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Erschienen in: BMC Cardiovascular Disorders 1/2020

Open Access 01.12.2020 | Research article

Higher incidence of perivalvular abscess determines perioperative clinical outcome in patients undergoing surgery for prosthetic valve endocarditis

verfasst von: Carolyn Weber, Parwis B. Rahmanian, Melanie Nitsche, Asmae Gassa, Kaveh Eghbalzadeh, Stefanie Hamacher, Julia Merkle, Antje-Christin Deppe, Anton Sabashnikov, Elmar W. Kuhn, Oliver J. Liakopoulos, Thorsten Wahlers

Erschienen in: BMC Cardiovascular Disorders | Ausgabe 1/2020

Abstract

Background

Cardiac surgery for prosthetic valve endocarditis (PVE) is associated with substantial mortality. We aimed to analyze 30-day and 1-year outcome in patients undergoing surgery for PVE and sought to identify preoperative risk factors for mortality with special regard to perivalvular infection.

Methods

We retrospectively analyzed data of 418 patients undergoing valve surgery for infective endocarditis between January 2009 and July 2018. After 1:1 propensity matching 158 patients (79 PVE/79 NVE) were analyzed with regard to postoperative 30-day and 1-year outcomes. Univariate and multivariable analyses were performed to identify potential risk factors for mortality.

Results

315 patients (75.4%) underwent surgery for NVE and 103 (24.6%) for PVE. After propensity matching groups were comparable with regard to preoperative characteristics, clinical presentation and microbiological findings, except a higher incidence of perivalvular infection in patients with PVE (51.9%) compared to NVE (26.6%) (p = 0.001), longer cardiopulmonary bypass (166 [76–130] vs. 97 [71–125] min; p < 0.001) and crossclamp time (95 [71–125] vs. 68 [55–85] min; p < 0.001). Matched patients with PVE showed a 4-fold increased 30-day mortality (20.3%) in comparison with NVE patients (5.1%) (p = 0.004) and 2-fold increased 1-year mortality (PVE 29.1% vs. NVE 13.9%; p = 0.020). Multivariable analysis revealed perivalvular abscess, sepsis, preoperative AKI and PVE as independent risk factors for mortality. Patients with perivalvular abscess had a significantly higher 30-day mortality (17.7%) compared to patients without perivalvular abscess (8.0%) (p = 0.003) and a higher rate of perioperative complications (need for postoperative pacemaker implantation, postoperative cerebrovascular events, postoperative AKI). However, perivalvular abscess did not influence 1-year mortality (20.9% vs. 22.3%; p = 0.806), or long-term complications such as readmission rate or relapse of IE.

Conclusions

Patients undergoing surgery for PVE had a significantly higher 30-day and 1-year mortality compared to NVE. After propensity-matching 30-day mortality was still 4-fold increased in PVE compared to NVE.
Patients with perivalvular abscess showed a significantly higher 30-day mortality and perioperative complications, whereas perivalvular abscess seems to have no relevant impact on 1-year mortality, the rate of readmission or relapse of IE.
Hinweise
Carolyn Weber and Parwis B. Rahmanian contributed equally to this work

Supplementary information

Supplementary information accompanies this paper at https://​doi.​org/​10.​1186/​s12872-020-01338-y.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Abkürzungen
AKI
Acute kidney injury
CI
Confidence interval
CoNS
Coagulase-negative staphylococci
CPB
Cardiopulmonary bypass
ESC
European society of cardiology
IE
Infective endocarditis
IQR
Interquartile range
NVE
Native valve endocarditis
OR
Odds ratio
PVE
Prosthetic valve endocarditis
SD
Standard deviation

Background

Among patients undergoing valve operation for infective endocarditis (IE), surgery for prosthetic valve endocarditis (PVE) has been associated with distinct mortality rates in cardiothoracic surgery [13]. PVE accounts for 10–30% of all cases of IE and occurs in 1–6% of patients with valve prostheses [46]. Clinical presentation is often atypical and negative echocardiographic findings are more common, leading to lower sensitivity of the Duke criteria in patients with suspected PVE [7]. Hence, timely diagnosis of endocarditis is more difficult in presence of a prosthetic valve compared with a native valve [5, 8, 9]. One of the reasons, for the higher rate of negative echocardiographic findings in PVE is, that vegetations occur less frequent, whereas periannular extensions are more common, which are more difficult to detect in echocardiography [4, 5].
Several factors have been associated with bad prognosis in PVE. Perivalvular infection is of a greater concern in PVE than NVE and occurs in 56–100% of PVE patients [1, 4, 10]. Previous studies suggested, that perivalvular infection worsens the prognosis, the perioperative mortality and the risk for reinfection or relapse of endocarditis [11, 12]. The extension of the infection beyond the valve annulus leads to technically more demanding operations, requiring radical debridement and reconstruction [10].
Therefore, we aimed to compare 30-day and 1-year outcome after valve surgery for NVE and PVE. Our second objective was to identify potential preoperative risk factors for mortality with special regard to perivalvular infection.

Methods

Study design

We performed a retrospective single-center analysis. Relevant clinical data of all consecutive patients undergoing surgery for IE between January 2009 and July 2018 were extracted from our institutional database.

Definition of IE and indication for surgery

IE was defined according to the recent modified Duke Criteria [13]. Surgery for IE was indicated according to the recent ESC guidelines for the management of infective endocarditis [9] and performed as previously described [14].

Data collection

Patients’ demographics, predisposing risk factors and symptoms at the time of onset of IE, echocardiographic and microbiological findings, perioperative data and relevant clinical outcomes were recorded. IE relevant 30-day and 1-year outcomes were reported for hospital stay and at follow-up, respectively. Follow-up was obtained by review of hospital medical records and interview of the patient’s physician. Median duration of the follow-up was 2.05 years [interquartile range (IQR) 0.04–4.69] with a completeness of 76.3%. The follow-up time for survival was measured from the date of operation to either the date of death or the date of the last contact with the patient. The study protocol was approved by the institutional review board (Ethics Committee of the Medical Faculty, University of Cologne, 17–407). Individual informed consent was waived due to the retrospective nature of the collected data.

Reporting mortality

30-day mortality (day 1–30) was reported as all-cause mortality within the first 30 days after surgery for IE, regardless of the patient’s location (at home or health care facility). 1-year mortality was reported as all-cause mortality occurring between day 31 and 365 after initial surgery. Long-term mortality was defined as all-cause mortality after day 365 and Kaplan-Meier analysis was used to test for differences in long-term survival .

Statistical analysis

Patients’ characteristics and pre-operative factors were described using mean values ± standard deviation (SD), median [(IQR)], or frequencies and percentages as indicated. Depending on data distribution group differences were compared using unpaired t-test, Mann-Whitney U test, Chi-squared test or Fisher’s exact test as appropriate. Log-rank test was used to test for differences in long-term mortality between PVE and NVE. A 1:1 propensity score matching was performed to exclude potential confounders between groups with a 0.01 caliper width. This propensity score-based matching procedure resulted in a total number of 158 patients. Matching variables were the following preoperative characteristics that showed statistically significant differences or that were considered clinically significant based on previous research: age, sex, aortic/mitral valve IE, preoperative acute kidney injury (AKI) and Staphylococcus aureus as causative microorganism. Potential risk factors for 30-day mortality (day 1–30) were assessed using logistic regression. We decided not to include EuroSCORE into the univariate analysis because EuroSCORE is per definition higher in patients with previous cardiac surgery. After univariate analysis all variables with a p-value less than 0.1 (female gender, age > 65 years, PVE, preoperative AKI, preoperative sepsis, perivalvular abscess, IE with Staphylococcus aureus) were entered into the multivariable model using a forward selection (likelihood ratio, pin = 0.05). Results are presented as odds ratio (OR) for 30-day mortality with corresponding 95% confidence interval (CI) and p-value. All reported p-values are two-sided and considered statistically significant if ≤5%. Statistical analyses were performed using SPSS Statistics Version 25 (IBM Corp., Armonk, NY, USA).

Results

Preoperative characteristics and risk factors

Data of 418 patients undergoing surgery for infective endocarditis were retrospectively analyzed. 315 patients (75.4%) underwent surgery for NVE and 103 patients (24.6%) for PVE. Table 1 summarizes patients’ demographics and preoperative characteristics. PVE patients in the unmatched cohort were significantly older (71.5 [62.0–76.6] vs. 62.7 [49.4–71.6]; p < 0.001), showed a higher proportion of female patients being affected (32.0% vs. 22.5%; p = 0.046) and were diagnosed with more preoperative AKI (67.0% vs. 54.9%; p = 0.031). In addition, the manifestation of IE differed between PVE and NVE patients (Table 2). The involvement of the aortic valve was more common in the PVE cohort (78.6% vs. 52.7%, p < 0.001), whereas mitral valve involvement occurred more often in NVE patients (54.3% vs. 25.2%, p < 0.001). Echocardiography revealed vegetations in 82.2% of NVE and 70.9% of PVE patients (p = 0.017). Inversely, PVE patients were diagnosed with more perivalvular infection. Hence, perivalvular abscess was diagnosed in 60.2% of the PVE and 27.0% of the NVE group (p < 0.001). Concerning the underlying microorganisms, Coagulase-negative Staphylococci (CoNS) were detected more often in PVE (15.5% vs. 8.3%; p = 0.033), whereas Streptococcus spp were more prevalent in NVE (26.7% vs. 9.7%; p < 0.001). The proportion of Staphylococcus aureus IE was comparable and occurred in PVE with 18.4% and NVE with 23.5% (p = 0.285). Clinical symptoms were similar among both groups (Table 2). Detailed findings regarding causative microorganisms are depicted in Fig. 1.
Table 1
Patients’ demographics and preoperative characteristics
 
ENTIRE COHORT
PROPENSITY MATCHED COHORT
NVE (n = 315)
PVE (n = 103)
P value
NVE (n = 79)
PVE (n = 79)
P value
Age
62.7
[49.4–71.6]
71.5
[62.0–76.6]
< 0.001
65.5
[55.5–72.2]
69.2
[55.5–75.5]
0.204
Female sex
71
(22.5%)
33
(32.0%)
0.046
22
(27.8%)
19
(24.1%)
0.586
BMI
25.5
[23.2–28.1]
26.0
[23.9–28.7]
0.273
25.4
[23.7–28.8]
26.1
[23.9–28.7]
0.548
BSA
1.98
[1.83–2.12]
1.94
[1.74–2.10]
0.238
1.97
± 0.21
1.97
± 0.24
0.349
COPD
29
(9.2%)
9
(8.7%)
0.886
10
(12.7%)
8
(10.1%)
0.617
Diabetes
81
(25.7%)
34
(33.0%)
0.150
21
(26.6%)
25
(31.6%)
0.484
Peripheral vascular disease
23
(7.3%)
12
(11.7%)
0.167
6
(7.6%)
7
(8.9%)
0.772
Preoperative AKI
173
(54.9%)
69
(67.0%)
0.031
54
(68.4%)
52
(65.8%)
0.735
Preoperative dialysis
30
(9.5%)
13
(12.6%)
0.889
6
(7.6%)
13
(16.5%)
0.176
Coronary artery disease
80
(25.4%)
36
(35.5%)
0.060
23
(29.1%)
22
(27.8%)
0.860
Prior PCI
18
(5.7%)
14
(13.6%)
0.054
4
(5.1%)
8
(10.1%)
0.124
Immunosuppression
5
(1.6%)
2
(1.9%)
0.811
1
(1.3%)
1
(1.3%)
1.000
HIV
9
(2.9%)
1
(1.0%)
0.233
0
(0%)
1
(1.3%)
0.238
Alcohol abuse
37
(11.7%)
4
(3.9%)
0.020
8
(10.1%)
3
(3.8%)
0.118
Intravenous drug abuse
22
(7.0%)
6
(5.8%)
0.683
5
(6.3%)
6
(7.6%)
0.755
History of neoplasm
33
(10.5%)
10
(9.7%)
0.824
12
(15.2%)
6
(7.6%)
0.133
LVEF
  < 30%
7
(2.2%)
2
(1.9%)
0.865
1
(1.3%)
2
(2.5%)
0.559
 30–50%
63
(20%)
30
(29.1%)
0.532
16
(20.3%)
23
(29.1%)
0.268
  > 50%
238
(75.6%)
70
(70.0%)
0.129
62
(78.5%)
53
(67.1%)
0.108
NYHA class
 I + II
55
(17.5%)
19
(18.4%)
0.925
20
(25.3%)
14
(17.7%)
0.245
 III + IV
251
(80.0%)
80
(77.7%)
0.662
59
(74.7%)
63
(79.7%)
0.448
 Log. EuroSCORE
7.6
[4.4–18.1]
9.8
[22.3–36.2]
< 0.001
7.9
[4.1–16.3]
17.5
[7.9–33.7]
< 0.001
 EuroSCORE II
7.0
[5.0–10.0]
11.0
[8.0–13.0]
< 0.001
7.0
[5.0–9.0]
10.0
[7.0–12.3]
< 0.001
Data presented as mean ± standard deviation, number (percent) or median [IQR], respectively. AKI, acute kidney injury; BMI, body mass index; BSA, body surface area; COPD, chronic obstructive pulmonary disease; HIV, human immunodeficiency virus; IQR, interquartile range; NYHA, New York Heart Association; PCI, percutaneous coronary intervention; TIA, transient ischemic attack
Table 2
Manifestation of IE according to the modified Duke Criteria
 
ENTIRE COHORT
PROPENSITY MATCHED COHORT
NVE (n = 315)
PVE (n = 103)
P value
NVE (n = 315)
PVE (n = 103)
P value
MICROBIOLOGY
 Positive Blood culture
263
(83.5%)
77
(74.8%)
0.279
65
(82.3%)
58
(73.4%)
0.505
Streptococcus spp
84
(26.7%)
10
(9.7%)
< 0.001
20
(25.3%)
8
(10.1%)
0.011
Staphylococcus spp
98
(31.1%)
35
(34.0%)
0.587
20
(25.3%)
24
(30.4%)
0.478
Staph. aureus
74
(23.5%)
19
(18.4%)
0.285
16
(20.3%)
15
(19.0%)
0.841
CoNS
26
(8.3%)
16
(15.5%)
0.033
5
(6.3%)
9
(11.4%)
0.263
Enterococcus spp
44
(14.0%)
17
(16.5%)
0.527
15
(19.0%)
16
(20.3%)
0.841
ECHOCARDIOGRAPHY
 Vegetation
259
(82.2%)
73
(70.9%)
0.017
65
(82.3%)
59
(74.7%)
0.307
 Vegetation length (cm)
1.6
[1.1–2.0]
1.2
[0.8–1.7]
0.009
1.5
± 0.6
1.3
± 0.7
0.357
Leftsided IE
Aortic valve
166
(52.7%)
81
(78.6%)
< 0.001
52
(65.8%)
58
(73.4%)
0.299
Mitral valve
171
(54.3%)
26
(25.2%)
< 0.001
23
(29.1%)
26
(32.9%)
0.606
Rightsided IE
Tricuspid valve
21
(6.7%)
1
(1.0%)
0.046
6
(7.6%)
1
(1.3%)
0.053
Pulmonary valve
1
(0.3%)
1
(1.0%)
0.439
0
(0%)
1
(1.3%)
0.238
Perivalvular infection
Perivalvular abscess
85
(27.0%)
62
(60.2%)
< 0.001
21
(26.6%)
41
(51.9%)
0.001
Perforation
83
(26.3%)
21
(20.4%)
0.224
10
(12.7%)
19
(24.1%)
0.064
Fistula
1
(0.3%)
13
(12.6%)
< 0.001
1
(1.3%)
10
(12.7%)
0.005
SYMPTOMS
 Fever
201
(63.8%)
72
(69.9%)
0.259
60
(75.9%)
55
(69.6%)
0.371
 Sepsis
233
(74.0%)
68
(66.0%)
0.119
41
(51.9%)
38
(48.1%)
0.633
 IE-related neurologic complications
99
(31.4%)
28
(27.2%)
0.416
23
(29.1%)
22
(27.8%)
0.860
TIA
13
(4.1%)
1
(1.0%)
0.122
3
(3.8%)
0
(0%)
0.305
Stroke
47
(14.9%)
17
(16.5%)
0.698
11
(13.9%)
14
(17.7%)
0.513
Intracranial bleeding
5
(1.6%)
3
(2.9%)
0.394
1
(1.3%)
3
(3.8%)
0.311
Other
33
(10.5%)
7
(6.8%)
0.270
8
(10.1%)
5
(6.3%)
0.385
 Septic embolism
115
(36.5%)
29
(28.2%)
0.188
25
(31.6%)
24
(30.4%)
0.239
 Cardiogenic shock
46
(14.6%)
9
(8.7%)
0.126
7
(8.9%)
8
(10.1%)
0.786
Data presented as mean ± standard deviation, number (percent) or median [IQR], respectively. d, days; IE infective endocarditis; IQR, interquartile range; TIA, transient ischemic attack
After propensity matching there were no statistically significant differences regarding preoperative characteristics, clinical symptoms and manifestation of IE, except a higher rate of perivalvular infection (51.9% vs. 26.6%, p = 0.001) (Tables 1 and 2). Due to the complexity of operation, CPB and crossclamp time were significantly longer in patients with PVE (CPB time: 166 [76–130] vs. 97 [71–125] min; p < 0.001; crossclamp time: 95 [71–125] vs. 68 [55–85] min; p < 0.001) (Additional file 1: Table S1).

30-day and 1-year clinical outcomes

30-day and 1-year clinical outcomes are depicted in Table 3. With regard to 30-day outcome, PVE was associated with a significantly higher 30-day mortality. After propensity-matching 30-day mortality was still 4-fold increased in PVE compared to NVE (20.3% vs. 5.1%; p = 0.004). Concerning the incidence of postoperative complications, matched cohorts were comparable except a longer time of ventilation (28.3 [15–113] vs. 16.8 [12–46] hours; p = 0.017), longer ICU (5.0 [2.0–12.0] vs. 3.0 [1.0–6.0] days; p = 0.042) and hospital stay (15.0 [11.0–20.0] vs. 12.0 [7.0–17.0] days; p = 0.015) in the PVE cohort.
Table 3
30-day and 1-year clinical outcomes
 
ENTIRE COHORT
PROPENSITY MATCHED COHORT
NVE (n = 315)
PVE (n = 103)
P value
NVE (n = 315)
PVE
(n = 103)
P value
30-DAY OUTCOME
 30-day mortality
26
(8.3%)
22
(21.4%)
< 0.001
4
(5.1%)
16
(20.3%)
0.004
 Myocardial infarction
1
(0.3%)
1
(1.0%)
0.439
0
(0%)
1
(1.3%)
0.238
 New pacemaker *
23
(7.3%)
20
(19.4%)
< 0.001
8
(10.1%)
11
(13.9%)
0.463
 New postoperative cerebrovascular events
15
(4.8%)
8
(7.8%)
0.252
6
(7.6%)
4
(5.1%)
0.499
Stroke
14
(4.4%)
5
(4.9%)
0.862
6
(7.6%)
3
(3.8%)
0.294
Intracranial bleeding
1
(0.3%)
3
(2.9%)
0.077
0
(0%)
1
(1.3%)
0.238
 Postoperative AKI
107
(34.0%)
47
(45.6%)
0.035
33
(41.8%)
32
(40.5%)
0.872
 Re-exploration for bleeding
45
(14.3%)
26
(25.2%)
0.009
10
(12.7%)
17
(21.5%)
0.129
 Tracheostomy
38
(12.1%)
21
(20.4%)
0.036
10
(12.7%)
15
(19.0%)
0.276
 Time of ventilation (h)
18.2
[11–68]
32.8
[17–120]
< 0.001
16.8
[12–46]
28.3
[15–113]
0.017
 ICU stay (d)
4.0
[2.0–8.0]
5.0
[3.0–13.0]
0.009
3.0
[1.0–6.0]
5.0
[2.0–12.0]
0.042
 Hospital stay (d)
12.0
[8.0–16.0]
14.5
[10.0–20.0]
0.007
12.0
[7.0–17.0]
15.0
[11.0–20.0]
0.015
1-YEAR OUTCOME
 1-year mortality
53
(16.8%)
34
(33.0%)
< 0.001
11
(13.9%)
23
(29.1%)
0.020
 Re-admission to hospital
94
(29.8%)
33
(32.0%)
0.478
31
(39.2%)
23
(29.1%)
0.835
 Relapse of endocarditis
10
(3.2%)
3
(2.9%)
0.938
3
(3.8%)
2
(2.5%)
1.000
 New pacemaker*
5
(1.6%)
4
(3.9%)
0.177
2
(2.5%)
1
(1.3%)
0.792
 AKI during follow-up
23
(7.3%)
13
(12.6%)
0.071
11
(13.9%)
8
(10.1%)
0.883
Data presented as mean ± standard deviation, number (percent) or median [IQR], respectively. AKI, acute kidney injury; ICU, intensive care unit; IQR, interquartile range; TIA, transient ischemic attack; * for AV-higher grade
In addition, 1-year mortality was significantly higher in PVE (29.1%) compared to NVE (13.9%, p = 0.020) in the matched cohort. Kaplan-Meier survival analysis revealed a significantly decreased long-term survival of patients undergoing surgery for PVE compared to NVE in the unmatched cohort (log-rank p = 0.019; Fig. 2a). After propensity matching no significant difference with regard to long-term survival could be found (log-rank p = 0.174; Fig. 2b).

Factors associated with mortality

Univariate analysis revealed the following preoperative variables as factors associated with 30-day mortality: preoperative AKI, PVE, preoperative sepsis, perivalvular abscess, IE with Staphylococcus aureus (Additional file 1: Table S2).Stepwise multivariable logistic regression analysis revealed perivalvular abscess (OR 1.864 [1.002–3.465]; p = 0.049), preoperative AKI (OR 2.720 [1.307–5.657]; p = 0.007) and preoperative sepsis (OR 2.281 [1.123–4.636]; p = 0.023) as independent risk factors for 30-day mortality. In addition, PVE was independently predictive for 30-day mortality (OR 2.699 [1.496–4.871]; p = 0.001) (Table 4).
Table 4
Multivariable analysis of risk factors associated with 30-day mortality in patients undergoing surgery for IE
INDEPENDENT RISK FACTORS FOR 30-DAY MORTALITY
 
OR
95%CI
P value
PVE
2.699
1.496–4.871
0.001
Preoperative AKI
2.720
1.307–5.657
0.007
Preoperative sepsis
2.281
1.123–4.636
0.023
Perivalvular abscess
1.864
1.002–3.465
0.049
CI, confidence intervall; IE infective endocarditis; OR, odds ratio

Patients with perivalvular abscess

Patients with perivalvular abscess showed no statistically significant differences regarding preoperative characteristics except a higher rate of peripheral vascular disease (12.2% vs. 6.2%, p = 0.033). Regarding the manifestation of IE, we found no difference in the distribution of underlying causative microorganisms. But patients with perivalvular abscess were diagnosed more with IE of the aortic valve (76.4% vs. 49.5%; p < 0.001) whereas patients without perivalvular abscess showed more mitral valve IE (56.0% vs. 33.8%; p < 0.001). Operation, CPB and crossclamp time were significantly longer in patients with perivalvular abscess due to the higher complexity of operation.
Patients with perivalvular abscess showed an impaired perioperative outcome with a significantly higher 30-day mortality (17.7% vs. 8.0%; p = 0.003), a higher need for postoperative pacemaker implantation for higher AV-grade (15.5% vs. 7.3%; p = 0.007), an increased rate of postoperative cerebrovascular events (8.8% vs. 4.0%; p = 0.042) and postoperative AKI (45.6% vs. 33.1%; p = 0.012). However, perivalvular abscess seems not to influence 1-year mortality (20.9% vs. 22.3%; p = 806) and postoperative long-term complications, such as readmission to hospital, relapse of IE or AKI during the follow-up (Table 5).
Table 5
Characteristics and outcomes of patients with and without perivalvular abscess
 
- Perivalvular abscess (n = 275)
+ Perivalvular abscess (n = 148)
P value
Age
64.3 [50.6–72.9]
65.0 [50.3–74.0]
0.778
Female sex
61 (22.3%)
43 (29.1%)
0.122
BMI
25.8 [23.5–28.3]
25.4 [23.4–28.7]
0.597
BSA
1.98 [1.83–2.12]
1.96 [1.74–1.96]
0.309
COPD
26 (9.5%)
14 (9.5%)
0.999
Diabetes
78 (28.4%)
39 (26.4%)
0.659
Peripheral vascular disease
17 (6.2%)
18 (12.2%)
0.033
Preoperative AKI
156 (56.7%)
90 (60.8%)
0.417
Coronary artery disease
71 (25.8%)
46 (31.1%)
0.248
Immunosuppression
3 (1.1%)
4 (2.7%)
0.229
HIV
6 (2.2%)
4 (2.7%)
0.739
Alcohol abuse
26 (9.5%)
15 (10.1%)
0.821
Intravenous drug abuse
19 (6.9%)
9 (6.1%)
0.774
History of neoplasm
27 (9.8%)
16 (10.8%)
0.747
LVEF
< 30%
4 (1.5%)
5 (3.4%)
0.201
30–50%
61 (22.8%)
33 (22.4%)
0.942
> 50%
203 (75.7%)
109 (74.1%)
0.809
MICROBIOLOGY
 Positive Blood culture
224 (89.6%)
119 (84.4%)
0.132
 Streptococcus spp.
69 (25.1%)
26 (17.6%)
0.077
 Staphylococcus spp.
83 (30.2%)
51 (34.5%)
0.367
 Staph aureus
61 (22.2%)
33 (22.3%)
0.978
 CoNS
23 (8.4%)
19 (12.8%)
0.142
 Enterococcus spp.
39 (14.2%)
22 (14.9%)
0.849
ECHOCARDIOGRAPHY
 Vegetation
226 (82.5%)
110 (74.8%)
0.062
Leftsided IE
 Aortic valve
136 (49.5%)
113 (76.4%)
< 0.001
 Mitral valve
154 (56.0%)
50 (33.8%)
< 0.001
Rightsided IE
 Tricuspid valve
19 (6.9%)
4 (2.7%)
0.069
 Pulmonary valve
1 (0.7%)
1 (0.4%)
0.663
SYMPTOMS
 Fever
169 (61.5%)
107 (72.3%)
0.026
 Sepsis
136 (49.5%)
84 (56.8%)
0.152
 IE-related neurologic complications
85 (30.9%)
43 (29.1%)
0.692
 Septic embolism
99 (36.1%)
47 (32.2%)
0.658
 Cardiogenic shock
31 (11.3%)
25 (16.9%)
0.104
OPERATION
 Operation time (min)
195 [155–245]
230 [178–314]
< 0.001
 CPB time (min)
106 [83–142]
138 [100–182]
< 0.001
 Crossclamp time (min)
69 [53–95]
87 [67–115]
< 0.001
30-DAY OUTCOME
 30-day mortality
22 (8.0%)
26 (17.7%)
0.003
 Myocardial infarction
1 (0.4%)
1 (0.7%)
0.663
 New pacemaker *
20 (7.3%)
23 (15.5%)
0.007
 New postoperative cerebrovascular events
11 (4.0%)
13 (8.8%)
0.042
 Postoperative AKI
91 (33.1%)
67 (45.6%)
0.012
 Re-exploration for bleeding
43 (15.7%)
28 (18.9%)
0.398
 Tracheostomy
33 (12.0%)
26 (17.7%)
0.108
 Time of ventilation (h)
19.8 [12.0–68.9]
26.6 [12.3–117.6]
0.118
 ICU stay (d)
4.0 [2.0–8.0]
5.0 [2.0–10.0]
0.103
 Hospital stay (d)
12.0 [9.0–17.0]
12.0 [9.0–17.0]
0.992
1-YEAR OUTCOME
 1-year mortality
35 (22.3%)
18 (20.9%)
0.806
 Re-admission to hospital
86 (58.5%)
44 (55.0%)
0.610
 Relapse of endocarditis
10 (6.9%)
4 (5.3%)
0.631
 AKI during follow-up
23 (15.9%)
14 (18.2%)
0.659
Data presented as number (percent) or median [IQR], respectively. AKI, acute kidney injury; BMI, body mass index; BSA, body surface area; COPD, chronic obstructive pulmonary disease; HIV, human immunodeficiency virus; ICU, intensive care unit; IE, infective endocarditis; IQR, interquartile range; *for higher AV-grade

Discussion

Incidence of PVE

Although the incidence of PVE is relatively low, there is an increasing number of patients with PVE [15]. PVE occurs in 1–6% of patients with valve prostheses [46] and accounted for over 20% of all IE cases in a prospective, multicenter, international registry, reflecting a considerably higher proportion of PVE compared to earlier reports [4]. The proportion of PVE to NVE is comparable with our data, including 24.6% of PVE cases in our cohort of patients undergoing surgery for IE.

Postoperative outcome of patients undergoing surgery for PVE compared to NVE

Our retrospective analysis revealed PVE as independent risk factor for mortality. PVE patients of our cohort had a significantly higher 30-day mortality compared to NVE patients (21.4% vs. 8.3%; p < 0.001). These findings were also reported by Romano et al. who found a higher in-hospital mortality in their PVE group, compared to their NVE group (24.2% vs. 6.6%, p < 0.0001) [2]. Even after propensity-matching, we still observed a 4-fold increased 30-day mortality in PVE compared to NVE.
Operation for PVE in comparison with NVE has been linked to worse outcomes and the 30-day mortality remains high. Our data demonstrate that the higher mortality of patients undergoing surgery PVE compared to NVE occurs in the early postoperative phase and up to one year postoperatively. Afterwards the Kaplan Meier curve shows parallel slopes, thus a similar long-term survival beyond the first year after surgery. This is in line with findings of Alonso-Valle et al., who found highest mortality rates during the first 3 months. After this period the survival of the patients remained stable [6]. Likewise, Manne et al. found a significantly higher 30-day mortality (13% vs 5.6%, p < 0.01) in patients with PVE compared to NVE, but long-term survival was not significantly different (35% vs. 29%, p = 0.19) [16], which is similar in our study. In addition, data of the Cleveland Clinic suggest, that early mortality is significantly higher in patients with PVE, whereas 1-year survival is comparable [16]. This is in line with the findings of Edlin et al., reporting on similar long-term survival in patients with PVE compared to NVE [15].
Several factors have been associated with the increased mortality in PVE including increased age [17], female sex [18], congestive heart failure [19], staphylococcal infection [4] and renal dysfunction [20]. In several other previous studies, periannular complications were also associated with significantly higher in-hospital mortality [1, 4, 6, 18]. In line with this, our multivariate analysis revealed PVE, preoperative AKI, preoperative sepsis and perivalvular abscess as independent risk factors for mortality.

Perivalvular infection

In our cohort we could detect significantly more perivalvular abscesses in 60.2% of PVE compared to 27.0% of NVE patients (p < 0.001). This is in line with other studies reporting on periannular extensions in 56–100% of patients with PVE [10]. Due to frequent presence of perivalvular infection, surgery for PVE is technically more demanding than for NVE, as it requires radical debridement and complex surgical intervention [8, 10]. This is reflected in the longer CPB and crossclamp times in our PVE group, which might be a surrogate parameter for the complexity of procedure. In several previous studies, periannular complications were associated with significantly higher in-hospital mortality [1, 4, 6, 18, 21]. In accordance, we found a 30-day mortality rate of 17.7% in patients with perivalvular abscess, which was significantly higher compared to patients without perivalvular abscess (8.0%) (p = 0.003). Besides the higher 30-day mortality, patients with perivalvular abscess suffered from more postoperative complications, such as the need of postoperative pacemaker implantation, new postoperative cerebrovascular events and postoperative AKI. Our data suggest, that perivalvular abscess influences 30-day mortality and perioperative complications, but has no relevant impact on 1-year mortality or long-term complications in terms of readmission to hospital, relapse of IE or AKI during the follow-up. Therefore, we suppose that the difference in survival during the first year after surgery for PVE and NVE might be attributed to the higher prevalence of perivalvular abscess in PVE patients, which is associated with a higher rate of 30-day mortality and perioperative complications, but has no impact on 1-year mortality, readmission rate or relapse of IE.

Impaired timely diagnosis of PVE

Timely diagnosis of PVE can be difficult as clinical presentation is frequently atypical and results of blood cultures and echocardiography are more often negative, leading to lower sensitivity of the Duke criteria [79]. This is supported by our data, showing a significantly lower rate of vegetations in echocardiography for patients with PVE (70.9% vs. 82.2%; p = 0.017). Hence, we suggest that early detection and diagnosis of PVE is essential to prevent an increase of perivalvular destruction. Several studies have investigated the sensitivity and specificity of PET/CT or SPECT/CT imaging in patients with suspected IE [22, 23]. PET-CT increased the sensitivity and specificity of the modified Duke criteria from 70 to 95%, reducing the number of patients with „possible IE “from 56 to 32% [22, 23]. A combination of TTE, TEE and CT can increase the sensitivity for the detection of valvular and perivalvular complications in IE [11]. Therefore, early detection of perivalvular lesions by using CT imaging should be considered in suspected IE as implemented in the recent ESC guidelines for the management of IE [9].

Distribution of causative microorganisms

Besides more perivalvular infection, the spectrum of microorganisms that cause PVE seems to differ from those detected in NVE. Several studies reported, that Staphylococci were more frequent in PVE, with a predominance of Staphylococcus aureus or CoNS [4, 24, 25]. Previous studies revealed, that IE due to Staphylococcus aureus is characterized by aggressive disease with increased risk of embolism, stroke and mortality [26]. However, the incidence of Staphylococcus aureus IE was comparable between PVE and NVE patients in our cohort. Nevertheless, we included infection with Staphylococcus aureus as matching variable in our propensity matching. Although we could not find a difference in the incidence of Staphylococcus aureus IE, patients with PVE were diagnosed more often with CoNS compared to NVE patients. As ubiquitous skin commensals, CoNS are often associated with health-care contact and invasive procedures [7]. They colonise indwelling lines and devices and are the most common isolate in early prosthetic valve endocarditis [6, 7, 25]. Staphylococci and gram-negative microorganisms have been suspected to occur as nosocomial perioperative infection during a period when the prosthetic valve is not completely endothelialized [5]. Therefore strict hygiene during health-care contact and invasive procedures in patients with prosthetic valves is essential.

Limitations

Our study has several limitations that need to be considered for the interpretation of the results. First, the retrospective design and analysis of a limited number of patients from a single center institution reduces the generalizability. In addition, a powerful multivariable analysis of all possible predictors was restricted by the total patient number. Moreover, although we attempted to correct for confounders between groups by propensity matching, there might still remain differences between groups. Finally, we included a very recent patients’ cohort, therefore the 1-year follow-up is not completed in all patients. Nevertheless, despite the limited sample size, our study still comprises a relatively large IE cohort compared to the recent literature and provides meaningful results due to propensity matching.

Conclusions

Considering patients with similar risk profiles, our analysis revealed PVE as an independent risk factor for mortality. PVE was associated with significantly higher 30-day and 1-year mortality compared to NVE. After propensity-matching 30-day mortality was still 4-fold increased in PVE compared to NVE.
The higher incidence of perivalvular abscess seems to determine clinical outcome. Patients with perivalvular abscess showed a significantly higher 30-day mortality and perioperative complications, whereas perivalvular abscess seems to have no relevant impact on 1-year mortality, the rate of readmission or relapse of IE. We suggest, that the higher prevalence of perivalvular abscess in patients undergoing surgery for PVE might have an important impact on the impaired outcome during the first year after surgery for PVE. Therefore, early detection and diagnosis of patients with PVE is crucial and CT imaging should be evaluated in suspected PVE.

Supplementary information

Supplementary information accompanies this paper at https://​doi.​org/​10.​1186/​s12872-020-01338-y.

Acknowledgements

Not applicable.
The study protocol was approved by the institutional review board (Ethics Committee of the Medical Faculty, University of Cologne, 17–407). Individual informed consent was waived due to the retrospective nature of the collected data.
Not applicable.

Competing interests

The authors declare, that they have no competing interests.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.

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Metadaten
Titel
Higher incidence of perivalvular abscess determines perioperative clinical outcome in patients undergoing surgery for prosthetic valve endocarditis
verfasst von
Carolyn Weber
Parwis B. Rahmanian
Melanie Nitsche
Asmae Gassa
Kaveh Eghbalzadeh
Stefanie Hamacher
Julia Merkle
Antje-Christin Deppe
Anton Sabashnikov
Elmar W. Kuhn
Oliver J. Liakopoulos
Thorsten Wahlers
Publikationsdatum
01.12.2020
Verlag
BioMed Central
Erschienen in
BMC Cardiovascular Disorders / Ausgabe 1/2020
Elektronische ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-020-01338-y

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