Treatment of Infective Endocarditis:

Transcription

1 Treatment of Infective Endocarditis: A 1-Year Comparative Analysis JAMES V. RICHARDSON, M.D., ROBERT B. KARP, M.D., JOHN W. KIRKLIN, M.D., AND WILLIAM E. DISMUKES, M.D. SUMMARY The results of surgical and non-surgical treatment of active infective endocarditis in 182 patients over a 1-year period were analyzed. Heart failure, annular and myocardial abscesses, heart block, and coronary embolism, seen most frequently with staphylococcal and fungal endocarditis, were the primary causes of death in both native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE). In NVE, surgery significantly improved the survival in patients with moderate or severe heart failure (P <.5) and in all patients with staphylococcal endocarditis (P <.3). In PVE, surgery significantly influenced survival in patients with moderate or severe heart failure (P <.5) and in the entire group with late PVE (P <.1). Early surgery is recommended for patients with native valve endocarditis and moderate or severe heart failure; those patients with staphylococcal NVE, regardless of hemodynamic state, should undergo early valve replacement. Early surgery is recommended for PVE patients with moderate or severe heart failure. We also recommend early valve replacement for early and late staphylococcal PVE. EFFECTIVE ANTIBIOSIS has favorably influenced the natural history of infective endocarditis. This disease was once universally fatal; now, survival rates of greater than 5% are achieved.' The addition of cardiac valve replacement to the treatment regimen has further improved survival. Despite these measures and despite increased awareness regarding the influence of heart failure on survival in both medically and surgically treated patients, mortality remains near 3%.2, 3 We have analyzed the data from patients treated for active infective endocarditis at the University of Alabama Medical Center from in an attempt to delineate the factors related to this continuing mortality, and to recommend appropriate patient management programs. Material and Methods Active bacterial and fungal endocarditis was treated in 182 patients at the University of Alabama from January 1967 through June Patients who had controlled inactive disease and were hospitalized for elective valve replacement were excluded. Involvement of native cardiac valves (primary endocarditis) (NVE) occurred in 135 patients, of whom 54 were treated non-surgically and 81 were treated surgically. Prosthetic valve endocarditis (PVE) occurred in 47 patients, 12 of whom were managed non-surgically and 35 surgically. Of these 47 patients, 39 (85%) developed endocarditis on mechanical prostheses and eight (15%) on tissue valves. Of those tissue valves infected, seven (88%) were homografts. In the overall From the Departments of Surgery and Medicine, University of Alabama School of Medicine and Medical Center, Birmingham, Alabama. Dr. Richardson's present address: Department of Cardiothoracic Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa Address for reprints: Robert B. Karp, M.D., Department of Surgery, University of Alabama Medical Center, University Station, Birmingham, Alabama Received May 1, 1978; revision accepted June 19, Circulation 58, No. 4, groups, 128 (7%) were males, and 54 (3%) were females. The mean age was 44 years (range 6-79 years) for the entire group. The distribution of native and prosthetic valves is shown in table 1. Heart failure was categorized as absent-mild, moderate or severe. Mild heart failure was characterized by tachycardia and mild or moderate dyspnea with activity, responding well to treatment. Moderate heart failure (New York Heart Association (NYHA) Class II-Ill) was characterized by signs of pulmonary venous hypertension and fluid retention, with or without gallop rhythm, which responded to digitalis administration. Severe heart failure (NYHA Class IV) was characterized by similar findings, and did not respond to the administration of digitalis and diuretics. To eliminate minor ECG changes seen with digitalis administration, heart block was considered present only if second degree or complete atrioventricular (AV) block existed. Serious ventricular arrhythmias were defined as ventricular tachycardia and ventricular fibrillation. The phrase low cardiac output was used to describe a syndrome of hypotension, decreased or absent pedal pulses, and oliguria. Peripheral embolism was diagnosed by sudden loss of a major pulse, sudden ischemia or gangrene occurring in a digit. Coronary embolism was suspected in the presence of sudden serious ventricular arrhythmias and was confirmed when significant myocardial necrosis was detected (Q waves or persistent ST changes, LDH, > LDH2, CPK-MB > 5) or emboli were seen at autopsy. Renal embolism was suspected when hematuria occurred and was confirmed in most patients by angiography or excretory urogram. Cerebral embolism was diagnosed when sudden neurological deterioration occurred in patients in whom elimination of hemorrhagic cerebrovascular accidents was possible. The non-surgical treatment of NVE and PVE consisted of organism-specific antibiotics, digitalis and diuretics if heart failure developed, and general supportive care. Serious ventricular arrhythmias were 589

2 59 CIRCULATION VOL 58, No 4, OCTOBER 1978 TABLE 1. Infective Endocarditis ( ) NVE PVE No. % of Total No. % of Total Aortic 68 51%, 32 68% Mitral 36 27% 11 23% Aortic and mitral 24 18C/ 4 9% Tricuspid 4 3% Mitral and tricuspid 2 1%' Aortic, mitral and tricuspid 1 1% Total 135 1%7 47 1% Abbreviations: NVE = native valve endocarditis; PVEprosthetic valve endocarditis. treated with lidocaine and procainamide or cardioversion. Development of moderate or severe heart failure or major embolism, regardless of hemodynamic status, generally resulted in surgical treatment. Operations performed in patients with mild heart failure were termed elective (next convenient operative date); most of these patients had evidence of worsening heart failure or had arrhythmias. Urgent operations (next day) were performed in patients with mild heart failure and major emboli, major emboli only, moderate heart failure only or major emboli and moderate heart failure. Emergency (immediate) operations were performed in patients with severe heart failure and low cardiac output (table 2). Patients requiring urgent or emergency operation characteristically had sudden worsening of heart failure. Surgical treatment of NVE was instituted in 81 patients (table 2). No patient was treated surgically for the primary indication of resistant organism. All patients had undergone antibiotic therapy ranging from one day to seven weeks (mean three weeks). Most patients were digitalized, and a few had preoperative anticoagulation. Repair of mitral cusp perforations was done in two patients, and reconstruc- TABLE 2. Infective Endocarditis ( ) Indications No. of % of for operation patients total { Heart failure only 57 7% NVE Major emboli only 2 Major emboli and 3% heart failure 22 27% Total 81 1% t Heart failure only 26 74% Major emboli and PVE heart failure 8 23% j Emboli and resistant infection 1 3% Total 35 1% Abbreviations: NVE = native valve endocarditis; PVE = prosthetic valve endocarditis. tion of the left ventricular outflow tract was necessary in one patient. Antibiotics were generally continued in the postoperative period for four to six weeks. The absence of viable organisms in surgical specimens generally shortened the postoperative antibiotic treatment period to two to three weeks. Surgical treatment of PVE was used in 35 patients (table 2). The degree of heart failure and major emboli dictated the urgency of operation in this group also. In early PVE (infections occurring within 6 days of operation),4 elective operations were performed in four patients (22%), urgent operations in nine patients (5%), and emergency operations in five patients (28%). In late PVE (infections occurring over 6 days after operation),4 elective operations were performed in three patients (18%), urgent operations in 11 patients (64%), and emergency operations in three patients (18%). All patients had undergone some antibiotic therapy ranging in duration from two weeks to two months (mean 4.5 weeks). Valve replacement and debridement of infective tissue were performed in all cases; reconstruction of the left ventricular outflow tract was necessary in five patients. Antibiotics were generally continued in the postoperative period for four to six weeks. The absence of viable organisms in surgical specimens generally shortened the postoperative antibiotic period to two to four weeks. Early mortality refers to death in hospital following operation or within 3 days after initiation of treatment. Follow-up data were obtained from hospital and office records, questionnaires to patients and family physicians and telephone conversations. Date of inquiry was July Follow-up was obtained in 92% of the surgical patients and 8% of the non-surgical patients. Statistical analyses were performed using the chi square and Fisher's tests. Survival curves were calculated by the method of Berkson.5 Early Results Native Valve Endocarditis Thirty-five (26%, CL* 22%-3%) of 135 patients with NVE died in the hospital. Surgical treatment in 81 patients (mortality 11 patients, 14%, CL 9%-19%) resulted in significantly better survival than did nonsurgical therapy in 54 patients (death in 26 patients, 48%, CL 36%-6%) (P <.1). In aortic valve endocarditis, the mortality of non-surgical treatment was 5% (13 of 26 patients, CL 32%-62%) and the mortality of surgical treatment was 13% (nine of 67 patients, CL 9%-19%) (P <.2). Similarly, in mitral valve endocarditis, the mortality of nonsurgical treatment was 5% (18 of 36 patients, CL 39%-58%), which differed significantly from the mortality of the surgical group (mortality 15%, four of 27 patients, CL 8%-25%) (P <.5). Heart failure significantly influenced mortality in *CL refers to 7% confidence limits.

3 TREATMENT OF INFECTIVE ENDOCARDITIS/Richardson et al. 591 TABLE 3. Native Valve Infective Endocarditis ( ) Non-surgical treatment Surgical treatment Heart No. of Hospital deaths No. of Hospital deaths Significance failure patients No. % CL patients No. % CL level Absent mild % 6%-26% % 3%-12% P =.2 Moderate % 63% 52%-73% % 2% 1%-33% P <.3 Severe 2 2 (55%-75%) 1% 39%-1% 12 4 (17%-35%) 33% 18%-52% P =.8 Total % 37%-52%/ % 1%-19% P =.1 both surgical and non-surgical patients (table 3). The mortality early after surgical treatment was significantly lower than with non-surgical treatment when moderate or severe heart failure was present. Of interest, the mortality for patients with absent-mild heart failure who required isolated mitral valve replacement was one (9%, CL 1%-33%) in 11 patients; mortality for those who required isolated aortic valve replacement was 1 (3%, CL.5%-i 1%) in 31 patients. Heart block occurred in three patients, all of whom survived. Low cardiac output was seen in 18 (I 1%) of the 135 patients with native valve endocarditis. Low cardiac output was statistically correlated with severe heart failure (P <.1), and the presence of clinically suspected or confirmed coronary emboli (P <.1). The hospital mortality of patients with low cardiac output treated surgically was 5% (five of 1 patients, CL 3%-7%), which was significantly better than that of patients treated non-surgically (eight deaths in eight patients, CL 79%-1%) (P <.2). The urgency of operation, reflecting the hemodynamic state and the occurrence of major embolism, was a determinant of survival. The hospital mortality was significantly higher when the operation was done urgently or as an emergency than when done electively (table 4). Organisms were isolated from 118 (87%) of the 135 patients with NVE, and from seven patients (7%) a second organism was isolated (table 5). The organisms were primarily gram positive. Surgery favorably influenced survival when staphylococci were the causative organisms. Survival in infections caused by streptococci and gram negative organisms was not influenced by surgical intervention. Staphylococcal endocarditis was not associated with more severe degrees of heart failure compared with streptococcal endocarditis (P -.2). Of patients in whom cultures were obtained (71, 88%), those who had positive cultures at operation had a mortality of 7% (one of 14), compared with a 14% (eight of 57) mortality in patients with negative cultures (P >.1). Our small experience with gram negative and fungal endocarditis, in contrast with Boyd's experience,6 is presumably related to the infrequency with which drug addicts are seen in our hospital. There were only three known intravenous drug abusers, all of whom had tricuspid valve endocarditis, and were treated nonsurgically. One had fungal endocarditis and died, and the other two had staphylococcal endocarditis and survived. Embolic phenomena occurred 59 times in the group with NVE, often multiple in the same patient. In both patients with fungal endocarditis, embolism occurred. Postoperative complications occurred in 2 (25%) of the 81 patients undergoing surgical treatment. Low cardiac output and early valve dehiscence were the primary causes of early death. Three patients required reoperation for early valve dehiscence; two of these had positive cultures at the time of the first operation. Twenty-two patients (2 surgical, two non-surgical autopsied) had annular and/or myocardial abscesses. Fifteen (68%) of these had staphylococcal infections. Both patients with fungal endocarditis had annular/myocardial abscesses at autopsy. Four of these patients had coronary emboli (P <.1 for the comparison with incidence in patients without abscesses), and five had heart block (P <.2). The overall mortality associated with annular abscesses was 45% (1 of 22 patients, CL 33%-59%), which was TABLE 4. Native Valve Infective Endocarditis Operative No. of Hospital deaths category patients No. % Cl Significance level Elective %7c 2%-12% P =.14 Urgent % 9%-26% ) P=.4 V P =.21i Emergency % 18%-52% ) Total %7o 1%-19%

4 592 CIRCULATION VOL 58, No 4, OCTOBER 1978 TABLE 5. Native Valve Infective Endocarditis Non-surgical treatment Surgical treatment Organism* No. of Hospital deaths patients No. NO CL No. of patients No. Hospital deaths NO CL Significance level Staphylococcus % 29%-6% %o 6%-25% P.3 Aureus %o 33%-67%o % 1%-38% Epidermidis 2 %ox %7-61% 9 %C/ %-19%o Streptococcus %o 15%-37% %o 9%o-23% P=.32 Gram negative % 32%/-8%, 2 1 5%O 7%-43%7 P =.86 Pneumococcus %o 54%-98% 2 %7O %-61% P=.4 Fungus 2 2 1% 39%-1% - - Diphtheroids 1 1 1% 14%-1% % 14%-1%o Hemophilus 1 1 1%7 14%-1% - - *118 patients, in seven in whom a second organism was found. TABLE 6. Prosthetic Valve Endocarditis Non-surgical treatment Surgical treatment Type No. of Hospital deaths Hospital deaths patients No. No. % CL No. No. % CL Significance level Early %o 54%/-98% % 52%o-79% P >.2 Late %o 38%-88% % 8%-32% P <.1 Total % 56%-89% % 33%-53% P <.5 significantly worse than the group in whom no such with only three of 17 (18%) patients dying in hospital abscesses were found (mortality 18%, 12 of 68 patients (table 6). CL 13%-24%) (P <.5). The mortality associated Involvement of an aortic valve prosthesis resulted in with myocardial abscesses was 43% (six of 14 pa- a mortality of 43% (12 of 28 patients, CL 32%-54%) in tients, CL 27%-6%) as compared to 23% (18 of 8 the surgical group and 88% (seven of eight patients, patients, CL 17%-28%) in patients with no myocar- CL 64%-98%) in the non-surgical group (P <.3). dial abscesses (P <.1). Of the five patients requiring reconstruction or patching of the left ventricular outflow tract, two of the Prosthetic Valve Endocarditis three hospital deaths were due to ruptured false aneurysms or redehiscence of the valve. Involvement Twenty-four (51%, CL 43%-6%) of 47 patients of a mitral valve prosthesis resulted in a mortality of with PVE died in the hospital. Overall survival was 4% (two of five patients, CL 14%-71%) in the nonsignificantly better in patients treated surgically (table surgical group and a mortality of 5% (five of 1 6). In the 24 patients with early PVE, the hospital patients, CL 3%-7%) in the surgical group mortality was high (17 patients, 71%, CL 56%-82%), (P >.7). and the results of surgical and non-surgical treatment In all patients who had at least moderate heart were similar. The surgical treatment of patients with failure, and in the group as a whole, surgical treatment late PVE significantly improved survival, however, was significantly better than non-surgical treatment TABLE 7. Prosthetic Valve Endocarditis Non-surgical treatment Surgical treatment Degree of Hospital deaths Hospital deaths Significance heart failure No. No. % CL No. No. % CL level Mild %o 5%-58% 1 4 4% 22%-58% P =.8 Moderate 4 4 1% 62%/-1% % 21%-5% P =.3 Severe 4 4 1%'o 62%-1% % 38%-83% P =.1 Total % 54%-89% % 33%-53% P <.2

5 TREATMENT OF INFECTIVE ENDOCARDITIS/Richardson et al. 593 TABLE 8. Prosthetic Valve Endocarditis Treated Surgically Category of operation No. of patients Hospital deaths No. % CL Elective % 1%-55% Urgent 2 8 4% 27%-54% Emergency % 38%-83% Total % 33%-53% (table 7). The urgency of operation did not affect hospital mortality (table 8). Low cardiac output was present in seven (15%, CL 9%-22%) of the 47 patients and was most common in patients with severe heart failure. None of the three patients treated non-surgically survived, and 75% (three of four patients) died with surgical treatment (P >.3). Infecting organisms were primarily gram positive (table 9). Overall, the mortality of staphylococcal endocarditis (15 deaths in 24 patients, 62%, CL 5%-74%) was significantly higher than that of streptococcal infection (three of 11 patients, 27%, CL 1l%-48%) (P <.5). Within any subset of patients according to organism, surgical treatment did not result in a significantly lower mortality. Of the patients who had positive cultures at surgery, 47% (nine of 19, CL 34%-62%) died. This was not significantly different from the group who were bacteriologically sterile at surgery (six deaths in 16 patients, 38%, CL 23%-54%) (P >.15). There were 13 instances of embolic phenomena. All of the patients with fungal prosthetic valve endocarditis had major systemic and cerebral emboli (P <.1). All of these patients had permanent neurologic disability. Annular and/or myocardial abscesses were present in 32 (68%) of the 47 patients with PVE, 16 (5%) of whom died. Staphylococci were the most common organisms in this group. Four of the five patients with fungal PVE had annular and/or myocardial abscesses; three died. Late Results Native Valve Endocarditis Follow-up analysis was possible in 24 of the 3 patients (8%) who left the hospital alive after nonsurgical treatment. The follow-up period was two to 74 months, mean 38 months. Their actuarial survival was as good as those patients treated surgically (fig. 1). The two late deaths were from a perforated duodenal ulcer and from progressive heart failure. Six patients (25%) have subsequently required valve replacement. Three (12%) of the patients had relapses, were re-treated and survived (fig. 2). In those surviving long-term without the need for valve replacement, most patients were in NYHA Class II (table 1). Seventy patients with NVE treated surgically left the hospital alive, and follow-up was available in 65 (91%). The follow-up period was three to 121 months, mean 43 months. Their actuarial survival as compared to non-surgical patients is shown in figure 1. The actuarial survival is compared to a series of isolated mitral valve replacement and isolated aortic valve replacement from our institution in figure The causes of late death are shown in Table 11. There were no cases of relapse of the endocarditis late postoperatively, despite positive cultures in 2% of the patients at the time of operation (fig. 2). When last contacted, 55 patients (85%) were Class I or II, while 1 patients (15%) were Class III or IV (table 1). Late paravalvular leaks occurred in nine patients (14%), and in two of these the leak was felt to be contributory to their subsequent deaths. The remaining seven patients were functional Class II or III. Late reoperation was carried out in seven patients (1 1%), three for paravalvular leaks, three for homograft failure, and one because of the calculated risk of poppet escape (Braunwald-Cutter prosthesis)9 (fig. 2). Prosthetic Valve Endocarditis Three patients treated non-surgically for PVE survived the period of hospitalization. One patient is well, and two had significant paravalvular incompetence (fig. 4). In one, valve replacement at a later date (five TABLE 9. Prosthetic Valve Endocarditis Non-surgical treatment Surgical treatment Organism No. of* Hospital deaths No. of Hospital deaths patients No. % CL patients No. % CL Staphylococcus 5 4 8% 47%-97% % 43%-71% Aureus 1 1 1% 14%-1% 4 2 5% 18%-82% Epidermidis % 37%-97% % 43%-75% Streptococcus % 4%-76% % 9%-5% Gram negative % 37%-97% Fungus 5 3 6% 29%-86% Diphtheroids 1 1 1% 14%-1% 3 % %47% Total % 52%-83% % 34%-54% *One patient had two organisms isolated. Abbreviation: ;-,L = 7% confidence linmits.

6 594 IK CI RCULATION VOL 58, No 4, OCTOBER 1978 (5 z :D U) z >~ F ~ - FIGURE 1. Native valve endocarditis comparison of surgical and non-surgical patient survival (P >.1 at two years). lr LLJ -_ HZ IS F- a HQ ZO _ - Hospital Dismissal xsurgical treatment (Nx8l) O =Non-surgical treatment (Nz54) I =-t SEM ( ) - No. patients at risk YEARS AFTER HOSPITAL DISMISSAL months) was done; the other patient is moderately incapacitated (Class III). Twenty patients with PVE treated surgically left the hospital alive. One has been lost to follow-up. The range of follow-up was one to 7 months, mean 26 months (fig. 4). The one late death was from myocardial infarction. Sixteen patients (85%) were NYHA functional Class I or II, and three patients (15%) were functional Class III or IV (table 12). Late paravavular leaks occurred in eight patients (23%), two of whom required reoperation. There were no recurrent infections despite the fact that 1 surviving patients (5%) had positive valve cultures at the time of surgery. Discussion The hemodynamic state clearly remains the most important determinant of survival in primary infective endocarditis. Griffin et al.,1 from this institution and others,'1 have reported mortality rates of up to FIGURE 2. Native valve endocarditis probability of event-free survival comparing surgical and non-surgical patients (P <.1 at two years). 85% when patients with moderate and severe heart failure were treated non-surgically. Indeed, the reported non-surgical mortality for patients with only mild heart failure and aortic insufficiency was > 6O%. It is only in the group of patients without heart failure that non-surgical mortality approaches Native Valve Infective Endocarditis Hospital Sur- TABLE 1. vivors (83 Patients) Non-surgical* Surgical NYHA Class No. of patients % No. of patients % I % II 13 72% 36 56% III 3 17% 6 9% IV 2 11% 4 6% *Only those placement. patients not requiring subsequent valve re-

7 TREATMENT OF INFECTIVE ENDOCARDITIS/Richardson et al. 595 r (24) - (5 z C/) z F: Qo - a- ~ * =AVR8 O =MVR7 * =NVE I =±SEM ( ) =No. patients at risk FIGURE 3. Native valve endocarditis - comparison ofsurgical patients with isolated aortic and mitral valve replacement series (P >.1 at three years). that of elective cardiac valve replacement for infective endocarditis. In patients with absent-mild heart failure in this study, the non-surgical mortality was 14% twice that of surgical therapy (6%) (P >.2). Surgical mortality for patients requiring isolated mitral valve replacement with absent or mild heart failure was 9%, which was not significantly different than that of mitral valve replacement for other acquired valvular disease in our hospital.7 Surgical mortality for this group in whom isolated aortic valve replacement was required was 3%, which was not significantly different from recent mortality of aortic valve replacement for other acquired diseases in our institution.8 When moderate or severe heart failure was present, surgery clearly had a distinct advantage over non-surgical treatment (P <.1). The increased mortality seen in patients requiring urgent and emergency operations reflects the deleterious effects of heart failure on survival even when surgical treatment is performed (P <.3). Obviously, many patients evolved from non-surgical to surgical treatment and thus, the overall superiority of surgical management does not reflect patient selection. The infecting organism seems to be important in survival, according to our data and data of others.'2 13 Staphylococcal endocarditis was associated with a mortality of 44% treated non-surgically, but more importantly, was associated with multiple complicating events. Annular and myocardial abscesses were statistically correlated with staphylococcal infections. Furthermore, coronary emboli were correlated with annular abscesses, and heart block was associated with myocardial abscesses. Heart failure was not worse when staphylococcal endocarditis occurred. The majority (67%) of patients who had postoperative paravalvular leaks had staphylococcal infections and annular abscesses. All of these complicating events were associated with mortality rates of 45%-73%. 4 5 Surgical treatment, however, reduced the overall mortality of staphylococcal endocarditis to 13% (P=.3). Cerebral and coronary embolism were associated with mortality rates of 37% to 73%, both of which were favorably influenced by the surgical treatment of endocarditis. Despite the fact that 2% of the patients requiring valve replacement had uncontrolled infection at the time of operation, no cases of subsequent PVE occurred. This is similar to the experience of Utley"4 and Okies,"5 in which reinfections have been rare in such patients, and emphasizes the importance of adequate TABLE 1 1. Late Death.s in Surgical Group Native Valve Endocarditis Interval since surgery Cause of death 2 months Re-dehiscence of valve - reoperated - home died at 3 months CVA - thrombotic 3 months Staphylococcal pneumonia 6 months Late PVE - E. coli treated medically 6 months Hereditary telangectasia - hemorrhage 9 months Unknown 12 months ltecurrent ventricular tachyeardia 24 months CVA -? embolus 24 months Unknown 34 months Pulmonary embolus - myocardial fibrosis 36 months Acute myocardial infarction 48 months Automobile accident 6 months Respiratory failure Abbreviations: CVA = cerebrovascular accident; PVE prosthetic valve endocarditis.

8 596 CIRCULATION VOL 58, No 4, OCTOBER 1978 (9 z > D cn U) 2 ~ -O =late PVE ) =early PVE US W-41=NVE l- =PVE, non-suw ( ) =No.patientsc,15) FIGURE 4. Prosthetic valve endocarditis (PVE) - comparison of surgical and nonsurgical survivors. "Non-surgical" includes survivors with both early and late PVE. After the initial mortality difference, actuarial survival is similar. Native valve sur- ;URGICAL gical curve is included, and the similarity REATMENT between late PVE surgical group and the native valve endocarditis (NVE) surgical rgicfraltent Ot nsk grouip is seen. Dismiml YEARS AFTER HOSPITAL DISMISSAL Native valve endocarditis surgical patients included for comparison debridement of the infected area. We have no preference regarding the type of valve substitute inserted, since no reinfection occurred in our series regardless of whether mechanical or tissue valves were used. The functional and actuarial results of patients surviving non-surgical treatment is comparable to that of the surgical group (fig. 1), but 25% of the non-surgical patients subsequently required valve replacement (fig. 2). An additional 12% of the non-surgical group had bacteriological relapses and required retreatment (fig. 2). This represents a significantly less chance of eventfree (relapse, operation) survival in the non-surgical group compared to the surgical group at two years (P <.1). The long-term functional result of the surgical group was quite satisfactory and comparable to groups of patients requiring aortic and mitral valve replacement for acquired valvular disease in our hospital.7' Reoperation has been required in 11% of patients, but in only 4% for paravalvular leaks thought to be related to the original infective process. Actuarial survival of this group is similar to that of aortic and mitral valve replacement for other acquired valvular disease7' 8 (fig. 3). Late deaths were generally related to problems other than the original infective process. We would, therefore, recommend that all patients with NVE who develop moderate or severe heart failure undergo immediate valve replacement regardless of the infective state. Patients who have absentmild heart failure should be considered at great risk' TABLE 12. NYHA Functional Class of Surgically Prosthetic Valve Endocarditis (19 patients) Treated Class I 5 pts. (27% ) Class II 11 pts. (58%) Class III 1 pt. (5%) Class IV 2 pts. (1%') and should be followed closely; immediate valve replacement is indicated if coronary embolism or progression of heart failure occurs which may be sudden. Patients who have staphylococcal endocarditis, regardless of hemodynamic state, should undergo valve replacement early (two to seven days following diagnosis) in their course in an effort to prevent the multiple complicating events associated with such infections and, therefore, improve survival. Major embolism remains a clear indication for urgent valve replacement,6' 12 especially if coronary embolism is suspected or confirmed.'5 Fungal endocarditis is also a strong indication for early valve replacement because of the high associated embolic rate and difficulty in obtaining bacteriological cure. 16 Our small experience with endocarditis in drug abusers does not permit comments on early surgical management and late results in such patients.6 In PVE mortality remains high despite aggressive non-surgical and surgical treatment. The mortality of early PVE was not significantly improved by surgical treatment in this study, but 73% of the surgical patients had serious hemodynamic instability at the time of operation. The surgical treatment of late PVE clearly has a distinct advantage over non-surgical therapy (P <.1), and is not significantly different from the overall mortality of the surgical treatment of NVE (P >.2). This reflects, to some degree, the slightly better preoperative hemodynamic state of this group compared to the group with early PVE, fewer abscesses and perhaps less virulent organisms.4 We believe that this suggests a similarity between late PVE and NVE. In PVE also, mortality was higher within either treatment group when more severe heart failure was present. Between groups surgery offered a distinct advantage over non-surgical therapy when heart failure of all degrees was considered (P <.2). When moderate heart failure was present, surgery significantly improved -survival (P <.3); in the sub-

9 TREATMENT OF INFECTIVE ENDOCARDITIS/Richardson et al. 597 group with severe heart failure surgery improved survival, but not to a definite statistically significant degree (P=.1). Staphylococcal prosthetic endocarditis was associated with a non-surgical and surgical mortality which was significantly worse than that of streptococcal infections (P <.5). Additionally, annular and myocardial abscesses were found in 7% of our surgical and autopsied patients with PVE.12 Staphylococcal infections were clearly associated with the majority of these annular and myocardial abscesses (P <.5). The other complicating events (heart block and coronary emboli) and the high mortality associated with these abscesses were most often in this group of prosthetic infections also. The functional results and actuarial survival of those patients surviving surgical treatment of PVE is similar to that of patients with NVE (P >.5) (fig. 4) and of patients who had valve replacement for acquired valvular disease.7 8 Paravalvular leaks occurred more frequently in this subgroup compared to NVE and were related to annular complications. No episodes of recurrent PVE occurred despite the fact that 5% had positive cultures at the time of surgery. Late deaths have been unusual and were not related to the original infective process. We agree with Saffle,'7 Karchmer,18 and others19 that a more aggressive surgical approach toward PVE is indicated. All patients who have moderate or severe heart failure or evidence of large paravalvular leaks should undergo immediate valve replacement early in their course, since surgery offered a distinct advantage over non-surgical treatment. We expect that the overall mortality in this group would, therefore, improve and approach that seen with valve replacement for native valve endocarditis and rheumatic disease.17 We also recommend that most patients with early PVE, especially those with staphylococcal infections, undergo early valve replacement in an effort to reduce the incidence of complicating events and the alarmingly high mortality. We would expect the mortality for this group of patients to be reduced significantly also.17 Indications for operation in late PVE parallel those for native valve endocarditis. Patients with moderate or severe heart failure should undergo urgent operation. Non-surgical treatment in patients with absent to mild heart failure should be satisfactory unless the organism is staphylococcus or progression to moderate or severe heart failure occurs. We agree with Utley"5 that fungal endocarditis is an indication for urgent valve replacement because of the high associated embolic rate and resistance of fungus to non-surgical treatment. Major embolism,'5' 16, 2 especially coronary embolism, remains an indication for urgent valve replacement. Although we have a very small experience with resistant bacterial infections, we agree that this constitutes a relatively strong indication for valve replacement also.2 Acknowledgment We appreciate the assistance of Eugene H. Blackstone, M.D., for statistical analyses; Drs. Rodney Snow and C. Glenn Cobbs for help in locating some of the patients; and Ms. Mary Wirt for her expert clerical help. References 1. Lerner PI, Weinstein L: Infective endocarditis in the antibiotic era. N EngI J Med 274: 199, Parrot JC, Hill JD, Keith WJ, Gerbode F: The surgical management of bacterial endocarditis: a review. Ann Surg 183: 289, Jung JY, Saals SB, Almond CH: The case of early surgical treatment of left-sided primary infective endocarditis: a cumulative review. J Thorac Cardiovasc Surg 7: 59, Dismukes WE, Karchmer AW, Buckley MJ: Prosthetic valve endocarditis - an analysis of 38 cases. Circulation 48: 365, Berkson J, Gage RP: Calculation of survival rates in cancer. Mayo Clin Proc 25: 27, Boyd AD, Spencer FC, Isom OW et al: Infective endocarditis: An analysis of 54 surgically treated patients. J Thorac Cardiovasc Surg 73: 23, Allan WB, Karp RB, Kouchoukos NT: Mitral valve replacement. Arch Surg 19: 642, Karp RB, Kirklin JW, Kouchoukos NT, Pacifico AD: Comparison of three devices to replace the aortic valve. Circulation 5 (suppl 11): , Blackstone EH, Kirklin JW, Pluth JR, Turner ME, Parr GVS: The performance of the Braunwald-Cutter aortic prosthetic valve. Ann Thorac Surg 23: 32, Griffin FM, Jones G, Cobbs CG: Aortic insufficiency in bacterial endocarditis. 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J Thorac Cardiovasc Surg 69: 255, Saffle JR, Gardner P, Schoenbaum SC, Wild W: Prosthetic valve endocarditis, the case for prompt valve replacement. J Thorac Cardiovasc Surg 73: 416, Karchmer AW, Dismukes WE, Buckley MJ, Austen WG: Late prosthetic valve endocarditis. Am J Med 64: 199, Okies JE, Viroslav J, Williams TW: Endocarditis after cardiac valvular replacement. Chest 59: 198, Slaughter L, Morris JE, Starr A: Prosthetic valvular endocarditis: a 12-year review. Circulation 47: 1319, 1973

10 Treatment of infective endocarditis: a 1-year comparative analysis. J V Richardson, R B Karp, J W Kirklin and W E Dismukes Circulation. 1978;58: doi: /1.CIR Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX Copyright 1978 American Heart Association, Inc. All rights reserved. Print ISSN: Online ISSN: The online version of this article, along with updated information and services, is located on the World Wide Web at: published Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: Subscriptions: Information about subscribing to Circulation is online at: