A previously unreported case of small-vessel myocardial vasculitis presenting as restrictive cardiomyopathy and congestive heart failure is described. The hemodynamic study, showing severely increased and equalized diastolic pressures in atrial and ventricular chambers, and cardiac MRI, showing normal pericardium and ventricular endomyocardial biopsy, not including myocardial vascular component, were insufficient to make a diagnosis. This made a thoracotomy and surgical cardiac biopsy necessary. Steroids and cyclophosphamide, introduced after histologic evidence of necrotizing vasculitis, unassociated with a systemic disease, became available and improved the clinical profile and the diastolic dysfunction at two-dimensional echocardiographic Doppler analysis.
(CHEST 1997; 111:1462-64)
Key words: heart failure; myocardial vasculitis; restrictive cardiomyopathy
Abbreviations: LV=left ventricular; RV=right ventricular
The term "restrictive cardiomyopathy" defines a group of disorders characterized primarily by diastolic dysfunction, with impairment of ventricular firing by unyielding endocardial, subendocardial, or myocardial tissue. A restrictive hemodynamic pattern may be due to infiltrative and storage diseases or to endomyocardial fibrosis,3 or the pattern may be primary. If a restrictive cardiomyopathy is clinically suspected, cardiac hemodynamics, angiography, and MRI implemented by ventricular endomyocardial biopsy enable it to be differentiated from constrictive pericarditis and allow identification of the underlying myocardial disorder. Confirmation of the latter pathologic finding is crucial in order to provide appropriate treatment and improve prognosis, particularly for patients with sarcoidosis or an eosinophilic endomyocardial disease. In this case report, we present a previously unreported case of idiopathic myocardial vasculitis, presenting as a restrictive cardiomyopathy with severe heart failure, which needed a thoracotomy and surgical cardiac biopsy for both diagnosis and treatment.
A 61-year-old woman was admitted to the hospital because of severe congestive heart failure unresponsive to digitalis, angiotensin-converting enzyme inhibitors, and diuretic therapy. Two years earlier she had developed chest pain and dyspnea on effort, which became progressive and resistant to therapy.
Physical examination showed a seriously ill patient, with dyspnea at rest, systemic venous congestion, peripheral edema, an enlarged liver, and ascites. Cardiac auscultation revealed a protodiastolic gallop rhythm (130 beats per minute) unaccompanied by murmurs. Blood pressure was 90/60 mm Hg. Results of routine laboratory tests (hematologic, biochemical, and urine analysis, including thyroid function tests) were within normal limits. Serum and urine immunoelectrophoresis showed mild hypogammaglobulinemia (IgG, 645 mg/100 mL; normal value, 800 to 1800). Chest x-ray film showed a mildly enlarged cardiac silhouette due to prominence of the third left arch.
The ECG showed sinus rhythm with first-degree atrioventricular block and diffuse low QRS voltages A two-dimensional echocardiogram revealed mild increased thickness of the ventricular wall (ventricular septum, 12 mm, left ventricular (LV) posterior free wall, 11 mm), normal ventricular dimension (LV end-diastolic diameter, 42 mm; LV end-systolic diameter, 36 mm), dilated atria (left atrial diameter, 46 mm), normal LV contractility (LV ejection fraction, 0.60), mild pericardial effusion, Doppler evidence of marked abnormality of diastolic function (shortening of the isovolumic relaxation period, increased and rapid E wave with enhanced E/A ratio, shortening of the deceleration time), and mild tricuspid regurgitation with pulmonary artery systolic pressure of 42 mm Hg. The myocardial mass, assessed using the echocardiographic method of Devereux and Reichek, was 195 g (body surface, 1.5 [m.sup.2]).
The MRI showed normal pericardial thickness with mild pericardial effusion, dilatation of the atria and the venae cavae, normal biventricular cavity size, and mildly thickened ventricular walls suggestive of restrictive cardiomyopathy. There was no alteration of signal intensity suggesting myocardial infiltration was documented by MRI.
At this point, cardiac catheterization with coronary angiography and right ventricular endomyocardial biopsy was performed. Cardiac catheterization showed elevation, with equalization, of mean right atrial, left and right ventricular end-diastolic and wedge pressures (measuring on all sides 25 mm Hg) and a dip-and-plateau pattern suggestive of constrictive pericarditis (Fig 1). LV angiography revealed a normal diastolic dimension and ejection fraction. Coronary angiography showed normal epicardial coronary arteries. Right ventricular (RV) endomyocardial biopsy with extraction of three specimens showed interstitial edema with focal replacement fibrosis, a normal endocardial layer, and negative Congo-red stain for amyloid deposition; unfortunately, no vessels were included in the biopsy specimens. However, a new LV biopsy was not considered since the usual disorders causing a restrictive cardiomyopathy are associated with endocardial thickening or myocardial infiltration or both, which were ruled out by the present biopsy. Because of the severity of symptoms and the diagnostic doubts arising from MRI, the hemodynamic study, and endomyocardial biopsy, which showed normal histologic features, the patient was subjected to thoracotomy, which showed a normal pericardium, moderate pericardial effusion, and thickened and skiff cardiac walls. Several surgical cardiac biopsies were performed.
[Figure 1 ILLUSTRATION OMITTED]
Histologic findings of the surgical biopsies revealed prominent inflammatory infiltrates around myocardial arterioles and venules associated focally with fibrinoid necrosis of the vascular wall and microaneurysm formation (Fig 2). Inflammatory infiltrates were represented mostly by lymphocytes, plasma cells, and histiocytes with some neutrophils and the occasional presence of eosinophils. On the basis of histologic investigations, immunologic studies, including measurement of antinuclear and anti-DNA antibodies, anti-heart antibodies, antineutrophil cytoplasmic antibodies and hepatitis B antigenemia were obtained giving negative results; circulating immunocomplexes ([is less than] 0.6 [mu]g/mL, normal value [less than or equal to] 5) and serum complement (C3, 67 mg/100 mL; normal value, 55 to 120; C4, 11 mg/100 mL; normal value, 20 to 50) were in the normal range, while no cryoglobulins were detected in the serum. Special stains (Giemsa, Grocott's methenamine silver) of paraffin sections failed to identify infectious agents (bacteria, Rickettsia, fungi) on vessel walls. No analysis of pulmonary venous Doppler profile could be obtained, while a study of myocardial blood flow was not considered because of the severe clinical condition of the patient.
[Figure 2 ILLUSTRATION OMITTED]
After the histologic changes were revealed, the patient was treated with sterodis (prednisone, 1.5 mg/kg for 1 week, tapered to 1 mg/kg/d) and cyclophosphamide (2 mg/kg/d), in addition to diuretics (furosemide .25 mg tid and spironolactone, 100 mg bid). After 2 weeks of treatment, the clinical symptoms improved, the peripheral e edema and ascites disappeared, dyspnea was reduced, and physical effort was better tolerated (New York Heart Association class changed to 2 from 4). Two-dimensional echocardiogram showed a reduced thickness of the ventricular wall (ventricular septum, 10.5 mm. left ventricular free wall, 10 mm); Doppler study of mitral valve flow evidenced a reduction of E wave with reduced E/A ratio and a normalization of isovolumic relaxation period and of deceleration fume) Control myocardial mass was 163 g.
At 6-month follow-up, the clinical improvement was maintained on combined low doses of cyclophosphamide (0.5 mg/kg/d) and prednisone (0.33 mg/kg/d).
A severely compromised diastolic function causing cardiac failure is a relatively uncommon condition which divides the differential diagnosis between constrictive pericarditis and restrictive cardiomyopathy. Cardiac catheterization, angiography, and MRI, supported by endomyocardial biopsy, are usually able to differentiate the two pathophysiologic processes and, in the case of restrictive cardiomyopathy, to provide a histologic definition of the underlying myocardial disorder. In our case, because of discordant results between hemodynamics suggesting a constrictive pericarditis, MRI showing a normal pericardium and a normal RV endomyocardial biopsy, thoracotomy and surgical cardiac biopsy became necessary. Extensive review articles provide evidence that a combination of hemodynamic criteria including (1) equalization of RV end-diastolic pressure and LV end-diastolic pressure, (2) RV systolic pressure 50 mm Hg or less, (3) ratio of RV end-diastolic pressure to RV systolic pressure of one third or more, can identify a constrictive pericarditis with a predictive accuracy of more than 90%,6 In our patient, such criteria were associated with a restrictive disease. Moreover, when normal pericardial structure coexists with hemodynamic parameters suggestive of constrictive pericarditis, ventricular endomyocardial biopsy is able to provide a conclusive diagnosis. In our case, even this latter procedure failed to identify the myocardial disorder since as the vascular component was not included in the biopsy specimens. An LV biopsy was not considered subsequently since the pathophysiologic features of restrictive cardiomyopathy usually imply the occurrence of endocardial thickening or myocardial infiltration or both, that were both absent in the RV biopsy. Myocardial vasculitis responsible for a restrictive cardiomyopathy has not, to the best of our knowledge, been reported previously in the medical literature. From a histologic point of view, the vasculitis was necrotizing, was limited to small myocardial vessels, and was idiopathic in origin. The absence of antinuclear and anti-DNA antibodies, with normal circulating immunocomplexes and C3-C4, ruled out a collagen vascular disease, while negative antineutrophil cytoplasmic antibodies and lack of granulomatous lesions in the myocardium made lymphomatoid Wegener's granulomatosis unlikely. Furthermore, because of the absence of appreciable numbers of neutrophils and eosinophils in the inflammatory infiltrates, a hypersensitivity vasculitis, was ruled out, while arteritis nodosa is not known to affect the small vessels while sparing the great and middle-sized arteries, As far as treatment of restrictive cardiomyopathy is concerned, this is problematic and often disappointing; our report identifies a treatable form of cardiomyopathy in which a consistent and sustained improvement, confirmed by echocardiographic reduction of myocardial mass, was obtained following a steroidal and immunosuppressive regimen.
In conclusion, a primary necrotizing vasculitis of myocardial small vessels may give rise to a severely compromised diastolic function and should be taken into consideration when a differential diagnosis of restrictive cardiomyopathy with heart failure is made.
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(*) From the Istituto di Cardiologia, Universita Cattolica del Sacro Cuore, Rome, Italy.
Manuscript received June 10, 1996; revision accepted October 3.
Reprint requests: Dr. Frustaci Istituto di Cardiologia, Universita Cattolica del Sacro Cuore, Largo Gemelli 8, 00168 Roma, Italy
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