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February 26, 2017
Infective Endocarditis Emanuel Libman

Emanuel Libman (1872-1946)

Libman E, Celler HL. The etiology of subacute infective endocarditis. Amer J Med Sci, 1910, 140, 516-27.





Libman E. A study of the endocardial lesions of subacute bacterial endocarditis. Amer J Med Sci, 1912, 144, 313-27.





Libman E, Sacks B. A hitherto undescribed form of valvular and mural endocarditis. Arch Intern Med, 1924, 33, 701-37.


Emanuel Libman
Portrait of Emanuel Libman
Portrait of Emanuel Libman
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Emanuel Libman was a brilliant American physician who made important contributions to the knowledge of infective endocarditis and described the subacute forms of this affection.

In 1909, Libman and Celler reported their study on a group of patients with "subacute bacterial endocarditis."  They described a series of 43 patients with endocarditis that was evolving for a long period of time (from four months to a year or even a year and half).

They characterized the clinical presentation as follows: "Fever was present in all the cases, at times quite low, at times high and intermittent, with or without chills..malaise and gastric or intestinal disturbances were frequently present; sweats occurred in nearly all the cases,.. In all the cases there was progressive weakness and emaciation.  The spleen was nearly always enlarged and palpable. Pains were quite constant...The painful erythematosus cutaneous nodules, the diagnostic value of which has been particularly emphasized by Osler, seem to be pathognomonic..Hematuria, microscopic or macroscopic, occurred quite commonly."

Postmortem examination was performed in 19 patients. The distribution of the valvular lesions was: Mitral valve (n=10), aortic valve (n=2) and mitral and aortic valves (n=7). In their pathological findings, these authors noted:  "The process was always engrafted on a previously diseased valve, and the history nearly always pointed to earlier attacks of rheumatism.  The lesion was vegetative in type, not ulcerative.  When the aortic valve was involved there was a marked tendency for the process to spread down and attack the wall of the ventricle, the ventricular surface of the aortic flap of the mitral valve, and the chordae tendineae. If the mitral valve was involved, the process spread over the wall of the left auricle and involved the chordae tendineae. The latter were often torn.  At time the auricular lesion was much more extensive than the valvular lesion."

In their study, Blood cultures were made in 36 patients. In 35 cases, they identified an "atypical cocci" which was a non-hemolytic streptococcus. The authors then reviewed the literature regarding the bacteriologic findings in endocarditis and commented on Schotmuller's observation who had also isolated streptococcus viridians as the agent responsible of subacute endocarditis. They also stressed that these microorganisms grew very slowly and were not very pathogenic in animal model.

In the closure of the article, Libman and Celler stated:

"Since 1902 we have made 2750 blood cultures. Many cases of acute endocarditis were studied in which ordinary streptococci, staphylococci, pneumococci, and the gonococcus were found. But these organisms have not thus far been encountered in any blood culture made in the type of endocarditis [subacute forms] to which this paper is devoted. Some of these cases present such a typical symptom complex that a clinical diagnosis can be made with a fair degree of certainty...The absolute diagnosis must, for the present, rest on the cultural study of the blood."

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In 1912, Libman published another important article in which he described the "bacteria-free stage of subacute bacterial endocarditis."

At that time, Libman had studied at least 90 patients with subacute infective endocarditis. He noted that in his series, in eleven patients, valvular lesions were in a healed stage with no identifiable pathogenic bacteria.  He also reported that repeated blood cultures, made during life, were negative in all these cases.

Libman provided a detailed account of these eleven cases and emphasized the fact that clinical symptoms were similar between the bacterial and healed stages:  "...This [fever] is found in all of the non-bacterial cases,.., but it is a less marked feature and the temperatures are low for much longer periods...Splenic enlargement seems to persist in the non-bacterial stage...Pains may be just as severe in the bacteria-free cases; the same holds true of joint pains. ...Painful cutaneous erythematosus nodules were not observed in the bacteria-free cases except in one case...Sternal tenderness is equally frequently met  with in both groups of cases...Petechiae occur in the bacteria-free cases, but are not as abundant and do not occur so frequently...hematuria needs further investigation."

The causes of death in this group were: severe anemia, chronic glomerulonephritis with renal failure, and peripheral embolization.

Libman suggested three stages in the evolution of subacute bacterial endocarditis: the bacterial, bacteria-free healing, and the bacteria-free healed stage.  The closing comments of his paper were:

"I believe that I have brought forward sufficient evidence to prove that subacute bacterial endocarditis is a disease in which healing can occur from the bacteriological, pathological, and clinical standpoints, although the evidence of complete recovery from the clinical side is still very meager."

The main message of this work was that although these patients had recovered from their valvular infection, the prognosis of subacute bacterial endocarditis remained poor. The outcome in most these  patients was fatal because of the occurrence of complications such as glomerulonephritis, and peripheral embolization.

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In 1924, Libman and Sacks wrote an article entitled "A hitherto undescribed form of valvular and mural endocarditis." In this study, they reported four cases of valvular disease with vegetations that did not resemble infective endocarditis or rheumatic valve disease. They named this new affection of unknown etiology "atypical verrucous endocarditis".

Their study included four patients (three female, one male) aged from 10 to 37 years old. None of these patients had a prior history of heart disease.

The clinical findings were pericarditis, petechiae, arthritis, erythematosus and purpuric rashes, ulcerative lesions of the mucous membranes, pleuropulmonary symptoms, embolic phenomena, enlargement of the liver and spleen, and acute glomerulonephritis. Two patients had facial lesions which resembled acute lupus erythematosus. The evolution of the disease was subacute lasting from 4 to 9 months. Repeated blood cultures were negative in all four patients.

The immediate cause of death was renal failure in two patients, pneumonia and cerebral embolism in one patient, and pneumonia in the remaining one.

At postmortem examination, the distribution of endocardial lesions was as follows: tricuspid valve (n=4), pulmonary valve (n=2), mitral valve (n=4), and aortic valve (n=2).

The vegetations on the mitral valve were localized on the atrial side of the leaflets close to the free margin except for the case 4, in which the lesions were localized on the ventricular side of the posterior leaflet.

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Libman also noted an extension of the mitral lesions toward the endocardium of the left ventricle: "The inflammatory process had spread from the ventricular aspect to the posterior cusp of the mitral valve and the line of attachment of the latter downward along the mural endocardium of the posterior wall of the left ventricle."

The microscopic findings were not uniform, but presented certain characteristics in common:

"The vegetative lesions on the heart valves were capped by blood platelet thrombus deposit showing various degrees of hyaline change. In places, the vegetations were covered with endothelium but large areas remained denuded.  In the deeper layers, there were focal and diffuse cellular infiltration...In places, the entire thickness of the valve was affected by the inflammatory process...In the older lesions, there were areas of fibroblastic invasion, hyalinization of the newly-formed connective tissue and extensive vascularization...The mural lesions presented a picture similar to that seen on the heart valves...The endocarditic lesions in all cases were free of demonstrable bacteria...The heart muscle showed no Aschoff bodies."

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The microscopic analysis of the mural endocardium showed similar lesions to that seen on the valves. Libman, however, noted that the superficial platelet thrombus deposit was more extensive. There were also cellular accumulations in the subendocardial tissues and extensive fibrosis in the deeper layers, indicating a healing process.

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In this article, Libman and Sacks provided the first description of immune-mediated valvular disease (e.g. systemic lupus erythematosus) with the formation of non-bacterial valvular vegetations. This type of endocarditis has become known as "Libman-Sacks disease."

The summary of this article is depicted below.

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George Baehr


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