Case Study
Alfred Reinhart was born in 1907 with a brilliant mind. He contracted rheumatic fever at age 13 and was hospitalized at Peter Bent Brigham Hospital in Boston. Despite losing a year of school, he excelled in his studies. He was admit- ted to Harvard College at age 17 and subse- quently to Harvard Medical School in 1928 at age 21. Rheumatic fever left him with severe aor- tic insufficiency and for about 10 years he had 0 diastolic blood pressure. His own onset of endo- carditis, caused by Streptococcus viridans, was recognized by him in May 1931, many months before the diagnosis was accepted by his treating physicians. He faced this “incurable” disease with dignity and went on to provide a vivid and detailed chronicle of his symptoms.
The following is his description of extrasys- toles, which troubled him greatly [1]:
The extrasystole has always affected me as if it were a cannon ball, shot point blank at my brain. The sensa- tion is that of a terrific explosion, occurring within the narrow and limited confines of a calcified skull, which refuses to yield to the compressive force. It is like an irresistible force against an immovable object.
Most of the time I am helpless before it and simply wait patiently in terror until the ordeal has passed.
Reinhart was convinced he had endocarditis when he noticed petechiae on his wrist [1]:
At any rate, at approximately one-quarter to twelve that night, I remember distinctly getting up from my chair and from the table, where my books lay, and tak- ing off my suit coat. No sooner had I removed the left arm of my coat, than there was on the ventral aspect of
my left wrist a sight which I never shall forget until I die. There greeted my eyes about fifteen or twenty bright red, slightly raised, hemorrhagic spots about 1 millimeter in diameter which did not fade on pressure and which stood defiant, as if they were challenging the very gods of Olympus. I had never seen such a sight before, I have never seen such a sight since, and I hope I shall never see such a sight again. 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.”
He died of endocarditis in October 1931, after suf- fering complications including splenic infarcts, retroperitoneal hemorrhage, embolic stroke, sub- arachnoid hemorrhage, and pulmonary edema.
The case of Alfred Reinhart illustrates many of the protean manifestations of endocarditis, vividly described by a keen observer with med- ical knowledge. Despite major advances in the diagnosis and treatment of endocarditis since Reinhart’s death, endocarditis remains an elu- sive diagnosis, and the complications which afflicted Reinhart are still observed today.
Historical Perspectives
Historical perspectives are fraught with interpre- tation and bias. For this author, particular points of interest include recollections and reminis- cence from almost 50 years of medical learning and practice, as an observer to both the science and the management of endocarditis and the personal triumphs and failures in the care of patients with endocarditis. Although these biases will be apparent in this review, my goal is to
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Perspectives on the History of Endocarditis
Allan Ronald
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provide my perspective on what many regard as the most fascinating of infectious diseases.
Several authors attribute the initial description to clinicians and pathologists in the 17thand 18th centuries who described the clinical course and autopsies in patients who in retrospect almost cer- tainly had bacterial endocarditis. This includes Rivierins in 1646, Lancisi in 1707, Glynn in 1749, Morgagni in 1769, and Baillie in 1793 [2]. Baillie clearly differentiated rheumatic endocarditis from what we now know as bacterial endocarditis [3].
Corvisart in 1806 described the “warty” lesions on heart valves and some of these appear, in retro- spect, to have been bacterial vegetations [4].
Over the next 75 years, however, rheumatic endocarditis and bacterial endocarditis were not clearly differentiated clinically or pathologically.
In1852 Kirkes was the first to describe emboli arising from heart valves in cerebral, renal, splenic and other arteries [5]. Subsequently Virchow and Beckmann each described embolic phenomena and showed that they contained ele- ments which appeared to be bacteria [6,7].
Specifically, Heiberg described chains of cocci in vegetation [8].
In 1859 Quinquaud used the term “chronic”
to describe a patient and this allowed subacute bacterial endocarditis to be differentiated from acute [9]. Cayley in 1877 first used the term
“infective endocarditis” and this replaced the earlier term “ulcerative endocarditis” [10]. A major advance occurred when Osler in his Gulstonian Lecture in 1885 reported on the clinical course and outcome of 209 cases [11].
He first identified the tendency of bacteria to localize on “diseased valves.” He also was the first to mention the importance of bacterial culture.
Meanwhile in Paris, Jaccoud had described endocarditis, and subsequently in France it is often referred to as “Jaccoud’s disease” [12]. The long duration of the illness and its subacute presentation was emphasized by both Osler and Jaccoud [11,12].
Numerous other individuals have made important contributions. At the end of the 19th century, the clinical course of endocarditis and its microbial etiology were described fully [11–15]. Thayer and Blumer recovered gono- cocci in the bloodstream of a patient with endo- carditis in 1895 and subsequently reviewed a 100 cases of gonococcal endocarditis [13]. Lenhartz introduced material from a vegetative lesion into the urethra of a male patient and produced classical gonococcal urethritis [14]. Schott-
muller isolated the organism which he initially called Streptococcus mitiorseu viridans [15].
The clinical features, including fever and murmur, were well described by Osler in his classic presentations [11,16,17]. The appearance of a new murmur and the clinical features of embolic phenomena were identified as being particularly important for the diagnosis of bac- terial endocarditis.
In 1893 Osler saw one of his initial patients and described the “red swollen areas on her fin- gertips” [16]. Janeway in 1899 described the painless lesions on the palms and soles which now bear his name [18].
Horder carried out classical studies linking ante-mortem blood cultures to post-mortem valve cultures and published these in 1905 [19].
From this time on, positive blood cultures became the sine qua non for diagnosing endo- carditis in the vast majority of patients and this remains as important today as it was in 1906.
A paradigm shift in management occurred in 1944 when Loewe and colleagues treated seven consecutive patients successfully with penicillin [20]. Change occurred rapidly with increasing access to penicillin and other antibiotics. By 1947 Seabury reported on the Penicillin Era and showed that it completely changed the practice of infectious diseases and cardiology as it per- tained to bacterial endocarditis [21].
These advances were occurring as a part of medical practice as I commenced medical school in 1957. Infectious or bacterial endocarditis was still largely cared for, at least in Canada, by car- diologists, who had a variable interest in microbes and antibiotics. The importance of blood cultures and antimicrobial susceptibility tests including bactericidal tests had been identi- fied. The broad-spectrum bacteriostatic drugs, such as the tetracyclines and chloramphenicol, were shown to be relatively ineffective. The dose of penicillin was gradually increased, initially from 100,000 units a day, which cured only 41%
of patients, to 600,000 units a day, which was still associated with a substantial mortality [21,22] At 5 million units daily, the mortality was reduced to 36%. Increasing the dose of penicillin now administered intravenously and in association with streptomycin was quickly recognized as the regimen of choice for penicillin-susceptible streptococci [23].
Anderson and Keefer followed 222 patients who were “responsive to antibiotic therapy”
[24]. Of those who responded with negative blood cultures, 21 died within a year—12 from
2 Endocarditis: Diagnosis and Management
heart failure, 3 from cerebral emboli, and 2 from renal failure. An additional 10% died between one and three years, primarily of heart failure.
The risk of reinfection/year was about 2%.
Huge advances have occurred in the diagnosis and management of bacterial endocarditis dur- ing the past 40 years and this history is docu- mented within the remaining chapters in this book. The important of enterococcal, staphylo- coccal, and fastidious Gram-negative rod endo- carditis have all been recognized, and strategies for early diagnosis and treatment are now rou- tine in most centers. The Duke criteria for diag- nosis and its continued modification has made the diagnosis more precise [25]. The diagnosis and management of prosthetic valve infections have also become an important part of the over- all management of endocarditis. The appropri- ate timing for surgical interventions has also become more evidence based.
The role of echocardiography has markedly changed the management of bacterial endo- carditis and given us a tool that has enabled more sensitive and specific diagnosis to occur.
Today it is difficult to envision management of endocarditis without access to this technology.
In particular, transesophageal echocardiogra- phy has become routine for excluding this diag- nosis in patients with bacteremia, particularly with staphylococci [26].
Recent advances have enabled the diagnosis of very fastidious microorganisms, including Coxiella bruneti, Bartonella sp., and others to now occur with both serologic and cultural tests [27]. Infective endocarditis of unknown etiology is now less common due to continued improve- ments in microbial diagnosis particularly with the advent of nucleic technologies.
The prevention of endocarditis remains con- troversial and largely expert consensus-based rather than based on solid scientific evidence.
Our current dilemmas in this regard are well reviewed in a subsequent chapter.
Infective endocarditis remains a fascinating illness and continues to intrigue us as clinicians and as individuals attempting to understand the complex biologic processes of host and microbe interactions. Certainly there will be more to learn about this disease. However, we have reached the point in 2006 where we can usually precisely diagnose the infection, localize it to a site on the endocardium, treat it with an established effec- tive regimen, manage complications including surgical interventions with a low mortality, and expect a favorable outcome in over 90% of
patients. This is remarkable progress over the past six decades since the advent of penicillin.
Only the future will identify further landmark events that will be highlighted by individuals recording their memories of this disease. In the meantime, as physicians seeing patients with a wide variety of symptoms, we must continue to remember the lessons learned, obtain blood cul- tures before antimicrobial therapy is instituted and be aware of the many, many presentations of this fascinating illness.
Key Points
1. There have been major advances in the diag- nosis and treatment of endocarditis over the past 60 years.
2. The advent of antibiotics has dramatically improved the prognosis of patients with endocarditis.
3. Endocarditis remains an elusive diagnosis because of its many disguises.
4. Early diagnosis and prompt antibiotic ther- apy are the most effective way to minimize mortality and morbidity.
References
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3. Baillie M. The morbid anatomy of some of the most important parts of the human body. 2nd ed. London, J Johnson and G Nichol, 1793.
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Perspectives on the History of Endocarditis 3
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23. Wallach R, Pomerantz N. Streptomycin in the treat- ment of subacute bacterial endocarditis. New Engl J Med 1949;241:690–694.
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Edwards Bros, 1948, chapter 8, pp 13–37.
25. Durack DT, Lukes AS, Bright DK. New criteria for diag- nosis of infective endocarditis: Utilization of specific echocardiographic findings. Duke Endocarditis Service.
Am J Med 1994 Mar;96(3):200–9.
26. Roe MT, Abramson MA, Li J, Heinle SK, Kisslo J, Corey GR, Sexton DJ. Clinical information determines the impact of transesophageal echocardiography on the diagnosis of infective endocarditis by the Duke criteria.
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27. Raoult D, Casalta JP, Richet H, Khan M, Bernit E, Rovery C, Branger S, Gouriet F, Imbert G, Bothello E, Collart F, Habib G. Contribution of systematic serologi- cal testing in diagnosis of infective endocarditis. J Clin Microbiol 2005:43;5238–42.
4 Endocarditis: Diagnosis and Management
