- Email: [email protected]
Emergency Surgery for Native Mitral Valve Endocarditis: The Impact of Septic and Cardiogenic Shock
Sandro Gelsomino, MD, PhD, Jos G. Maessen, MD, PhD, Frederik van der Veen, MD, PhD, Ugolino Livi, MD, Attilio Renzulli, MD, Fabiana Lucà, MD, Rocco Carella, MD, Elena Crudeli, MD, Antonio Rubino, MD, Carlo Rostagno, MD, Claudio Russo, MD, Valentino Borghetti, MD, Cesare Beghi, MD, Michele De Bonis, MD, PhD, Gian Franco Gensini, MD, and Roberto Lorusso, MD, PhD Department of Heart and Vessels, Careggi Hospital, Florence, Italy; Department of Cardiothoracic Surgery, University Hospital, Maastricht, The Netherlands; Santa Maria Della Misericordia Hospital, Udine, Italy; Cardiac Surgery Unit, Magna Graecia University of Catanzaro, Catanzaro, Italy; Cardiac Surgery Unit, Niguarda Hospital, Milan, Italy; Cardiac Surgery, Civic Hospital, Terni, Italy; University of Parma, Parma, Italy; Cardiac Surgery Unit, San Raffaele Hospital, Milan, Italy; and Community Hospital, Brescia, Italy
Background. Limited information exists about the real impact of the etiology of shock on early and late outcome after emergency surgery in acute native mitral valve endocarditis (ANMVE). This multicenter study analyzed the impact of the etiology of shock on early and late outcome in patients with ANMVE. Methods. Data were collected in eight institutions. Three hundred-seventy-nine ANMVE patients undergoing surgery on an emergency basis between May 1991 and December 2009 were eligible for the study. According to current criteria used for the differential diagnosis of shock, patients were retrospectively assigned to one of three groups: group 1, no shock (n ⴝ 154), group 2, cardiogenic shock (CS [n ⴝ 118]), and group 3, septic shock (SS [n ⴝ 107]). Median follow-up was 69.8 months. Results. Early mortality was significantly higher in patients with SS (p < 0.001). At multivariable logistic regression analysis, compared with patients with CS, patients with SS had more than 3.8 times higher risk of
death. That rose to more than 4 times versus patients without shock. In addition, patients with SS had 4.2 times and 4.3 times higher risk of complications compared with patients with CS and without shock, respectively. Sepsis was also an independent predictor of prolonged artificial ventilation (p ⴝ 0.04) and stroke (p ⴝ 0.003) whereas CS was associated with a higher postoperative occurrence of low output syndrome and myocardial infarction (p < 0.001). No difference was detected between groups in 18-year survival, freedom from endocarditis, and freedom from reoperation. Conclusions. Our study suggests that emergency surgery for ANMVE in patients with CS achieved satisfactory early and late results. In contrast, the presence of SS was linked to dismal early prognosis. Our findings need to be confirmed by further larger studies.
M
and late outcome of these critically ill patients. The aim of this study was, therefore, to perform a long-term multicenter evaluation in patients with ANMVE requiring emergency surgery and to analyze the impact of the shock etiology on outcome.
itral valve endocarditis accounts for 35% to 50% of valve endocarditis [1] and in the last decade, there has been a trend toward earlier operation under these circumstances due to lower postoperative mortality rate, enhanced feasibility of mitral valve repair [2], and reduced systemic embolization [3]. Nonetheless, acute native mitral valve endocarditis (ANMVE) still represents a surgical challenge, with an operative mortality as high as 30% [4]. This rate further increases for emergency procedures in patients with shock [5]. Nonetheless, few data are available regarding long-term results after emergency surgery in ANMVE, and limited information exists about the real impact of the etiology of shock on early Accepted for publication Nov 7, 2011. Address correspondence to Dr Gelsomino, Experimental Surgery Unit, Department of Heart and Vessels, Careggi Hospital, Viale Morgagni 85, Florence 50134, Italy; e-mail: [email protected].
© 2012 by The Society of Thoracic Surgeons Published by Elsevier Inc
(Ann Thorac Surg 2012;93:1469 –76) © 2012 by The Society of Thoracic Surgeons
Patients and Methods Patient Selection The Ethics Committee of each participating institution approved the study and waved the need for patient consent according to the national law regulating observational retrospective studies (Law nr.11960, released on 13/7/2004). Data of patients with ANMVE who had undergone emergency surgery between May 1991 and December 2009 were stored in a common database and were sent to 0003-4975/$36.00 doi:10.1016/j.athoracsur.2011.11.025
ADULT CARDIAC
Emergency Surgery for Native Mitral Valve Endocarditis: The Impact of Septic and Cardiogenic Shock
1470 ADULT CARDIAC
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
a core laboratory (Careggi Hospital, Florence, Italy) for analysis. Indications for emergency surgery, defined as surgery required within 24 hours at the time of hospital admission, included hemodynamic instability, severe acute valve regurgitation, valve rupture, and presence of abscesses, pseudoaneurysms, or fistulas [6]. The number of patients per year coming from the eight institutions was comparable (mean 2.6 ⫾ 0.2, p ⬎ 0.05). Furthermore, when we accounted for hypothetical differences between institutions regarding preoperative and operative data, no significant difference was found between centers (data not shown). Previous mitral valve repair/ replacement and native/prosthetic aortic valve or tricuspid valve endocarditis were exclusion criteria. Median follow-up was 69.8 months (interquartile range, 28.8 to 135.9).
Definitions A scientific committee (see Acknowledgments) consisting of three anesthesiologists, three cardiologists, and one cardiac surgeon, all blinded to the aims of the study, reviewed charts and analyzed data to confirm the diagnosis of AMVE on the basis of modified Duke criteria [7] and American College of Cardiology/American Heart Association guidelines [6] and to assign patients to one of three groups: no shock, cardiogenic shock (CS), or septic shock (SS). Cardiogenic shock was defined on the basis of hemodynamic and clinical criteria [8, 9]. Septic shock was defined following American College of Chest Physicians/ Society of Critical Care Medicine guidelines [10]. In borderline cases, patients were assigned to the septic group in the presence of (1) indexed left ventricular end-diastolic area (LVEDA) less than 5.6 cm2/m2, or (2) inferior vena cava dimension less than 2 cm with caval respiratory index greater than 50% or plasma procalcitonine greater than 10 ng/m, or both [11–15].
Study Population Three hundred seventy-nine patients were eligible for the study. One hundred fifty-four (40.6%) patients who did not meet the inclusion criteria for shock, but required emergency surgery [6], belonged to the no-shock group (group 1), 118 patients (31.1%) were assigned to the CS group (group 2), and 107 patients (28.3%) to the SS group (group 3). Baseline patient characteristics and operative data are shown in Tables 1 and 2.
Echocardiography Transthoracic echocardiography and transesophageal echocardiography were routinely performed in all patients before surgery, and a transthoracic echocardiogram was repeated at follow-up visits. Measurements of inferior vena cava diameters were obtained from longaxis subxiphoid view, and preload was assessed at intraoperative transesophageal echocardiography by measuring the left ventricular end diastolic area index (LVEDAI) [12–15].
Statistical Analysis Continuous variables were presented as mean and standard deviation, categorical variables as percentage, and
Ann Thorac Surg 2012;93:1469 –76
nonnormally distributed variables as median and interquartile range. The association between the independent variables was assessed by analysis of variance, the Kruskal-Wallis and Mantel-Haenszel tests where appropriate, or Fisher’s exact test when some categories involved few observations. Tukey’s and Dunn’s post-hoc tests were employed for multiple comparisons. Multivariable logistic regression analysis was performed to select independent predictors of early death and postoperative events. Thirty-six variables were chosen based on existing Society of Thoracic Surgeons risk adjustment models [16] and investigated for their predictive value. To enhance the accuracy of the model, the number of variables was reduced using variable clustering (PROC VARCLUS; SAS/STAT 9; SAS Institute, Cary, NC). We also investigated interactions between SS, CS, and other key risk factors selected on the basis of published papers [17]. Goodness of fit (Hosmer-Lemeshow) and accuracy (concordance) indexes of the regression models were satisfactory. Freedom from events were estimated by use of the Kaplan-Meier method, and the log rank test was employed to detect differences between groups. Bivariate and multivariable Cox proportional hazard regression models were employed to determine the independent predictors of long-term survival. We used SPSS 12 (SPSS, Chicago, IL) for these calculations. Supplemental data for statistical analysis include: 1) variables tested in uni- and multivariable analysis; and 2) goodness of fit and predictive accuracy of multivariable models. These supplemental data files are available at http://www.sandrogelsomino.eu/supplementalfiles/ annthoracsurg/2011/312025.pdf.
Results Early Outcome Eighty-two patients (21.6%) died either during their hospital stay or within 30 days of operation. The causes of death were sepsis (35.4%), respiratory failure (19.5%), multiorgan failure (15.8%), myocardial infarction (13.4%), massive bleeding (10.9%), and other causes (5%). Early mortality did not change over time (1991 to 1993, 23.5%; 1994 to 1996, 24.0%; 1997 to 1999, 23.0%; 2000 to 2002, 23.0%; 2003 to 2005, 22.0%; 2006 to 2009, 22.2%; p ⫽ 0.9). Early (30-day) death was higher in mitral valve replacement compared with mitral valve repair, but this difference did not reach statistical significance (23.0% [38 of 165] versus 20.5% [45 of 214], p ⫽ 0.66). Early mortality was significantly higher among patients with SS (65.8%) compared with CS (19.5%, p ⬍ 0.001) and no shock (14.6%, p ⬍ 0.001). At multivariable logistic regression analysis (Table 3), SS was an independent predictor of early death (p ⬍ 0.001), whereas no shock (p ⫽ 0.57) and CS (p ⫽ 0.26) were not significant. Postoperative complications occurred in 96 patients (25.3%). The overall complication rate was significantly higher in group 3 (60.4%) than in group 2 (27.1%, p ⫽
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
1471 ADULT CARDIAC
Ann Thorac Surg 2012;93:1469 –76
Table 1. Patient Profile
Patient Data Age, years Sex female/male Systemic hypertension Diabetes mellitus Chronic renal failure COPD LV dysfunction (LVEF ⱕ35%) CVD CAD Preoperative diagnosis of MVD Cerebral embolization Noncerebral embolization Secondary AV endocarditis Secondary TV endocarditis Vegetations at TEE Bacteriology Staphylococcus aureus Streptococcus viridans Streptococcus bovis Streptococcus mitis Enterococcus faecalis Streptococcus sanguinis Staphylococcus epidermidis Gemella morbillorum Staphylococcus capitis Pneumococcus Streptococcus mutans Streptococcus agalactiae Candida albicans Negative hemoculture Intraaortic balloon pump
All (n ⫽ 379)
Group 1 No Shock (n ⫽ 154)
Group 2 Cardiogenic Shock (n ⫽ 118)
Group 3 Septic Shock (n ⫽ 107)
p Value
56.1 ⫾ 9.1 149/226 (39.3/60.7) 127 (33.5) 112 (29.5) 41 (10.8) 47 (12.4) 33 (8.7) 64 (16.8) 31 (8.1) 76 (20.1) 42 (11.1) 29 (7.6) 99 (26.1) 20 (5.2) 107 (28.2)
53.0 ⫾ 6.6 65/89 (42.2/57.8) 53 (34.4) 46 (29.8) 18 (11.6) 19 (12.3) 8 (5.1)a 23 (14.9) 12 (7.7) 26 (16.9) 3 (1.9)b 2 (1.3)b 35 (22.7) 7 (4.5) 16 (10.3)b
55.4 ⫾ 8.9 44/74 (37.3/62.7) 41 (34.7) 36 (30.5) 21 (17.7) 15 (12.7) 17 (14.4)c 24 (20.3) 12 (10.1) 21 (17.8) 1 (0.8)c 2 (1.7)c 27 (22.9) 6 (5.0) 21 (17.8)c
61.0 ⫾ 11.3 40/67 (37.4/62.6) 33 (30.8) 30 (28.0) 10 (9.3) 13 (12.1) 8 (7.4) 17 (15.8) 7 (6.5) 23 (21.4) 38 (35.5) 25 (23.3) 37 (34.5) 7 (6.5) 70 (65.4)
0.13 0.6 0.86 0.79 0.44 ⬎0.9 0.06 0.08 0.63 0.76 ⬍0.001 ⬍0.001 0.42 0.9 ⬍0.001
133 (35.1) 57 (15.0) 37 (9.8) 32 (8.4) 14 (3.6) 9 (2.6) 12 (3.1) 8 (2.1) 9 (2.6) 7 (1.8) 5 (1.3) 6 (1.5) 7 (1.8) 43 (11.8) 187 (49.3)
44 (28.6)b 23 (14.9) 16 (10.4)b 17 (11.0) 5 (3.2) 3 (2.0) 5 (3.2) 2 (1.3) 3 (2.0) 3 (2.0) 2 (1.3) 3 (2.0) 3 (2.0) 25 (16.2)b 75 (48.7)ab
33 (27.9)c 21 (17.8) 18 (15.3)c 9 (7.6) 6 (5.2) 3 (2.5) 1 (0.8) 3 (2.5) 6 (5.2) 3 (2.5) 0 (0) 3 (2.5) 1 (0.8) 11 (9.4) 109 (92.3)c
Continuous variables are presented as mean ⫾ SD; discrete variables are presented as percentage (parentheses). b c 2; group 1 versus 3; group 2 versus 3.
56 (52.4) 13 (12.2) 3 (2.8) 6 (5.6) 3 (2.8) 3 (2.8) 6 (5.6) 3 (2.8) 0 (0) 1 (0.9) 3 (2.8) 0 (0) 3 (2.8) 7 (6.5) 3 (2.8) a
Significance group 1 versus
AV ⫽ aortic valve; CAD ⫽ coronary artery disease; COPD ⫽ chronic ischemic pulmonary disease; CVD ⫽ cerebrovascular disease; left ventricular; LVEF ⫽ left ventricular ejection fraction; MVD ⫽ mitral valve disease; TEE ⫽ transesophageal echocardiography; tricuspid valve.
0.007) and group 1 (12.5%, p ⬍ 0.001). Septic shock was a multivariable predictor of postoperative complications (p ⬍ 0.001). In addition, sepsis was found to be also a predictor of prolonged artificial ventilation (p ⫽ 0.04) and stroke (p ⫽ 0.003), whereas cardiogenic shock was associated with higher postoperative occurrence of low output syndrome and myocardial infarction (p ⬍ 0.001). When we allowed for interaction between shock and other risk factors (Table 4), the association of septic shock with both early death and postoperative complications was noted across all subgroups of patients. Septic shock was associated with unfavorable outcomes also in lowrisk subgroups, and its effect was generally attenuated in higher-risk patients. In contrast, cardiogenic shock had lower early death odds ratios in the absence of advanced
0.03 0.74 0.06 0.09 0.7 0.8 0.19 0.8 0.49 0.5 0.45 0.5 0.45 0.06 ⬍0.001
LV ⫽ TV ⫽
age, left ventricular dysfunction, renal dysfunction, and multiple valve procedures.
Long-Term Results Thirty-one patients (10.4%) died during the follow-up period, for a Kaplan-Meier survival rate of 55.2% at 18 years (Fig 1A). Causes of death were cancer (32.3%), infection (29.0%), myocardial infarction (22.6%), and unknown (16.1%). No difference was detected in 18-year survival among groups (Fig 1B), whereas patients receiving mitral valve repair showed better 18-year survival than patients undergoing mitral valve replacement (Fig 1C). At Cox regression analysis, both CS and SS were not significant predictors of late death (p ⫽ 0.48 and p ⫽ 0.80, respectively).
1472 ADULT CARDIAC
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
Ann Thorac Surg 2012;93:1469 –76
Table 2. Operative Data
Operative Data Pathologic findings APM rupture PPM rupture PMs rupture Chordal rupture Chordal elongation Leaflet perforation Annular abscess Mitral valve replacement Biological Mechanical Size (mm) Mitral valve repair Quadrangular resection Double orifice Artificial chordae Triple orifice Pericardial patch Leaflet repair Cordal shortening Transposition of chordae Isolated annuloplasty
All (n ⫽ 379)
Group 1 No Shock (n ⫽ 154)
Group 2 Cardiogenic Shock (n ⫽ 118)
Group 3 Septic Shock (n ⫽ 107)
p Value
2 (0.5) 11 (2.9) 5 (1.4) 107 (28.2) 4 (1.0) 218 (57.5) 32 (8.5) 165 (43.5) 111 (29.3) 54 (14.3) 27 (27–29) 214 (56.4) 31 (8.1) 26 (6.8) 15 (3.9) 15 (3.9) 49 (12.9) 39 (10.2) 6 (1.5) 3 (0.7) 30 (9.9)
0 (0) 4 (2.6) 0 (0) 47 (30.5)a 2 (1.3) 101 (65.6) 0 (0)a 62 (40.2) 39 (25.3) 23 (14.9) 27 (27–29) 92 (59.8) 18 (11.6) 14 (9.0) 6 (3.8) 6 (3.8) 20 (12.9)b 16 (10.3)b 2 (1.29) 1 (0.64) 12 (7.7)
2 (1.7) 4 (3.3) 2 (1.7) 42 (35.6)c 2 (1.7) 61 (51.8) 5 (4.2)c 63 (53.4) 45 (38.1) 18 (15.2) 27 (27–29) 55 (46.7) 6 (10.9) 6 (10.9) 3 (5.4) 3 (5.4) 17 (31.0)c 11 (20.1) 1 (0.84) 1 (0.84) 6 (10.9)
0 (0) 3 (2.8) 3 (2.8) 18 (16.8) 0 (0) 56 (52.3) 27 (25.3) 40 (37.3) 27 (25.2) 13 (12.2) 27 (27–29) 67 (62.6) 7 (10.4) 6 (8.9) 6 (8.9) 6 (8.9) 12 (18.0) 12 (18.0) 3 (2.8) 1 (0.93) 12 (18.0)
0.56 0.67 0.67 0.45 0.23 1.3 ⬍0.001 0.07 0.42 0.8 ⬎0.9 0.2 0.7 0.07 0.08 0.09 0.06 0.07 0.06 0.8 0.08
Nonnormally distributed variables are presented as median (interquartile range); discrete variables are presented as percentage (parentheses). a b c Significance group 1 versus 3; group 1 versus 2; group 2 versus 3. APM ⫽ anterior papillary muscle;
PMs ⫽ papillary muscles;
PPM ⫽ posterior papillary muscle.
The recurrence of endocarditis was observed in 19 patients (5 patients in group 1, 8 patients in group 2, and 6 patients in group 3). Overall, freedom from recurrent endocarditis (Fig 2A) at 18 years was 89.7%. No difference was detected in 18-year freedom from recurrent endocarditis between groups (Fig 2B) and in mitral valve repair versus replacement (Fig 2C). Eighteen-year freedom from reoperation (Fig 3A) was 70.7%, and no significant difference was detected be-
tween groups (Fig 3B). Finally, 18-year freedom from reoperation was higher among patients receiving mitral valve repair, but this difference did not reach statistical significance (Fig 3C). At the end of the study, 247 patients were alive, not lost to follow-up, and not reoperated on for mitral valve failure or endocarditis. Two hundred twenty-two patients (89.9%) were in New York Heart Association functional class II or less. No difference in postoperative New York
Table 3. Adjusted Odds Ratios for Effect of Septic Shock, Cardiogenic Shock, and Endocarditis Without Shock on Major Postoperative Complications
Postoperative Complications Early death Any postoperative complication Prolonged artificial ventilation Stroke Low output syndrome Mediastinitis Bleeding Myocardial infarction Pacemaker implantation CI ⫽ confidence interval.
No Shock Odds Ratio (95% Bias-Corrected CI)
Cardiogenic Shock Odds Ratio (95% Bias-Corrected CI)
Septic Shock Odds Ratio (95% Bias-Corrected CI)
1.17 (1.09–1.28) 1.10 (1.26–0.57) 0.15 (0.05–0.4) 0.07 (0.03–0.09) 0.16 (0.07–0.21) 0.11 (0.02–0.54) 0.06 (0.01–0.13) 0.22 (0.07–0.46) 0.03 (0.01–0.09)
1.31 (0.80–1.72) 1.13 (0.23–1.57) 0.11 (0.04–0.73) 0.09 (0.05–1.01) 4.26 (2.12–6.57) 0.05 (0.02–0.10) 0.02 (0.01–0.03) 3.26 (2.02–5.29) 0.08 (0.03–0.13)
5.07 (3.10–7.54) 4.82 (3.46–6.25) 3.25 (3.03–4.64) 3.85 (3.15–5.26) 0.05 (0.01–0.09) 0.21 (0.11–0.49) 0.02 (0.01–0.04) 0.05 (0.01–0.08) 1.04 (1.01–1.08)
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
1473
Table 4. Adjusted Odds Ratios for Effect of Septic Shock and Cardiogenic Shock on Early Outcomes in Specific Populations Cardiogenic Shock Early Death Variable Age ⱖ65 years No Yes Preoperative LV dysfunction No Yes Multiple valve procedures No Yes Preoperative renal dysfunction No Yes CI ⫽ confidence interval;
Septic Shock
All Complications
Early Death
All Complications
OR
CI
OR
CI
OR
CI
OR
CI
1.0 1.6
0.8–1.5 1.1–2.0
1.2 1.1
0.5–1.6 0.3–1.4
6.2 4.5
3.1–8.4 2.3–6.1
5.4 4.0
2.6–7.3 2.0–5.3
0.5 2.1
0.2–1.2 1.7–2.5
1.0 1.2
0.4–1.5 0.6–1.6
6.1 4.3
3.3–8.2 2.6–6.3
5.0 4.6
2.4–6.7 2.2–6.0
0.4 2.2
0.2–1.1 1.6–2.6
0.8 1.4
0.2–1.2 1.0–1.9
5.8 5.1
2.8–7.7 2.0–6.9
5.3 3.7
2.6–7.0 2.0–4.3
0.3 2.9
0.1–0.6 1.6–3.1
0.5 1.7
0.1–0.9 1.0–2.1
5.8 4.9
2.8–7.3 2.2–6.1
5.0 3.9
2.5–6.9 2.1–5.1
LV ⫽ left ventricular;
OR ⫽ odds ratio.
Heart Association class was found between groups (p ⫽ 0.64).
Comment We evaluated long-term postoperative results of emergency surgery for AMVE in patients with shock (either cardiogenic or septic) from a multicenter experience to determine whether a specific etiology of the shock translated into worse postoperative outcome.
How to Differentiate Cardiogenic From Septic Shock In AMVE, CS and SS may coexist, making the differential diagnosis difficult. Indeed, myocardial dysfunction frequently accompanies SS. The onset of sepsis is frequently accompanied by hypovolemia due to both arterial and venous dilation and the leakage of plasma into the extravascular space [18]. If this hypovolemia is corrected by aggressive intravenous administration of fluids, it will lead to low systemic vascular resistance, normal or increased cardiac output, tachycardia, and elevation of oxygen concentrations in pulmonary artery blood. This hyperdynamic shock syndrome occurs in more than 90% of patients, and it has been categorized as “distributive shock” to emphasize the presumed maldistribution of blood flow to various tissues [19]. In an advanced state of the disease, myocardial function worsens, cardiac output falls, and progressive cardiac failure occurs. These patients die of a cardiogenic form of SS, a mixture of distributive and cardiogenic shock patterns. Our patients underwent early surgery, and presumably for this reason, almost all subjects with SS in our cohort showed a distributive pattern with hyperdynamic state and increased cardiac index. There were only 3 patients with cardiac index still high but less than 4 L · min⫺1 · m⫺2 (3.4, 3.6, and 3.8, respectively), but none had a cardiac index less than 3 L · min⫺1 · m⫺2.
However, in all centers, transesophageal echocardiography was routinely performed in the preoperative period, which helped to identify the principal causes of circulatory insufficiency implicated in sepsis. In particular, the presence of hypovolemia and hyperdynamic status is an important sign that facilitates differential diagnosis. In borderline cases, other indexes have been demonstrated to help in the differential diagnosis. The LVEDAI at transesophageal echocardiography has been confirmed by recent studies to accurately assess the preload. All patients assigned to the septic group had a LVEDAI less than 5.6 cm2/m2, which is the reference cutoff [14, 15]. Furthermore, all patients assigned to the SS group had a inferior vena cava dimension less than 2 cm and caval respiratory index greater than 50%. Finally, in four centers, starting from 2003, procalcitonine, which has been demonstrated to be a reliable marker for diagnosis of SS with a cutoff value of 10 ng/mL [15], was tested in 79 patients (21%).
Clinical Implications The principal dilemma is whether to operate early on patients with AMVE to limit the risk of emboli and severe cardiac insufficiency, or to delay surgical intervention until resolution of the infection to reduce the risk of operation and of relapse. Our data suggest that for patients without shock and for patients with CS, a prompt intervention is recommended, providing satisfactory early and late results. These findings are in accordance with Revilla and colleagues [20] who found that congestive heart failure was not significantly associated with death in endocarditis patients with an early procedure. In contrast, emergency surgery did not ensure, for patients with SS, acceptable postoperative results. Similarly, Hill and coworkers [21] showed that SS was an independent predictive factor of 6-month mortality. In contrast to congestive heart failure, SS represents uncontrolled systemic and disseminated infection that cannot
ADULT CARDIAC
Ann Thorac Surg 2012;93:1469 –76
1474 ADULT CARDIAC
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
Ann Thorac Surg 2012;93:1469 –76
lective removal of inflammatory mediators or bacterial products, or both. Nonetheless, the ability of these procedures to improve clinical outcomes (mortality, organ failure) is still under investigation [22]. It is worth noting that, in our experience, only a small percentage of patients with SS (2.8%) received an intraaortic balloon pump (IABP) in the perioperative period, and this approach could be partially responsible for
Fig 1. (A) Overall 18-year actuarial survival (continuous line) and 95% confidence interval (dotted lines). (B) Actuarial survival by group: group 1 (diamonds), no shock; group 2 (triangles), cardiogenic shock; and group 3 (squares), septic shock. (C) Actuarial survival by surgical procedure: mitral valve (MV) repair (diamonds) versus replacement (triangles).
be resolved by a local cardiac intervention, and it may explain, for these authors, why SS was associated with a high mortality rate. Our results emphasize that SS per se does not represent an indication for surgery, but it mandates different approaches addressing the disseminated infection. Extracorporeal blood purification therapies such as coupled plasma filtration-adsorption have been proposed for patients with sepsis to improve outcomes, as these therapies can alter the host inflammatory response by nonse-
Fig 2. (A) Freedom from recurrent endocarditis (continuous line) and 95% confidence interval (dotted lines). (B) Freedom from recurrent endocarditis: group 1 (diamonds), no shock; group 2 (triangles), cardiogenic shock; and group 3 (squares), septic shock. (C) Freedom from recurrent endocarditis: mitral valve (MV) repair (diamonds) versus replacement (triangles).
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
1475
Thus, the efficacy of IABP for SS has not been clearly defined yet, and this issue warrants further evaluation. However, what we could expect from the use of IABP for SS is a lowering of the dosage of detrimental vasopressors and a prolongation of survival time [23], which could be used to enable causal antisepsis therapy time to work. Knowing that prognosis depends on “early goal-directed therapy,” we should start very early in the process because IABP needs more than 3 hours and as long as 24 hours to be fully effective [26]. Nonetheless, complications with IABP may be higher for SS owing to coagulation problems due to septic disseminated intravascular coagulation [26]. Finally, in our study, the percentage of mitral valve repairs in SS patients was higher than in the other two groups (63%, versus 47% in CS and 60% in NS), and mitral repair, irrespective of the presence or etiology of shock, translated into better long-term survival.
Study Limitations
Fig 3. (A) Freedom from reoperation (continuous line) and 95% confidence interval (dotted lines). (B) Freedom from reoperation: group 1 (diamonds), no shock; group 2 (triangles), cardiogenic shock; and group 3 (squares), septic shock. (C) Freedom from reoperation: mitral valve (MV) repair (diamonds) versus replacement (triangles).
the poor early outcome. Indeed, in a recent work, Solomon and colleagues [23] demonstrated, in a canine model of SS, that intraaortic balloon counterpulsation prolongs survival time and lowers vasopressor requirements. Moreover, in newborn lambs infected with group B streptococci, hemodynamics were improved by IABP as indicated by an increase in cardiac output and decrease in pulmonary resistance [24]. Conversely, in a porcine model of endotoxemic shock, IABP was of no benefit [25].
This study reveals the obvious limitations related to the multicenter and retrospective format of data collection. Indeed, the original data were not acquired in a standard registry or data system, and criteria and guidelines were retrospectively applied. That means that the original findings were not used; rather, the data were reinterpreted and the assignation to cardiogenic or septic shock was done retrospectively. In addition, we could not include in our analysis the time course between diagnosis and the occurrence of shock because many patients were referred to us already in shock from different hospitals. We cannot, therefore, exclude the possibility that some patients developed valve dysfunction-related or infective-related shock that could have been prevented by a more timely surgical intervention. Furthermore, for the same reasons, we do not have information on the time elapsed between the start of antibiotic therapy and the occurrence of shock. Thus, we cannot exclude the possibility that our poor results might be due to inadequate or not timely antimicrobial treatment of the infection. Moreover, no information is provided on the inclusion bias (the patients who did not undergo operation at all, as well as the patients who underwent operation later than 24 hours after admission with the same indications). Indeed, analysis with time after admission as a continuous factor would perhaps be more informative. That will be the subject of an ongoing study. Additionally, clinical evaluation and procedures were performed in different centers by different surgeons who might have differently assessed and evaluated the clinical or cardiopulmonary conditions. However, we accounted for hypothetical differences in preoperative and operative characteristics among institutions participating in the study, and no significant difference was found. Furthermore, the study was conducted over an 18-year period, but we did not account for changes and advances made over this period, including valve types, antibiotic regimens, and critical care. Early mortality did not change over time in all institutions. However, over the
ADULT CARDIAC
Ann Thorac Surg 2012;93:1469 –76
1476 ADULT CARDIAC
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
years, had patient selection as well as the perioperative management and the surgical techniques been adapted, these results point to an inclusion bias toward the enrollment of more difficult patients. Unfortunately, such an analysis was not made. Moreover, better survival of patients receiving mitral valve repair compared to mitral valve replacement might be attributable to the selection of better risk patients. In fact, our analysis did not take into account the microorganism involved in patients undergoing repair versus replacement and the degree of tissue destruction. In other words, the result may be affected by institutional bias related to replacing valves that are difficult to repair. Finally, some overlap cannot be excluded in the assignment of patients to SS and CS groups, and that must be taken into account when analyzing our findings as it could introduce bias to our analysis. In conclusion, emergency surgery in patients with ANMVE and CS achieved satisfactory early and late results. On the contrary, the presence of SS suggests careful evaluation of emergency operation against delayed surgery, with adequate preoperative patient stabilization or treatment with new modalities. Further studies on this controversial issue are still needed to confirm our findings. We gratefully acknowledge the members of the scientific committee: Stefano Romagnoli, Stefano Bevilacqua, Francesco Ciappi (Anesthesiology, Careggi Hospital, Florence, Italy); Sabina Caciolli, Marco Chioccioli, Carmelo Massimiliano Rao (Cardiology, Careggi Hospital, Florence, Italy); and Giuseppe Billè (Cardiac Surgery, Careggi Hospital, Florence, Italy). We are grateful to Prof James Douglas for the English revision of the manuscript and to Dr Orlando Parise for statistical analysis.
References 1. Wallace SM, Walton BI, Kharbanda RK, Hardy R, Wilson AP, Swanton RH. Mortality from infective endocarditis: clinical predictors of outcome. Heart 2002;88:53– 60. 2. Feringa HH, Shaw LJ, Poldermans D, et al. Mitral valve repair and replacement in endocarditis: a systematic review of literature. Ann Thorac Surg 2007;83:564 –71. 3. Muehrcke DD, Cosgrove DM, Lytle BW, et al. Is there an advantage to repairing infected mitral valves? Ann Thorac Surg 1997;63:1718 –24. 4. Iung B, Rousseau-Paziaud J, Cormier B, et al. Contemporary results of mitral valve repair for infective endocarditis. J Am Coll Cardiol 2004;43:386 –92. 5. Verheul H, Van den Brink RR, Van Vreeland T, Moulijn AC, Duren DR, Dunning AJ. Effects of changes in management of active infective endocarditis on outcome in 25-year period. Am J Cardiol 1993;72:682–7. 6. Nishimura RA, Carabello BA, Faxon DP, et al. ACC/AHA 2008 guideline update on valvular heart disease: focused update on infective endocarditis. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2008;118:887–96. 7. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30:633– 8.
Ann Thorac Surg 2012;93:1469 –76
8. Hollenberg S, Kavinsky CJ, Parrillo JE. Cardiogenic shock. Ann Intern Med 1999;131:47–59. 9. Mehta RH, Grab JD, O’Brien SM, et al, for The Society of Thoracic Surgeons National Cardiac Database Investigators. Clinical characteristics and in-hospital outcomes of patients with cardiogenic shock undergoing coronary artery bypass surgery: insights from The Society of Thoracic Surgeons National Cardiac Database. Circulation 2008;117:876 – 85. 10. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864 –74. 11. de Werra I, Jaccard C, Corradin SB, et al. Cytokines, nitrite/ nitrate, soluble tumor necrosis factor receptors and procalcitonin concentrations: comparisons in patients with septic shock, cardiogenic shock and bacterial pneumonia. Crit Care Med 1997;25:607–13. 12. Royse CF, Barrington MJ, Royse AG. Transesophageal echocardiography values for left ventricular end-diastolic area and pulmonary vein and mitral inflow Doppler velocities in patients undergoing coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2000;14:130 –2. 13. Kircher BJ, Himelman RB, Schiller NB. Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava. Am J Cardiol 1990;66:493– 6. 14. Capomolla S, Febo O, Caporotondi A, et al. Non-invasive estimation of right atrial pressure by combined Doppler echocardiographic measurements of the inferior vena cava in patients with congestive heart failure. Ital Heart J 2000;1: 684 –90. 15. Aouifi A, Piriou V, Bastien O, et al. Usefulness of procalcitonin for diagnosis of infection in cardiac surgical patients. Crit Care Med 2000;28:3171– 6. 16. Edwards FH, Peterson ED, Coombs LP, et al. Prediction of operative mortality after valve replacement surgery. J Am Coll Cardiol 2001;37:885–92. 17. de Kerchove L, Vanoverschelde JL, Poncelet A, et al. Reconstructive surgery in active mitral valve endocarditis: feasibility, safety and durability. Eur J Cardiothorac Surg 2007;31: 592–9. 18. Nduka OO, Parrillo JE. The pathophysiology of septic shock. Crit Care Clin 2009;25:677–702. 19. Parker MM, Shelhamer JH, Natanson C, Alling DW, Parrillo JE. Serial cardiovascular variables in survivors and nonsurvivors of human septic shock: heart rate as an early predictor of prognosis. Crit Care Med 1987;15:923–9. 20. Revilla A, López J, Vilacosta I, et al. Clinical and prognostic profile of patients with infective endocarditis who need urgent surgery. Eur Heart J 2007;28:65–71. 21. Hill EE, Herregods MC, Vanderschueren S, Claus P, Peetermans WE, Herijgers P. Outcome of patients requiring valve surgery during active infective endocarditis. Ann Thorac Surg 2008;85:1564 – 69. 22. Rimmelé T, Kellum JA. Clinical review: blood purification for sepsis. Crit Care 2011;15:205. 23. Solomon SB, Minneci PC, Deans KJ, et al. Effects of intraaortic balloon counterpulsation in a model of septic shock. Crit Care Med. 2009;37:7–18. 24. Pribble CG, Shaddy RE. Intra-aortic balloon counterpulsation in newborn lambs infected with group B streptococcus. ASAIO Trans 1991;37:33–7. 25. Engoren M, Habib RH. Effects of intraaortic balloon augmentation in a porcine model of endotoxemic shock. Resuscitation 2004;60:319 –26. 26. Werdan K, Russ M, Buerke M. Intraaortic balloon counterpulsation in cardiogenic shock. In: Vincent JL, ed. Yearbook of intensive care medicine. Heidelberg ,Germany: SpringerVerlag, 2010:107–18.
Background. Limited information exists about the real impact of the etiology of shock on early and late outcome after emergency surgery in acute native mitral valve endocarditis (ANMVE). This multicenter study analyzed the impact of the etiology of shock on early and late outcome in patients with ANMVE. Methods. Data were collected in eight institutions. Three hundred-seventy-nine ANMVE patients undergoing surgery on an emergency basis between May 1991 and December 2009 were eligible for the study. According to current criteria used for the differential diagnosis of shock, patients were retrospectively assigned to one of three groups: group 1, no shock (n ⴝ 154), group 2, cardiogenic shock (CS [n ⴝ 118]), and group 3, septic shock (SS [n ⴝ 107]). Median follow-up was 69.8 months. Results. Early mortality was significantly higher in patients with SS (p < 0.001). At multivariable logistic regression analysis, compared with patients with CS, patients with SS had more than 3.8 times higher risk of
death. That rose to more than 4 times versus patients without shock. In addition, patients with SS had 4.2 times and 4.3 times higher risk of complications compared with patients with CS and without shock, respectively. Sepsis was also an independent predictor of prolonged artificial ventilation (p ⴝ 0.04) and stroke (p ⴝ 0.003) whereas CS was associated with a higher postoperative occurrence of low output syndrome and myocardial infarction (p < 0.001). No difference was detected between groups in 18-year survival, freedom from endocarditis, and freedom from reoperation. Conclusions. Our study suggests that emergency surgery for ANMVE in patients with CS achieved satisfactory early and late results. In contrast, the presence of SS was linked to dismal early prognosis. Our findings need to be confirmed by further larger studies.
M
and late outcome of these critically ill patients. The aim of this study was, therefore, to perform a long-term multicenter evaluation in patients with ANMVE requiring emergency surgery and to analyze the impact of the shock etiology on outcome.
itral valve endocarditis accounts for 35% to 50% of valve endocarditis [1] and in the last decade, there has been a trend toward earlier operation under these circumstances due to lower postoperative mortality rate, enhanced feasibility of mitral valve repair [2], and reduced systemic embolization [3]. Nonetheless, acute native mitral valve endocarditis (ANMVE) still represents a surgical challenge, with an operative mortality as high as 30% [4]. This rate further increases for emergency procedures in patients with shock [5]. Nonetheless, few data are available regarding long-term results after emergency surgery in ANMVE, and limited information exists about the real impact of the etiology of shock on early Accepted for publication Nov 7, 2011. Address correspondence to Dr Gelsomino, Experimental Surgery Unit, Department of Heart and Vessels, Careggi Hospital, Viale Morgagni 85, Florence 50134, Italy; e-mail: [email protected].
© 2012 by The Society of Thoracic Surgeons Published by Elsevier Inc
(Ann Thorac Surg 2012;93:1469 –76) © 2012 by The Society of Thoracic Surgeons
Patients and Methods Patient Selection The Ethics Committee of each participating institution approved the study and waved the need for patient consent according to the national law regulating observational retrospective studies (Law nr.11960, released on 13/7/2004). Data of patients with ANMVE who had undergone emergency surgery between May 1991 and December 2009 were stored in a common database and were sent to 0003-4975/$36.00 doi:10.1016/j.athoracsur.2011.11.025
ADULT CARDIAC
Emergency Surgery for Native Mitral Valve Endocarditis: The Impact of Septic and Cardiogenic Shock
1470 ADULT CARDIAC
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
a core laboratory (Careggi Hospital, Florence, Italy) for analysis. Indications for emergency surgery, defined as surgery required within 24 hours at the time of hospital admission, included hemodynamic instability, severe acute valve regurgitation, valve rupture, and presence of abscesses, pseudoaneurysms, or fistulas [6]. The number of patients per year coming from the eight institutions was comparable (mean 2.6 ⫾ 0.2, p ⬎ 0.05). Furthermore, when we accounted for hypothetical differences between institutions regarding preoperative and operative data, no significant difference was found between centers (data not shown). Previous mitral valve repair/ replacement and native/prosthetic aortic valve or tricuspid valve endocarditis were exclusion criteria. Median follow-up was 69.8 months (interquartile range, 28.8 to 135.9).
Definitions A scientific committee (see Acknowledgments) consisting of three anesthesiologists, three cardiologists, and one cardiac surgeon, all blinded to the aims of the study, reviewed charts and analyzed data to confirm the diagnosis of AMVE on the basis of modified Duke criteria [7] and American College of Cardiology/American Heart Association guidelines [6] and to assign patients to one of three groups: no shock, cardiogenic shock (CS), or septic shock (SS). Cardiogenic shock was defined on the basis of hemodynamic and clinical criteria [8, 9]. Septic shock was defined following American College of Chest Physicians/ Society of Critical Care Medicine guidelines [10]. In borderline cases, patients were assigned to the septic group in the presence of (1) indexed left ventricular end-diastolic area (LVEDA) less than 5.6 cm2/m2, or (2) inferior vena cava dimension less than 2 cm with caval respiratory index greater than 50% or plasma procalcitonine greater than 10 ng/m, or both [11–15].
Study Population Three hundred seventy-nine patients were eligible for the study. One hundred fifty-four (40.6%) patients who did not meet the inclusion criteria for shock, but required emergency surgery [6], belonged to the no-shock group (group 1), 118 patients (31.1%) were assigned to the CS group (group 2), and 107 patients (28.3%) to the SS group (group 3). Baseline patient characteristics and operative data are shown in Tables 1 and 2.
Echocardiography Transthoracic echocardiography and transesophageal echocardiography were routinely performed in all patients before surgery, and a transthoracic echocardiogram was repeated at follow-up visits. Measurements of inferior vena cava diameters were obtained from longaxis subxiphoid view, and preload was assessed at intraoperative transesophageal echocardiography by measuring the left ventricular end diastolic area index (LVEDAI) [12–15].
Statistical Analysis Continuous variables were presented as mean and standard deviation, categorical variables as percentage, and
Ann Thorac Surg 2012;93:1469 –76
nonnormally distributed variables as median and interquartile range. The association between the independent variables was assessed by analysis of variance, the Kruskal-Wallis and Mantel-Haenszel tests where appropriate, or Fisher’s exact test when some categories involved few observations. Tukey’s and Dunn’s post-hoc tests were employed for multiple comparisons. Multivariable logistic regression analysis was performed to select independent predictors of early death and postoperative events. Thirty-six variables were chosen based on existing Society of Thoracic Surgeons risk adjustment models [16] and investigated for their predictive value. To enhance the accuracy of the model, the number of variables was reduced using variable clustering (PROC VARCLUS; SAS/STAT 9; SAS Institute, Cary, NC). We also investigated interactions between SS, CS, and other key risk factors selected on the basis of published papers [17]. Goodness of fit (Hosmer-Lemeshow) and accuracy (concordance) indexes of the regression models were satisfactory. Freedom from events were estimated by use of the Kaplan-Meier method, and the log rank test was employed to detect differences between groups. Bivariate and multivariable Cox proportional hazard regression models were employed to determine the independent predictors of long-term survival. We used SPSS 12 (SPSS, Chicago, IL) for these calculations. Supplemental data for statistical analysis include: 1) variables tested in uni- and multivariable analysis; and 2) goodness of fit and predictive accuracy of multivariable models. These supplemental data files are available at http://www.sandrogelsomino.eu/supplementalfiles/ annthoracsurg/2011/312025.pdf.
Results Early Outcome Eighty-two patients (21.6%) died either during their hospital stay or within 30 days of operation. The causes of death were sepsis (35.4%), respiratory failure (19.5%), multiorgan failure (15.8%), myocardial infarction (13.4%), massive bleeding (10.9%), and other causes (5%). Early mortality did not change over time (1991 to 1993, 23.5%; 1994 to 1996, 24.0%; 1997 to 1999, 23.0%; 2000 to 2002, 23.0%; 2003 to 2005, 22.0%; 2006 to 2009, 22.2%; p ⫽ 0.9). Early (30-day) death was higher in mitral valve replacement compared with mitral valve repair, but this difference did not reach statistical significance (23.0% [38 of 165] versus 20.5% [45 of 214], p ⫽ 0.66). Early mortality was significantly higher among patients with SS (65.8%) compared with CS (19.5%, p ⬍ 0.001) and no shock (14.6%, p ⬍ 0.001). At multivariable logistic regression analysis (Table 3), SS was an independent predictor of early death (p ⬍ 0.001), whereas no shock (p ⫽ 0.57) and CS (p ⫽ 0.26) were not significant. Postoperative complications occurred in 96 patients (25.3%). The overall complication rate was significantly higher in group 3 (60.4%) than in group 2 (27.1%, p ⫽
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
1471 ADULT CARDIAC
Ann Thorac Surg 2012;93:1469 –76
Table 1. Patient Profile
Patient Data Age, years Sex female/male Systemic hypertension Diabetes mellitus Chronic renal failure COPD LV dysfunction (LVEF ⱕ35%) CVD CAD Preoperative diagnosis of MVD Cerebral embolization Noncerebral embolization Secondary AV endocarditis Secondary TV endocarditis Vegetations at TEE Bacteriology Staphylococcus aureus Streptococcus viridans Streptococcus bovis Streptococcus mitis Enterococcus faecalis Streptococcus sanguinis Staphylococcus epidermidis Gemella morbillorum Staphylococcus capitis Pneumococcus Streptococcus mutans Streptococcus agalactiae Candida albicans Negative hemoculture Intraaortic balloon pump
All (n ⫽ 379)
Group 1 No Shock (n ⫽ 154)
Group 2 Cardiogenic Shock (n ⫽ 118)
Group 3 Septic Shock (n ⫽ 107)
p Value
56.1 ⫾ 9.1 149/226 (39.3/60.7) 127 (33.5) 112 (29.5) 41 (10.8) 47 (12.4) 33 (8.7) 64 (16.8) 31 (8.1) 76 (20.1) 42 (11.1) 29 (7.6) 99 (26.1) 20 (5.2) 107 (28.2)
53.0 ⫾ 6.6 65/89 (42.2/57.8) 53 (34.4) 46 (29.8) 18 (11.6) 19 (12.3) 8 (5.1)a 23 (14.9) 12 (7.7) 26 (16.9) 3 (1.9)b 2 (1.3)b 35 (22.7) 7 (4.5) 16 (10.3)b
55.4 ⫾ 8.9 44/74 (37.3/62.7) 41 (34.7) 36 (30.5) 21 (17.7) 15 (12.7) 17 (14.4)c 24 (20.3) 12 (10.1) 21 (17.8) 1 (0.8)c 2 (1.7)c 27 (22.9) 6 (5.0) 21 (17.8)c
61.0 ⫾ 11.3 40/67 (37.4/62.6) 33 (30.8) 30 (28.0) 10 (9.3) 13 (12.1) 8 (7.4) 17 (15.8) 7 (6.5) 23 (21.4) 38 (35.5) 25 (23.3) 37 (34.5) 7 (6.5) 70 (65.4)
0.13 0.6 0.86 0.79 0.44 ⬎0.9 0.06 0.08 0.63 0.76 ⬍0.001 ⬍0.001 0.42 0.9 ⬍0.001
133 (35.1) 57 (15.0) 37 (9.8) 32 (8.4) 14 (3.6) 9 (2.6) 12 (3.1) 8 (2.1) 9 (2.6) 7 (1.8) 5 (1.3) 6 (1.5) 7 (1.8) 43 (11.8) 187 (49.3)
44 (28.6)b 23 (14.9) 16 (10.4)b 17 (11.0) 5 (3.2) 3 (2.0) 5 (3.2) 2 (1.3) 3 (2.0) 3 (2.0) 2 (1.3) 3 (2.0) 3 (2.0) 25 (16.2)b 75 (48.7)ab
33 (27.9)c 21 (17.8) 18 (15.3)c 9 (7.6) 6 (5.2) 3 (2.5) 1 (0.8) 3 (2.5) 6 (5.2) 3 (2.5) 0 (0) 3 (2.5) 1 (0.8) 11 (9.4) 109 (92.3)c
Continuous variables are presented as mean ⫾ SD; discrete variables are presented as percentage (parentheses). b c 2; group 1 versus 3; group 2 versus 3.
56 (52.4) 13 (12.2) 3 (2.8) 6 (5.6) 3 (2.8) 3 (2.8) 6 (5.6) 3 (2.8) 0 (0) 1 (0.9) 3 (2.8) 0 (0) 3 (2.8) 7 (6.5) 3 (2.8) a
Significance group 1 versus
AV ⫽ aortic valve; CAD ⫽ coronary artery disease; COPD ⫽ chronic ischemic pulmonary disease; CVD ⫽ cerebrovascular disease; left ventricular; LVEF ⫽ left ventricular ejection fraction; MVD ⫽ mitral valve disease; TEE ⫽ transesophageal echocardiography; tricuspid valve.
0.007) and group 1 (12.5%, p ⬍ 0.001). Septic shock was a multivariable predictor of postoperative complications (p ⬍ 0.001). In addition, sepsis was found to be also a predictor of prolonged artificial ventilation (p ⫽ 0.04) and stroke (p ⫽ 0.003), whereas cardiogenic shock was associated with higher postoperative occurrence of low output syndrome and myocardial infarction (p ⬍ 0.001). When we allowed for interaction between shock and other risk factors (Table 4), the association of septic shock with both early death and postoperative complications was noted across all subgroups of patients. Septic shock was associated with unfavorable outcomes also in lowrisk subgroups, and its effect was generally attenuated in higher-risk patients. In contrast, cardiogenic shock had lower early death odds ratios in the absence of advanced
0.03 0.74 0.06 0.09 0.7 0.8 0.19 0.8 0.49 0.5 0.45 0.5 0.45 0.06 ⬍0.001
LV ⫽ TV ⫽
age, left ventricular dysfunction, renal dysfunction, and multiple valve procedures.
Long-Term Results Thirty-one patients (10.4%) died during the follow-up period, for a Kaplan-Meier survival rate of 55.2% at 18 years (Fig 1A). Causes of death were cancer (32.3%), infection (29.0%), myocardial infarction (22.6%), and unknown (16.1%). No difference was detected in 18-year survival among groups (Fig 1B), whereas patients receiving mitral valve repair showed better 18-year survival than patients undergoing mitral valve replacement (Fig 1C). At Cox regression analysis, both CS and SS were not significant predictors of late death (p ⫽ 0.48 and p ⫽ 0.80, respectively).
1472 ADULT CARDIAC
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
Ann Thorac Surg 2012;93:1469 –76
Table 2. Operative Data
Operative Data Pathologic findings APM rupture PPM rupture PMs rupture Chordal rupture Chordal elongation Leaflet perforation Annular abscess Mitral valve replacement Biological Mechanical Size (mm) Mitral valve repair Quadrangular resection Double orifice Artificial chordae Triple orifice Pericardial patch Leaflet repair Cordal shortening Transposition of chordae Isolated annuloplasty
All (n ⫽ 379)
Group 1 No Shock (n ⫽ 154)
Group 2 Cardiogenic Shock (n ⫽ 118)
Group 3 Septic Shock (n ⫽ 107)
p Value
2 (0.5) 11 (2.9) 5 (1.4) 107 (28.2) 4 (1.0) 218 (57.5) 32 (8.5) 165 (43.5) 111 (29.3) 54 (14.3) 27 (27–29) 214 (56.4) 31 (8.1) 26 (6.8) 15 (3.9) 15 (3.9) 49 (12.9) 39 (10.2) 6 (1.5) 3 (0.7) 30 (9.9)
0 (0) 4 (2.6) 0 (0) 47 (30.5)a 2 (1.3) 101 (65.6) 0 (0)a 62 (40.2) 39 (25.3) 23 (14.9) 27 (27–29) 92 (59.8) 18 (11.6) 14 (9.0) 6 (3.8) 6 (3.8) 20 (12.9)b 16 (10.3)b 2 (1.29) 1 (0.64) 12 (7.7)
2 (1.7) 4 (3.3) 2 (1.7) 42 (35.6)c 2 (1.7) 61 (51.8) 5 (4.2)c 63 (53.4) 45 (38.1) 18 (15.2) 27 (27–29) 55 (46.7) 6 (10.9) 6 (10.9) 3 (5.4) 3 (5.4) 17 (31.0)c 11 (20.1) 1 (0.84) 1 (0.84) 6 (10.9)
0 (0) 3 (2.8) 3 (2.8) 18 (16.8) 0 (0) 56 (52.3) 27 (25.3) 40 (37.3) 27 (25.2) 13 (12.2) 27 (27–29) 67 (62.6) 7 (10.4) 6 (8.9) 6 (8.9) 6 (8.9) 12 (18.0) 12 (18.0) 3 (2.8) 1 (0.93) 12 (18.0)
0.56 0.67 0.67 0.45 0.23 1.3 ⬍0.001 0.07 0.42 0.8 ⬎0.9 0.2 0.7 0.07 0.08 0.09 0.06 0.07 0.06 0.8 0.08
Nonnormally distributed variables are presented as median (interquartile range); discrete variables are presented as percentage (parentheses). a b c Significance group 1 versus 3; group 1 versus 2; group 2 versus 3. APM ⫽ anterior papillary muscle;
PMs ⫽ papillary muscles;
PPM ⫽ posterior papillary muscle.
The recurrence of endocarditis was observed in 19 patients (5 patients in group 1, 8 patients in group 2, and 6 patients in group 3). Overall, freedom from recurrent endocarditis (Fig 2A) at 18 years was 89.7%. No difference was detected in 18-year freedom from recurrent endocarditis between groups (Fig 2B) and in mitral valve repair versus replacement (Fig 2C). Eighteen-year freedom from reoperation (Fig 3A) was 70.7%, and no significant difference was detected be-
tween groups (Fig 3B). Finally, 18-year freedom from reoperation was higher among patients receiving mitral valve repair, but this difference did not reach statistical significance (Fig 3C). At the end of the study, 247 patients were alive, not lost to follow-up, and not reoperated on for mitral valve failure or endocarditis. Two hundred twenty-two patients (89.9%) were in New York Heart Association functional class II or less. No difference in postoperative New York
Table 3. Adjusted Odds Ratios for Effect of Septic Shock, Cardiogenic Shock, and Endocarditis Without Shock on Major Postoperative Complications
Postoperative Complications Early death Any postoperative complication Prolonged artificial ventilation Stroke Low output syndrome Mediastinitis Bleeding Myocardial infarction Pacemaker implantation CI ⫽ confidence interval.
No Shock Odds Ratio (95% Bias-Corrected CI)
Cardiogenic Shock Odds Ratio (95% Bias-Corrected CI)
Septic Shock Odds Ratio (95% Bias-Corrected CI)
1.17 (1.09–1.28) 1.10 (1.26–0.57) 0.15 (0.05–0.4) 0.07 (0.03–0.09) 0.16 (0.07–0.21) 0.11 (0.02–0.54) 0.06 (0.01–0.13) 0.22 (0.07–0.46) 0.03 (0.01–0.09)
1.31 (0.80–1.72) 1.13 (0.23–1.57) 0.11 (0.04–0.73) 0.09 (0.05–1.01) 4.26 (2.12–6.57) 0.05 (0.02–0.10) 0.02 (0.01–0.03) 3.26 (2.02–5.29) 0.08 (0.03–0.13)
5.07 (3.10–7.54) 4.82 (3.46–6.25) 3.25 (3.03–4.64) 3.85 (3.15–5.26) 0.05 (0.01–0.09) 0.21 (0.11–0.49) 0.02 (0.01–0.04) 0.05 (0.01–0.08) 1.04 (1.01–1.08)
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
1473
Table 4. Adjusted Odds Ratios for Effect of Septic Shock and Cardiogenic Shock on Early Outcomes in Specific Populations Cardiogenic Shock Early Death Variable Age ⱖ65 years No Yes Preoperative LV dysfunction No Yes Multiple valve procedures No Yes Preoperative renal dysfunction No Yes CI ⫽ confidence interval;
Septic Shock
All Complications
Early Death
All Complications
OR
CI
OR
CI
OR
CI
OR
CI
1.0 1.6
0.8–1.5 1.1–2.0
1.2 1.1
0.5–1.6 0.3–1.4
6.2 4.5
3.1–8.4 2.3–6.1
5.4 4.0
2.6–7.3 2.0–5.3
0.5 2.1
0.2–1.2 1.7–2.5
1.0 1.2
0.4–1.5 0.6–1.6
6.1 4.3
3.3–8.2 2.6–6.3
5.0 4.6
2.4–6.7 2.2–6.0
0.4 2.2
0.2–1.1 1.6–2.6
0.8 1.4
0.2–1.2 1.0–1.9
5.8 5.1
2.8–7.7 2.0–6.9
5.3 3.7
2.6–7.0 2.0–4.3
0.3 2.9
0.1–0.6 1.6–3.1
0.5 1.7
0.1–0.9 1.0–2.1
5.8 4.9
2.8–7.3 2.2–6.1
5.0 3.9
2.5–6.9 2.1–5.1
LV ⫽ left ventricular;
OR ⫽ odds ratio.
Heart Association class was found between groups (p ⫽ 0.64).
Comment We evaluated long-term postoperative results of emergency surgery for AMVE in patients with shock (either cardiogenic or septic) from a multicenter experience to determine whether a specific etiology of the shock translated into worse postoperative outcome.
How to Differentiate Cardiogenic From Septic Shock In AMVE, CS and SS may coexist, making the differential diagnosis difficult. Indeed, myocardial dysfunction frequently accompanies SS. The onset of sepsis is frequently accompanied by hypovolemia due to both arterial and venous dilation and the leakage of plasma into the extravascular space [18]. If this hypovolemia is corrected by aggressive intravenous administration of fluids, it will lead to low systemic vascular resistance, normal or increased cardiac output, tachycardia, and elevation of oxygen concentrations in pulmonary artery blood. This hyperdynamic shock syndrome occurs in more than 90% of patients, and it has been categorized as “distributive shock” to emphasize the presumed maldistribution of blood flow to various tissues [19]. In an advanced state of the disease, myocardial function worsens, cardiac output falls, and progressive cardiac failure occurs. These patients die of a cardiogenic form of SS, a mixture of distributive and cardiogenic shock patterns. Our patients underwent early surgery, and presumably for this reason, almost all subjects with SS in our cohort showed a distributive pattern with hyperdynamic state and increased cardiac index. There were only 3 patients with cardiac index still high but less than 4 L · min⫺1 · m⫺2 (3.4, 3.6, and 3.8, respectively), but none had a cardiac index less than 3 L · min⫺1 · m⫺2.
However, in all centers, transesophageal echocardiography was routinely performed in the preoperative period, which helped to identify the principal causes of circulatory insufficiency implicated in sepsis. In particular, the presence of hypovolemia and hyperdynamic status is an important sign that facilitates differential diagnosis. In borderline cases, other indexes have been demonstrated to help in the differential diagnosis. The LVEDAI at transesophageal echocardiography has been confirmed by recent studies to accurately assess the preload. All patients assigned to the septic group had a LVEDAI less than 5.6 cm2/m2, which is the reference cutoff [14, 15]. Furthermore, all patients assigned to the SS group had a inferior vena cava dimension less than 2 cm and caval respiratory index greater than 50%. Finally, in four centers, starting from 2003, procalcitonine, which has been demonstrated to be a reliable marker for diagnosis of SS with a cutoff value of 10 ng/mL [15], was tested in 79 patients (21%).
Clinical Implications The principal dilemma is whether to operate early on patients with AMVE to limit the risk of emboli and severe cardiac insufficiency, or to delay surgical intervention until resolution of the infection to reduce the risk of operation and of relapse. Our data suggest that for patients without shock and for patients with CS, a prompt intervention is recommended, providing satisfactory early and late results. These findings are in accordance with Revilla and colleagues [20] who found that congestive heart failure was not significantly associated with death in endocarditis patients with an early procedure. In contrast, emergency surgery did not ensure, for patients with SS, acceptable postoperative results. Similarly, Hill and coworkers [21] showed that SS was an independent predictive factor of 6-month mortality. In contrast to congestive heart failure, SS represents uncontrolled systemic and disseminated infection that cannot
ADULT CARDIAC
Ann Thorac Surg 2012;93:1469 –76
1474 ADULT CARDIAC
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
Ann Thorac Surg 2012;93:1469 –76
lective removal of inflammatory mediators or bacterial products, or both. Nonetheless, the ability of these procedures to improve clinical outcomes (mortality, organ failure) is still under investigation [22]. It is worth noting that, in our experience, only a small percentage of patients with SS (2.8%) received an intraaortic balloon pump (IABP) in the perioperative period, and this approach could be partially responsible for
Fig 1. (A) Overall 18-year actuarial survival (continuous line) and 95% confidence interval (dotted lines). (B) Actuarial survival by group: group 1 (diamonds), no shock; group 2 (triangles), cardiogenic shock; and group 3 (squares), septic shock. (C) Actuarial survival by surgical procedure: mitral valve (MV) repair (diamonds) versus replacement (triangles).
be resolved by a local cardiac intervention, and it may explain, for these authors, why SS was associated with a high mortality rate. Our results emphasize that SS per se does not represent an indication for surgery, but it mandates different approaches addressing the disseminated infection. Extracorporeal blood purification therapies such as coupled plasma filtration-adsorption have been proposed for patients with sepsis to improve outcomes, as these therapies can alter the host inflammatory response by nonse-
Fig 2. (A) Freedom from recurrent endocarditis (continuous line) and 95% confidence interval (dotted lines). (B) Freedom from recurrent endocarditis: group 1 (diamonds), no shock; group 2 (triangles), cardiogenic shock; and group 3 (squares), septic shock. (C) Freedom from recurrent endocarditis: mitral valve (MV) repair (diamonds) versus replacement (triangles).
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
1475
Thus, the efficacy of IABP for SS has not been clearly defined yet, and this issue warrants further evaluation. However, what we could expect from the use of IABP for SS is a lowering of the dosage of detrimental vasopressors and a prolongation of survival time [23], which could be used to enable causal antisepsis therapy time to work. Knowing that prognosis depends on “early goal-directed therapy,” we should start very early in the process because IABP needs more than 3 hours and as long as 24 hours to be fully effective [26]. Nonetheless, complications with IABP may be higher for SS owing to coagulation problems due to septic disseminated intravascular coagulation [26]. Finally, in our study, the percentage of mitral valve repairs in SS patients was higher than in the other two groups (63%, versus 47% in CS and 60% in NS), and mitral repair, irrespective of the presence or etiology of shock, translated into better long-term survival.
Study Limitations
Fig 3. (A) Freedom from reoperation (continuous line) and 95% confidence interval (dotted lines). (B) Freedom from reoperation: group 1 (diamonds), no shock; group 2 (triangles), cardiogenic shock; and group 3 (squares), septic shock. (C) Freedom from reoperation: mitral valve (MV) repair (diamonds) versus replacement (triangles).
the poor early outcome. Indeed, in a recent work, Solomon and colleagues [23] demonstrated, in a canine model of SS, that intraaortic balloon counterpulsation prolongs survival time and lowers vasopressor requirements. Moreover, in newborn lambs infected with group B streptococci, hemodynamics were improved by IABP as indicated by an increase in cardiac output and decrease in pulmonary resistance [24]. Conversely, in a porcine model of endotoxemic shock, IABP was of no benefit [25].
This study reveals the obvious limitations related to the multicenter and retrospective format of data collection. Indeed, the original data were not acquired in a standard registry or data system, and criteria and guidelines were retrospectively applied. That means that the original findings were not used; rather, the data were reinterpreted and the assignation to cardiogenic or septic shock was done retrospectively. In addition, we could not include in our analysis the time course between diagnosis and the occurrence of shock because many patients were referred to us already in shock from different hospitals. We cannot, therefore, exclude the possibility that some patients developed valve dysfunction-related or infective-related shock that could have been prevented by a more timely surgical intervention. Furthermore, for the same reasons, we do not have information on the time elapsed between the start of antibiotic therapy and the occurrence of shock. Thus, we cannot exclude the possibility that our poor results might be due to inadequate or not timely antimicrobial treatment of the infection. Moreover, no information is provided on the inclusion bias (the patients who did not undergo operation at all, as well as the patients who underwent operation later than 24 hours after admission with the same indications). Indeed, analysis with time after admission as a continuous factor would perhaps be more informative. That will be the subject of an ongoing study. Additionally, clinical evaluation and procedures were performed in different centers by different surgeons who might have differently assessed and evaluated the clinical or cardiopulmonary conditions. However, we accounted for hypothetical differences in preoperative and operative characteristics among institutions participating in the study, and no significant difference was found. Furthermore, the study was conducted over an 18-year period, but we did not account for changes and advances made over this period, including valve types, antibiotic regimens, and critical care. Early mortality did not change over time in all institutions. However, over the
ADULT CARDIAC
Ann Thorac Surg 2012;93:1469 –76
1476 ADULT CARDIAC
GELSOMINO ET AL ACUTE NATIVE MITRAL VALVE ENDOCARDITIS
years, had patient selection as well as the perioperative management and the surgical techniques been adapted, these results point to an inclusion bias toward the enrollment of more difficult patients. Unfortunately, such an analysis was not made. Moreover, better survival of patients receiving mitral valve repair compared to mitral valve replacement might be attributable to the selection of better risk patients. In fact, our analysis did not take into account the microorganism involved in patients undergoing repair versus replacement and the degree of tissue destruction. In other words, the result may be affected by institutional bias related to replacing valves that are difficult to repair. Finally, some overlap cannot be excluded in the assignment of patients to SS and CS groups, and that must be taken into account when analyzing our findings as it could introduce bias to our analysis. In conclusion, emergency surgery in patients with ANMVE and CS achieved satisfactory early and late results. On the contrary, the presence of SS suggests careful evaluation of emergency operation against delayed surgery, with adequate preoperative patient stabilization or treatment with new modalities. Further studies on this controversial issue are still needed to confirm our findings. We gratefully acknowledge the members of the scientific committee: Stefano Romagnoli, Stefano Bevilacqua, Francesco Ciappi (Anesthesiology, Careggi Hospital, Florence, Italy); Sabina Caciolli, Marco Chioccioli, Carmelo Massimiliano Rao (Cardiology, Careggi Hospital, Florence, Italy); and Giuseppe Billè (Cardiac Surgery, Careggi Hospital, Florence, Italy). We are grateful to Prof James Douglas for the English revision of the manuscript and to Dr Orlando Parise for statistical analysis.
References 1. Wallace SM, Walton BI, Kharbanda RK, Hardy R, Wilson AP, Swanton RH. Mortality from infective endocarditis: clinical predictors of outcome. Heart 2002;88:53– 60. 2. Feringa HH, Shaw LJ, Poldermans D, et al. Mitral valve repair and replacement in endocarditis: a systematic review of literature. Ann Thorac Surg 2007;83:564 –71. 3. Muehrcke DD, Cosgrove DM, Lytle BW, et al. Is there an advantage to repairing infected mitral valves? Ann Thorac Surg 1997;63:1718 –24. 4. Iung B, Rousseau-Paziaud J, Cormier B, et al. Contemporary results of mitral valve repair for infective endocarditis. J Am Coll Cardiol 2004;43:386 –92. 5. Verheul H, Van den Brink RR, Van Vreeland T, Moulijn AC, Duren DR, Dunning AJ. Effects of changes in management of active infective endocarditis on outcome in 25-year period. Am J Cardiol 1993;72:682–7. 6. Nishimura RA, Carabello BA, Faxon DP, et al. ACC/AHA 2008 guideline update on valvular heart disease: focused update on infective endocarditis. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2008;118:887–96. 7. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30:633– 8.
Ann Thorac Surg 2012;93:1469 –76
8. Hollenberg S, Kavinsky CJ, Parrillo JE. Cardiogenic shock. Ann Intern Med 1999;131:47–59. 9. Mehta RH, Grab JD, O’Brien SM, et al, for The Society of Thoracic Surgeons National Cardiac Database Investigators. Clinical characteristics and in-hospital outcomes of patients with cardiogenic shock undergoing coronary artery bypass surgery: insights from The Society of Thoracic Surgeons National Cardiac Database. Circulation 2008;117:876 – 85. 10. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864 –74. 11. de Werra I, Jaccard C, Corradin SB, et al. Cytokines, nitrite/ nitrate, soluble tumor necrosis factor receptors and procalcitonin concentrations: comparisons in patients with septic shock, cardiogenic shock and bacterial pneumonia. Crit Care Med 1997;25:607–13. 12. Royse CF, Barrington MJ, Royse AG. Transesophageal echocardiography values for left ventricular end-diastolic area and pulmonary vein and mitral inflow Doppler velocities in patients undergoing coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2000;14:130 –2. 13. Kircher BJ, Himelman RB, Schiller NB. Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava. Am J Cardiol 1990;66:493– 6. 14. Capomolla S, Febo O, Caporotondi A, et al. Non-invasive estimation of right atrial pressure by combined Doppler echocardiographic measurements of the inferior vena cava in patients with congestive heart failure. Ital Heart J 2000;1: 684 –90. 15. Aouifi A, Piriou V, Bastien O, et al. Usefulness of procalcitonin for diagnosis of infection in cardiac surgical patients. Crit Care Med 2000;28:3171– 6. 16. Edwards FH, Peterson ED, Coombs LP, et al. Prediction of operative mortality after valve replacement surgery. J Am Coll Cardiol 2001;37:885–92. 17. de Kerchove L, Vanoverschelde JL, Poncelet A, et al. Reconstructive surgery in active mitral valve endocarditis: feasibility, safety and durability. Eur J Cardiothorac Surg 2007;31: 592–9. 18. Nduka OO, Parrillo JE. The pathophysiology of septic shock. Crit Care Clin 2009;25:677–702. 19. Parker MM, Shelhamer JH, Natanson C, Alling DW, Parrillo JE. Serial cardiovascular variables in survivors and nonsurvivors of human septic shock: heart rate as an early predictor of prognosis. Crit Care Med 1987;15:923–9. 20. Revilla A, López J, Vilacosta I, et al. Clinical and prognostic profile of patients with infective endocarditis who need urgent surgery. Eur Heart J 2007;28:65–71. 21. Hill EE, Herregods MC, Vanderschueren S, Claus P, Peetermans WE, Herijgers P. Outcome of patients requiring valve surgery during active infective endocarditis. Ann Thorac Surg 2008;85:1564 – 69. 22. Rimmelé T, Kellum JA. Clinical review: blood purification for sepsis. Crit Care 2011;15:205. 23. Solomon SB, Minneci PC, Deans KJ, et al. Effects of intraaortic balloon counterpulsation in a model of septic shock. Crit Care Med. 2009;37:7–18. 24. Pribble CG, Shaddy RE. Intra-aortic balloon counterpulsation in newborn lambs infected with group B streptococcus. ASAIO Trans 1991;37:33–7. 25. Engoren M, Habib RH. Effects of intraaortic balloon augmentation in a porcine model of endotoxemic shock. Resuscitation 2004;60:319 –26. 26. Werdan K, Russ M, Buerke M. Intraaortic balloon counterpulsation in cardiogenic shock. In: Vincent JL, ed. Yearbook of intensive care medicine. Heidelberg ,Germany: SpringerVerlag, 2010:107–18.