Haemophilus Parainfluenzae Mitral Valve Vegetation without Hemodynamic Abnormality Demonstration
VIRINDERJIT GEORGE
by Angiography and Serial Echocardiography
S. BAMRAH.
W. WILLIAMS.
MD
MD*
CHARLES V. HUGHES. MD HAROLD D. ROSE. MD
FELIX E. TRISTANI, MD Milwaukee. Wisconsin
The occurrence of Haemopbilus parainfluenzae endocarditb on a previously normal mitral valve of a drug addict is described. A large mitral valve vegetation was demonstrated by serial ecbocardiograpby and cineangiograpby. Tbe vegetation did not produce hemodynamic abnormalities preventing detection by physical examination. Multiple septic emboli to various organs, including brain, resulted in death. The role of serial echocardiography and the levophase of right heart cineangiograpby in detecting mitral valve vegetation in a patient suspected of having infective endocardftis is emphasized. The occurrence of infective endocarditis on a previously normal valve without resultant hemodynamic abnormality is unusual. Confirmation of the diagnosis and localization of the site of endocardial infection presents a diagnostic challenge. We recently had the opportunity of managing a patient with mitral valve endocarditis due to Haemophilus parainfluenzae. The role of serial echocardiograms and the demonstration of a large mitral valve vegetation during the levophase of pulmonary cineangiography form the basis of this report. CASE REPORT
From the Cardiovascular Section, Medical Service, Veterans Administration Center. Wood (Milwaukee), Wisconsin and the Department of Medicine, The Medical Collegeof Wisconsin, Milwaukee.Requestsfor reprints should be addressed to Dr. Virinderjit S. Bamrah, Cardiopulmonary Laboratory, Research Service/l51. Veterans Administration Center, Wood, Wisconsin 53193. Manuscript accepted August 30, 1978. l Present address: St. Louis University School of Medicine, 1325 S. Grand Blvd., St. Louis, Missouri 63104.
A 50 year old black man, a known heroin addict since 1944, was admitted to the Veterans Administration Center. Wood, Wisconsin, in April 1975. with fever. The cardiac examination disclosed no abnormalities except for a soft grade 1 to Z/6 apical short early systolic murmur. Multiple blood cultures grew Streptococcus faecalis. The findings on an echocardiographic examination were within normal limits except for a somewhat paradoxic motion of the ventricular septum [Figure I). A repeat echocardio&m obtained two weeks later remained unchanged. The diagnosis of valvular endpcarditis could not be documented. However, the patient was treated with intravenous penicillin G (40 million units daily) and intramuscular streptomycin (2 g daily) for 42 days. The patient was discharged to be followed in the Drug Abuse Outpatient Clinic. In May 1976. the patient was readmitted to the hospital with fever, frontal headaches and lethargy. He admitted to occasional intravenous injections of heroin which had been filtered through a saliva-moistened cigarette filter. There was no history of congestive heart failure. Numerous needle punctures were present on the forearms. The liver was moderately enlarged and tender, and the spleen was palpable. A soft grade l-2/6 apical systolic murmur was unchanged from the previous admission. The leukocyte count was 13,OWmm” with mild leftward shift of the differential, and the hematocrit value was 47.5 per cent. Total bilirubin was 0.8 rng/lOO ml. Urinalysis showed 2+ proteinuria and 20 red blood cells per high power field on several occasions. The patient became progressively confused and disoriented. The cerebrospinal fluid and
March 1979
The American Journal of Medicine
Volume 66
543
H. PARAINFLUENZAE
MITRAL
VALVE VEGETATION-BAMRAH
ET AL.
figure 1. Echocardiographicscan from the apex of the heart towards the base. The arrows show a normal anterior mitral valve -... _ -. . leaflet in 1975. The chamber sizes are normal. CW = chest wall, tVS = interventricular septum, PW = posterior wall of left ventricle, A0 = aorta, LA = left atrium, MV = mitral valve.
brain scan were within normal limits. Six blood cultures yielded Haemophilus parainfluenzae. Therapy with intravenous ampicillin (12 g/day) was initiated along with prednisone and BenadryP because of a history of allergy to penicillin. During this admission the echocardiogram revealed a wide band of intense, irregular and shaggy-appearing “echoes” on the anterior mitral leaflet. This mass of “echoes” was seen both during systole and diastole [Figure 2). The remainder of the echocardiographic observations were identical to those on the previous examination. There was no evidence of right or left ventricular volume overload to suggest tricuspid or mitral insufficiency, respectively. The second echocardiogram examination suggested the development of a large vegetation on the mitral valve. However, the absence of clinical evidence of mitral ingufficiency in the presence of a la’rge vegetatidn seemed inconsistent
Figure 2. Echocardiogram in 1976 showing a band of irregular “shaggy” echoes on the mitral valve. These abnormal echoes were thought to represent a vegetation on the mitral valve. This mass was present on the mitral valve both during systole (open arrow) and diastole (closed arrow). Abbreviations are the same as in Figure 1.
544
March 1979
The American Journal of Medicine
Therefore,’ cardiac catheterization was performed which showed normal right and left heart pressures. More specifically, the pulmonary artery wedge pressure was: a wave = 4 mm Hg. v wave = 5 mm Hg with a mean of 3 mm Hg. The left ventricular systolic and enddiastolic pressures were 140 and 7 mm Hg, respectively. There was no diastolic gradient across the mitral orifice. There was no hemodynamic or angiographic evidence of tricuspid or mitral regurgitation. During levophase of pulmonary angiography a 1 by I cm radiolucent rnas on the atria1 side of the mitral valve was visualized (Figure 31.This mass appeared to move back and forth with the mitral leaflets; it could not be seen during selective left ventriculography. The selective left ventricular angiogram demonstrated an abnormally wide mitral annulus and slight mitral valve prolapse without mitral regurgitation (Figure 4). The left vfmtricular size and ejection fraction were normal. An aortogram showed a normal aortic valve. The patient experienced chills during cardiac catheterization, and the blood for cultures collected at this time from various cardiac chambers yielded H. parainfluenzae. The presence of a vegetation on the mitral valve was confirmed with cineangiography, and the ampicillin therapy was continued for a total of six weeks. The patient became afebrile after 19 days of therapy, and repeat blood cultures appeared sterile. Three days after the completion of ampicillin therapy the patient again became febrile, and his clinical status deteriorated. Repeated examination of the cerebrospinal fluid, as well as brain, liver and spleen scans, disclosed no abnormalities. The remainder of the hospital court was complicated by fever, gross hematuria, jaundice, the appearance of Roth’s spots, multiple petechial hemorrhages and progressive mental obtundation. The recurrence of fever was attributed to systemic vasculitis secondary to known penicillin allergy, at which time methyl prednisolone therapy was initiated. After completion of ampicillin therapy, 18 blood cultures initially appeared negative, however, three of these subsequently yielded tiny colonies of H. parainfluenzae on subcultures. High dose chloramphenicol(8 g daily,
Volume 66
H. PARAINFLUENZAE
MITRAL
VALVE
VEGETATION--BAMRAH
ET AL.
intravenously) was initiated. The patient died nine days after antimicrobial therapy was reinstituted. At autopsy the heart showed moderate cardiomegaly (500 g) with hypertrophy of the left ventricle (1.9cm wall thickness). A large, tannish gray and brown vegetation with an irregular and granular surface was seen adherent to the atria1 side of the mitral valve (Figure 5). The papillary muscles, chordae tendinae and the undersurface of the mitral valve were normal. The cusps of the mitral valve were normal on gross and microscopic examinations. The aortic and tricuspid valves were normal. There was no evidence of myocarditis. The brain, kidneys and spleen showed evidence of multiple old and fresh infarcts.
COMMENTS
Figure 3. Levophase of pulmonary angiogram in 30 degree right anterior oblique view shows a 1 by 1 cm radiolucent “mass” enclosed within the ring of white arrows. This mass is seen in the left ventricle (LV) during diastole. It moved into the left atrium (LA) during systole. The black arrows indicate the edges of the atrioventricular groove.
Figure 4. End-systolic frame of selective left ventricukgram in right anterior oblique,view. The outline of the mitral valve is illustrated with black and white dots. There is no evidence of mitral regurgitation despite the presence of a slight prolapse of mitral valve. MVP = mitral valve prolapse, LV = left ventricle.
This patient presents several interesting and unusual features of infective endocarditis. The disease generally affects patients with preexistent valvular abnormalities; however, infection of a normal valve by a virulent microorganism does occur in the setting of intravenous drug abuse [l]. H. parainfluenzae is a normal inhabitant of the human nasopharynx, has little intrinsic invasive potential and rarely causes endocarditis in the absence of preexistent valvular disease [2]. The course of H. parainfluenzae endocarditis has been reported to be of subacute variety [2]. Our patient was a heroin addict and had a normal mitral valve by echocardiographic and autopsy examinations. The engrafting of H. parainfluenzae vegetation on the atria1 side of the normal mitral valve, without actual damage to the valve, is unusual. Furthermore, no hemodynamic abnormality was produced by this large vegetation. The diagnosis of H. parainfluenzae bacteremia may be easily overlooked because growth in blood cultures may be slow and only become apparent as minute colonies after many days of incubation. In our patient, the diagnosis was initially documented with blood
Figure 5. A large 4.5 by 2 cm vegetation is seen on the mitral valve on an autopsy examination of the heart. The left atrium and left ventricle have been opened and their free wall reflected back to obtain an adequate view of the mitral valve.
March 1979
The American Journal of Medicine
Volume 66
545
H. PARAINFLIJENZAE
MITRAI. VALVE VE(;ETATION-UAMRAH
cultures. The organism was sensitive in vitro to ampicillin by the Kirby-Bauer disc-sensitivity method. Since the Haemophilus was highly fastidious and could not be maintained in subcultures, we were unable to determine serum bacteriocidal levels to monitor the ampicillin therapy. However, after six weeks of ampicillin therapy, 18 blood cultures appeared sterile, three of which subsequently yielded tiny colonies of H. parainfluenzae on initial subcultures. This emphasizes the need to hold blood cultures a minimum of 14 days, and to frequently subculture the blood on chocolate agar with incubation in a carbon dioxide environment, as recommended by Dahlgren et al. (31. In addition, our case demonstrates that 12 g of ampicillin daily was an inadequate dose for complete bacteriologic cure. Blair et al. (41also suggested that a higher dose (20 g/day) of ampicillin be used in H. parainfluenzae endocarditis. Serial echocardiographic examinations proved to be of diagnostic benefit by demonstrating the development of a vegetation on the mitral valve. A recent study in-
ET AL
dicated that patients with infective endocarditis in whom vegetations are recognizable by echocardiography have a poor prognosis because of valvular damage, heart failure and embolization 15).This was borne out in our patient who experienced multiple embolic episodes involving various organs, including brain. Chunn et al. [6] also reported a high incidence of large systemic emboli occurring during the course of H. parainfluenzae endocarditis. The demonstration of vegetation by levophase of right heart cineangiocardiography has not received proper emphasis in the literature [i’]. The vegetations of infective endocarditis may not cause valvular damage. Moreover, they can actually be located on the mural endocardium. The diagnosis of endocarditis may not be suspected under these circumstances. Thus, a high index of suspicion is necessary in these patients, and contrast cineangiography combined with serial echocardiography can be valuable tools in establishing the diagnosis.
REFERENCES Buchbinder NA, Roberts WC: Left-sided valvular active infective endocarditis. A study of 45 necropsy patients. Am 1CardioI58: 20,1972. Weinstein L, Rubin RH: Infective endocarditis-1973. Prog Cardiovasc Dis 16: 239,1973. Dahlgren J, Tally FP, Brothers G, et al.: Haemophilus parainfluenzae endocarditis. Am ] Clin Pathol62: 607.1974. Blair DC, Walker W, Sodeman T. et al.: Bacterial endocarditis due to Haemophilus parainfluenzae. Chest 71: 146,1977.
546
March 1979
The American Journal of Medicine
5.
Wann LS. Dillon JC, Weyman AE, et al.: Echocardiography in bacterial endocarditis. N Engl J Med 295: 185.1976. 6. Chunn Cl, Jones SR. McCutchen ]A. et al.: Haemophilus parainfluenzae endocarditis. Abstracts of the 15th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC.. September 24-26.1975. 7. Matula G, Karpman LS. Frank S. et al.: Mitral obstruction from staphylcccccal endocarditis. corrected surgically. JAMA 288: 58. 1975.
Volume 66
VIRINDERJIT GEORGE
by Angiography and Serial Echocardiography
S. BAMRAH.
W. WILLIAMS.
MD
MD*
CHARLES V. HUGHES. MD HAROLD D. ROSE. MD
FELIX E. TRISTANI, MD Milwaukee. Wisconsin
The occurrence of Haemopbilus parainfluenzae endocarditb on a previously normal mitral valve of a drug addict is described. A large mitral valve vegetation was demonstrated by serial ecbocardiograpby and cineangiograpby. Tbe vegetation did not produce hemodynamic abnormalities preventing detection by physical examination. Multiple septic emboli to various organs, including brain, resulted in death. The role of serial echocardiography and the levophase of right heart cineangiograpby in detecting mitral valve vegetation in a patient suspected of having infective endocardftis is emphasized. The occurrence of infective endocarditis on a previously normal valve without resultant hemodynamic abnormality is unusual. Confirmation of the diagnosis and localization of the site of endocardial infection presents a diagnostic challenge. We recently had the opportunity of managing a patient with mitral valve endocarditis due to Haemophilus parainfluenzae. The role of serial echocardiograms and the demonstration of a large mitral valve vegetation during the levophase of pulmonary cineangiography form the basis of this report. CASE REPORT
From the Cardiovascular Section, Medical Service, Veterans Administration Center. Wood (Milwaukee), Wisconsin and the Department of Medicine, The Medical Collegeof Wisconsin, Milwaukee.Requestsfor reprints should be addressed to Dr. Virinderjit S. Bamrah, Cardiopulmonary Laboratory, Research Service/l51. Veterans Administration Center, Wood, Wisconsin 53193. Manuscript accepted August 30, 1978. l Present address: St. Louis University School of Medicine, 1325 S. Grand Blvd., St. Louis, Missouri 63104.
A 50 year old black man, a known heroin addict since 1944, was admitted to the Veterans Administration Center. Wood, Wisconsin, in April 1975. with fever. The cardiac examination disclosed no abnormalities except for a soft grade 1 to Z/6 apical short early systolic murmur. Multiple blood cultures grew Streptococcus faecalis. The findings on an echocardiographic examination were within normal limits except for a somewhat paradoxic motion of the ventricular septum [Figure I). A repeat echocardio&m obtained two weeks later remained unchanged. The diagnosis of valvular endpcarditis could not be documented. However, the patient was treated with intravenous penicillin G (40 million units daily) and intramuscular streptomycin (2 g daily) for 42 days. The patient was discharged to be followed in the Drug Abuse Outpatient Clinic. In May 1976. the patient was readmitted to the hospital with fever, frontal headaches and lethargy. He admitted to occasional intravenous injections of heroin which had been filtered through a saliva-moistened cigarette filter. There was no history of congestive heart failure. Numerous needle punctures were present on the forearms. The liver was moderately enlarged and tender, and the spleen was palpable. A soft grade l-2/6 apical systolic murmur was unchanged from the previous admission. The leukocyte count was 13,OWmm” with mild leftward shift of the differential, and the hematocrit value was 47.5 per cent. Total bilirubin was 0.8 rng/lOO ml. Urinalysis showed 2+ proteinuria and 20 red blood cells per high power field on several occasions. The patient became progressively confused and disoriented. The cerebrospinal fluid and
March 1979
The American Journal of Medicine
Volume 66
543
H. PARAINFLUENZAE
MITRAL
VALVE VEGETATION-BAMRAH
ET AL.
figure 1. Echocardiographicscan from the apex of the heart towards the base. The arrows show a normal anterior mitral valve -... _ -. . leaflet in 1975. The chamber sizes are normal. CW = chest wall, tVS = interventricular septum, PW = posterior wall of left ventricle, A0 = aorta, LA = left atrium, MV = mitral valve.
brain scan were within normal limits. Six blood cultures yielded Haemophilus parainfluenzae. Therapy with intravenous ampicillin (12 g/day) was initiated along with prednisone and BenadryP because of a history of allergy to penicillin. During this admission the echocardiogram revealed a wide band of intense, irregular and shaggy-appearing “echoes” on the anterior mitral leaflet. This mass of “echoes” was seen both during systole and diastole [Figure 2). The remainder of the echocardiographic observations were identical to those on the previous examination. There was no evidence of right or left ventricular volume overload to suggest tricuspid or mitral insufficiency, respectively. The second echocardiogram examination suggested the development of a large vegetation on the mitral valve. However, the absence of clinical evidence of mitral ingufficiency in the presence of a la’rge vegetatidn seemed inconsistent
Figure 2. Echocardiogram in 1976 showing a band of irregular “shaggy” echoes on the mitral valve. These abnormal echoes were thought to represent a vegetation on the mitral valve. This mass was present on the mitral valve both during systole (open arrow) and diastole (closed arrow). Abbreviations are the same as in Figure 1.
544
March 1979
The American Journal of Medicine
Therefore,’ cardiac catheterization was performed which showed normal right and left heart pressures. More specifically, the pulmonary artery wedge pressure was: a wave = 4 mm Hg. v wave = 5 mm Hg with a mean of 3 mm Hg. The left ventricular systolic and enddiastolic pressures were 140 and 7 mm Hg, respectively. There was no diastolic gradient across the mitral orifice. There was no hemodynamic or angiographic evidence of tricuspid or mitral regurgitation. During levophase of pulmonary angiography a 1 by I cm radiolucent rnas on the atria1 side of the mitral valve was visualized (Figure 31.This mass appeared to move back and forth with the mitral leaflets; it could not be seen during selective left ventriculography. The selective left ventricular angiogram demonstrated an abnormally wide mitral annulus and slight mitral valve prolapse without mitral regurgitation (Figure 4). The left vfmtricular size and ejection fraction were normal. An aortogram showed a normal aortic valve. The patient experienced chills during cardiac catheterization, and the blood for cultures collected at this time from various cardiac chambers yielded H. parainfluenzae. The presence of a vegetation on the mitral valve was confirmed with cineangiography, and the ampicillin therapy was continued for a total of six weeks. The patient became afebrile after 19 days of therapy, and repeat blood cultures appeared sterile. Three days after the completion of ampicillin therapy the patient again became febrile, and his clinical status deteriorated. Repeated examination of the cerebrospinal fluid, as well as brain, liver and spleen scans, disclosed no abnormalities. The remainder of the hospital court was complicated by fever, gross hematuria, jaundice, the appearance of Roth’s spots, multiple petechial hemorrhages and progressive mental obtundation. The recurrence of fever was attributed to systemic vasculitis secondary to known penicillin allergy, at which time methyl prednisolone therapy was initiated. After completion of ampicillin therapy, 18 blood cultures initially appeared negative, however, three of these subsequently yielded tiny colonies of H. parainfluenzae on subcultures. High dose chloramphenicol(8 g daily,
Volume 66
H. PARAINFLUENZAE
MITRAL
VALVE
VEGETATION--BAMRAH
ET AL.
intravenously) was initiated. The patient died nine days after antimicrobial therapy was reinstituted. At autopsy the heart showed moderate cardiomegaly (500 g) with hypertrophy of the left ventricle (1.9cm wall thickness). A large, tannish gray and brown vegetation with an irregular and granular surface was seen adherent to the atria1 side of the mitral valve (Figure 5). The papillary muscles, chordae tendinae and the undersurface of the mitral valve were normal. The cusps of the mitral valve were normal on gross and microscopic examinations. The aortic and tricuspid valves were normal. There was no evidence of myocarditis. The brain, kidneys and spleen showed evidence of multiple old and fresh infarcts.
COMMENTS
Figure 3. Levophase of pulmonary angiogram in 30 degree right anterior oblique view shows a 1 by 1 cm radiolucent “mass” enclosed within the ring of white arrows. This mass is seen in the left ventricle (LV) during diastole. It moved into the left atrium (LA) during systole. The black arrows indicate the edges of the atrioventricular groove.
Figure 4. End-systolic frame of selective left ventricukgram in right anterior oblique,view. The outline of the mitral valve is illustrated with black and white dots. There is no evidence of mitral regurgitation despite the presence of a slight prolapse of mitral valve. MVP = mitral valve prolapse, LV = left ventricle.
This patient presents several interesting and unusual features of infective endocarditis. The disease generally affects patients with preexistent valvular abnormalities; however, infection of a normal valve by a virulent microorganism does occur in the setting of intravenous drug abuse [l]. H. parainfluenzae is a normal inhabitant of the human nasopharynx, has little intrinsic invasive potential and rarely causes endocarditis in the absence of preexistent valvular disease [2]. The course of H. parainfluenzae endocarditis has been reported to be of subacute variety [2]. Our patient was a heroin addict and had a normal mitral valve by echocardiographic and autopsy examinations. The engrafting of H. parainfluenzae vegetation on the atria1 side of the normal mitral valve, without actual damage to the valve, is unusual. Furthermore, no hemodynamic abnormality was produced by this large vegetation. The diagnosis of H. parainfluenzae bacteremia may be easily overlooked because growth in blood cultures may be slow and only become apparent as minute colonies after many days of incubation. In our patient, the diagnosis was initially documented with blood
Figure 5. A large 4.5 by 2 cm vegetation is seen on the mitral valve on an autopsy examination of the heart. The left atrium and left ventricle have been opened and their free wall reflected back to obtain an adequate view of the mitral valve.
March 1979
The American Journal of Medicine
Volume 66
545
H. PARAINFLIJENZAE
MITRAI. VALVE VE(;ETATION-UAMRAH
cultures. The organism was sensitive in vitro to ampicillin by the Kirby-Bauer disc-sensitivity method. Since the Haemophilus was highly fastidious and could not be maintained in subcultures, we were unable to determine serum bacteriocidal levels to monitor the ampicillin therapy. However, after six weeks of ampicillin therapy, 18 blood cultures appeared sterile, three of which subsequently yielded tiny colonies of H. parainfluenzae on initial subcultures. This emphasizes the need to hold blood cultures a minimum of 14 days, and to frequently subculture the blood on chocolate agar with incubation in a carbon dioxide environment, as recommended by Dahlgren et al. (31. In addition, our case demonstrates that 12 g of ampicillin daily was an inadequate dose for complete bacteriologic cure. Blair et al. (41also suggested that a higher dose (20 g/day) of ampicillin be used in H. parainfluenzae endocarditis. Serial echocardiographic examinations proved to be of diagnostic benefit by demonstrating the development of a vegetation on the mitral valve. A recent study in-
ET AL
dicated that patients with infective endocarditis in whom vegetations are recognizable by echocardiography have a poor prognosis because of valvular damage, heart failure and embolization 15).This was borne out in our patient who experienced multiple embolic episodes involving various organs, including brain. Chunn et al. [6] also reported a high incidence of large systemic emboli occurring during the course of H. parainfluenzae endocarditis. The demonstration of vegetation by levophase of right heart cineangiocardiography has not received proper emphasis in the literature [i’]. The vegetations of infective endocarditis may not cause valvular damage. Moreover, they can actually be located on the mural endocardium. The diagnosis of endocarditis may not be suspected under these circumstances. Thus, a high index of suspicion is necessary in these patients, and contrast cineangiography combined with serial echocardiography can be valuable tools in establishing the diagnosis.
REFERENCES Buchbinder NA, Roberts WC: Left-sided valvular active infective endocarditis. A study of 45 necropsy patients. Am 1CardioI58: 20,1972. Weinstein L, Rubin RH: Infective endocarditis-1973. Prog Cardiovasc Dis 16: 239,1973. Dahlgren J, Tally FP, Brothers G, et al.: Haemophilus parainfluenzae endocarditis. Am ] Clin Pathol62: 607.1974. Blair DC, Walker W, Sodeman T. et al.: Bacterial endocarditis due to Haemophilus parainfluenzae. Chest 71: 146,1977.
546
March 1979
The American Journal of Medicine
5.
Wann LS. Dillon JC, Weyman AE, et al.: Echocardiography in bacterial endocarditis. N Engl J Med 295: 185.1976. 6. Chunn Cl, Jones SR. McCutchen ]A. et al.: Haemophilus parainfluenzae endocarditis. Abstracts of the 15th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC.. September 24-26.1975. 7. Matula G, Karpman LS. Frank S. et al.: Mitral obstruction from staphylcccccal endocarditis. corrected surgically. JAMA 288: 58. 1975.
Volume 66
