According to the 7th Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) annual report, there are currently around 2500 left ventricular assist devices (LVADs) implanted annually for the treatment of advanced heart failure, and this number is expected to grow exponentially in the future.1 Despite constant improvements in LVAD technology, which has been translated to improved quality of life and increased overall survival, driveline infections (DLIs) still represent one of the leading LVAD-related complications with an estimated prevalence of 14–48%.2,3 Driveline infection has been associated with increased mortality, risk of pump thrombosis, and stroke as well as with increased hospitalization rates, and the financial burden of readmission is estimated at $7000 (direct hospital cost).4,5
Driveline infection is commonly defined as an infection involving the soft tissues surrounding the driveline exit site, typically accompanied by erythema, warmth, and purulent discharge.6 The International Society of Heart and Lung Transplantation defines three stages of DLI ranging from minor erythema that requires no systemic treatment to superficial infection and deep infection, the latter demands hospital admission in most cases.6 Driveline infection likely begins with disruption or trauma to the barrier between the skin and driveline, the latter, itself a foreign material, plays a major role in the pathogenesis of DLI.7 Driveline infection-associated risk factors may include younger age, malnutrition, exit-site trauma, duration of LVAD support, and comorbidities, such as diabetes and chronic kidney disease (CKD).3,8–12 Low and high body mass index (BMI) have also both been suggested as risk factors for DLI by some studies, whereas other authors failed to establish any association between body weight and DLI in this patient cohort.13,14 This lack of consensus and contradictory clinical data most likely reflect the differences in patient population and variations in definition of DLI across the different LVAD centers.
This investigation aimed to explore a potential association between DLI and BMI in the modern-era LVAD patient population in an effort to provide evidence to provide further evidence to the current contradictory clinical data.
In a retrospective, single-center study, 222 consecutive advanced heart failure patients who underwent continuous-flow LVAD implantation between May 2012 and July 2016 were enrolled. Patients with <30 days of LVAD support, and patients requiring biventricular VAD support were excluded from the study. All patients were implanted with either HeartMate II (Thoratec Corporation, Pleasanton, CA), HeartWare Ventricular Assist Device (HVAD) (HeartWare International Inc., Framingham, MA), or HeartMate 3 (Thoratec Corporation, Pleasanton, CA) continuous-flow LVADs. Enrolled subjects were then divided into either the DLI group (N = 45) or the non-DLI group (N = 177) based on whether they had experienced at least one episode of DLI. All patient follow-ups on the outpatient basis were per the institution’s protocol. At baseline and at each follow-up visit, clinical, laboratory, and LVAD-related data were collected. Body mass index was calculated using height and weight at time of LVAD implant using the standard equation (BMI = mass [kg]/height [m2]). Driveline infection was characterized according to the INTERMACS registry definition of the percutaneous site infection.1 In accordance with the World Health Organization's definition, obesity was defined as BMI ≥30 kg/m2. Chronic kidney disease was defined as baseline serum creatinine >1.4 mg/dl.
Data are summarized and presented using standard statistical descriptors: frequencies, percentages, mean, median, standard deviation, and percentile. Categorical variables were compared with χ2 test. All continuous variables were tested for normality of distribution using Shapiro–Wilk test. Normally distributed variables were presented as mean and standard deviation, and the t-test was used to compare the variables. The correlation between variables was explored with Pearson’s correlation test. Statistical significance was set at p <0.05.
Baseline patient characteristics are reported in Table 1. Of the 222 included patients, the majority were male (80%) with the underlying diagnosis of heart failure being nonischemic heart failure in 56% and ischemic heart failure in 44%. The prevalence of comorbidities was fairly standard for this patient population and comparable with the INTERMACS registry.1
HeartMate II LVAD devices were implanted in 164 (74%) patients, 52 (23%) patients received an HVAD and 6 (3%) received the HeartMate3. With regards to the LVAD treatment strategy, 144 (65%) patients received an LVAD as a destination therapy and 78 (35%) as bridge to transplant. 56% of the patients were in INTERMACS profile 1 or 2 at the time of LVAD implantation and the rest were in INTERMACS profile 3 or 4.
Patients were divided into two groups: DLI (N = 45, 20%) and non-DLI (N = 177, 80%) based on whether they had experienced at least one DLI event. The characteristics of both groups are shown in Table 2. The average time (standard deviation) to DLI onset after LVAD implantation was 296 days (±292 days). The two groups did not significantly differ in gender, heart failure etiology, or comorbidities, including risk factors for an infection such as diabetes and CKD. Additionally, no significant differences were found regarding biochemical parameters, LVAD treatment strategy or INTERMACS profiles at the time of LVAD implantation. However, our data suggest that patients who developed DLI had a higher BMI (Figure 1A) and were younger (Figure 1B) in comparison to patients who did not develop DLI. There was a significant positive correlation between BMI and DLI (p < 0.0001), and age was negatively correlated with DLI (p = 0.01).
When the patients were stratified according to BMI, 29% of patients with BMI ≥30 kg/m2 (obese) were shown to develop DLI in comparison to only 13% of patients with BMI <30 kg/m2 (nonobese) (p = 0.0009), which is statistically significant (Figure 1C).
Additionally, the potential association between patients’ BMI and the time-to-first DLI was explored, but no correlation was found between the two parameters (p = 0.25, R2 = 0.005) (Figure 1D).
The data from this patient cohort confirms that higher BMI is associated with a higher prevalence of DLI in advanced heart failure patients undergoing LVAD support. Further, the patients who developed DLI were younger. We, however, did not find a correlation between the time-to-first DLI and BMI.
Apart from heart transplantation, LVAD therapy currently represents a reliable treatment strategy for the management of patients with advanced heart failure. Although initially this therapy was reserved for a bridge-to-transplant approach with relatively short LVAD support times, recently, there has been a significant increase in the use of LVADs as a destination treatment option.1 With expanded indications for LVAD use, an exponential growth in the number of LVAD patients and in the length of LVAD support is expected in the coming years.1
Technical advances in LVAD technology (switch from large, pulsatile pumps to nonpulsatile intrapericardial pumps) and changing the driveline design (bend reliefs, introduction of polyurethane or silicone coating instead of Dacron velour) have led to a significant decrease of DLI in this patient cohort.1 Unfortunately, LVAD infections and especially DLI still continue to represent one of the most common and debilitating complications in this patient cohort.1 Current literature suggest the prevalence of DLI in second- or third-generation LVADs being around 15%, and several patient-associated risk factors for the DLI (age, nutritional status, use of inotropic support, CKD, and diabetes) have already been established.3,9,15–17 Published data have shown that patients with poor nutrition prior LVAD implantation, patients with CKD (especially if renal replacement therapy is needed), and patients with diabetes are up to 70% more prone to LVAD infections than patients in which these risk factors are absent.9
Studies associating DLI and patients’ body weight are conflicting. Several recent investigations failed to observe a direct relationship between DLI and BMI.3,18–20 Nevertheless Raymond and coworkers21 did show a significant increase in the incidence of DLI in patients with higher BMI. Importantly, this patient population was mostly supported with pulsatile first-generation LVADs, which can hardly be compared with modern-era LVADs. Furthermore, HVAD patients with DLI were also reported to have a higher BMI than those who did not develop DLI.14 Our results use current-era LVADs and support the association of DLI and BMI in advanced heart failure patients undergoing LVAD mechanical circulatory support.
The pathophysiology of DLI in patients with higher BMI is multifactorial and complex. A recent National Surgical Quality Improvement Program (NSQIP) analysis confirmed previously published association between obesity and surgical wound infections.22
There is strong evidence indicating that increased BMI negatively impacts immune function and host defense and that it promotes systemic inflammatory response in obese individuals as considerable discrepancies in leucocyte number and subset counts and phagocytic and oxidative burst activity of monocytes between normal-weight and obese individuals.23 Additionally, circulating mononuclear cells in obese people exhibit a proinflammatory state compared with nonobese persons.23 Furthermore, impaired lymphocyte proliferation to polyclonal stimulation has also been reported in obese people, blunting their response to potential pathogens that may cause DLI.23
Type II diabetes, a common complication of obesity, is further associated with impaired immune cell activity.24 Interestingly, in our patient cohort, diabetes was not established as a risk factor for DLI. This is most likely because of the selection bias as patients with advanced heart failure who have diabetes and diabetes-associated end-organ damage are often not considered suitable candidates for mechanical circulatory support or heart transplantation.
Our data additionally suggest that younger age may be a risk factor for DLI. This is in line with previously published data.3 This finding is thought to be because of higher activity rates, and therefore increased risk for driveline exit-site trauma, in the younger population.3 Additionally, compliance with healthcare provider instruction on VAD handling, medication and attention to wound care may possibly account for higher DLI in younger LVAD population.
This study does have limitations that are inherent to retrospective data analysis. Additionally, the sample size of patients who developed DLI was relatively small. Furthermore, our patients were supported with three different types of LVADs, which may have also affected our results. Last, in comparison to other trials, the majority of our patients were a part of destination therapy protocol, which means our study population may be different from the ones reported in the previous studies. Nevertheless, we feel that our data are representative of the current-era real-life LVAD patient population and may add to the understanding and the management of DLI in this patient cohort.
The data suggest that higher BMI is associated with the development of DLI in patients with advanced heart failure undergoing LVAD support. As DLI can significantly impact patient quality of life and increase the risk of patients’ mortality, pump thrombosis, and stroke as well as hospitalization rates, all risk factors, associated with DLI, have to be addressed and managed meticulously in order to effectively decrease the rates of DLI. Traditional and novel therapeutic approaches of obesity management such as laparoscopic sleeve gastrectomy may decrease the rates of DLI in obese patients undergoing LVAD support even further and should be considered in this patient cohort. Further, transcutaneous energy transfer that is currently being introduced in the clinical setting may represent a key solution to the DLI.
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