Ramin Sam, MD

San Francisco General Hospital, California, United States

Until the advent of the 19th century there had been autopsy reports of patients who may had suffered from infective endocarditis, but little was known of the disease and there had been no description of it.1 By the beginning of the 20th century, however, infective endocarditis had become a well described entity and all its clinical features had become known, but there was no effective treatment and the disease was uniformly fatal. The 20th century saw major advances in diagnosis and management, so that at present ninety percent of patients have a favorable outcome.1 Yet much remains to be done if mortality from this disease is to be further reduced.

In Paris in 1806, Jean Corvisart first used the term vegetations to describe the abnormalities seen at autopsy in patients dying from endocarditis.2 Almost thirty years later, Bouillaud described the inflammation of the endocardium (a term that he coined) of the heart.2 In England, in 1852, Kirkes showed that these vegetations may break off the valves of the heart and travel to distant sites, causing ischemia, infarction, and abscesses in affected organs.2 Just four years later, in Germany, Virchow looked at the vegetations under microscope and described numerous granules, this at a time when the existence of bacteria was still not known.2 In Paris, Charcot and Vulpian in 1861, thought that a special “morbid poison” could affect the endocardial surface of the heart and travel to the spleen and kidneys, also to the brain, eyes, and skin.2 A major advance came in 1869 when Winge observed fine fibrinous threads on microscopic examination of an endocarditis specimen, and postulated these to be “parasitic organisms.”2 In 1872 Heiberg called this organism a leptothrix (a term used by botanists).2 Soon after, Klebs from Germany expressed his conviction that all endocarditis is caused by bacteria.2 In 1903, Schottmuller first isolated and named streptococcus viridians.1

In 1885 Osler gave a famous lecture to the Royal College of Physician in London on the topic of endocarditis, summarizing his review of the records of 200 patients with this disorder.3 He included fever and a new murmur in his classic presentations; and in 1893 described the red swollen areas occurring on the fingertips that became known as Osler’s nodes; and six years later Janeway described the painless lesions on the palms and soles.2 Later Litten described retinal hemorrhages.3

As early as 1880, Doleris in Paris was able to perform blood cultures in patients with endocarditis and noticed that blood cultures were more often positive at the time of fever.2 Netter and Grancher provided further evidence of the value of blood cultures by obtaining the same organism from blood samples and cultures of the aortic valve.2 In 1908 Sir William Osler wrote that “with carefully made blood cultures one should now be able to determine the presence of the septicemia; this was easily done in three of my recent cases.”2

After the above descriptions solidified the understanding of endocarditis, experiments were carried out in animals in an attempt to induce endocarditis. It was soon discovered that at least in animals it is necessary to have a damaged valve and then bacteremia in order to induce endocarditis.

Yet despite the growing understanding of endocarditis, treatment remained non-existent. In 1931, the Harvard educated physician Alfred Reinhart, who had suffered rheumatic fever as a child developed fifteen or twenty bright red, slightly raised, hemorrhagic spots on his wrist. He wrote, “I took one glance at the pretty little collection of spots and turned to my sister-in-law, who was standing nearby, and calmly said, I shall be dead within six months.”1 His prediction was all too accurate. But eight year later came the first reports of the use of sulfonamides; however cure rates achieved were only 4-6%.4 In 1945, Loewe et al. in New York cured seven patients with endocarditis of bacteremia by using penicillin, although two of the patients subsequently developed severe heart failure and one died.5 In early studies, the cure rates obtained with penicillin were about 70%.4,6

Before the mid-1940s, it was realized that transient bacteremia from dental extraction could lead to endocarditis in previously damaged valves.4 In 1951, Hunter from Washington University in St. Louis suggested that antibiotic prophylaxis in patients with damaged valves undergoing high risk procedures may be indicated.6

By the late 20th century, it was realized more definite diagnostic criteria for the diagnosis of endocarditis were needed. Pelletier and Petersdorf in 1977 proposed the first case definition for infective endocarditis, but relied heavily on pathological evaluation of the valve, which often was clinically impractical.7 In 1981, the von Reyn criteria were created which used persistent bacteremia, evidence of active endocardial pathology, presence of a new regurgitant murmur, predisposing valvular heart disease, and presence of emboli or splinter hemorrhages as criteria useful to diagnose endocarditis.7 In 1994 finally the Duke criteria were created and then tested experimentally: they are still in use today and are similar to the von Reyn criteria, except that now findings on echocardiography became further important diagnostic criteria.8 The Duke criteria employ major and minor criteria similar to the Jones criteria used for acute rheumatic fever. By these criteria, the patient is diagnosed as either definite, possible, or rejected endocarditis. Most recently transesophageal echocardiography is found to have a positive predictive value of 90% and a negative predictive value of 100% for diagnosing endocarditis.7 The trend now is to use transesophageal echocardiography to make a definite diagnosis of this once incurable and dreaded disease.


  1. Ronald A. Perspectives on the history of endocarditis. Endocarditis (ed.) Chan KL, Embil JM, Springer, London, 2006, pp. 1-4.
  2. Contrepois A. Notes on the early history of infective endocarditis and the development of an experimental model. Clin Infect Dis 1995,20:461-466.
  3. Osler W. Galstonian lectures on malignant endocarditis. Lancet 1885;1:415-418;459-464;505-508.
  4. Seabury JH. Subacute bacterial endocarditis, experiences during the past decade. Arch Intern Med 1947;79:1-21.
  5. Loewe L, Rosenblatt P, Greene HJ, Russel M. Combined penicillin and heparin therapy of subacute bacterial endocarditis. Progress report of seven consecutive successfully treated patients. JAMA 1944;124:144-149.
  6. Hunter TH. Bacterial endocarditis. Am Heart J 1951;42:472-482.
  7. Sexton DJ. Infective endocarditis: Historical and Duke criteria. UpToDate 2013, 1-7.
  8. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: Utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med 1994;96(3):200-209.


Ramin Sam, MD, San Francisco General Hospital
Ramin Sam, MD, San Francisco General Hospital
Ramin Sam, MD, San Francisco General Hospital

RAMIN SAM, MD, is the Associate Clinical Professor of Health Sciences at San Francisco General Hospital in California.