As the number of patients with end-stage heart failure continues to grow, while the availability of donor organs for heart transplantation remains limited, the use of mechanical circulatory support devices (MCSDs) as a bridge to heart transplantation has increased dramatically.1 Implantable durable MCSD includes ventricular assist devices and the total artificial heart (TAH). According to a recent report from the Interagency Registry for Mechanically Assisted Circulatory Support, 301 patients, representing 1.9% of the total US population undergoing durable MCSD, had received a TAH.2 Infectious complications are common in patients with durable left ventricular assist devices, with an incidence of infection between 18% and 59%.3 However, data on infections in patients with a TAH are limited to two small case series.4,5 Therefore, further characterization of causes and risk factors of such infections could modify current treatment protocols and potentially improve clinical outcomes. The further goal would be to have a standardization of definitions of infections in patients with TAH, as it already exists for ventricular assist devices.6
Patients who received a CardioWest TAH at Virginia Commonwealth University (VCU) between January 1, 2010 and December 31, 2011 were identified from the VCU Mechanical Circulatory Support Clinical Database. The VCU institutional review board approved the protocol, after request of exempt review under the category of a secondary data analysis of existing data. Therefore no consent was required. Retrospective data extraction from medical records was performed from the time of TAH implantation until heart transplantation or death, whichever came first. Data consisted of patient demographics, comorbidities, date of TAH implant, duration of support until transplantation or death, infection location, infection onset, antibiotic treatment, microbiology, and ancillary tests. Blood and other appropriate cultures were routinely obtained whenever a suspicion of infection was present. This information was entered in case report forms in the software Epi Info (Centers for Disease Control and Prevention, Atlanta, GA). A new database was created for research purposes with de-identified data.
Infections were classified as confirmed (whenever the patient chart specified a diagnosis of infection confirmed by culture) or suspected (there was no specific diagnosis of infection, cultures were negative but antibiotics course was administered for leukocytosis or fever). All infections were tracked, irrespective of the relation to the TAH implant. Patients with and without infections received similar treatment except for the use of antibiotics in patients with infections. Analysis of data was performed with Epi Info and Office Excel (Microsoft Corporation, Redmond, WA).
Twenty-seven men and five women received a TAH between January 2010 and December 2011 at VCU Medical Center. The mean age was 49.5 ± 11.2 years (range 24–68 years). Other baseline characteristics are presented in Table 1. Duration of TAH support ranged from 1 to 1,334 days, with a mean duration of 225 days and a median of 120 days. All patients undergoing TAH implantation received perioperative antibiotic prophylaxis. The duration of prophylaxis ranged from 3 to 7 days, with the most common regimen consisting of vancomycin, piperacillin/tazobactam, and fluconazole. In penicillin-allergic patients, levofloxacin was substituted for piperacillin/tazobactam. The TAH driveline dressing care was performed using sterile technique. The site was cleansed with ChloraPrep (BD Worldwide, Franklin Lakes, NJ) (2 minute dwell time), then with sterile saline using a figure eight technique, then dried with 4 × 4s, covered with split gauze and 4 × 4s, and then secured with tape.
Of the 32 patients, 4 (12.5%) died before transplantation, and 28 (87.5%) received a heart transplant. Causes of death were pneumonia (n = 1), TAH malfunction (n = 1), refractory cardiogenic shock (n = 1), and respiratory failure (n = 1). Thus, only one death was attributed to infection. The one-year post transplant survival rate was 82%. On Kaplan–Meier analysis, the one-year survival was similar in those with and without any infection after TAH implantation (82% vs. 83%, log rank test: p = 0.9).
Seventy documented and 13 suspected infections developed in 25 of 32 patients (78%). This represented 4.15 events per patient year. The mean duration of TAH in patients who developed an infection was 259 days (median of 121 days), and the mean duration of TAH in patients who did not develop an infection was 106 days (median 104 days). The patient who died of cardiogenic shock belonged to the group that did not develop an infection and had only one day of TAH support. Patients with an infection stayed in the intensive care unit after implantation of the TAH for 26 ± 31 days versus 10 ± 8 days in those without an infection (p = 0.19).
The most common locations of infection were the urinary tract (n = 26), the respiratory tract (n = 18), and the bloodstream (n = 11). There were five pump infections and two driveline infections, developing at a median of 168 and 106 days, respectively (Figure 1). The number of infections per patient ranged from 0 to 10. Sixteen different pathogens were identified; the most common were: Klebsiella pneumoniae (n = 15), coagulase-negative Staphylococci (n = 10), Enterococcus species (n = 9), and Enterobacter species (n = 8). Table 2 lists all of the isolated pathogens. Figure 2 illustrates the sites of infection associated with the most common pathogens. All infected patients underwent a full course of antibiotic treatment before undergoing heart transplantation, with the exception of two patients with pump infection and one with a simple urinary tract infection. The diagnosis of five pump infections was made when the pathogen found in the blood cultures was also identified in the tissue samples of the patients obtained at the time of TAH explantation.
To our knowledge, this is the largest reported series to systematically document the occurrence of infections in patients with a TAH. Similar to previous reports, we found that the incidence of infections was extremely high in this population.4,5 The most common locations of infection were the urinary tract, the respiratory tract, and the bloodstream, and many patients had multiple infections. Given the lack of standardization regarding the definition of TAH-related infections, we reported all infections which were documented or suspected in our patient population, regardless of direct association to the device itself. Therefore, the high frequency of infections likely represents, in part, those common to all critically ill patients.
Other definitional issues arise because during implantation of the entire native heart as well as the proximal portions of the great arteries are excised. This makes the distinction between endocarditis, pericarditis, and mediastinitis challenging. Therefore, infections in any of these locations were considered to represent pump infection. We observed five pump infections in our TAH population, representing 16% of patients and 6% of all infections. Driveline infections were relatively uncommon (7%, 0.1 events per patient year) and the rate in our TAH population appears to compare favorably to that associated with other types of durable MCDS.3,7,8 Nevertheless, further efforts to reduce these rates are warranted.
In the previously reported two cases series there is no specification of the most common pathogen found in their population. In our patient population, the most common isolated pathogens were K. pneumoniae, coagulase-negative Staphylococci, and Enterococcus species. The latter two pathogens are biofilm-forming bacteria which have been well-described as common pathogens responsible for ventricular assistant device infections.9 The high frequency of K. pneumoniae infection likely relates to its propensity to cause respiratory and urinary tract infections in critically ill patients, irrespective of TAH implantation. There was no unusual organism antibiotic resistance.
Although the incidence of infections was quite high, only one death was considered to be directly related to infection and no deaths were directly related to pump or driveline infections. Therefore, infectious complications do not appear to be a major impediment to intermediate-duration support with a TAH in patients awaiting heart transplantation.
In patients undergoing TAH as a bridge to cardiac transplantation, infections were common. However, mortality directly attributable to infection was infrequent.
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