| Abstract|| |
Microfibrillar cardiomyopathy is a very rare cause of restrictive cardiomyopathy (RCM). The index case was a male patient who presented with shortness of breath and pedal edema. Further clinical investigations favored a clinical diagnosis of RCM. An endomyocardial biopsy revealed subendocardial and interstitial hyaline eosinophillic material resembling amyloid that did not stain with Congo red. An electron microscopic examination showed that this material was composed of twisted linear and bundles of tangled microfibrils. The etiology of the microfibrillar deposition is currently unknown. The pathologists should entertain the diagnosis of microfibrillar cardiomyopathy in suspected cases of amyloidosis that are negative for Congo red.
Keywords: Amyloid, electron microscopic examination, microfibrillar cardiomyopathy, microfibrils, restrictive cardiomyopathy
|How to cite this article:|
Kumar N, Ray R. Microfibrillar cardiomyopathy: A rare case. Indian J Pathol Microbiol 2011;54:790-2
| Introduction|| |
Restrictive cardiomyopathy (RCM) is a primary disease of cardiac muscle characterised by impaired filling with normal or decreased diastolic ventricle volume. The left ventricular systolic function usually remains normal in the early phase of the disease, and the thickness of the left ventricle wall is also within the normal range.  A classical case of a RCM has a stiff and small left ventricle (not dilated) with marked atrial dilatation and normal systolic function in the absence of any pericardial disease. 
RCM is categorised into the primary and secondary types according to etiology. In the primary or idiopathic type of RCM, no specific cause is found.  Secondary RCM often occurs as a result of an infiltrative process such as amyloidosis, sarcoidosis, hemochromatosis, and abnormalities related to desmin. , Secondary RCM may be associated with endomyocardial fibrosis, loffler syndrome, scleroderma, and postradiotherapy effects. The microfibril deposition is one of the rare causes of infiltrative secondary RCM. ,
Till now two case series had described the deposition of microfibrils in the interstitium of heart. One series showed deposition of microfibrils in cyclosporin-treated cardiac transplants.  The other series of four cases were idiopathic in nature.  We had seen a case of microfibrillar cardiomyopathy on endomyocardial biopsy. The case is being reported for its rarity.
| Case Report|| |
The index case was 44-year-old male who was admitted in a private hospital with a history of shortness of breath (NYHA class IV) for the last 4-5 years. He later developed pedal edema. Subsequent investigations (echocardiography and Doppler imaging) revealed features of RCM. Both the atria were dilated. Both the ventricles had normal systolic function along with moderate mitral and tricuspid regurgitation. His coronary angiogram was normal.
The diagnostic specimen was an endomyocardial biopsy that was sent to our pathology department. The endomyocardial biopsy comprised of three fragments. The endocardium was unremarkable. The subendocardium and interstitium showed deposition of extracellular eosinophillic amorphous hyaline material. Some of the cardiomyocytes were atrophied. The blood vessels were unremarkable. The material resembled amyloid on hematoxylin and eosin stain. However, special stains for amyloid like Congo red stain, crystal violet and thioflavin-T were all negative [Figure 1].
|Figure 1: Hyaline eosinophillic material deposition within the interstitium and around cardiomyocytes (a, b, hematoxylin and eosin, ×200). Higher magnification showing the same material around cardiomyocytes (c, hematoxylin and eosin, ×400). Special stain Congo red shows that the material lacks congophillia (d, congo red × 400)|
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The tissue was then retrieved from the paraffin block and processed for an electron microscopic (E/M) examination. Under normal circumstances, the interstitial connective tissue matrix of the heart is composed of collagens (primarily types I, III, and IV), laminin, fibronectin, proteoglycans, elastin, and microfibrils.  Microfibrils are small (range, 4-25 nm length and mean, 8-12 nm diameter) and are often found in association with elastic fibers. , The microfibrils display a "beads on a string" structure. The average periodicity of these beaded microfibrils when isolated and in the untensioned state is 56 nm (range, 33-165 nm).  Electron microscopy of the present case showed bundles and tangled masses of microfibrils that were lying loose in the interstitial space. These microfibrillar masses did not form parallel arrays and were away from cardiomyocytes, sarcolemma, or basal lamina. This is unlike amyloidosis where the deposition is around the cardiomyocytes. At higher magnification, twisting of individual fibrils was noted [Figure 2].
|Figure 2: Loose aggregates of microfibrils lying diffusely within the interstitium (a, EM bar 1 µm). A highly magnified view of microfibrils reveals they are slightly curvilinear with a suggestion of branching and twisting (b, EM bar 0.2 µm)|
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The clinical details, histopathological findings, and an EM picture of the index case would best fit with the diagnosis of microfibrillar cardiomyopathy. The patient was lost to follow up and hence further clinical course could not be assessed.
| Discussion|| |
Microfibrillar cardiomyopathy is a rare form of infiltrative heart disease leading to RCM. , Till date, only two case series regarding microfibrillar-related cardiomyopathy are available.
Myles et al. had described a series of cyclosporin-treated cardiac transplant patients. In this study, eight cases had interstitial microfibril accumulation as seen on electron microscopy. The fibrils were hollow, beaded and they measured 8-10 nm in diameter. The authors suggested that these microfibrils may be related to cyclosporin-induced fine interstitial fibrosis that can reverse following withdrawal of cyclosporin.  Factor et al. had first time described idiopathic microfibrillar cardiomyopathy in four patients. The endomyocardial biopsy of these patients showed a similar type of deposition in the subendocardial region and in interstitium. Electron microscopy had proven the presence of microfibrils.  The histopathological examination of present case also revealed interstitial accumulation of hyaline eosinophillic material similar to amyloid. This material did not stain with Congo red, crystal violet, and thioflavin-T. Electron microscopy confirmed the presence of microfibrils.
Prognosis of microfibrillar cardiomyopathy is difficult to determine since only a few cases have been described in the literature. Factor et al. had documented four cases, all of whom had a short follow-up. In their study, only one case had a follow-up for 2 years and was doing well. No comment regarding the clinical course of the present case is possible as the patient lost to follow up. Because of scarcity of the available literature it is difficult to provide the precise management protocol of microfibrillar cardiomyopathy. However, hypothetically such a case will probably be an ideal candidate for heart transplantation.
In summary, we have identified a case with features of RCM that had an amyloid-like material deposition in the interstitium. The electron microscopy showed accumulation of microfibrils. The exact etiology of the microfibrillar deposition is unknown. The pathologists should be aware of this entity. All cases with Congo red negative amyloid like deposition should be subjected to electron microscopic examination to rule out the possibility of microfibrillar cardiomyopathy.
| Acknowledgments|| |
We are grateful to the Department of Pathology, AIIMS, for providing the facilities and resources.
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Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]