Transcatheter aortic valve implantation (TAVI) is a minimally invasive procedure used to treat severe symptomatic aortic stenosis. It involves the delivery of a tissue valve mounted on a collapsible stent through a catheter into the aortic annulus. In most cases, the procedure is performed percutaneously through the femoral artery, although it can also be done through surgical exposure of the femoral artery, with a mini-thoracotomy to access the aorta or with transapical access through the left ventricle. TAVI has been established as an effective therapy for patients in whom surgical aortic valve replacement is not an option and for other high-risk patients. In the past decade, increasing numbers of TAVI procedures have been done globally each year. Understanding and mitigating the risks and complications of the procedure, such as postprocedural infections, is paramount. Only limited data are currently available to describe the infectious morbidity. In this study, we describe the incidence of infections associated with TAVI at an academic teaching hospital, and we identify risk factors associated with the development of these infections.
METHODS
This observational retrospective cohort study included all patients who underwent TAVI at Sunnybrook Health Sciences Centre (a 1,275-bed university-affiliated teaching hospital in Toronto, Ontario) between January 2012 and March 2015. All procedures were performed under general anesthesia in a cardiac catheterization procedure room. Standard antimicrobial prophylaxis was a single pre-procedure dose of cefazolin or vancomycin for those with a history of significant penicillin allergy. The medical records of these patients were reviewed, and data were extracted using a standard form. Centers for Disease Control (CDC)/National Healthcare Safety Network (NHSN) criteria for healthcare-associated infections were used for identifying infections.Reference Horan, Andrus and Dudeck 1 Standardized definitions were used for identification of infective endocarditis and other TAVI-related complications.Reference Kappetein, Head and Généreux 2 Infections were tracked for 30 days post procedure (1 year for infective endocarditis).
Fisher’s exact test or Student’s t test was used, as appropriate, to test for associations of variables with infectious complications. We performed a multivariate logistic regression analysis that initially included all variables with P<0.10 in the univariate analyses. A backward stepwise algorithm was then used to eliminate variables to arrive at a final model that included 4 variables. The model was assessed using the Hosmer and Lemeshow goodness of fit test. Statistical analyses were done using R (version 3.2.2, The R Foundation for Statistical Computing).
RESULTS
In total, 270 patients underwent TAVI during the study period. Among these, 14 patients were excluded due to incomplete documentation, and 3 patients were excluded because they died during the procedure, leaving 253 patients in the final analysis. In the 30 days following TAVI, the most common complications were hemorrhage (in 78 patients, incidence 30.8%), arrhythmias requiring pacemaker insertion (42 patients, 16.6%), and infection (35 patients, 13.8%). The median time from TAVI to the onset of symptoms of infection was 5.5 days (interquartile range, 3–9 days). The infections included symptomatic urinary tract infections (16 patients), pneumonia (11), surgical site infections (Reference van der Boon, Nuis and Benitez4), Clostridium difficile infection (Reference Kappetein, Head and Généreux2), and other infections (Reference van der Boon, Nuis and Benitez4). In this study, 4 patients developed infective endocarditis within 1 year of TAVI (incidence, 1.6%). The causes of infective endocarditis in 3 patients were Streptococcus gallolyticus, Streptococcus sanguinus, and Abiotrophia species, and 1 patient who had already been on antibiotic treatment when blood cultures were obtained met criteria for culture-negative endocarditis. A total of 8 patients experienced >1 infection during 30 days of follow-up, and infection was the primary reason for hospital readmission in 8 patients. The microorganisms identified in cultures of specimens obtained from infected sites were typical of those usually associated with these infections (Online Supplementary Table).
Other serious complications occurring within 30 days post TAVI included vascular complications (dissections, occlusions) in 22 (8.7%) patients, stroke (8; 3.2%), and death (12; 4.7%). Although we were unable to determine whether infection caused or contributed to death, 8 of those who developed a post-TAVI infection (22.9%) died, including 3 patients with bloodstream infection and 2 patients with pneumonia. In contrast, only 4 of those patients who did not develop an infection (1.8%) died (P<.001). Infection was also associated with prolonged length of hospital stay (median 15 days for those with infection as compared to 6 days for those without infection; P<.001).
Patient characteristics and procedure-related variables associated with the development of infection are summarized in Tables 1 and 2. In univariate analysis, underlying chronic obstructive pulmonary disease (COPD), congestive heart failure, a surgical transfemoral approach, procedure duration ≥220 minutes (75th percentile for procedure duration), and a postprocedural stroke were associated with the development of infection. In multivariate analysis, the presence of COPD (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.1–1.4; P=.003), postprocedural hemorrhage requiring transfusion (OR, 1.2; 95% CI, 1.0–1.3; P=.03), and post-operative stroke (OR, 1.6; 95% CI, 1.3–2.1; P<.001) were each independently associated with post-TAVI infection (Table 2).
TABLE 1 Variables Associated With Infection Occurring Following Transcatheter Aortic Valve Implantation (TAVI)
NOTE. BMI, body mass index; COPD, chronic obstructive pulmonary disease; STS, Surgical Thoracic Society; AV, aortic valve; SD, standard deviation; LV, left ventricular.
TABLE 2 Multivariate Analysis of Variables Associated With Infection Following TAVI
NOTE. TAVI, transcatheter aortic valve implantation; COPD, chronic obstructive pulmonary disease.
DISCUSSION
Although the number of patients undergoing TAVI is rapidly increasing, few studies have described the infection-related morbidity associated with this procedure. Infection was reported to be the most common cause of death in those who died more than 48 hours but less than 30 days after the procedure, and infection was also a major cause of hospital readmission.Reference Van Mieghem, van der Boon and Nuis 3 Our post-TAVI infection rate of 13.8% is similar to the 10%–20% found in other studies, despite varying surveillance methods.Reference van der Boon, Nuis and Benitez 4 , Reference Barbash, Finkelstein and Barsheshet 5 The incidence of infective endocarditis in the first year post-TAVI in our study (1.6%) was also consistent with previous reports indicating that this life-threatening complication may occur in up to 3.4% of patients.Reference Amat-Santos, Messika-Zeitoun and Eltchaninoff 6 , Reference Olsen, de backer and Thyregod 7
Risk factors associated with the development of infection after TAVI are poorly understood, and many may not be modifiable. We identified underlying COPD as a risk factor, and other studies have identified additional patient-related characteristics such as obesity and increased Society of Thoracic Surgeons (STS) risk score as variables associated with an increased risk of infection.Reference van der Boon, Nuis and Benitez 4 , Reference Barbash, Finkelstein and Barsheshet 5 In univariate analysis, surgical cannulation of the femoral artery was associated with infection, as previously reported,Reference van der Boon, Nuis and Benitez 4 but unlike a previous study, we did not identify an increased risk of infection with a transapical approach,Reference Biancari, Rosato and D’Errigo 8 perhaps because only a few patients in our study had the procedure done in this way. We found that postprocedural hemorrhage requiring transfusion modestly but significantly increased the risk of infection. Because major bleeding following TAVI has been associated with the use of large bore arterial sheath,Reference Van Mieghem, Tchetche and Chieffo 9 the use of smaller bore instruments with some of the newer implantable devices should be considered when feasible. As reported previously, we found stroke complicating TAVI to be a strong predictor of infection.Reference van der Boon, Nuis and Benitez 4 The mechanism for this association may be multifactorial, including an increased risk of aspiration or use of urinary catheters. Evaluation of embolic protection devices to reduce the risk of embolic stroke following TAVI is warranted, and their use may also reduce the risk of infection.Reference Egron, Kütting, Marzelle, Becquemin, Schmitz-Rode and Steinseifer 10 Optimizing and reducing the use of urinary catheters may contribute to lowering the risk of postprocedural urinary tract infections.
The strengths of this study include the cohort study design and the use of standardized infection criteria. However, the study describes the experience of only a single academic center, with a relatively small number of infections. In our retrospective chart review, infections may have been missed or misdiagnosed. A few patients did not have a full year of follow-up for endocarditis post procedure. The results describe associations between certain variables and infection but do not necessarily imply a causal relationship. Although an effort was made to account for confounders in the analysis of variables associated with infection, we may not have accounted for all confounders.
In summary, infection is an important complication in patients undergoing TAVI, associated with increased morbidity and mortality. Our results contribute to a better understanding of the incidence and risks of infection in these patients. Modifications to the procedure or technique may reduce the risk of TAVI-related infection and other complications.
ACKNOWLEDGMENTS
Financial support. No financial support was provided for this study.
Potential conflicts of interest. H.C.W. reports having received grant support from Edwards LifeSciences. All other authors report no conflicts of interest relevant to this article.
SUPPLEMENTARY MATERIAL
To view supplementary material for this article, please visit http://dx.doi.org/doi:10.1017/ice.2016.128.
