Infectious endocarditis and congenital heart defects in adults

BACKGROUND: Infective endocarditis still remains a cardiological menace. However, the type of predisposing diseases has changed: the incidence of rheumatic heart disease in advanced countries has declined, advances made in the surgical and medicamentous treatment of inborn heart disease are the reasons why we are encountering, with increasing frequency, infective endocarditis which develops on their background. METHODS AND RESULTS: The objective of the investigation was to assess the frequency of infective endocarditis and predisposing diseases. During the time interval between 1987 and 1991 16 patients (50% younger than 50 years) were hospitalized with the diagnosis of infective endocarditis. Rheumatic valvular damage and inborn heart disease were the predisposing factor in 25%. All patients were younger than 30 years (mean 24, range 18-30), and half the patients suffered from defects of the ventricular septum. Other defects were tetralogy of Fallot and inborn aortic stenosis. In 10% of the patients infective endocarditis developed on the background of a mitral valve prolapse with regurgitation. Echocardiographic examination confirmed the diagnosis in almost 70% by revealing vegetation. Bacteriological examination revealed the agent in 60%, most frequently it was Streptococcus viridans. The mortality rate in the group was 13%. CONCLUSIONS: The recorded incidence of infective endocarditis, 1.5 pro mille, is consistent with data in the literature. Corrected and not corrected heart disease plays an important role as predisposing disease. Despite the opportunity of intensive antibiotic treatment, the mortality remains high--13%.     

Valve repair in infective endocarditis

From 1985 to 1995, 12 patients with native valve endocarditis underwent valve repair instead of replacement. Mean age was 41.9 years (range from 5 to 79 years). Eight patients had active and 4 patients inactive infection. The mitral valve was involved in 6 patients, the aortic valve in 1, both valves in 2, the tricuspid valve in 2, and the mitral and pulmonary valves in 1. The pathological findings were as follows: leaflet perforation in 2 patients, chordal rupture in 3, and vegetations in 10. Valve sparing procedures were carried out on the mitral valve in 8 patients, on the aortic valve in 1, on the tricuspid valve in 2, and on the pulmonary valve in 1. The following repair techniques were used: vegetectomy in 10 patients, leaflet patching in 2, posterior mitral leaflet resection in 3, mitral annuloplasty in 4, and pulmonary valve repair in 1. Uncontrolled sepsis, progressive heart failure, peripheral embolism, and echocardiographically demonstrated vegetations were the indications for surgery. There was no operative or late mortality and all infections were cured with no recurrences. One patient required valve replacement following aortic valve repair because of progressive aortic regurgitation. Postoperative Doppler echocardiography showed trivial to no regurgitation in 11 patients after valve repair. The overall outcome was favorable during the mean follow-up period of 39.3 months (range from 1 to 120 months). Reparative or reconstructive approaches for native valve endocarditis should be considered and can be successfully performed. Their advantages include (1) improved hemodynamics, (2) no recurrence, (3) no mortality, and (4) favorable long-term results.     

Adherence events in the pathogenesis of infective endocarditis

Inheritance of mitochondrial DNA (mtDNA) in Saccharomyces cerevisiae is usually biparental. Pedigree studies of zygotic first buds indicate limited mixing of wild-type (p+) parental mtDNAs: end buds are frequently homoplasmic for one parental mtDNA, while heteroplasmic and recombinant progeny usually arise from medial buds. In crosses involving certain petites, however, mitochondrial inheritance can be uniparental. In this study we show that mitochondrial sorting can be influenced by the parental mtDNAs and have identified intermediates in the process. In crosses where mtDNA mixing is limited and one parent is prelabeled with the matrix enzyme citrate synthase 1 (CS1), the protein freely equilibrates throughout the zygote before the first bud has matured. Furthermore, if one parent is p0 (lacking mtDNA), mtDNA from the p+ parent can also equilibrate; intracellular movement of mtDNA is unhindered in this case. Surprisingly, in zygotes from a p0 CS1+ x p+ CS1- cross, CS1 is quantitatively translocated to the p+ end of the zygote before mtDNA movement; subsequently, both components equilibrate throughout the cell. This initial vectorial transfer does not require respiratory function in the p+ parent, although it does not occur if that parent is p-. Mouse dihydrofolate reductase (DHFR) present in the mitochondrial matrix can also be vectorially translocated, indicating that the process is general. Our data suggest that in zygotes mtDNA movement may be separately controlled from the movement of bulk matrix constituents.     

Echocardiographic identification of infective endocarditis within a congenital left sinus of Valsalva-right atrial communication

A rare case is described of infective endocarditis within a congenital left sinus of Valsalva aneurysm to right atrial communication diagnosed by a combination of precordial and transesophageal echocardiography. The respective roles of precordial and transesophageal echocardiography in this case are discussed with regard to both diagnosis and surgical decision making.     

Circulating immune complexes in infective endocarditis

To examine further the role of immune-complex deposition in infective endocarditis, we studied 29 patients with infective endocarditis for presence of complement-containing circulating immune complexes. Ninety-seven per cent (28 of 29) had serum levels of immune complexes greater than 12 mug per milliliter. Mean levels in these patients were significantly higher than in patients with sepsis without endocarditis or in normal controls (P less than 0.05). Circulating immune-complex levels were correlated with longer duration of illness (P less than 0.025), extravalvular manifestations of endocarditis (P less than 0.025) and hypocomplementemia (P less than 0.05). Patients with right-sided endocarditis had significantly higher circulating immune-complex levels than patients with left-sided involvement (P less than 0.025). In general, levels fell to zero with successful antimicrobial or surgical therapy. This drop was concurrent with disappearance of extravalvular signs, blood cultures becoming sterile, and rise in serum complement levels. These findings support the concept that immune complexes may be important in the pathogenesis of infective endocarditis.     

Hospital practices influence the pattern of infective endocarditis

OBJECTIVE: To identify factors contributing to infective endocarditis at a major teaching hospital. METHODS: Retrospective review of clinical records of patients diagnosed with endocarditis by standard case definitions with respect to causative organisms, clinical features and outcome. RESULTS: One hundred and ninety-three episodes of endocarditis seen between 1979 and 1992 at Westmead Hospital, Sydney, were reviewed. In the 174 cases where the causative organism was isolated, 75 (43%) were Staphylococcus aureus and 50 (29%) were viridans streptococci. Nosocomial acquisition and/or inter-hospital transfer accounted for 83 episodes; 48 (58%) S. aureus (P < 0.001) and nine (11%) viridans streptococci (P < 0.001). In cases from the local community, viridans streptococci were more common than S. aureus (37% versus 25%); these included 18 episodes (14 S. aureus) in intravenous drug users. CONCLUSION: We conclude that, compared with community-acquired infections, the aetiology of endocarditis in a large teaching hospital is influenced strongly by the prevalence of nosocomial endocarditis and the need for interhospital transfer of complicated cases.     

Infective endocarditis. Implications for care of the adult with congenital heart disease

Infective endocarditis (IE) remains a severe complication for the adult with congenital heart disease (CHD). The last four decades have witnessed a radical transformation in the spectrum of IE, including the advent of cardiac surgery and the postantibiotic era. Because of the devastation caused by this disease, prevention is the hallmark. A clear understanding of the pathogenesis, clinical features, and management of IE is essential for any practitioner caring for adults with CHD.     

Conservative operation for infective endocarditis of the mitral valve

BACKGROUND: Subvalvular preservation is necessary to maintain left ventricular function, but accidental retention of infected tissue could cause postoperative endocarditis. METHODS: We examined 71 consecutive patients who underwent operation for mitral endocarditis. Endocarditis was uncontrolled and active in 24 patients, partially treated (unfinished antibiotic course) in 17, and healed in 30. RESULTS: Valves were repaired in 17% versus 59% versus 63% and replaced with subvalvular preservation in 25% versus 6% versus 3% of the uncontrolled active, partially treated, and healed groups, respectively. Thirty-day mortality was 29% versus 0% versus 3.3% (p=0.003), total mortality was 46% versus 18% versus 17% (p=0.035), and complications-related mortality was 38% versus 11% versus 13% (p=0.054), respectively. There was a trend toward lower complications-related mortality with subvalvular preservation than without. Postoperative endocarditis occurred in 3 of 30 patients without and 1 of 41 patients with subvalvular preservation. CONCLUSIONS: Postoperative mortality in uncontrolled active mitral endocarditis remains high, but results are good with partially treated or healed endocarditis. Subvalvular preservation improves outcome, does not increase postoperative endocarditis rates, and should be performed whenever feasible.     

Ceftriaxone and outpatient treatment of infective endocarditis

There are a total of 8000 cases of infective endocarditis yearly in the United States. Central nervous system metastatic infections are not uncommon in infective endocarditis. Because ceftriaxone is highly bound to serum proteins, there is concern that the drug is highly bound to serum proteins, there is concern that the drug might not penetrate well in the core of an infected vegetation. To date, there are two published studies on the treatment of nonenterococcal streptococcal endocarditis by ceftriaxone in humans. Ceftriaxone appears to be an attractive alternative antibiotic therapy to conventional regimens in the treatment of streptococcal endocarditis.     

Postoperative mortality in infective endocarditis: determinant factors

OBJECTIVE: It has been shown recently that 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) is expressed as at least 2 isozymes. In the liver, 11 beta-HSD1 converts cortisone to cortisol; in the kidney, 11 beta-HSD2 converts cortisol to cortisone. Conventional assessment of 11 beta-HSD activity in vivo has relied on gas chromatographic measurement of the ratios of conjugated cortisol and cortisone metabolites. However, these do not permit distinction between the tissue-specific activities of the enzymes and do not reflect all forms of 11 beta-HSD deficiency. In this report, we have assessed the usefulness of measuring unconjugated cortisol metabolites and free cortisol and cortisone in urine as indices of renal 11 beta-HSD activity in man. DESIGN: Six healthy male subjects established in sodium balance were given either glycyrrhetinic acid (170 mg t.d.s., to inhibit 11 beta-HSD2), carbenoxolone (100 mg t.d.s., to inhibit both 11 beta-HSD1 and 11 beta- HSD2) or both inhibitors in combination. MEASUREMENTS: Urinary electrolytes were measured and the concentrations of total and unconjugated urinary cortisol and its metabolites were determined by gas chromatography mass spectrometry. RESULTS: Glycyrrhetinic acid and carbenoxolone inhibited renal 11 beta-HSD2 to a similar degree, as judged by similar sodium retention. As previously reported, conventional measurement of ratios of total cortisol to cortisone metabolites were influenced to a greater extent by glycyrrhetinic acid (100-200% increase in ratio from baseline) than by carbenoxolone (< 30% increase). However, the effect of carbenoxolone was readily detected by measurement of urinary unconjugated cortisol/cortisone (130-480% increase of ratio from baseline) and also by measurement of ratios of unconjugated cortisol metabolites (60-130% increase). CONCLUSIONS: Measurement of free cortisol and cortisone in urine provides the most sensitive index of renal 11 beta-HSD activity. Measurement of total and conjugated urinary steroids is insensitive in circumstances where 11 beta-HSD activity in liver or elsewhere may be abnormal.     

Serologic study in patients with streptococcal infective endocarditis

BACKGROUND: Infective endocarditis is a systemic disease in which there are a continuously antigenic stimulation of immunologic system. Streptococcus is still the most frequent cause of infective endocarditis. PATIENTS AND METHODS: We investigated the presence of antibody (AB), total and IgM by indirect immune fluorescence technique, in four groups of population: streptococcal infective endocarditis (SIE), streptococcal bacteraemia (SB), Staphylococcus aureus endocarditis, and healthy people. Antigens used were: 1) their own strain isolated from the blood of patients with SIE and SB ?homologous AB?, and; 2) seven species of Streptococcus: Streptococcus intermedius, Streptococcus salivarius, Streptococcus bovis, Streptococcus sanguis I, Streptococcus sanguis II, nutritional dependent streptococci and Enterococcus faecalis (heterologous AB). RESULTS: Homologous antibodies: titers > or = 1/512 were found in all patients with SIE and only in 2 with SB (sensitivity 100% and specificity 93%). IgM titer (threshold 1/32) was positive only in patients with SIE (sensitivity 75,5% and specificity 100%). The fall of the AB titer was continuous and slow, despite the good clinical evolution of patients. (AB titers were > or = 1/512 and IgM > or = 1/64 in 30% of patients 1 year later). Heterologous AB: in spite of statistically significant difference found in SIE versus the other groups, sensitivity of this test (threshold 1/256) is low, confidence interval include expected random value (50%), specificity is 88%. CONCLUSIONS: The utility of homologous AB for diagnosing infective endocarditis is demonstrated. On the contrary for heterologous AB, antigenic common fractions must be found in the different species.     

Value and limitations of transesophageal echocardiography in infective endocarditis

Echocardiography has contributed considerably to the evolution in the management of patients with infective endocarditis. There is a clear hierarchy with respect to sensitivity of the different methods is superior when compared to 2-D and M-mode echocardiography in identifying both vegetations and perivalvular complications e.g. abscess formation, aneurysms, mural endocardial lesions. For patients with suspected endocarditis, in whom vegetations can not be clearly identified or in whom abscess formation is suspected with transthoracic echocardiography (TTE), transesophageal echocardiography (TEE) with mono- or multiplane scans has become the standard diagnostic procedure. For the examination of prosthetic valves it is the method of choice. It has even been suggested that it is employed as routine measure in all patients with suspected infective endocarditis. TEE is a safe semi-invasive technique with an extremely low complication rate and high sensitivity. Its specificity depends largely on the patient group which is examined. In patients with indicative clinical symptoms the specificity and the predictive value of vegetations are high. When used as screening method to assess echodense formations at cardiac valves particularly in the elderly, in whom degenerative changes prevail, its specificity and positive predictive value of vegetation-like structures are much lower. The negative predictive value of a negative transesophageal echocardiogram remains high, however. Valve abscesses are detected rarely by transthoracic echocardiography. It is the domain of TEE to assess them particularly in the aortic and mitral valve area. For them the specificity and positive predictive value of TEE in the diagnosis of infective endocarditis is high again. Of further importance was the observation that patients with vegetations of > 10 mm were more likely to suffer embolic complications. It should be noted, however, that infective endocarditis remains a clinical diagnosis: neither is the demonstration of a vegetation already the equivalent of endocarditis, nor does missing vegetations completely rule out the possibility of it. But without doubt, the presence of vegetations, of abscess formation or a concomitant pericardial effusion add valuable information to clinical diagnosis of infective endocarditis, which still needs a "high index of suspicion".     

Fatal Staphylococcus aureus infective endocarditis: the dental implications

Rates of infant mortality and prematurity or low birthweight serve as indirect measures of the health of a nation. This paper presents current population data documenting the still serious problem of perinatal outcome in the USA as well as in other economically developed countries. International comparisons suggest that nations which have the greatest inequality of income and social opportunity also have the most adverse perinatal, child and adult health outcomes. Furthermore, the data assert that these effects are independent of average national wealth or gross national economic productivity. Health status differs by social class and race, even among the most affluent sectors of the population. All social classes, even the wealthiest, suffer the health consequences of social inequalities. An explanatory socio-psychological theory of causality is proposed.     

Inbreeding and congenital heart diseases in a north Indian population

The study was performed in six mohallahs (colonies) of Aligarh City (North India). All six mohallahs are predominantly inhabited by Qureshi (meat sellers, a highly endogamous group) Muslims. A total of 1721 infants and children up to the age of 6 years were examined to determine the incidence of congenital heart diseases (CHD) in relation to the degree of consanguinity of the parents. Around 43% of the subjects were the offspring of consanguineous marriages including second-cousin, first-cousin-once-removed and first-cousin. A higher percentage of CHD was found in the offspring of consanguineous marriages: about 3.37% out of 741 children as compared to 1.22% in 980 offspring of non-consanguineous marriages, whereas in the first-cousin offspring, the percentage of CHD rose to 4.41%. The differences were found to be statistically significant. The present study suggests a genetic influence and also casts doubt on the applicability of a polygenic threshold model to all forms of cardiac malformation.     

Prevention of bacterial endocarditis

Alterations in the normal cell cycle lead to abnormal cell proliferation and to tumor development. To explore the role of the cyclin D/Cdk4 complex and the retinoblastoma protein (pRb) in the growth and spread of osteoblastic osteosarcoma (OS), 40 tumor samples were selected. In 17 of these cases, lung metastases occurred during follow-up. Expression of pRb, cyclin D1 and its catalytic subunit, Cdk4, was studied by immunohistochemistry and immunoblotting. As controls, non-neoplastic tissues surrounding the tumor were used. The expression level and pattern were compared to clinical outcome. Cdk4 was over-expressed in 80% of OS, independently of clinical outcome, and showed an intense and uniform distribution in tumor cells compared to normal cells. However, co-immunoprecipitation of Cdk4 with cyclin D1 revealed low levels of cyclin D/Cdk4 complex; 20 of 40 OS examined had a negative or minimal immunostaining for active pRb. The probability of relapse was significantly higher in pRb-negative than in the -positive patients (p < 0.05). The ratio of unphosphorylated/hyperphosphorylated pRb was lower in relapsed patients than in patients with no evident disease, though the difference was not statistically significant. High levels of pRb/cyclin D1 were found in all samples exhibiting functional pRb expression. Our results show that G1 phase deregulation is involved in formation and development of OS. The expression levels of both pRb and cyclin D1 had a clear correlation with clinical outcome, suggesting that these parameters could be used as prognostic markers.     

A case of infective endocarditis with the mycotic aortic valve aneurysm

A 49-year old man was admitted with a complaint of syncopal attack. Transient A.V block was detected and permanent pacemaker (DDD) was implanted. Five months later he was re-admitted because of dyspnea and palpitation. Infective endocarditis with aortic regurgitation and mycotic aortic valve aneurysm was diagnosed by echocardiography and cineangiography. The aortic valve and valve aneurysm were resected and AVR was performed using Bj?rk-Shiley disc valve (23A) in the usual manner. But 6 months later he suffered from acute cardiac failure due to perivalvular leakage. He died in spite of re-AVR with translocation method.     

The young platelet population in children with cyanotic congenital heart disease

Some morphological, biochemical and functional parameters of platelet population in children with cyanotic congenital heart disease (CCHD) were studied by making comparisons of the normal platelet population in both CCHD patients and controls. The mean volume of the platelets from cyanotic patients was greater than from normals. The platelet size distribution curves demonstrated a shift towards larger than normal size in the case of CCHD. The mean protein content, as well as the mean PF3 content of platelets was increased in CCHD. Following addition of kaolin, PF3 release was more rapid and of shorter duration with platelets from CCHD patients as compared to normal platelets. They also released more PF3 than did normal platelets. After addition of ADP, collagen, or adrenalin, platelets of CCHD patients were more responsive than similarly treated platelets from normals. Platelets from CCHD showed an increased initial rate of aggregation and greater maximum aggregation. These data suggested that the platelet population of CCHD patients consists of larger, younger and functionally more active platelets than does the platelet population of normals.     

Rupture of asymptomatic mycotic aneurysm after valve replacement in infective endocarditis

Mycotic cerebral aneurysms (MCA) are one of the most serious complications of infective endocarditis. The rupture of MCA in patients under anticoagulant therapy following valve replacement carries high mortality. We encountered this serious complication in a patient who had no neurologic symptoms. A 12-year-old girl was scheduled for mitral valve replacement (MVR) 5 weeks after antibiotic therapy for infective endocarditis caused by Staphylococcus aureus. Before the surgery, she did not have any neurologic symptoms or abnormal findings in CT scanning examination. The surgery to remove her mitral valve with bacterial vegetations and replace it with an artificial valve proceeded smoothly and she appeared to begin an uneventful postoperative recovery. However, she suddenly began to complain of severe headache and became unconscious on the fifth days after MVR. A CT scan showed cerebral herniation due to a major subdural hematoma. A ruptured MCA was detected in the orbito-frontal artery and clipped in an emergency operation. She was transferred to the intensive care unit and given continuous infusion of barbiturate to prevent increase of her intracranial pressure. CT scanning and arteriography 10 days after the MCA clipping, revealed a new subdural hematoma and MCA just proximal to the previous clip. It is important to bear in mind that patients with infective endocarditis can have mycotic cerebral aneurysms without any clinical neurologic symptoms.