Abstract
Objective:
This study sought to study incidence and outcomes of endocarditis after transcatheter aortic valve replacement (TAVR).
Background:
Data about endocarditis after TAVR are limited.
Methods:
We studied Medicare patients who underwent TAVR from 2012 to 2017 and identified patients admitted with endocarditis during follow up using a validated algorithm. The main study outcome was all-cause mortality.
Results:
Out of 134,717 patients who underwent TAVR, 1868 patients developed endocarditis during follow up (incidence 0.87%/year), with majority of infections (65%) occurring within one year. Incidence of endocarditis declined in recent years. The most common organisms were staphylococcus (22%), streptococcus (20%), and enterococcus (15.5%). Important predictors for endocarditis were younger age at TAVR, male sex, prior endocarditis, end-stage renal disease (ESRD), repeat TAVR procedures, liver and lung disease, and post-TAVR acute kidney injury (AKI). Thirty-day and one-year mortality were 18.5% and 45.6% respectively. After adjusting for comorbidities and procedural complications, endocarditis after TAVR was associated with three-fold higher risk of mortality (44.9 versus 16.2 deaths per 100 person-years, aHR 2.94, 95% CI 2.77–3.12, P<0.0001). ESRD (aHR 2.12, 95% CI 1.72–2.60), endocarditis complicated by cardiogenic shock (aHR 2.50, 95% CI1.56–4.02), ischemic stroke (aHR 1.56, 95% CI 1.07–2.28), intracerebral hemorrhage (aHR 1.67, 95% CI 1.01–2.76), AKI (aHR 1.44, 95% CI 1.27–1.63), blood transfusion (aHR 1.28, 95% CI 1.09–1.50), staphylococcal (aHR 1.71, 95% CI 1.49–1.97), and fungal endocarditis (aHR 1.72, 95% CI 1.23–2.39) (P<0.05 for all) portended higher mortality following endocarditis.
Conclusion:
The incidence of endocarditis after TAVR is low and declining. However, it is associated with poor prognosis with half the patients dying within one year.
Keywords: Transcatheter aortic valve replacement, prosthetic endocarditis, infective endocarditis
CONDENSED ABSTRACT
We studied 1868 patients who developed endocarditis after TAVR from 2012 to 2017. Incidence of endocarditis was 0.87% per year. Important predictors for endocarditis were younger age at TAVR, male sex, prior endocarditis, end-stage renal disease (ESRD), repeat TAVR procedures, liver and lung disease, and post-TAVR acute kidney injury (AKI). Thirty-day and one-year mortality were 18.5% and 45.6% respectively. After adjusting for comorbidities and procedural complications, endocarditis after TAVR was associated with three-fold higher risk of mortality. ESRD, endocarditis complicated by cardiogenic shock, ischemic stroke, intracerebral hemorrhage, AKI, blood transfusion, staphylococcal, and fungal endocarditis portended higher mortality following endocarditis.
INTRODUCTION
Transcatheter aortic valve replacement (TAVR) has become the mainstay of treatment of severe aortic stenosis (AS) worldwide.(1) As a result of evidence from the randomized controlled trials, TAVR indications have expanded to include severe AS patients with low surgical risk.(2,3) Given the increasing number of patients who undergo TAVR, it is important to study possible long-term complications after the procedure. As with any intracardiac device or prosthesis, there is a risk of infection and endocarditis in patients who undergo TAVR. Furthermore, with surgical AVR endocarditis, there are distinctive differences between early and late prosthetic endocarditis with outcomes being worse with early endocarditis.(4) Data about timing, incidence, management, and outcomes of endocarditis after TAVR are sparse. Current literature about endocarditis after TAVR is limited to small registries or follow up data from randomized controlled trials. (5–11)
The aims of this study were: 1) To calculate the incidence rate of endocarditis after TAVR in the United States, 2) To evaluate patient specific factors that are associated with development of endocarditis after TAVR and their impact on mortality, 3) To describe the microbiology, management, short and long-term outcomes of endocarditis following TAVR, 4) To explore if there is any difference in prognosis and outcomes between early (<12 months) and late (>12 months) endocarditis after TAVR.
METHODS
Study population
We identified patients who underwent TAVR from January 2012 through October 2017 and were enrolled in Medicare Fee-for-service, using the 100% Medicare Provider and Analysis Review (MEDPAR) Part A files from the Center for Medicare and Medicaid Services (CMS). These files include all hospital and skilled nursing facilities admissions for Medicare fee-for-service beneficiaries nationwide. ICD-9 procedure codes (35.05 and 35.06) were used to identify TAVR procedures for the period through September 2015, and ICD-10 procedure codes (02RF37Z, 02RF38Z, 02RF3JZ, 02RF3KZ, 02RF37H, 02RF38H, 02RF3JH, 02RF3KH, or X2RF332) were used for the period after September 2015. Patient demographics including age, sex, and race were extracted from Medicare enrollment files. Important comorbidities were identified with algorithms defined by Elixhauser et al (12), using ICD-9 and ICD-10 diagnoses codes on inpatient claims during the one year period prior to and including the index TAVR admission. ICD-9 and ICD-10 codes used to identify additional important comorbidities are shown in Supplemental Table 1. History of IV drug use was identified through codes utilized in prior studies.(13,14) The Institutional Review Board of the University of Iowa approved this study with waiver for individual informed consent.
Study Outcomes
The dates of beneficiary Medicare enrollment and death were obtained from the 100% Beneficiary Summary files or MedPAR hospital discharge records. Data on mortality was available for study participants through August 31, 2018.
We identified TAVR patients who were admitted after TAVR with the diagnosis of infective endocarditis using ICD-9 and ICD-10 codes (Supplemental Table 1). These ICD codes have been validated in prior studies against chart review and endocarditis defined by the modified Duke’s criteria and had sensitivity of 94%, specificity of 99% and positive predictive value of 94% (15). We restricted the diagnosis of endocarditis to the primary diagnosis or the first secondary diagnosis to ensure that the endocarditis was the main indication for the hospital admission and not a historic diagnosis. Patients were followed from the date of TAVR discharge and were censored due to death, Medicare disenrollment, or end of the study period. Follow-up of endocarditis readmissions occurred through December 2017, providing a minimum follow-up period of 60 days for all patients. We identified the microbial organisms of endocarditis using validated ICD-9 and ICD-10 codes that were utilized in prior studies (Supplemental Table 1) (16–18). Based on the time of occurrence of endocarditis after the index TAVR admission, patients were classified into 3 groups: very early (≤30 days), early (31 days- 1 year), and late (>1 year) endocarditis following definitions previously described (11). We studied 1) the crude and annualized incidence of endocarditis after TAVR; 2) patient specific factors associated with endocarditis after TAVR; 3) the impact of endocarditis on mortality after TAVR (as a time dependent covariate) and factors associated with worse outcomes after endocarditis, and 4) short and long-term mortality with early (< 1 year) versus late (> 1 year) endocarditis after TAVR.
Statistical analysis
To calculate crude incidence of endocarditis after TAVR, we divided the study duration into 6 months periods. For each time period (January 1st - June 30th and July 1st - December 31st), the denominator included the cumulative number of patients who underwent TAVR from the start of the study, were not censored by death, and did not experience endocarditis. The numerator included newly diagnosed cases with endocarditis in the corresponding time period. To calculate the annualized incidence rate, we divided the total number of endocarditis cases by total person-time for the whole study cohort to estimate the rate per 100 person-years. To determine patient-specific risk factors associated with endocarditis after TAVR, a time to event analysis was done using a multivariable Cox regression model while adjusting for the competing risk of death using Fine-Gray model (19). Adjusted hazards ratio (aHR) with 95% confidence intervals (CI) were calculated.
We estimated the impact of endocarditis on mortality after TAVR using a multivariable Cox proportional hazards regression with a time-dependent covariate for endocarditis. The model adjusted for age, sex, race, pre-existing comorbidities, and procedural complications. Because of the limitations of standard Kaplan-Meier to account for the time-dependent variable of endocarditis (20), we performed Mantel-Byar test to compare all-cause mortality between TAVR patients with and without endocarditis (21). Results of the tests were plotted using the non-parametric Simon-Makuch plot, which accounts for the time dependency of endocarditis (22). We also evaluated the relative impact of late versus early endocarditis on subsequent mortality.
Finally, we explored factors associated with higher mortality after endocarditis using a multivariable Cox regression model with robust standard error estimates to account for the clustering of patients within hospitals (23). A P value of 0.05 was the cutoff for statistical significance. The analysis was done with SAS version 9.4 (SAS Institute, North Carolina) and R 3.4.3 (R Foundation, Austria).
RESULTS
Incidence and timing of endocarditis after TAVR
Out of 134,717 patients who underwent TAVR during the study period, 1868 (1.39%) patients subsequently developed endocarditis. Table 1 compares the baseline characteristics of patients with versus without endocarditis after TAVR. Patients with endocarditis after TAVR were younger, more likely to be males, with a higher prevalence of drug use, diabetes, heart failure, anemia, chronic lung disease, and liver disease.
Table 1:
Baseline characteristics in TAVR patients who and who did not develop endocarditis in follow up
| N=134,717 | N=132,849 | N=1,868 | ||
|---|---|---|---|---|
| Age | 81.7±8.1 | 81.7±8.1 | 80.1±9.1 | <0.0001 |
| Male sex | 70988(52.7) | 69858(52.6) | 1130(60.5) | <0.001 |
| White race | 124,534(92.4) | 122804(92.4) | 1730(92.6) | 0.6 |
| Black race | 5364(4.0) | 5284(4.0) | 80(4.3) | |
| Hypertension | 126443(93.9) | 124693(93.9) | 1750(93.7) | 0.8 |
| Diabetes | 55758(41.4) | 54912(41.3) | 846(45.3) | 0.0006 |
| Liver disease | 5142(3.8) | 5034(3.8) | 108(5.8) | <0.0001 |
| Chronic kidney disease | 39069(29.0) | 38482(29.0) | 587(31.4) | 0.02 |
| End stage renal disease | 5012(3.7) | 4878(3.7) | 134(7.2) | <0.0001 |
| Heart failure | 107313(79.7) | 105774(79.6) | 1539(82.4) | 0.003 |
| Lung disease | 52419(38.9) | 51580(38.8) | 839(44.9) | <0.0001 |
| Prior stroke | 22925(17.0) | 22605(17.0) | 320(17.1) | 0.9 |
| Peripheral vascular disease | 48985(36.4) | 48286(36.4) | 699(37.4) | 0.3 |
| Coronary artery disease | 108441(80.5) | 106897(80.5) | 1544(82.7) | 0.02 |
| Smoking | 37534(27.9) | 36778(27.7) | 756(40.5) | <0.0002 |
| Prior revascularization | 49490(36.7) | 48711(36.7) | 779(41.7) | <0.0001 |
| Anemia | 55900(58.5) | 54959(41.4) | 941(50.4) | <0.0001 |
| Alcohol abuse | 2642(2.0) | 2593(2.0) | 49(2.6) | 0.04 |
| Connective tissue disease | 9092(6.8) | 8951(6.7) | 141(7.6) | 0.2 |
| Bicuspid | 1579(1.2) | 1562(1.2) | 17(0.9) | 0.3 |
| Aortic aneurysm | 2417(1.8) | 2387(1.8) | 30(1.6) | 0.5 |
| Preexisting atrial fibrillation | 58766(43.6) | 57842(43.5) | 924(49.5) | <0.0001 |
| Prior bleed | 46614(34.6) | 45895(34.6) | 719(38.5) | 0.0004 |
| Prior transplant | 902(0.7) | 884(0.7) | 18(1.0) | 0.11 |
| Coagulopathy | 30561(22.7) | 30013(22.6) | 548(29.3) | <0.0001 |
| Depression | 20650(15.3) | 20331(15.3) | 319(17.1) | 0.04 |
| Drug use | 936(0.7) | 914(0.7) | 22(1.2) | 0.01 |
| Hypothyroidism | 34748(25.8) | 34267(25.8) | 481(25.8) | 0.97 |
| Lymphoma | 2451(1.8) | 2408(1.8) | 43(2.3) | 0.1 |
| Electrolytes abnormality | 59701(44.3) | 58768(44.2) | 933(50.0) | <0.0001 |
| Metastatic disease | 1593(1.2) | 1573(1.2) | 20(1.1) | 0.7 |
| Obesity | 32736(24.3) | 32179(24.2) | 557(29.8) | <0.0001 |
| Psychosis | 3770(2.8) | 3700(2.8) | 70(3.8) | 0.02 |
| Pulmonary hypertension | 25899(19.2) | 25353(19.1) | 546(29.2) | <0.0001 |
| Tumor without metastasis | 6913(5.1) | 6815(5.1) | 98(5.3) | 0.8 |
| Underweight | 2189(1.6) | 2171(1.6) | 18(1.0) | 0.02 |
| Prior cerebral bleed | 915(0.7) | 899(0.7) | 16(0.9) | 0.4 |
| Prior Intra-cardiac defibrillator | 5800(4.3) | 5705(4.3) | 95(5.1) | 0.09 |
| Prior Permanent pacemaker | 18787(14.0) | 18501(13.9) | 286(15.3) | 0.09 |
| Prior cardiac device | 22960(17.0) | 22609(17.0) | 351(18.8) | 0.04 |
| Apical access | 10469(7.8) | 10266(7.7) | 203(10.9) | <0.0001 |
| TAVR-in-TAVR | 640(0.5) | 622(0.5) | 18(1.0) | 0.002 |
Values are presented as N (%) or Mean ± standard deviation
Supplemental Figure 1 shows crude incidence of endocarditis after TAVR in 6-month periods. The incidence of endocarditis after TAVR has been declining over the study period (Ptrend<0.01). The annualized incidence rate of endocarditis after TAVR was 0.87% (0.87 per 100 person-years). Incidence rate was 0.57 and 0.30 per 100 person-years for early and late endocarditis respectively. Very early endocarditis (≤30 days) occurred in 175 (9.4%) patients, early (31 days-1 year) in 1046 patients (56%), and late (>1 year) in 647 patients (34.6%).
An infectious organism was identified and coded in 70% of the cases. The main organisms identified were Staphylococcus (19.7%), Streptococcus (20%), and Enterococcus (15.5%), followed by Gram-negative bacteria (6.3%), anaerobes (2%), and fungi (3%) (Supplemental Figure 2). The prevalence of gram-negative and enterococcal endocarditis were numerically lower with apical compared to non-apical TAVR (4.9% versus 6.5%, and 13.8% versus 15.8%), and the prevalence of staphylococcal endocarditis was numerically higher (22.2% versus 19.3%). However, these differences were not statistically significant.
Predictors of endocarditis after TAVR
Predictors of endocarditis after TAVR included younger age at TAVR (aHR 0.98, 95% CI 0.97–0.99, P<0.0001), male sex (aHR 1.44, 95% CI 1.31–1.59, P<0.0001), prior endocarditis before TAVR (aHR 1.69, 95% CI 1.24–2.31, P<0.0001), end stage renal disease [ESRD] (aHR 1.45, 95% CI 1.18–1.78, P=0.0004), repeat TAVR procedures (TAVR-in-TAVR) (aHR 1.62, 95% CI 1.01–2.58, P=0.04), liver disease (aHR 1.30, 95% CI 1.07–1.59, P=0.01), lung disease (aHR 1.14, 95% 1.04–1.26, P=0.006), need for blood transfusion after TAVR (aHR 1.36, 95% CI 1.21–1.54, P<0.0001), preexisting atrial fibrillation (AF) (aHR 1.26, 95% CI 1.15–1.39, P<0.0001) and acute kidney injury (AKI) during TAVR admission (aHR 1.23, 95% CI 1.09–1.40, P=0.001) (Figure 1). Insertion of a new pacemaker during the index TAVR admission was not associated with increased risk of endocarditis at follow up.
Figure 1:
Important predictors of endocarditis.
Predictors of endocarditis after TAVR in a multivariable model. TAVR=Transcatheter aortic valve replacement, AF=Atrial fibrillation.
Early versus late endocarditis after TAVR
Supplemental Table 2 shows comorbidities of endocarditis patients at time of endocarditis admission, and differences between patients with early versus late endocarditis. Patients with late endocarditis were older (mean age 81.7±9.2 versus 80.4±9.4 years, P=0.006), but otherwise no difference between both groups in prevalence of most comorbidities including hypertension, diabetes mellitus, heart failure, coronary artery disease, AF, renal, liver and lung disease. Late endocarditis had higher prevalence of enterococcus and gram-negative endocarditis compared to early endocarditis (18.4% versus 14.0% and 8.2% versus 5.2%, P=0.01 for both). There was no difference in prevalence of staphylococcus, streptococcus, or fungal organisms in early versus late endocarditis.
In-hospital and short-term outcomes of endocarditis after TAVR
Median length of hospital stay during the endocarditis admission was 8 days (IQR 5–13 days). Overall, 14% required blood transfusion, 33.2% had an AKI, 36% needed intensive care unit admission, and 2.1% had an acute in-hospital ischemic stroke, with no difference between early and late endocarditis in these outcomes (Table 2). Pacemaker removal was performed in 4.3% of endocarditis patients, while insertion of a new pacemaker due to new-onset heart block was performed in 1%. Surgical AVR (SAVR) was performed in 3.8% (2% in the same index endocarditis admission and 1.8% in a follow up admission) and repeat TAVR was performed in 0.4% of endocarditis patients. Only 13% of the patients were discharged home, as the majority required either a skilled nursing facility (31.6%), or home-health care (20.4%). Four percent of the endocarditis patients were discharged to hospice.
Table 2:
In-hospital, short-term and intermediate-term outcomes with endocarditis after TAVR
| Variable | Overall N=1,868 | Early endocarditis N=1221 | Late endocarditis N=647 | P value |
|---|---|---|---|---|
| Blood transfusion | 262(14.0) | 181(14.8) | 81(12.5) | 0.2 |
| New pacemaker | - | 24(2.0) | - | 0.5 |
| Removal of PPM | 80(4.3) | 58(4.8) | 22(3.4) | 0.2 |
| Acute kidney injury | 620(33.2) | 398(32.6) | 222(34.3) | 0.5 |
| Cardiogenic shock | - | 16(1.3) | - | 0.5 |
| Requiring ICU admission | 672(36.0) | 452(37.0) | 220(34.0) | 0.2 |
| Length of ICU stay, days Median (IQR) | 5 (3–9) | 5 (2–9) | 5.5 (3–10) | 0.3 |
| Length of stay, days Median (IQR) | 8 (5–13) | 8 (5–13) | 8 (5–13) | 0.2 |
| Long acute care facility | 59(3.2) | 41(3.4) | 18(2.8) | |
| In-hospital stroke | 39(2.1) | 28(2.3) | 11(1.7) | 0.4 |
| In-hospital Intracranial hemorrhage | - | 11(0.9) | - | 0.9 |
| 30-day heart failure | 125(6.7) | 80(6.6) | 45(7.0) | 0.7 |
| 30-day stroke | 71(3.8) | 49(4.0) | 22(3.4) | 0.5 |
| 30-day mortality | 345(18.5) | 213(17.4) | 132(20.4) | 0.1 |
| 1-year mortality | 851(45.6) | 525(43.0) | 326(50.4) | 0.002 |
Values are presented as N (%) or Median (interquartile range)
Cells with N≤10, or cells that would reveal N<10 by calculation were suppressed with (−)
Overall, the 30-day mortality for endocarditis was 18.5% and one-year mortality was 45.6%. While there was no difference between late and early endocarditis in 30-day mortality (20.4% versus 17.4%, OR 1.21, 95% CI 0.95–1.55, P=0.1), late endocarditis was associated with higher 1-year mortality compared to early endocarditis (50.4% versus 43.0%, OR 1.34, 95% CI 1.11–1.63, P=0.002).
Long-term outcomes with endocarditis after TAVR
Median follow up after TAVR in the whole cohort was 655 days (IQR 395–1033), and median follow up after endocarditis admission was 362 days (IQR 52–780). After adjusting for age, sex, comorbidities, and procedural complications, endocarditis as a time-dependent covariate was associated with three-fold higher risk of mortality after TAVR (44.9 deaths versus 16.2 deaths per 100 person-year, aHR 2.94, 95% CI 2.77–3.12, P<0.0001) compared to patients who did not suffer from endocarditis after TAVR. Central illustration shows Simon-Makuch plot with endocarditis as a time dependent covariate. (Mantel-Byar test P value <0.0001).
Central illustration: Mortality with endocarditis after transcatheter aortic valve replacement.
Panel A: Impact of endocarditis on survival after TAVR.
Simon Makuch plot showing long-term mortality after TAVR with endocarditis as a time-dependent covariate. Mantel-Byar test P value<0.0001. Panel B: Factors associated with higher mortality in TAVR patients admitted with endocarditis in a multivariable model.
TAVR=Transcatheter aortic valve replacement
After adjusting for age, sex, comorbidities, and year of TAVR procedure, late endocarditis was associated with higher risk of long-term mortality compared to early endocarditis (58.0 deaths versus 39.8 deaths per 100 person-years, aHR 1.26, 95% CI 1.11–1.44, P<0.001) (Supplemental Figure 2).
Predictors of mortality after endocarditis
Important predictors of higher mortality with endocarditis after TAVR included older age (aHR 1.01, 95% CI 1.00–1.02, P=0.02), congestive heart failure (aHR 1.36, 95% CI 1.10–1.69, P=0.004), pulmonary hypertension (aHR 1.23, 95% CI 1.09–1.39, P=0.001), weight loss (aHR 1.25, 95% CI 1.07–1.45, P=0.004), ESRD (aHR 2.12, 95% CI 1.72–2.60, P<0.0001), preexisting AF (aHR 1.26, 95% CI 1.12–1.43, P=0.0003), endocarditis complicated with cardiogenic shock (aHR 2.50, 95% CI 1.56–4.02, P<0.0001), ischemic stroke (aHR 1.56, 95% CI 1.07–2.28, P=0.02), intracerebral hemorrhage (aHR 1.67, 95% CI 1.01–2.76, P0.04), AKI (aHR 1.44, 95% CI 1.27–1.63, P<0.0001), blood transfusion (aHR 1.28, 95% CI 1.09–1.50, P=0.003), staphylococcal (aHR 1.71, 95% CI 1.49–1.97, P<0.001), and fungal endocarditis (aHR 1.72, 95% CI 1.23–2.39, P<0.001). (Central illustration).
DISCUSSION
Our study has several important findings. First, the incidence of endocarditis after TAVR averaged 0.87% per year, with a declining trend over the study period. Nearly two-thirds of these cases occurred within the first year after TAVR with the most common identified organisms being streptococcus, staphylococcus, and enterococcus. Second, important predictors associated with endocarditis after TAVR included younger age, male sex, prior endocarditis, ESRD, repeat TAVR procedures (TAVR-in-TAVR), liver and lung disease, need for blood transfusion after TAVR, preexisting AF and post-TAVR AKI. Third, endocarditis after TAVR was associated with poor outcomes, where one in five patients died within 30 days and one in two patients died within one year. Over a median follow up of 655 days, endocarditis after TAVR was associated with a 3-fold increase in mortality compared with TAVR patients who did not suffer from endocarditis. Important predictors of mortality after endocarditis included older age, ESRD, weight loss, HF, pulmonary hypertension, AF, fungal and staphylococcal endocarditis, as well as endocarditis complicated with cardiogenic shock, AKI, blood transfusion, cerebral hemorrhage or ischemic stroke.
Few studies reported the incidence and outcomes of endocarditis after TAVR. However, these studies were limited to small sample sizes and reported a wide range of incidence (0.3% to 1.5% per year) (5,7–9,24). The multicenter nationwide cohort of the current study represents real-world data and increases the power of the study. Similar to prior reports, the incidence of endocarditis after TAVR in our study was < 1% per year (7,9,11,24), and is also similar to the reported incidence of prosthetic endocarditis after surgical AVR (11,25). However, our study is the first to show a declining trend in this incidence over the last 6 years. This is most probably due to the expansion of TAVR to lower risk patients with lower burden of comorbidities, as well as the advances in prosthesis design and delivery systems reducing the incidence of paravalvular leak and procedural complications (26), which has shown to be linked to an increased risk of endocarditis.(8)
The majority of endocarditis cases occurred in the first year after TAVR (64%), with high risk populations having younger age, male sex, with underlying comorbidities such as ESRD on hemodialysis, preexisting AF, chronic lung disease, and liver disease on multivariate analysis. These predictors were reported in prior univariate analyses from relatively smaller sample size cohorts (5,8,9,11,24,27). Our study finds additional high-risk features including prior history of endocarditis before TAVR, repeat TAVR procedures (TAVR-in-TAVR), as well as pulmonary hypertension and baseline anemia.
Gram-positive cocci represented the majority (~ 55%) of the causative organisms for endocarditis after TAVR in our study, followed less commonly by gram-negative and fungal infections. These findings are consistent with the reported organisms in the Placement of AoRTic TraNscathetER Valve Trial (PARTNER) trial (11), and also with what has been reported in surgical prosthetic valve endocarditis literature (28). Interestingly, while drug abuse was a modest predictor of endocarditis after TAVR across the whole cohort, it was strongly associated with staphylococcal and fungal endocarditis.
Endocarditis after TAVR was associated with dismal prognosis in the current study. In two prior small registry studies, one-year mortality after TAVR endocarditis was approximately 50% (6,9). In our study, after adjusting for all comorbidities, age, hospital TAVR volume, and TAVR procedural complications, endocarditis was associated with 3-fold increase in the risk of death compared to TAVR patients who do not develop endocarditis. Similar to prior reports of SAVR endocarditis, staphylococcal infection, fungal infection and occurrence of stroke in our study were associated with significantly higher mortality (28,29). In addition, weight loss, congestive HF, endocarditis with AKI, cardiogenic shock and intracerebral hemorrhage were also associated with higher mortality in our study.
Several factors could explain the dismal survival with endocarditis after TAVR. Prosthetic endocarditis in TAVR is associated with higher frequency of aortic abscess and fistula formation compared to SAVR endocarditis.(30) Furthermore, it can be complicated with severe valve obstruction (31,32), severe intra-valvular regurgitation (33), and conduction block (34). Similar to our study, prior studies have shown that a small proportion of TAVR endocarditis patients undergo surgical treatment and that majority are managed with conservative therapy with prolonged antibiotic therapy.(6,9,11) This is in contrast to contemporary management of SAVR endocarditis where surgical re-intervention is a cornerstone in management.(28) This is most probably due to the high surgical risk and the inoperability of TAVR patients, in addition to the surgical difficulties of removing the stent frame adherent to the aorta.(34) In a registry of 250 cases of TAVR endocarditis, surgical intervention was performed in only 15% of the cases despite having a clear indication for surgery in 82% of the cases.(24) As TAVR expands to include lower risk patients, rates of surgery to treat TAVR endocarditis could probably increase. In our study, surgical intervention did not improve thirty-day mortality on multivariable analysis, confirming similar finding from two previous small studies (24,35). Since the majority of endocarditis after TAVR in our study were caused by organisms that are more prevalent in nosocomial infections, it is important to minimize invasive procedures, vascular dwelling catheters insertions and maintain the strictest sterility when procedures are performed in TAVR patients. While the use of antibiotic prophylaxis could not be examined in the current study, it may not seem unreasonable to utilize antibiotic prophylaxis at the time of dental procedures, given the high percentage of streptococcal endocarditis.
Our study is the largest to date to report epidemiology and outcomes of endocarditis in TAVR patients in the US. However, we acknowledge certain limitations in our study. First, we lacked information regarding imaging and echocardiography data and antibiotic therapy which can be helpful in providing further insight into the disease. Furthermore, due to lack of imaging data, we lacked detailed information about the infected valve, and about certain complications (e.g. aortic root abscess, prosthetic dehiscence and large size vegetation, which would favor surgical intervention. We also lacked information about the type of valve implanted (self-expanding versus balloon-expanding valves). However, a recent report from an international registry showed that outcomes of endocarditis are similar between both types of valves.(6) Second, our study included only Medicare patients, which could limit generalizability of results to other populations. Last, microbial diagnosis was missing in 30% of the cases. It is unclear if this can be attributed to culture-negative endocarditis, which was reported to be as high as 20% of endocarditis after TAVR in prior studies (11,36). Endocarditis and microbiologic diagnosis in our study were based on ICD codes and it is possible that there is misclassification as we did not have access to blood cultures.
In conclusion, endocarditis after TAVR is rare and is declining in recent years. However, it remains associated with high morbidity and mortality rates. Given the poor prognosis of endocarditis after TAVR and the limited options for intervention and treatment, patients at high risk should be identified early and efforts should be implemented to prevent the infection.
Supplementary Material
PERSPECTIVES.
WHAT IS KNOWN?
Infective endocarditis is a serious complication after transcatheter aortic valve replacement (TAVR).
WHAT IS NEW?
Despite a decline in incidence of endocarditis after TAVR in recent years, it remains associated with significant morbidity and a 3-fold increase in mortality. Factors associated with mortality after TAVR-related endocarditis include age, heart failure, ESRD, prior atrial fibrillation, staphylococcal or fungal infection, and endocarditis complicated with ischemic stroke or intracerebral hemorrhage.
WHAT IS NEXT?
Research should focus on prevention of endocarditis after TAVR, and management strategies to mitigate the high mortality and morbidity.
Funding:
Dr. Mentias received support from National Institute of Health NRSA institutional grant (T32 HL007121) to the Abboud Cardiovascular Research Center. Dr. Sarrazin is supported by funding from the National Institute on Aging (NIA R01AG055663-01), and by the Health Services Research and Development Service (HSR&D) of the Department of Veterans Affairs.
ABBREVIATIONS AND ACRONYMS
- AKI
Acute kidney injury
- AF
Atrial fibrillation
- ESRD
End-stage renal disease
- HF
Heart failure
- TAVR
Transcatheter aortic valve replacement
Footnotes
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Disclosures:
Dr. Horwitz receives grant support from Edwards Lifesciences and Boston Scientific.
The remaining authors do not have any conflicts of interest or financial disclosures.
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