therefore confirm DLI) from all patients before starting antibiotics when patients live in geographically disparate areas from implanting center. Our center has adopted a broader definition of suspected DLI to ensure appropriate categorization for LVAD program quality metrics. This is the first study to distinguish between suspected and confirmed DLI, which likely represents a “real-world” approach to DLI management. Only the elimination of the percutaneous DL and the introduction of a fully implantable device powered by transcutaneous energy transfer systems would eliminate the risk of percutaneously introduced infections.
Our study has several important limitations. This is a single center, retrospective study that occurred in two different time periods, raising the concern for selection bias. Furthermore, both groups were consecutive which can add another confounder to the study. Despite this concern, our program has been consistent in other DL fixation and management techniques, including mandatory LVAD clinics and protocoled DL assessment. The analysis is limited by the short follow-up of EAS patients and the low number of confirmed infections. The follow up time in the EAS group was longer than in the NO EAS group. It is possible that the EAS may have been different among different implanting surgeons, however all of CF-LVADs at this institution were implanted by only one surgeon (S.M.), making this an unlikely reason for differences in EAS-related outcomes. A braided suture has been used in all patients and can theoretically increase risk of infection as compared with other sutures (like monofilament). Despite this choice of suture, all patients in the study had the same anchoring suturing approach, making comparison of external versus internal anchoring comparison valid. It is also possible that our management for suspected DLI, which includes treatment with antibiotics, may have reduced the true rate of confirmed DLI, however our DLI rates fall within reported infection rates in the literature.24,25 The trend for the increase in suspected cases of DLI in the NO EAS group could be explained in changes of DL management. Although DL care measures remained unchanged, caretakers became more vigilant about the significance of DL trauma with time, possibly leading to earlier detection of DLI (with negative cultures) and increased use of prophylactic antibiotics. We acknowledge that the trend for increase in suspected DLI could in parts explain the decrease in confirmed DLI over time and confound our results on the use of EAS.
Use of a temporary EAS does not reduce the risk of DLI and may increase the risk of confirmed DLI after device implantation. Driveline infection appears comparable among currently used CF-LVAD device types. These results should prompt the LVAD community to consider initiation of a prospective, randomized controlled trial that focuses on a standardizing DL fixation to improve DLI rates and elimination of direct external DL fixation.
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