Patients with SAPVE in this study were characterized by advanced age and marked comorbidity. A considerable percentage of this infection was acquired in the context of health care. The clinical course was usually complicated, and mortality was high. It should also be noted that a significant proportion of patients did not undergo surgery despite having a surgical indication.
Comparison of SAPVE with those caused by other microorganisms
The series presented in this article is the largest published to date, with SAPVE cases accounted for 16.7% of all cases of PVE. This percentage was lower than that found in series of PVE [9], [11], but similar to those of other studies [3], [7]. Another characteristic of our patients was the high proportion of cases diagnosed during the first year after valve implantation, as previously reported [21].
It should be noted that chronic respiratory diseases were more frequent in patients SAPVE. Obstructive pulmonary disease has been considered a risk factor for bacteremia from this species [22], probably because of the frequent need for hospital treatment and use of intravenous lines. Also noteworthy was the greater tendency of S. aureus to affect prostheses in mitral position, compared to PVE due to other microorganisms. Although this result has not been obtained in some studies [7], [10], other studies have found certain affinity of S. aureus to affect prostheses in the mitral position [3], but no explanation for this possible association has been found.
The most important difference between the two groups was the higher mortality associated with cases due to S. aureus [8], [21], [23]. It should be noted that 30% of the patients developed a stroke, a figure similar to that of previous studies [3], [24]. The higher frequency of persistent bacteremia, septic shock and stroke are factors clearly related to patient prognosis, as has been observed in other studies [2], [7], [8], [9], [10], [11], [25]. Despite the higher clinical severity, fewer patients with SAPVE were treated surgically compared to patients with PVE caused by other microorganisms [3], [6], [8], [9], [26].
Clinical characteristics of PVE due to methicillin-sensitive versus methicillin-resistant S. aureus
Studies that have compared the characteristics of PVE caused by MRSA in relation to those caused by MSSA have been few and with a relatively limited number of patients [3], [6], [7], [8]. The proportion of PVE caused by MRSA was 21% in our study, which is within the range of other published series (6–41%)[3], [6], [9], [11], [26], [27]. Differences in the characteristics of the patients studied and the time in which the studies were performed may account for the observed variability. These patients were also characterized by a more pronounced comorbidity, as well as by the frequent presence of an active neoplasm, circumstances that could be associated with a higher risk of colonization or MRSA infection [6], [28]. As expected, most of the cases due to MRSA were acquired in relation to health care. We also observed a certain tendency (without statistical significance) for PVE due to MRSA to appear during the first months after valve prosthesis implantation, as has been detected in other series [3].
In a series of patients with NVE and PVE due to S. aureus, a higher proportion of persistent bacteremia was observed in 26% of cases and was significantly more frequent in patients with MRSA [8]. Other variables related to this infectious complication were the nosocomial origin of IE, surgical intervention in the previous 6 months, the presence of a catheter and surgical site infection. In our series there were more cases of persistent bacteremia when the infection was caused by MRSA (22% versus 15%), but the difference did not reach statistical significance. There was also no evidence of differences in the risk of developing stroke, as was observed in a series of IE (native and prosthetic) caused by S. aureus [27].
In some series that included both PVE and NVE, there has been evidence of higher mortality in patients infected with MRSA, which has been related to less adequate treatment, in some cases because surgery was refused. [8], [27]. In another study, however, no relevant differences were found [6]. Although a higher mortality in patients with MRSA bacteremia than MSSA has been demonstrated in several studies [4], [5], we believe that the similar performance of surgery in both groups could justify the similar in-hospital mortality in our patients.
Characteristics of patients according to hospital mortality
The high in-hospital mortality, which has been repeated in different studies on SAPVE, should be noted. [3], [7], [9], [11]. This dramatic result should encourage us to investigate SAPVE in greater depth to develop strategies to reduce it. As expected, we found that age was associated with in-hospital mortality, a result similar to that found in other studies [9], [10]. It should be noted that in one of these studies all patients under 50 years of age who did not undergo surgery survived hospital admission [10].
In several previous studies stroke was identified as the main prognostic factor [9], [24]. In a recent investigation, 64% of patients with stroke died (especially when there was a significant hemorrhagic component) [3]. Ischemic stroke and cerebral hemorrhage increase morbidity, largely because they may hinder (or prevent) early valve replacement in these patients [29].
Heart failure is a very frequent complication in patients with SAPVE [3], [7], [10], [29], with an incidence higher than that found in patients with PVE due to other microorganisms [11]. This complication is usually due to extensive valve damage and is the most frequent cause of both surgical indication and the patient's own death[3], [9], [26]. In our series, the percentage of deceased patients with heart failure (62%) was twice that of survivors (33%), indicating its strong association with the patient's prognosis. Interestingly, a study by the ICE (International Collaboration on Endocarditis) showed that patients whose indication for surgery was a valvular or paravalvular complication underwent surgery more frequently than when the indication is heart failure (1)
Renal failure is another complication that appears very frequently when the bacteria product of PVE is S. aureus [3], [11]. Renal hypoperfusion, toxicity of certain drugs, renal embolism and immunological complications are frequent complications in cases of SAPVE and are associated with renal failure [3], [24], [30]. This complication has been associated with mortality in studies on PVE of diverse etiology [21] and showed a trend close to statistical significance in previous studies on SAPVE [7], [24].
Surgical treatment in patients with SAPVE
One of the characteristics repeatedly observed in the different published series is the small number of patients who undergo surgery [1], [3], [7], [9], [11], [23], [26], [29], [31]. The decision to forego surgery in patients with surgical indication has a significant impact on prognosis [9]. Although the mortality of patients with surgical indication who underwent surgery (48.9%) was lower than those who did not undergo surgery, but without statistical significance (58.1%, p = 0.220), other studies have found a greater difference in the prognosis of both groups (28.6% versus 53.3%) [29]. The high mortality, even in surgically operated patients, may have been related to a poor baseline clinical situation, determined by a rather advanced age and a high degree of comorbidity, which could lead to a higher mortality in the context of any eventual complication. Although patients older than 65 years tend to have a worse prognosis due to comorbidities, we consider that age alone should not be such a significant factor to exclude surgery [32], [33]. The reason most frequently given for excluding surgery was the existence of an ischemic stroke or intracerebral hemorrhage. A proper assessment of the type of stroke (ischemic versus hemorrhagic) and its extent is essential before discouraging surgery [3], [34], [35]. Severe systemic infection or greater surgical complexity in these patients could also be related to refusal of surgery [3], [9], [10].
Strategies to reduce the number of patients denied surgery may include better patient education about treatment options, adherence to recommended surgical timelines (emergent, urgent or elective) and facilitating transfers to hospitals with experience in complex surgery [8], [9], [11], [23]. Although the optimal moment to perform surgery is an unresolved issue [9], the observation by Sáez et al. that renal failure, stroke of emboligenic origin and septic shock are frequent during the first days after the diagnosis of renal failure, reinforce the need for surgery to be performed as soon as possible [3].
One of the most debated issues in recent years is whether surgery should be recommended for all patients. Current European and American endocarditis guidelines agree that the virulence of S. aureus determines the surgical indication in these patients [1], [15]. In fact, a recent meta-analysis analyzing five studies on the prognosis of patients with SAPVE showed a lower mortality with surgery [36]. John et al, also observed lower mortality in cases of PVE due to SA that were operated on during antibiotic treatment [26]. In this article, however, no distinction was made as to whether or not surgery was indicated according to clinical guidelines. Other studies argue that in order to recommend surgical treatment, it is necessary to consider the characteristics of the patients, since there is a group of patients without relevant cardiac or systemic complications whose evolution can be favorable without surgery [9], [10]. In this regard, Lalani et al. did not find that surgery per se improved prognosis in a series on PVE of various etiologies [23]. Our study supports that surgery should be recommended only in cases with a clear indication due to hemodynamic status, lack of infection control or high risk of embolism [1], [15]. A randomized trial of early surgery versus indication-based surgery would be most appropriate, but we consider that it would be a difficult study to carry out.
Limitations
Our study has several limitations, such as the fact that it was a multicenter study with possible differences in the type of patient and in the selection of treatment. It should also be noted that many patients were referred from hospitals without cardiac surgery, which could have influenced the etiology and certain characteristics of the patients studied. More severe or milder cases might have been transferred less frequently because surgical intervention can be ruled out at the outset. However, these differences should not be very important considering the fluid communication and adequate coordination between hospitals without cardiac surgery and referral hospitals.