Summary
Background
Staphylococcus aureus infective endocarditis (SAIE) is a serious and common disease.
Aims
To assess the clinical and echocardiographic characteristics and prognostic factors of left-sided native-valve SAIE, and to compare these characteristics between two periods (1990–2000 vs. 2001–2010).
Methods
This was a retrospective analysis of 162 cases of left-sided native-valve SAIE among 1254 patients hospitalized for infective endocarditis (IE) between 1990 and 2010.
Results
SAIE represented 18.1% of all cases of IE and 22.9% of cases of native-valve IE. Complications included heart failure in 44.7% of cases, acute renal failure in 23.3%, sepsis in 28.5%, neurological events in 35.8%, systemic embolic events in 54.9% and in-hospital mortality in 25.3%. Factors associated with in-hospital mortality were heart failure (odds ratio [OR] 2.5; P = 0.04) and sepsis (OR 5.3; P = 0.001). Long-term 5-year survival was 49.6 ± 4.9%. Factors associated with long-term mortality were heart failure (OR 1.7; P = 0.032), sepsis (OR 3; P = 0.0001) and delayed surgery (OR 0.43; P = 0.003). Comparison of the two periods revealed a significant increase in bivalvular involvement, valvular incompetence and acute renal failure from 2001 to 2010. No significant difference was observed in terms of in-hospital mortality rates (28.1% vs. 23.5%; P = 0.58) and long-term 5-year survival (45.0 ± 6.6% vs. 57.1 ± 6.4%; P = 0.33).
Conclusion
Mortality as a result of left-sided native-valve SAIE remains high. Factors associated with in-hospital mortality are heart failure and sepsis. Factors associated with long-term mortality are heart failure, sepsis and delayed surgery. Despite progress in surgical techniques, in-hospital mortality and long-term mortality have not decreased significantly between the two periods.
Résumé
Contexte
L’endocardite infectieuse à Staphylococcus aureus (SAIE) reste une maladie grave.
Objectif
Étudier les caractéristiques cliniques, échographiques, les facteurs pronostiques des SAIE sur valves natives gauches et comparer ces caractéristiques entre 2 périodes (1990–2000 vs 2001–2010).
Méthodes
Il s’agit d’une étude rétrospective analysant les données de 162 SAIE sur valves natives gauches entre 1990 et 2010.
Résultats
SAIE représente 18,1 % des EI et 22,9 % des EI sur valves natives. Elle se complique dans 44,7 % d’insuffisance cardiaque, 23,3 % d’insuffisance rénale aiguë, 28,5 % de sepsis, 35,8 % d’évènements neurologiques, 54,9 % d’embolies systémiques et de 25,3 % de mortalité hospitalière. Les facteurs associés à la mortalité hospitalière sont l’insuffisance cardiaque (OR 2,5 ; p = 0,04) et le sepsis (OR 5,3 ; p = 0,001). La mortalité globale à 5 ans est de 49,6 ± 4,9 %. Les facteurs associés à la mortalité globale sont l’insuffisance cardiaque (OR 1,7 ; p = 0,032), le sepsis (OR 3 ; p = 0,0001) et la chirurgie précoce (OR 0,43 ; p = 0,003). La comparaison des 2 périodes montre une majoration du taux d’insuffisance rénale aiguë, d’atteinte bivalvulaire et d’insuffisance valvulaire lors de la période 2001–2010. On ne retrouve pas de différence significative de la mortalité hospitalière (28,1 % vs 23,5 % ; p = 0,58) et de la survie globale à 5 ans (45,0 ± 6,6 % vs 57,1 ± 6,4 % ; p = 0,33).
Conclusion
La mortalité de SAIE sur valves natives gauches reste élevée. Les facteurs associés à la mortalité hospitalière sont l’insuffisance cardiaque et le sepsis. Les facteurs associés à la mortalité globale sont l’insuffisance cardiaque, le sepsis et la chirurgie précoce. Malgré les progrès chirurgicaux, on ne retrouve pas de baisse significative de la mortalité hospitalière et globale entre les deux périodes.
Background
Infective endocarditis (IE) is a serious disease, with an annual incidence of 3–10/100,000 in European countries and in North America . Despite improvements in diagnosis and effective therapeutic techniques, morbidity and mortality rates remain high. According to some authors , Staphylococcus aureus is currently the main microorganism responsible for IE in western countries, and is associated with a poorer prognosis than with other microorganisms. The incidence of S . aureus infective endocarditis (SAIE) ranges between 19% and 38% , and has shown a rise in recent decades , which can be explained by increased use of invasive procedures and intravascular devices and improved diagnostic techniques . In the literature, SAIE is associated with high mortality rates, ranging from 17% to 46% . Current guidelines recommend early surgical treatment of SAIE because of its severe prognosis. However, only one study has assessed the prognosis of left- and right-sided native-valve SAIE, and right-sided SAIE appears to be a very different clinical, echocardiographic, prognostic and therapeutic entity. The aim of this study was to determine the clinical and echocardiographic characteristics and prognostic factors of left-sided native-valve SAIE, and to compare these characteristics between two periods (1990–2000 vs. 2001–2010).
Methods
Between January 1990 and December 2010, 1254 consecutive patients from two French centres (Amiens: 542 patients; Marseille: 712 patients) with confirmed IE according to the Duke criteria were referred to our echocardiographic laboratory. The Duke criteria were applied retrospectively to patients hospitalized before their publication. All patients were examined by transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). SAIE accounted for 22.9% of cases of native-valve IE. A total of 162 patients (16.3%) had blood or valve cultures that were positive for S . aureus with definite acute left-sided native-valve IE (mitral and aortic valves), and were included in this study ( Fig. 1 ). These 162 patients were divided into two groups and compared: 64 patients (39.5%) hospitalized between 1990 and 2000 (group 1); and 98 patients (60.5%) hospitalized between 2001 and 2010 (group 2). Early surgical intervention was defined as surgery performed during hospitalization for management of IE , and was divided into three periods : emergency procedures on the first day after diagnosis; urgent procedures, between the second day and the eighth day; and elective procedures, after the eighth day. This study was approved by the local ethics committee of the two centres.
Clinical variables
Age, sex, presence of co-morbidity (history of diabetes, cancer, haematological malignancy, cirrhosis, renal failure, dialysis, heart failure or coronary artery disease), valvular heart disease, cardiac surgery and the presence of an intravascular device (venous catheter, pacemaker or dialysis device) were analysed. A co-morbidity index, taking into account the patient’s age and history, was calculated .
The following acute clinical events present on admission or occurring during hospitalization were recorded: heart failure, neurological event, embolism and severe sepsis. The portal of entry of the infection was investigated. Embolic events were diagnosed based on clinical signs and data derived from a non-invasive procedure (brain, chest and abdomen computed tomography). A neurological event was defined as the development of neurological symptomatic complications, such as ischaemic stroke with hemiplegia, haemorrhagic stroke, transient ischaemic attack, brain abscess, and features of encephalopathy or coma. Severe sepsis was defined as a systemic inflammatory syndrome secondary to an infectious process, leading to organ dysfunction, signs of hypoperfusion or hypotension.
Echocardiography
All patients were systematically assessed by TTE and by TOE. All echocardiographic studies were performed according to standard techniques and by experienced physicians during the acute phase of IE, without any complications. Standard definitions were used for vegetations, abscesses and other cardiac infective lesions . All TOE recordings were reviewed by an experienced physician to measure the maximum length of vegetations in various planes. The mobility of vegetations was graded on a scale from 1 to 4, with severe mobility corresponding to grade 4 . Valvular regurgitation was quantified by Doppler echocardiography using standard methods .
Follow-up
Follow-up data included surgical treatment and death occurring during hospitalization or follow-up. In-hospital mortality was defined as death occurring during the initial hospitalization for IE. Long-term mortality included death occurring during hospitalization and during follow-up. Follow-up was complete in 100% of cases, with a mean follow-up of 29 ± 34.3 months.
Statistical analysis
Statistical analysis was performed with SPSS software, version 21.0 (IBM, Armonk, NY, USA). Quantitative variables are expressed as means ± standard deviations. Comparisons between groups were carried out using Student’s t -test or the Chi 2 test. The cumulative probability of survival was estimated using the Kaplan–Meier actuarial method at 1-month intervals and reported as mean estimated survival ± standard error. The log-rank test was used to determine any significant differences. Multivariable analyses were performed, incorporating – as potential predictors of mortality – variables that correlated with mortality in univariate analysis, with P values ≤ 0.10. A multivariable logistic regression model was used for in-hospital mortality, and a Cox multivariable model was used for long-term mortality.
Results
Baseline characteristics
Of the 162 patients studied (105 men/57 women, mean age 56.9 ± 15 years), 29.0% had pre-existing valve disease ( Table 1 ). Forty patients (24.7%) had diabetes and 14.8% had neoplasia, with a mean co-morbidity index of 3.19 ± 2.7. IE involved the aortic valve in 38.8% of cases, the mitral valve in 53.8% of cases and both the mitral and aortic valves in 7.4% of cases. The main complications were heart failure (44.7%), acute renal failure (23.3%), sepsis (28.5%), neurological events (35.8%) and systemic embolism (54.9%). S . aureus was resistant to methicillin (MRSA) in 15.2% of cases. The portal of entry was identified in 69.1% of cases, with a predominance of cutaneous portals of entry (57.5%) ( Table 1 ). Vegetations were present in 92.0% of cases. The valve abscess, valve perforation and valve regurgitation rates were 27.3%, 24.1% and 49.4%, respectively ( Table 1 ). Early surgery was performed for 74 patients (45.7%). The main surgical procedure was bioprosthetic valve replacement. Thirty-eight procedures were performed on the aortic valve, 32 procedures on the mitral valve and 14 procedures on both the mitral and aortic valves. Operative mortality was 36.5% ( Table 1 ).
| All patients | Group 1 (1990–2000) | Group 2 (2001–2010) | P a | |
|---|---|---|---|---|
| ( n = 162) | ( n = 64) | ( n = 98) | ||
| Mean age (years) | 56.9 ± 15 | 57.3 ± 16.8 | 56.7 ± 17.5 | 0.8 |
| Men/women ( n / n ) | 105/57 | 44/20 | 61/37 | 0.5 |
| Co-morbidity index | 3.19 ± 2.7 | 3.16 ± 2.6 | 3.21 ± 2.8 | 0.48 |
| Valve disease | 47 (29.0) | 17 (26.6) | 30 (30.6) | 0.8 |
| Diabetes | 40 (24.7) | 16 (25.0) | 24 (24.5) | 1 |
| Neoplasm | 24 (14.8) | 11 (17.2) | 13 (13.3) | 0.5 |
| Endovascular material | 31 (19.1) | 9 (14.1) | 22 (22.4) | 0.22 |
| Heart failure | 72 (44.7) | 30 (46.9) | 42 (43.3) | 0.75 |
| Renal failure | 35 (23.3) | 5 (8.1) | 30 (31.6) | 0.001 |
| Sepsis | 45 (28.5) | 22 (34.9) | 23 (24.2) | 0.15 |
| Neurological event | 58 (35.8) | 23 (35.9) | 35 (35.7) | 1 |
| Systemic embolism | 89 (54.9) | 30 (46.9) | 59 (60.2) | 0.09 |
| MRSA | 22 (15.2) | 13 (25.5) | 9 (9.6) | 0.01 |
| Portal of entry of infection identified | 112 (69.1) | 42 (65.6) | 70 (71.4) | 0.48 |
| Skin | 93 (57.5) | 32 (50.0) | 61 (62.2) | 0.14 |
| Rhinopharynx | 11 (6.8) | 7 (10.9) | 4 (4.1) | 0.11 |
| Digestive | 4 (2.5) | 0 (0) | 4 (4.1) | 0.15 |
| Urological | 5 (3.1) | 3 (4.7) | 2 (2.0) | 0.8 |
| Aortic endocarditis | 63 (38.8) | 27 (42.2) | 36 (38.7) | 0.6 |
| Mitral endocarditis | 87 (53.8) | 36 (56.3) | 51 (52.0) | 0.34 |
| Mitral-aortic endocarditis | 12 (7.4) | 1 (1.7) | 11 (11.3) | 0.03 |
| Vegetations | 149 (92.0) | 57 (89.1) | 92 (93.9) | 0.37 |
| Length (mm) | 9.1 | 9.5 | 8.7 | 0.05 |
| Perforation | 39 (24.1) | 12 (18.8) | 27 (27.7) | 0.26 |
| Abscess | 44 (27.3) | 14 (21.9) | 30 (30.9) | 0.28 |
| Valve regurgitation | 80 (49.4) | 18 (28.1) | 62 (63.2) | 0.001 |
| Early surgery | 74 (45.7) | 25 (39.1) | 49 (50.0) | 0.2 |
| Emergency: on day 1 | 12 (7.4) | 4 (6.2) | 8 (8.2) | |
| Urgent: day 2 to day 8 | 40 (24.5) | 12 (18.8) | 28 (27.9) | |
| Elective: after day 8 | 23 (14.2) | 9 (14.1) | 14 (14.1) | |
| In-hospital mortality | 41 (25.3) | 18 (28.1) | 23 (23.5) | 0.58 |
| Operative mortality | 27 (36.5) | 12 (35.3) | 15 (37.5) | 1 |
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