(Circulation. 1997;95:1654-1657.)
© 1997 American Heart Association, Inc.
Articles |
Fulminant Myocardial Failure in a Previously Healthy Young Man
Presented January 8, 1996, at the Hôpital Cardiologique, Louis Pradel, Lyon, France.
From the Service de Cardiologie (P.C., G.K.), the Service de Bactériologie (F.V., J.E.), and the Department of Pathology (A.T., R.L.), Hôpital Cardiologique Louis Pradel, Lyon, and the Unité des Rickettsies, Faculté de Médecine, Marseille (P.B., D.R.), France.
Correspondence to Paul Touboul, MD, Hôpital Cardiologique Louis Pradel, BP Lyon Montchat, 69394 Lyon Cedex 03, France.
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Case Presentation (Philippe Chevalier, MD) |
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 Top Case Presentation (Philippe... Clinical Discussion (Paul...Pathological Findings (Robert...Bacteriological Findings (Didier...Clinical SummaryFinal DiagnosisReferences |
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History
A 15-year-old boy was admitted to the intensive care unit of our institution in early November 1992 because of rapidly progressive heart failure with fever. The patient was a secondary school pupil, living with his parents and his brother, all of whom were well and resided in a city suburb, spending occasional weekends in the country. There was no family history of heart disease. The boy had no cardiovascular risk factors, history of intravenous drug abuse, or risk factors for human immunodeficiency virus. The patient had undergone an appendectomy 8 years earlier. He had been exposed to a parturient cat in July 1992, and his brother had been hospitalized for 2 days in October 1992 for unexplained fever and abdominal pain. The patient had been well until 7 days earlier, when headaches and fever occurred. Three days later, he developed a cough, followed by upper abdominal discomfort and vomiting. The general practitioner diagnosed an acute bronchitis and prescribed oral amoxicillin. At that time, physical examination and cardiac auscultation were noted as normal. Over the course of the following days, the patient became dyspneic and was admitted to the hospital.
Initial Clinical Findings
On admission the boy was pale and anxious. He had pyrexia of
38°C, a heart rate of 120 beats per minute, a respiratory rate of 30
breaths per minute, and a blood pressure of 110/82 mm Hg. Physical
examination revealed an S3 sound with a 2/6 precordial
murmur. Bibasilar inspiratory crackles were also present; the liver
extended 3 cm below the right costal margin, and the jugular veins were
distended to 10 cm above the sternal angle. No peripheral edema,
cyanosis, rash, or lymphadenopathy was found. The abdominal and
neurological examinations were normal.
Most of the laboratory findings, including white blood cell count, hemoglobin, platelets, erythrocyte sedimentation rate, C-reactive protein, and serum creatinine, were within the normal ranges. The prothrombin time was markedly prolonged (international normalized ratio, 2.9); arterial blood gas analysis showed a slight hypoxemia with alkalosis (Po2, 67 mm Hg; pH, 7.5).
The ECG showed sinus rhythm of 120 beats per minute, with nonspecific ST-segment and T-wave abnormalities. A radiograph of the chest showed slight cardiomegaly, with blood vessels in the upper lobes that were more engorged than those at the bases. Pulmonary interstitial edema in both bases and a left pleural effusion were also seen. On echocardiography, the left ventricle was markedly enlarged, with diffuse hypokinesis and no definite pericardial effusion.
A diagnosis of viral myocarditis was initially considered, and cardiac catheterization was performed. Mean capillary wedge pressure was 22 mm Hg, mean pulmonary arterial pressure was 30 mm Hg (40/20), and cardiac index was 2 L·min-1·m-2. Coronary angiography revealed normal vessels. Right ventricular endomyocardial biopsies were made, and the specimen was used for histology and culture.
Subsequent Hospital Course
On November 11, positive serology for Q fever was obtained, and
treatment with doxycycline (200 mg BID) and ofloxacin (400 mg BID) was
commenced. The patient's serum antibodies reacted only against phase
II of the nine mile strain of Coxiella burnetii. A first
serum reacted with titers of 400 for IgG and 25 for IgM
(Table
). Culture of the first myocardial biopsy yielded
C burnetii.
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On December 6, despite antibiotic treatment and inotropic support, the hemodynamic status continued to deteriorate. Because right ventricular systolic function was judged to be only moderately impaired, a left ventricular assist device (BVS 5000; Abiomed Inc) was implanted. On day 5 after implantation, attempts at weaning the patient off left ventricular assist remained unsuccessful, and a cardiac transplantation was performed.
There were no signs of allograft rejection, but the posttransplantation course was complicated by pneumonia. The patient underwent a left lower lobe resection because of empyema and pyothorax. Although Enterococcus faecalis and Candida albicans were identified as the culprit microorganisms, this definitive procedure was chosen because of the posttransplantation immunosuppression. Subsequently, the patient developed edematous pancreatitis, followed by a consumptive coagulopathy refractory to transfusion of platelets and coagulation factors. Acute serum testing demonstrated a fourfold rise in titers for cytomegalovirus and respiratory syncytial virus.
The patient died of multiple organ failure 2 months after initial admission.
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Clinical Discussion (Paul Touboul, MD, and Gilbert Kirkorian, MD) |
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TopCase Presentation (Philippe...Clinical Discussion (Paul...Pathological Findings (Robert...Bacteriological Findings (Didier...Clinical SummaryFinal DiagnosisReferences |
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This 15-year-old boy without any medical history presented with acute myocardial dysfunction and fever. The most striking aspect of this case is the rapid progression to intractable heart failure over a 1-month period. We organize our discussion around the clinical findings. There are many causes of acute heart failure with a dilated heart.1 An acute process, myocardial or pericardial, can by itself lead to cardiac failure, but more commonly, preexisting cardiac disease is aggravated by a precipitating factor. A process of elimination determines the cause of acute heart failure. General physical examination did not reveal any evidence for an extracardiac disorder. Autoimmune disorders, such as systemic lupus erythematosus, can cause acute heart failure but are usually associated with other clinical findings and an abnormal erythrocyte sedimentation rate, which were not present in this patient.
It would be unusual for a 15-year-old boy to have unrecognized ischemic heart disease in the absence of coronary risk factors. Moreover, the ECG showed no evidence of myocardial infarction. Although the heart can be directly involved in metastatic cancer, diffuse myocardial involvement is uncommon in this setting.2
Pericardial disease frequently occurs in young patients, and cardiac tamponade can also present with jugular venous distension, dyspnea, and low cardiac output. Signs of pulsus paradoxus, ie, inspiratory systolic blood pressure decreased by >10 to 12 mm Hg, is usually found in pericardial tamponade but was not mentioned here. The heart sounds were not muffled, and echocardiography did not reveal pericardial fluid or a localized diastolic compression of the right atrium and the right ventricle. Preexisting cardiac disease decompensated by a benign viral infection is also unlikely, given the fatal outcome.
Finally, because a preceding respiratory febrile illness was evident clinically, the history suggests that cardiac involvement may have been part of an ongoing infectious process. The absence of specific auscultatory and echocardiographic findings made a diagnosis of valvular endocarditis unlikely. Giant cell myocarditis may account for a rapid decline in left ventricular function, but the diagnosis can be made only by histological study.3 Fulminant myocarditis is capable of producing acute dilated cardiomyopathy,4 5 but in most cases the heart is only slightly dilated at echocardiography.6 In the present case, the echocardiographic findings could have been explained by preexisting myocardial disease, but there are no features in the clinical history suggestive of dilated cardiomyopathy. Clinically significant acute myocarditis is most commonly caused by viruses, but in our patient, initial serological findings were not suggestive of any viral infections. The exact pathogenesis of myocarditis has yet to be elucidated, although strong evidence suggests that there is an autoimmune component to myocardial destruction. In the present case, the time lag between heart failure and the initial symptoms favors this hypothesis.
In our opinion, the initial symptoms of our patient were typical of acute Q fever. Pneumonia with headaches and fever, cough, upper abdominal discomfort, vomiting, and dyspnea are classic manifestations of acute Q fever.7 Thus, considering the clinical history together with culture and serological findings, we believe Q fever myocarditis associated with profound systolic dysfunction is the most likely diagnosis in this case.
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Pathological Findings (Robert Loire, MD, and Alain Tabib, MD) |
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TopCase Presentation (Philippe...Clinical Discussion (Paul...Pathological Findings (Robert...Bacteriological Findings (Didier...Clinical SummaryFinal DiagnosisReferences |
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Endomyocardial biopsy, after staining with hematoxylin-eosin, did not reveal an inflammatory process despite serum studies that suggested Q fever. A sampling error may have accounted for this result.8 Examination of the heart obtained after transplantation revealed a flabby organ (weight, 450 g), with predominantly left ventricular dilatation. In both the right and left endocardium, there was a diffuse proliferation of interstitial connective tissue without cellular infiltration. The walls of some small endocardial vessels were thickened with interstitial fibrosis. There was irregular hypertrophy of myocytes and dense interstitial fibrosis without evidence of an inflammatory-cell infiltrate. The pericardium demonstrated inflammatory changes with a fibrinous pattern. There were few areas of mononuclear cell infiltrates (Fig 1
).
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Indirect immunofluorescent antibody examination of the biopsy specimen
showed C burnetii in large clusters of organisms. Culture of
the myocardium after cardiac transplantation did not yield C
burnetii, although indirect immunofluorescent antibody and
immunoalkaline phosphatase labeling of C burnetii in the
paraffin-embedded myocardium still showed small clusters of infected
cells (Fig 2). Gram and silver staining of myocardial
specimens did not demonstrate any microorganisms. Culture of the lung
demonstrated cytomegaloviruses but did not yield C burnetii.
Although isolation of C burnetii from an affected organ
usually proves its pathogenetic role, one may also consider the
possibility that the histological lesion corresponded exclusively to a
cardiomyopathy and that the C burnetii infection was
coincidental. To the best of our knowledge, C burnetii has
not previously been isolated directly from human myocardium.
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Bacteriological Findings (Didier Raoult, MD, Jerome Etienne, MD, Philippe Brouqui, MD, and François Vandenesch, MD) |
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TopCase Presentation (Philippe...Clinical Discussion (Paul...Pathological Findings (Robert...Bacteriological Findings (Didier...Clinical SummaryFinal DiagnosisReferences |
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C burnetii is an extremely infectious gram-negative intracellular pathogen.9 The reservoir of C burnetii is wide; cattle, goats, and sheep are frequently involved, but cats, dogs, and rabbits have been reported as a source of infection.10 In theory, any parturient mammal could be considered a source of infection. In our patient, the only risk factor found was his contact in July 1992 with a parturient cat, a well-established epidemiological exposure.11
When grown in ova or in cells, C burnetii exhibits a
phase-variation phenomenon caused by a lipopolysaccharide alteration
that is equivalent to the smooth-rough variation observed in
Enterobacteriaceae. Phase I is infectious and is recovered from
infected animals, and phase II is obtained after
subcultures.12 Paradoxically, the humoral response of an
acutely infected human being is directed mainly against phase II. As a
diagnostic test, serology with indirect immunofluorescence is the most
convenient tool. The presence of an IgG anti–phase II titer of 
200
and an IgM anti–phase II titer of 50 suggests recent infection.
In mammals, C burnetii results in a nonsterile immunity, because the organism persists in the infected host. It is believed that factors in the host (immunosuppression or cardiovascular abnormality) allow C burnetii to cause clinical infection. The fact that few pathological changes, especially the lack of inflammation, were observed in the myocardium of this patient may, paradoxically, explain the fatal progression of disease. In acute Q fever, the most typical pathological change is the presence of granulomas in the liver or bone marrow, revealing an effective T-cell response.13 This is an unusual finding in cases of chronic Q fever,14 leading some authors to suggest that chronic Q fever occurs with the help of T-cell immunosuppression.13 15 Thus, one can hypothesize that the fatal outcome in this case may be due to an unadapted T-cell response toward C burnetii. The coagulation profile, with an isolated increased prothrombin time, was supportive of the presence of a lupus-like anticoagulant in the serum frequently reported in patients with acute Q fever.16
Therapy with 200 mg/d doxycycline for 3 weeks is the treatment of choice in acute Q fever. In some cases, however, short-term steroid therapy has been prescribed simultaneously, especially when acute Q fever coexists with an autoimmune response.17 The treatment failure in the present case may be explained by the severity of the disease. However, it is remarkable that C burnetii–infected cells, shown by immunohistochemistry, were still present after doxycycline therapy. In our opinion, the cause of death in this patient was due to infectious complication of heart transplantation rather than to Q fever itself.
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Clinical Summary |
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TopCase Presentation (Philippe...Clinical Discussion (Paul...Pathological Findings (Robert...Bacteriological Findings (Didier...Clinical SummaryFinal DiagnosisReferences |
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In summary, the case of a young patient who rapidly developed intractable heart failure necessitating mechanical circulatory support followed by cardiac transplantation is presented. The initial seroimmunological profile suggested an acute form of Q fever. Culture of one specimen of an endomyocardial biopsy yielded C burnetii and thus firmly established the link between the microorganism and myocardial failure. In addition, the diagnosis of myopericarditis was suggested by histological examination. Documented cases of isolation of pathogens in human myocardium are rare. Endomyocardial biopsy is a useful diagnostic procedure and should be performed more frequently.
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Final Diagnosis |
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TopCase Presentation (Philippe...Clinical Discussion (Paul...Pathological Findings (Robert...Bacteriological Findings (Didier...Clinical SummaryFinal DiagnosisReferences |
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Fulminant Q fever perimyocarditis.
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Footnotes |
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The editor of Clinicopathological Conferences is Herbert L. Fred, MD, St Luke's Episcopal Hospital/Texas Heart Institute, 6720 Bertner Ave, Room B524 (MC1-267), Houston, TX 77030-2697.
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