Novel Insights from Clinical Experience Cardiology 2011;118:251–255 DOI: 10.1159/000329062
Received: April 24, 2011 Accepted after revision: April 26, 2011 Published online: July 12, 2011
Primary Systemic Amyloidosis Presenting as Constrictive Pericarditis Vikas Singh Joel E. Fishman Carlos E. Alfonso Leonard H. Miller School of Medicine, University of Miami, Miami, Fla., USA
Established Facts • Cardiac amyloidosis presents as restrictive cardiomyopathy. • Cardiac MRI is highly sensitive and specific for the identification of cardiac involvement in systemic amyloidosis. • Differentiation of constrictive from restrictive cardiomyopathy is challenging.
Novel Insights • Cardiac amyloidosis can present as selective constrictive pericarditis. • Cardiac MRI may fail to identify cardiac involvement in amyloidosis in cases of selective pericardial deposition of amyloid. • Constrictive pericarditis can be distinguished from restrictive cardiomyopathy by a combination of noninvasive and invasive studies.
Abstract The most frequent presentation of cardiac amyloidosis is with endomyocardial deposition, and resultant restrictive cardiomyopathy. We present a case of primary systemic amyloidosis causing constrictive pericarditis (CP) and conges-
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tive heart failure without clinical evidence of endomyocardial deposition. A comprehensive evaluation by noninvasive and invasive studies facilitated the differentiation of CP from restrictive cardiomyopathy and the patient was effectively treated with pericardectomy. To our knowledge, this is the first documented case of primary systemic amyloidosis causing selective CP with successful antemortem diagnosis and treatment in a young man. Copyright © 2011 S. Karger AG, Basel
Vikas Singh, MD Cardiovascular Division, University of Miami Hospital 1400 N.W. 12th Avenue, Suite 1179 Miami, FL 33136 (USA) Tel. +1 786 991 8555, E-Mail vsingh @ med.miami.edu
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Key Words Cardiac amyloidosis ⴢ Constrictive pericarditis ⴢ Restrictive pericarditis ⴢ MRI ⴢ Cardiac catheterization
Introduction
Case Report A 21-year-old Caucasian male was admitted to the hospital for evaluation of progressive dyspnea and bilateral lower extremity edema. These symptoms began 2 years ago when, at an outside hospital, he was diagnosed with bacterial pneumonia complicated by a right sided parapneumonic effusion which required drainage. Subsequently, he had several recurrences of loculated pleural effusion requiring right thoracotomy and pleurodesis 2 months prior to admission. Over the prior 2 months, he had also experienced progressive dyspnea and diarrhea, in addition to generalized edema and anasarca. He denied smoking, regular alcohol use or any recreational drug use. Upon admission, his respiratory rate was 20/min, pulse 100 beats/min and blood pressure was 118/59 mm Hg. Physical exam revealed pallor, 3+ pitting edema of both legs extending from ankles to thigh, decreased bilateral basilar breath sounds, pitting abdominal wall edema and hepatomegaly. An elevated jugular venous pressure and Kussmaul sign were found but no pericardial rub was heard. Chest X-ray demonstrated large bilateral pleural effusions with a loculated hydropneumothorax at the right apex and right base. EKG demonstrated sinus tachycardia with nonspecific T wave flattening in the inferior and lateral leads. Severe hypoalbuminemia was noted with a serum albumin of 1.7 g/dl. Serum protein electrophoresis showed hypoalbuminemia, hypogammaglobulinemia without any evidence of monoclonal gammopathy. Thoracentesis yielded transudative pleural effusions. Further pertinent negative findings included celiac antibody panel, hepatitis panel for types A, B and C, HIV, EBV, rheumatoid factor, antineutrophil antibody, and anti-Smith antibody. Stool demonstrated an elevated ␣1-antitrypsin clearance. CT of abdomen showed
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Fig. 1. Contrast-enhanced CT in sagittal reformat demonstrates
pericardial thickening, predominately anterior and inferior to the right ventricle (arrow).
hepatosplenomegaly, ascites and anasarca. Biopsies were obtained from the intestines and liver demonstrating extensive pericellular fibrosis with bridging and areas of cirrhosis as well as venous outflow impairment suggesting congestive heart failure. Transthoracic echocardiogram demonstrated small ventricles with no evidence suggestive of infiltrative disease, preserved ventricular systolic function, normal sized atrium and moderate pulmonary hypertension with an estimated right ventricular systolic pressure of 50/27 mm Hg. Contrast-enhanced chest CT demonstrated a thickened, noncalcified pericardium measuring up to 7 mm in thickness, especially anterior and inferior to the right ventricle (fig. 1). Although noncontrast CT was not performed, the pericardium appeared to show diffuse enhancement. Bilateral pleural effusions and lung consolidation were also noted. To further evaluate for both myocardial and pericardial pathologies, cardiac MR was performed on a 1.5-T MR scanner (GE Signa HDx 15; Milwaukee, Wisc., USA). Real-time cine MR in the short axis demonstrated respiratory variation in septal motion consistent with ventricular interdependence (fig. 2a, b). Biventricular volumes and function were normal. T1-weighted dark blood images demonstrated thickened hypointense pericardium (fig. 3), which demonstrated enhancement after administration of gadolinium contrast (Magnevist, 0.2 mmol/kg) (fig. 4a, b). The myocardium did not demonstrate characteristic contrast enhancement of amyloid infiltration. A cardiac catheterization was performed which demonstrated elevated right-sided pressures (mean right atrial and right ventricular pressures of 24 and 27 mm Hg, respectively), and moderate pulmonary hypertension (mean pulmonary artery pressure of 37 mm Hg) with equalization of diastolic pressures and a characteristic dip-n-plateau configuration of the ventricular pressure tracings. Simultaneous left and right ventricular pressure recordings also showed evidence of ventricular interdependence with a !5-mm Hg difference between left and right ventricular diastolic pressures, further supporting the diagnosis of CP (fig. 5). He underwent surgery with sternotomy and pericardectomy. Pericar-
Singh/Fishman/Alfonso
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Amyloidosis may occur as a primary or secondary phenomenon with amyloid deposition occurring systemically in internal organs including the liver, kidneys, gastrointestinal tract, skin and myocardium. The most frequent presentation of cardiac amyloidosis is with endomyocardial deposition and resultant restrictive cardiomyopathy (RCM). Pericardial amyloid involvement has also been described, although very rarely, and is usually only seen in high-grade disease [1]. Differentiation between restrictive and constrictive pathology has often posed a challenge, and requires a precise evaluation of the noninvasive studies and hemodynamics. Although more than 15 years ago a report documented amyloidosis causing constrictive pericarditis (CP) and sparing the myocardium, the diagnosis was made only after the patient’s demise [2]. We currently present a case of primary systemic amyloidosis causing CP and congestive heart failure. To our knowledge, this is the first documented case of primary systemic amyloidosis causing CP with successful antemortem diagnosis and treatment.
Fig. 2. Two still images from real-time cine
Fig. 3. T1-weighted axial image of the
heart demonstrates pericardial thickening anterior to the right ventricle (arrow).
a A
b B
a A
b B
Fig. 4. Delayed post-contrast images of the heart in 4-chamber view (a) and short axis (b) demonstrate enhancement of the pericardium (arrows). There is no characteristic myocardial enhancement to suggest amyloid infiltration.
Fig. 5. Simultaneous recordings of left and right ventricular pressures demonstrated evidence of ventricular interdependence and equalization of diastolic pressures.
Primary Systemic Amyloidosis Presenting as Constrictive Pericarditis
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MR in short axis demonstrates septal flattening and deviation toward the left ventricle during patient inspiration (a, arrow), while the septum demonstrates normal curvature during expiration (b). This is consistent with increased ventricular interdependence and is characteristic of CP. Also note the large left pleural effusion (high signal posterior and inferior to the heart).
Discussion
Cardiac amyloidosis is described as an extracellular infiltration of the myocardium by amyloid as part of systemic amyloidosis or as localized phenomenon [3]. The most frequent manifestation of amyloid heart disease is RCM. In addition, amyloid deposition may also cause conductive disease. Predominant amyloid deposition in the pericardium causing CP (as in this case) is extremely rare. Although many reports have noticed the similarities in clinical and hemodynamic manifestations of CP and RCM [4–6], distinguishing the two conditions has always posed a diagnostic challenge. Making an early diagnosis and differentiating between CP and RCM is essential as the median survival after developing heart failure is less than 6 months in untreated patients [7]. In addition, CP is potentially treatable by pericardial stripping [8], while RCM is not, and a misdiagnosis of CP can lead to futile surgery in a patient with an otherwise normal pericardium [4]. In contrast to the previously reported case of pericardial amyloid deposition discovered on autopsy findings [2], our case represents the first report of a successful antemortem diagnosis and treatment for CP secondary to pericardial amyloid deposition in a young male. In this case the diagnosis of CP was supported by complementary findings on noninvasive studies including echocardiogram, cardiac CT and MRI, and confirmed with invasive hemodynamic evaluation by simultaneous left and right heart catheterization. In the current case, while the pericardium was not markedly calcified, pericardial thickening was noted by both CT of chest and MRI, which reported a pericardial thickness of 5 and 4 mm, respectively. In patients with systemic amyloidosis, cardiac MRI is highly sensitive and specific for the identification of cardiac involvement [9]. Importantly, in the current patient MRI failed to show any definite evidence for amyloidosis of the heart neither by characteristic delayed gadolinium enhancement pattern nor by decreased cardiac function. However, the combination of pericardial thickening and pericardial enhancement, tubular appearance of the ventricles, and increased ventricular interdependence as demonstrated on real-time cine MRI 254
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suggested pericardial constriction. This was further followed by a cardiac catheterization during which simultaneous recordings of LV and RV pressures demonstrated evidence of ventricular interdependence and equalization of diastolic pressures throughout the cardiac chambers with less than 5 mm Hg variant during diastole and inspiration suggesting CP (fig. 5). The diagnosis of CP due to amyloidosis was finally confirmed when an 8-mm-thick pericardium was removed from the heart and demonstrated apple green birefringence with Congo red stain. Nine months after the procedure, the patient continues to be followed without any recurrence of his symptoms. Surprisingly, his serum proteins have almost normalized, demonstrating that part of his protein-losing enteropathy was due to CP, another unusual finding which has been rarely reported in the past [10]. Our current case demonstrates that although amyloid deposition more commonly occurs in the myocardium, rarely it can also deposit primarily within the pericardium leading to CP. Although a myocardial biopsy was not performed and we cannot exclude some degree of endomyocardial deposition, the hemodynamics, MRI findings and clinical improvement after pericardectomy suggest the primary etiology of the congestive right-sided heart failure was related to CP. The reason for amyloid deposition is unclear. What role if any the prior recurrent, pulmonary infections played is unknown and whether the amyloid deposition was a primary or secondary process is unclear. However, this case demonstrates that amyloid deposition can occur primarily within the pericardium, with or without any clinically evident endomyocardial deposition, and this could contribute to the development of constrictive pericardial disease.
Conclusion
CP should be considered in the differential diagnosis of patients presenting with signs of right heart failure of unknown etiology. Early diagnosis of CP and its differentiation from RCM is essential as the former can be treated effectively with pericardectomy. Further, although amyloid deposition within the myocardium or other tissues may suggest a restrictive process, it is important to carefully evaluate the hemodynamics and other complementary data and exclude superimposed constrictive pericardial disease.
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dium stained positive with Congo red. Congo red staining of liver and intestinal tissue also demonstrated apple green birefringence consistent with amyloidosis. The patient was discharged with a diagnosis of primary amyloidosis as no secondary cause could be identified.
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