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Eur J Cardiothorac Surg 2009;35:123-129. doi:10.1016/j.ejcts.2008.08.033
Copyright © 2009, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.
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Infective endocarditis in elderly patients: clinical characteristics and outcome

Jean Paul Remadib,*, Georges Nadjia, Thomas Goissena,b, N. Alphonse Zomvuamab, Claire Sorela, Christophe Tribouilloya

a Department of Cardiovascular Disease, INSERM, ERI-12, Amiens University Hospital, France
b Department of Cardiovascular Surgery, Amiens University Hospital, France

Received 22 April 2008; received in revised form 13 August 2008; accepted 22 August 2008.

* Corresponding author. Address: Cardio-vascular Surgery Unit, Amiens University Hospital, Avenue René Laënnec, 80054 Amiens, Cédex 1, France. Tel.: +33 3 22 45 59 25; fax: +33 3 22 45 53 31. (Email: jprema{at}voila.fr).


   Abstract
Top
 Abstract
1. Introduction
 2. Patients and methods
 3. Results
 4. Comments
 5. Conclusion
 References
 
Background: The aim of this study was to describe a single unit experience for the treatment of acute infective endocarditis, for patients older than 75 years and to analyse the results of early surgery. Patients and methods: From January 1991 to June 2006 348 consecutive patients with definite acute infective endocarditis, according to Duke criteria, were prospectively enrolled in our database. Among these, 75 patients older than 75 years (mean age 79.8 ± 4 years) were analysed and compared to 273 younger patients. Results: The patients older than 75 years (group A, 75 patients) had a more severe clinical status than the younger patients (group B, 273 patients) with a comorbidity index amounting to 4.9 ± 1.8 and 2.9 ± 1.0 respectively (p = 0.0001). Patients were treated medically (group A 53 pts vs group B 124 pts) or surgically (group A 22 pts vs group B 149 pts) (p = 0.001). The in-hospital mortality rate for group A and B was comparable (16% vs 19%; p = 0.3). Multivariate analysis identified for patients older than 75 years, severe sepsis (p = 0.001, OR = 12, CI [6–24]), and major neurological events (p = 0.02, OR = 3, CI [1.1–7.5]) as the two factors related to higher in-hospital mortality and surgery (p = 0.006, OR = 0.4, CI [0.2–0.7]) as the factor related to a lower in-hospital mortality. The overall survival of the older group at 36 months was 40.8 ± 6.8%. Multivariate analysis for older patients identified comorbidity index (p = 0.001) (HR 1.1, CI [1–1.2]), severe sepsis (p = 0.0001) (HR 3.3, CI [2.2–5.2]), valvular prosthesis (p = 0.0002) (HR 2.4, CI [1.5–4]) and major neurological event (p = 0.04) (HR 1.7, CI [1–3]) as factors related to overall mortality and surgery (p = 0.001) (HR 0.4, CI [0.3–0.6]) as a factor related to a better overall survival. Conclusion: The immediate results of treatment for endocarditis are comparable between elderly and younger patients. The long-term prognosis for the elderly patients is worse, mainly related to a higher comorbidity index. Surgery in elderly patients may be a reasonable option, and should be considered in selected elderly patients.

Key Words: Endocarditis • Elderly patients • Surgery


   1. Introduction
Top
 Abstract
 1. Introduction
2. Patients and methods
 3. Results
 4. Comments
 5. Conclusion
 References
 
Despite dramatic improvements in the natural history of infective endocarditis (IE) subsequent to the introduction of antimicrobial therapy, this entity remains a serious disease that requires surgical intervention in up to 20–40% of involved patients [1–3]. The management of patients with IE is evolving in parallel to advancements in diagnosis as well as medical and surgical therapy [4]. Valve replacement was initially relegated to a salvage manoeuvre, but surgical treatment has become an effective and accepted early option for selected patients with IE [5]. Thus, valve surgery is currently performed in at least 25% of patients with active IE [5,6].

Acute IE in elderly patients is relatively frequent, ranging from 15 to 30% of all the IE [4,7,8]. Medical or surgical treatment of acute IE for older patients remains critical because of associated comorbidities with an increased presence of chronic medical disease. Moreover, few data are available in the literature on IE in elderly patients.

We present here the first study to our knowledge, which analyses clinical feature results of early surgical treatment for the elderly patients and long-term outcome of patients older than 75 years, treated in a single unit for acute IE.


   2. Patients and methods
Top
 Abstract
 1. Introduction
 2. Patients and methods
3. Results
 4. Comments
 5. Conclusion
 References
 
2.1 Patients
Between January 1990 and December 2006, 348 consecutive patients with definite IE according to the Duke criteria were referred to our echocardiographic laboratory and prospectively enrolled. All patients were examined by transthoracic (TTE) and transoesophageal echocardiography (TEE). Seventy-five consecutive patients were older than 75 years (47 men and 28 women, mean age 79.8 ± 4 years) (group A) and 273 patients were younger than 75 years (205 men and 68 women, mean age 56.4 ± 13 years) (group B). The Duke criteria were applied retrospectively to patients hospitalised before publication of the Duke criteria in 1994 [9,10]. All the patients underwent systematic transthoracic and transoesophageal echocardiographic studies. All patients were scheduled for 4–6 weeks of antibiotic treatment. This study was approved by the locals ethics committee.

2.2 Clinical parameters
Age, gender, presence of comorbidities, valvular heart disease, valve prosthesis, cardiac surgery, presence of an intravascular device (venous catheter, pacemaker, and dialysis device) and the portal of entry were analysed. A comorbidity index was calculated (Charlson score) [11]. The following acute clinical events present on admission or occurring during hospitalisation were recorded: moderate to severe congestive heart failure, neurological events, peripheral embolism, and severe sepsis. The duration of symptoms before admission (interval between the presumed onset of symptoms and the date of admission for IE) and the portal of entry of the infection were investigated. The diagnosis of embolic events was based on clinical signs and data derived from non-invasive procedures (cerebral and thoracic-abdominal computed tomographic scans were performed in 60% of patients) [9]. A major neurological event was defined by the development of an ischaemic stroke with haemiplegia, a haemorrhagic stroke, a cerebral abscess, features of encephalopathy or coma [12]. A minor neurological event was defined by a transient ischaemic attack or cerebral embolic accident with no serious clinical signs [12]. Severe sepsis was defined as a systemic inflammatory syndrome secondary to an infectious process, leading to organ dysfunction, signs of hypoperfusion or hypotension [13].

2.3 Echocardiography
Echocardiography was performed on a Hewlett Packard Sonos phased-array Ultrasound System (HP 1000, HP 2500 or HP 5500) using a 2.5-MHz transthoracic transducer and a 5-MHz transoesophageal transducer. Transthoracic echocardiography (TTE) was systematically completed by TEE. All echocardiographic studies were performed by standard techniques and by experienced echocardiographers during the acute phase of IE without any complications. Standard definitions were used for vegetations, abscesses and other cardiac infective lesions [14–16]. All TEE recordings were reviewed by an experienced echocardiographer to measure in various planes the maximum length of vegetations. The mobility of vegetation was graded on a scale of 1–4 with severe mobility corresponding to grade 4 [17]. Valvular regurgitation was quantified by Doppler echocardiography using the standard methods [14,17,18].

2.4 Surgery and follow-up
Follow-up data included surgical treatment and death occurring during initial hospitalisation or follow-up. Surgical therapy was based on clinical judgment of treating physician and of the surgical team, according to conventional guidelines predominantly in presence of complications such as embolism event, large vegetation, heart failure, uncontrolled infection, severe regurgitation, or evidence of perivalvular extension [8]. All patients were scheduled for four to six weeks of antibiotics. Early surgery operation was defined by surgery performed within 30 days after diagnosis of acute IE. Late surgery was defined by surgery performed over 30 days after initialisation of antibiotic therapy and during the six-month follow up. Patients were treated medically (group A 53 pts –30% vs group B 124 pts –70%) or surgically (group A 22 pts –31% vs group B 149 pts –69%) (p = 0.001). Operative mortality was defined as any death occurring during the initial hospitalisation or within 30 days of operation for discharged patients [19]. Overall mortality was defined as death occurring during the hospitalisation for IE and during the follow-up after hospitalisation for IE. The follow-up was completed in 100% of cases with a mean patient follow-up of 28.8 ± 1.1 months.

2.5 Statistical analysis
Statistical analysis was performed with SPSS 9.0 software. Data were expressed as the mean ± standard deviation. Comparisons between the two groups were performed by Student's test or Mann–Whitney test for non normally distributed data and the chi-square test or Fischer's test for cell frequencies superior or equal to 5. A Cox univariate model was performed to determine the relationship between patient's baseline characteristics and mortality. The cumulative probability of survival was estimated using the Kaplan–Meier actuarial method at one-month interval and reported as a mean estimated survival ± standard error. The log-rank test was used to determine any significant differences. Multivariate analyses were performed incorporating as potential predictors of mortality comorbidity index and variables related to mortality in univariate analysis (p value ≤0.10). A multivariate logistic regression model was used for in-hospital mortality and a Cox multivariate model for overall mortality. A probability of p value <0.05 was considered statistically significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
4. Comments
 5. Conclusion
 References
 
3.1 Patient characteristics
The patients older than 75 years (group A) had a more severe clinical status than the younger patients (group B), with a comorbidity index amounting to 4.9 ± 1.8 and 2.9 ± 1.0 respectively (p = 0.0001) (Table 1 ). The sex ratio (M/F) was significantly lower for the older patients (1.67 vs 3, p = 0.025). The duration of symptoms (delay between the onset of the symptoms and the diagnosis) was shorter for group A. No difference was observed between the two groups concerning fever level and biological data. Prosthetic IE and pace maker line infection were significantly more frequent in group A. The redo procedure rate was significantly higher for group A. Right side IE trend tended to be more frequent in group A (16%) than in group B (9.5%) (p = 0.09). No difference was observed among groups concerning echocardiographic data, except for the severe regurgitation rate, which was less frequent in the elderly group.


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  		Table 1 Clinical characteristics of groups.
 
Embolism risk was not significantly different between groups (Table 1). Considering only the left side IE the embolism risk of the elderly patients was higher but remains similar to the younger patient. CHF was the main endocarditis complication, significantly less frequent for the older patients, and related to a lower incidence of severe regurgitation.

The germs encountered (Fig. 1 ) were similar between the two groups of patients. The streptococcus and staphylococcus rates were 37.4%, 36 % and 34.1%, 30.1% for groups A and B respectively. If we considered only the patients operated on, the staphylococcus coagulase negative was significantly more frequent into group A (27.8% vs 3.8%, p = 0.007). The portal of entry was found only in half of the cases in the two groups (48% group A, 55.3% group B). The repartition of these portal of entry were respectively for the groups A and B: cutaneous 14.7% and 22.7%, rhinopharynx 12% and 14.3%, intestinal 18.7% and 16.1%, urologic 4% and 3.3%.


Figure 1
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  		Fig. 1. Germ distribution for the two groups. The distribution of the germs was similar for old and young patients. Staphylococcus aureus was the more frequent germ encountered for the whole population.

 
A surgery procedure was performed more frequently in group B (p = 0.0001). Aortic mechanical replacement was significantly more frequent in group B (n = 35–23.4%) versus no patient in group A (p = 0.001). The pace maker line extraction represented half of the procedures performed for the older patients. The other surgeries procedures are listed in Table 2 .


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  		Table 2 Surgery procedures for the two groups of patients.
 
3.2 In-hospital mortality
The in-hospital mortality rate for group A and for group B amounted to 16% (n = 12) and to 19% (n = 52) respectively (ns) (Table 1). The operative mortality (OM) rate for group A and for group B were 9% (n = 2) and 11.4% (n = 17) (ns) respectively. After exclusion of the right side IE the difference between the in-hospital mortality of groups = A and group B was not significantly different: 15.9% (n = 10) and 19% (n = 47) (ns). The main causes of death in group A included: cardiac failure in eight patients, neurological events in seven, and sudden or unknown death in eight. Univariate analysis revealed that factors related to in-hospital mortality for older patients (group A) were severe sepsis (p = 0.0001), major neurological events (p = 0.0006). Multivariate analysis identified, severe sepsis (p = 0.001-OR = 12, CI [6–24]), major neurological events (p = 0.02, OR = 3, CI [1.1–7.5]) and early surgery (p = 0.006, OR = 0.4, CI [0.2–0.7]) as independent factors related to in-hospital mortality.

3.3 Mortality at 36 months
The overall survival at 36 months for group A and for group B were 40.8 ± 6.8% and 61.4 ± 3.2% respectively (p = 0.03) (Fig. 2 ). The causes of late death included heart failure in five patients, neurological events in two, neoplasm in three, sudden death in one, myocardial infarction in one, and was unknown in eight. Among the patients operated on after the discharge, no redo procedure was necessary for endocarditis. For group A, univariate analysis revealed that factors related to overall mortality were the comorbidity index, history of renal failure, and surgery (Table 3 ). Multivariate analysis identified for older patients (group A) comorbidity index (p = 0.001) (HR 1.1, CI [1–1.2]), severe sepsis (p = 0.0001) (HR 3.3, CI [2.2–5.2]), valvular prosthesis (p = 0.0002) (HR 2.4, CI [1.5–4]), major neurological event (p = 0.04) (HR 1.7, CI [1–3]) and surgery (p = 0.001) (HR 0.4, CI [0.3–0.6]) as factors related to overall mortality.


Figure 2
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  		Fig. 2. Actuarial survival curves. Overall survival at 36 months was significantly lower for the group A.

 

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  		Table 3 Association between patient characteristics and in-hospital and overall mortality for elderly patients.
 
3.4 Surgery in elderly patients
A total of 29.3% of the elderly patients were operated on compared to 54.5% of the younger patients (p = 0.001). For group A compared to medically managed patients, operated patients had a lower comorbidity index and no severe sepsis (Table 4 ). In the older group, the hospital mortality rate after surgical and medical treatment amounted to 9.1% and 18.9% respectively (p = 0.12). The predominance of right side IE in the older group operated on (9/22) could explain this relatively low operative mortality rate. If we exclude the right side IE the operative mortality rate amounted to 18.2%. The main indications of the surgical treatment for the elderly patients were cardiac failure 22.7% (5 pts), severe sepsis 27.3% (6 pts) and pace maker line infection 22.7% (5 pts). Abscess (9.1%), embolism risk 4.5% and valvular regurgitation 9.1% were less frequent early surgical indications. The PM line extraction represented half of the surgical procedures (Table 2).


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  		Table 4 Comparison between medical and surgical group of IE for elderly patients.
 

   4. Comments
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Comments
5. Conclusion
 References
 
In our observational study including a large cohort of 348 patients with definite acute IE according to Duke criteria examined by transthoracic and transoesophageal echocardiography, the main observations are that: 1. clinical presentation of acute IE of elderly patients is quite different than younger patients with a poor clinical status and more right side IE; 2. the long-term prognosis is worse than the younger population; 3. surgery for elderly patients is associated with a better early and late survival than medical treatment alone. These results suggested that early surgery is a reasonable treatment option in selected elderly patients with acute IE to improve the outcome. Surgery is generally considered in early prosthetic valves IE [8]. We previously reported in a bicentre study that early surgery must be recommended in prosthetic valve IE complicated by valve dysfunction, abscess formation, conduction abnormalities, and large vegetation, particularly if staphylococci are the infecting agent [19]. As a poor general condition may constitute a contraindication, surgical treatment was less frequently performed in our study in older patients with a high comorbidity index (Table 4). Thus surgery in IE is sometimes not performed because of a prohibitive operative risk related to severe clinical features and/or multi-organ failure due to severe sepsis. Our study used a validated comorbidity index to analyse the impact of comorbidity on risk of death. This index incorporates both the number and severity of underlying disease [11].

4.1 Analysis of clinical characteristics of elderly patients
In the present study the sex ratio was lower for the elderly group because the life expectancy of the female population is better in Western countries, and in consequence the female sex rate is higher in this class of age. The shorter duration of symptoms before diagnosis for elderly patients could be explained by a lack of functional reserves and a greater medical care of elderly patients.

Conversely, previous reports have shown a more severe prognosis in advanced age related to less severe initial symptoms and delayed diagnosis, or in other reports authors found a similar initial presentation and outcome between younger and older patients [4,7]. The germs encountered in our study were the same for the young and the old patients. Conversely, some authors found some germs related to acute IE of elderly patients [4,7]. Particularly, we did not find in our study, a higher streptococcus bovis rate for elderly patients, in spite of the higher neoplasm rate in this class of age. If we analysed only left side IE the germs distribution remains similar. In our study, right side IE was more frequent for elderly patients, related to a higher pace maker rate. Those endocarditis are known to have a better prognostic than the left side IE [20]. This point could introduce a bias into our study. Therefore we compared the two groups of patients, considering only the left side IE, excluding the right side IE. The in-hospital mortality rates were not statistically different for the left side IE and for the right side IE, 15.9% and 8.3% respectively (p = 0.45). Multivariate analysis identified in left side IE the same three factors related to hospital mortality and the same five factors (comorbidity index, severe sepsis, valvular prosthesis, major neurological event and surgery) related to overall mortality, added by severe mobility of vegetation (p = 0.04). The greater tendency of the left side IE to provide more severe embolism could explain the relation between overall mortality and the severe mobility of vegetation, which was not found for the whole population of elderly patients including right side IE.

4.2 Outcome and management
Classically we found, like some authors [1,2,21], severe sepsis and major neurological event to be related to a worse early and late outcome. In our series the in-hospital mortality was comparable for the older and the younger patients. Controversial results are found in literature about immediate outcome of elderly patients treated for endocarditis [4,7]. ‘Elderly’ is not defined identically (for example >70 years or >75 years) for all the authors and could explained this discrepancy of the results of previous reports. In our series the cut-off for the age of population was defined as 75 years. This age is now recognised as the accurate definition of ‘elderly patients’. Therefore our study shows the first results published about a population of elderly patients treated for acute IE endocarditis, to provide us information on this specific population of patients. Surgical management of elderly patients is in our study a reasonable option, which is the single factor predictive of a better early- and long-term survival. In elderly patients, decisions about surgery and its timing are often problematic due to the lack of evidence from randomised controlled studies. In most cases, thorough consultation between the medical and the surgical teams is necessary to analyse the best strategy. Surgery in our cohort was performed according to conventional guidelines, predominantly in the presence of complications such as embolism event, large vegetation, heart failure, uncontrolled infection, severe regurgitation, or evidence of perivalvular extension [3,8,9]. Congestive heart failure, the current leading cause of death for patients with native valve IE [9,21,22], has constituted the indication for early surgery in about 21% of our patients. Cardiac failure is usually caused by valvular incompetence due to destruction of valve tissue. In the current study, 22% of patients treated surgically had severe valve regurgitation. Others series reported that infections caused by certain microorganisms more likely require surgical intervention because of their power to destroy tissue, or their resistance to antimicrobial [12,21,22]. Accordingly, 14% of our patients in early surgery group had uncontrolled infection. A more aggressive therapeutic strategy is needed in patients with intra-cardiac devices [3]. In our study, we confirmed that prosthetic valve IE is an independent predictor of six-month mortality.

4.3 Limitations of the study
We cannot rule out the possibility that our elderly patients may represent a selected cohort from referral centres with more severe illness than the average population. Surgical therapy was based on clinical judgment of physician and of the surgical team, according to conventional guidelines and surgery was not based on randomised assignment. However, a randomised trial comparing the surgical and medical strategies in elderly patients with IE has never been performed and seems ethically unacceptable. Therefore, some differences in baseline characteristics between the surgical group and the medical group are observed. Multivariate analysis, as we performed in the present study, provides an opportunity to allow for these differences.


   5. Conclusion
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Comments
 5. Conclusion
References
 
In our study, early surgery performed in 29.3% of elderly patients is independently associated with reduced overall mortality after adjustment for other variables associated with mortality. Therefore, early surgery has the potential to improve survival in elderly patients with acute IE and should be considered in selected patients to improve outcome.


   References
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Comments
 5. Conclusion
 References
 

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