CMR characteristics in cardiac amyloidosis

Transcription

1 CMR characteristics in cardiac amyloidosis Award: Certificate of Merit Poster No.: 406 Congress: ESCR 2012 Type: Scientific Exhibit Authors: A. Capelastegui, T. Salinas Yeregui, E. Astigarraga, A. Cabrera, M. Aduna; Bilbao/ES Keywords: Cardiac, Hematologic, MR, Contrast agent-intravenous, Diagnostic procedure, Imaging sequences, Hematologic diseases DOI: /ESCR.2012.P-406 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 25

2 Purpose The purpose of this study is to describe Cardiac Magnetic Resonance (CMR) findings in cardiac amyloidosis and to assess its value in the management of these patients. Strengths and limitations of CMR in diagnosis and follow-up of cardiac amyloidosis are discussed. The amyloidoses are a group of systemic disorders characterized by the deposition in organs and tissues of an insoluble proteinaceous material known as amyloid. There are many types of amyloidoses, classified after the amyloid protein type. Cardiac amyloidosis usually occurs during primary amyloidosis (the most common form), but other forms can also result in heart involvement (Figure I). Fig. 1: Characteristics of principal forms of amyloidosis with cardiac involvement. References: - Bilbao/ES Cardiac amyloidosis is classified as a restrictive cardiomyopathy that usually presents as a diastolic heart failure. Its diagnosis is important, as in certain cases it is the first manifestation of a systemic amyloidosis, and also because it is a determinant of treatment options and clinical outcome. Endomyocardial biopsy is considered the gold-standard diagnostic method, but it is not routinely used as it is invasive and limited to experienced centers. In clinical practice the diagnosis is accepted after demonstration of amyloid in an extracardiac biopsy, in the appropriate clinical setting and supported by imaging findings. Imaging plays therefore an important role, favoring the suspected diagnosis in some cases, giving the diagnostic clue in others. Echocardiography is the preferred imaging technique, but has some limitations that are overcome by CMR. In 2005, Maceira and cols described a typical pattern of cardiac amyloidosis at CMR and recognized the importance Page 2 of 25

3 of disturbances in gadolinium kinetics due to amyloid deposition. However, it is often considered a challenging radiological diagnosis, as it is an infrequent disease and also due to technical issues that compromise the quality of CMR in these cases. Images for this section: Fig. 1: Characteristics of principal forms of amyloidosis with cardiac involvement. Page 3 of 25

4 Methods and Materials We retrospectively review the CMR studies and clinical characteristics of patients with a diagnosis of cardiac amyloidosis over the past 5 years at our hospital. We review the clinical records of the patients to study clinical presentation, diagnostic methods, suspected diagnosis when referred to CMR, treatments received and clinical outcome. CMR was performed on a 1,5 T scanner (Magnetom Symphony and Magnetom Avanto from Siemens) using a standard cardiac protocol that always included cine imaging (steady state free precession sequences) and delayed contrast enhancement (inversionrecovery sequences) in different cardiac planes, and quantitative ventricular analysis after a stack of short axis cine sequences. Gadolinium was injected at a dose of 0,2 mmol per kilogram of body weight and images were obtained 10 to 20 minutes postinjection, after adjusting inversion time (TI) with a TI scout; in some cases early contrast-enhanced images were additionally obtained 4 to 6 minutes postinjection. Three experienced cardiac radiologists evaluated the following signs at CMR: - Delayed myocardial enhancement: enhancement pattern in the left ventricle (LV), enhancement in other cavities (right ventricle (RV), atria), and signs of abnormal gadolinium kinetics (endocavitary blood pool washout, difficulty in determining the optimal TI to null myocardial signal). Enhancement inlvwas classified as focal intramyocardial, global subendocardial or global transmural. - Myocardial hypertrophy: LV, right ventricle, interatrial septum. In the LV, hypertrophy was defined as myocardial telediastolic thickness #12 mm, and was classified as limited to interventricular septum, concentric or with a variable involvement of segments. In the RV, hypertrophy was defined as a thickness #5 mmin the inferior wall. In the interatrial septum, hypertrophy was assessed qualitatively. - LV ejection fraction and telediastolic volume (TDV), after calculation with a dedicated software (Argus, from Siemens). Atrial dilatation was defined when transverse diameter on four-chamber view exceeded 4,5 cm. - Presence of pleural and/or pericardial effusion. Results Page 4 of 25

5 Clinical findings (Figure 2) We studied 13 patients, representing 0,5% of CMR performed at our institution over the past 5 years. These patients ranged in age form 39 to 89 years (mean, 67 years), and showed a male predominance (5 females and 8 males). The clinical characteristics are summarised in Figure 2. Fig. 2: Clinical findings in patients with cardiac amyloidosis References: - Bilbao/ES Diagnosis. Eight patients had a biopsy-proven diagnosis: 2 endomyocardial and 6 extracardiac biopsies (rectal mucosa in 2 cases, lung, muscle, bone marrow and abdominal subcutaneous fat tissue). In the remaining 5 patients the diagnosis was accepted on the medical records of the patient based on typical clinical and imaging (echocardiography and CMR) findings. Only in two cases the nature of the amyloid protein was determined, and corresponded to AL. Amyloidosis type. Nine patients were classified into primary amyloidosis: 6 with extracardiac positive biopsy (one of them classified as AL protein), 2 with endomyocardial positive biopsy (in one case amyloid type was characterized as AL, and the other had associated monoclonal Page 5 of 25

6 gammopathy), and finally one patient with multiple myeloma without any biopsy performed. In the remaining 4 patients it was assumed a diagnosis of senile type amyloidosis. Clinical presentation. In the majority of patients in our series (10/13) the diagnosis of amyloidosis was established after the development of cardiac manifestations, although heart involvement is usually considered a late manifestation of the disease. These patients presented with right heart failure (7 cases), but also with other symptoms (chest pain, syncope, and palpitations due to arrhythmia). Only in 3 patients a diagnosis of extracardiac amyloidosis had already been established prior to CMR examination (diagnosed 1, 6 and 14 years ago), due to kidney (2 cases) and pulmonary involvement; one of them developed heart failure leading to death, one is asymptomatic from the cardiologic point of view and the other one has an arrhythmia. In the group of primary amyloidosis, 8 had monoclonal gammopathy and 5 had multiorganic involvement. Only 2 patients had concomitant coronary artery disease; in both cases successful revascularization had been previously performed and imaging findings were typical. Suspected diagnosis at time of CMR. In 10 patients, CMR was ordered to evaluate a possible infiltrative cardiomyopathy (mainly amyloidosis) due to echocardiographic findings (restrictive pattern and hypertrophy of the LV, sometimes with a highly refractive texture); 3 of these 10 patients had a known systemic amyloidosis at the time of CMR. Therefore, in the majority of patients cardiac amyloidosis was suspected when referred to CMR. However in our experience (although not part of this study), CMR does not confirm the majority of cases where echocardiography suspects cardiac amyloidosis. In the remaining 3 patients, cardiac amyloidosis was not suspected initially. These 3 patients had been admitted to hospital, and CMR was ordered to investigate the cause of dyspnea and edemas (two cases) or chest pain with cardiac enzymes elevation; cardiac catheterization revealed normal coronaries in two cases, and coronary artery disease successfully revascularized in the third one. Management and clinical outcome. In the group of primary amyloidosis, 4 patients received one or more cycles of chemotherapy to treat the clonal plasma cell dyscrasia and in 3 cases autologous bone marrow transplantation was performed. One patient was proposed for cardiac transplantation, although no follow-up is available in this case. At the time of data collection for this study, more than half of the patients (7/13) had died due to amyloidosis; in 6 of them the primary cause of death was endstage heart failure. Death occurred with an interval after CMR ranging from 4 to 22 months (medium, 9 months). These data confirm the poor clinical outcome of cardiac amyloidosis. The other 6 patients are still alive, with a survival time from diagnosis of cardiac amyloidosis varying between 3 and 13 months. Two of these patients have been admitted to hospital (twice and three times since the diagnosis) due to heart failure, one patient with a longstanding amyloidosis is asymptomatic from the cardiological point Page 6 of 25

7 of view, and the other 3 are under cardiological surveillance without major complications. CMR findings In every case MR suggested or favored the diagnosis of cardiac amyloidosis due to a typical combination of findings. Gadolinium kinetics (Figure 3). All patients (100%) showed abnormal gadolinium kinetics due to contrast uptake by amyloid deposition in organs and tissues all over the body. An abnormal washout was found in 11 cases and in another 11 it was difficult to find an optimal TI to null myocardial signal; 9 patients presented both signs. This feature is the reason of the suboptimal quality of contrast-enhanced images in many cases. It is important to pay attention to this sign as it is the only one specific for cardiac amyloidosis (not described in other cardiomyopathies). Fig. 3: Signs of abnormal gadolinium kinetics in cardiac amyloidosis References: - Bilbao/ES LV enhancement (Figure 4). All patients (100%) had myocardial enhancement in LV due to expansion of extracellular space by deposition of amyloid. The most frequent pattern was global subendocardial (7/13), Page 7 of 25

8 followed by global transmural (4/13). In the remaining 2 cases, there was a focal myocardial enhancement; in one of them the enhancement was only visible in early images after contrast administration. Myocardial enhancement was always consistent with a nonischemic type, but as an isolated sign it needs to be distinguished from other cardiomyopathies. Fig. 4: Myocardial enhancement in LV in cardiac amyloidosis References: - Bilbao/ES LV hypertrophy (Figure 5). All patients (100%) had interventricular septum hypertrophy, with a myocardial thickness ranging between 12 and 23 mm (medium 16,5 mm). Myocardial hypertrophy was concentric in 6 cases, in 2 was confined to interventricular septum and in 5 had a variable distribution. Increased myocardial thickness is due to amyloid deposition between fibers, and therefore does not reflect a true myocardial hypertrophy. Increased myocardial thickness has poor specifity, and the differential diagnosis of cardiac amyloidosis and concentric hypertrophic cardiomyopathy may be difficult. Hypertrophy was in many cases accompanied by hyperintensity on STIR images, although no specific evaluation of this feature was performed. Page 8 of 25

9 Fig. 5: LV myocardial hypertrophy in cardiac amyloidosis References: - Bilbao/ES Involvement of RV and atria (Figure 6). All patients (100%) had some evidence of involvement of 6ther cardiac chamber by amyloid deposition, either as hypertrophy, enhancement or both signs. Ten patients showed hypertrophy (10 in the RV, 5 in the interatrial septum). In 9 cases there was an abnormal enhancement of these structures: 7 in RV, interatrial septum and atria, 1 in RV, and 1 in RV and interatrial septum. Page 9 of 25

10 Fig. 6: Cardiac amyloidsis involvement in other chambers of the heart. References: - Bilbao/ES Effusions (Figure 7). Eleven patients (84 %) had pleural and/or pericardial effusion: 10 pericardial effusions, 10 pleural effusions (9 bilateral, 1 left). The effusions can be related either to congestive heart failure, or to deposition of amyloid in pleural and pericardial surfaces. Page 10 of 25

11 Fig. 7: Other findings in cardiac amyloidosis: effusions, volumetric analysis. References: - Bilbao/ES Quantitative analysis. All patients had a preserved LV systolic function, with an ejection fraction ranging from 51 to 78% (medium 61%). Telediastolic volumes of LV were normal in all patients except one. Although atrial dilatation with normal-size ventricles is a feature of restrictive cardiomyopathy, only in 5 cases the atria were dilated. Two cases are particularly interesting, as they illustrate the correlation between clinical and radiologic findings with prognostic implications, and also the difficulties of an early diagnosis of cardiac amyloidosis. First case (Figures 8 and 9) corresponds to a 70 years-old male, who was admitted to hospital due to an atypical chest pain with elevation of cardiac enzymes and a suspected diagnosis of myocarditis. He had been admitted to the hospital for three times over the past two years due to similar episodes; coronary disease was excluded by means of cardiac catheterization and stress test. 4 CMR performed over the following 3 years show the progression of the disease, until the patient died from congestive heart failure. First CMR showed focal intramyocardial enhancement, initially interpreted Page 11 of 25

12 as myocarditis, according to clinical suspicion. On a second CMR 6 months later, contrast enhancement persisted and the patient developed effusions. He was also being evaluated for polymyalgias (finally diagnosed of muscular amyloidosis after a muscle biopsy). At the time of the third CMR, echocardiography revealed a restrictive pattern; at CMR, enhancement of the LV changed to a global subendocardial pattern. Fig. 8: Case 1: serial CMR show progression of the disease over 3 years. References: - Bilbao/ES Page 12 of 25

13 Fig. 9: Case 1: CMR findings correlate with clinical evolution. References: - Bilbao/ES Every sign on CMR showed progression from initial examination: LV hypertrophy, myocardial contrast enhancement, involvement of other cardiac chambers and effusions. The pattern of contrast enhancement began as focal intramyocardial and evolved to a global pattern, first subendocardial and in the late stages it was diffuse transmural. Second case (Figure 10) corresponds to a 58 years-old female who had been diagnosed of primary amyloidosis with an extensive multiorganic involvement (lungs, pancreas, breast, skin and digestive system). She presented 14 years ago with pulmonary involvement and had been treated with cycles of chemotherapy and two autologous bone marrow transplantations. Two previous echocardiograms were normal. CMR was performed as part of this study, as she didn't have any cardiac symptoms or signs. CMR revealed subtle findings, probably related to a limited cardiac involvement: focal intramyocardial enhancement and non-severe LV hypertrophy (13 mm), limited to the interventricular septum. Page 13 of 25

14 Fig. 10: Case 2: subtle findings in a patient with minimal cardiac involvement. References: - Bilbao/ES Both cases presented with a limited cardiac involvement (partial focal intramyocardial LV enhancement) and absence of some of the typical signs described for cardiac amyloidosis. In the first case, clinical presentation was misleading, and the diagnosis of cardiac amyloidosis was delayed until clear imaging and clinical findings developed. In the second case, the known multiorganic amyloidosis allowed an assumption that CMR findings were due to cardiac involvement, although the clinical relevance of this finding should be assessed in future examinations. Therefore, diagnosis of cardiac amyloidosis in the early stages may be difficult, and should be considered in the differential diagnosis of many nonischemic cardiomyopathies. In addition, it still has to be determined if CMR can detect subclinical cardiac involvement, as it is already known with autopsy or endomyocardial biopsy. These two cases also provide evidence of a correlation between the CMR findings, the cardiac amyloid burden and the clinical expression of the disease. Although it is difficult to extract prognostic implications from a single examination, CMR would probably be a valuable imaging technique to monitor treatment and disease progression. Further Page 14 of 25

15 studies are needed to prove if CMR findings correlate with the speed of progression of the disease or the different forms of amyloidosis. Images for this section: Fig. 2: Clinical findings in patients with cardiac amyloidosis Page 15 of 25

16 Fig. 3: Signs of abnormal gadolinium kinetics in cardiac amyloidosis Page 16 of 25

17 Fig. 4: Myocardial enhancement in LV in cardiac amyloidosis Page 17 of 25

18 Fig. 5: LV myocardial hypertrophy in cardiac amyloidosis Page 18 of 25

19 Fig. 6: Cardiac amyloidsis involvement in other chambers of the heart. Page 19 of 25

20 Fig. 7: Other findings in cardiac amyloidosis: effusions, volumetric analysis. Page 20 of 25

21 Fig. 8: Case 1: serial CMR show progression of the disease over 3 years. Page 21 of 25

22 Fig. 9: Case 1: CMR findings correlate with clinical evolution. Page 22 of 25

23 Fig. 10: Case 2: subtle findings in a patient with minimal cardiac involvement. Page 23 of 25

24 Conclusion Cardiac amyloidosis is an infrequent disease, and has in general poor clinical outcome. Cardiac involvement may be the first manifestation of the disease and patients are generally referred for CMR evaluation of a suspected amyloidosis after echocardiographic findings. A combination of features at CMR can be considered typical for cardiac amyloidosis: myocardial hypertrophy and enhancement in the LV (usually with a global pattern) and also in other cardiac chambers, abnormal gadolinium kinetics and pleuropericardial effusions. Diagnostic difficulties are encountered however when evaluating by CMR a suspected amyloidosis: differential diagnosis with other cardiomyopathies (particularly of early-stage amyloidosis, when the typical constellation of findings is not present), lack of specificity of the above mentioned signs when interpreted in isolation, and technical issues related to the deposition of amyloid in organs and tissues that may compromise the quality of CMR images. An atypical clinical presentation may also delay the diagnosis. CMR facilitates the non-invasive detection of cardiac amyloidosis and allows longitudinal assessment of the course of the disease, although further studies are needed to provide data regarding prognostic implications of image findings. Awareness of this disease and accurate use of diagnostic imaging techniques such as CMR may result in an improved and earlier diagnosis of cardiac amyloidosis, allowing prompt initiation of therapy. References - Maceira AM, Joshi J, Prasad SK, et al. Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation 2005;111: Falk RH. Diagnosis and management of the cardiac amyloidoses. Circulation2005; 112: Vanden Driesen RI, Slaughter RE, Strugnell WE. MR findings in cardiac amyloidosis. AJR Am J Roentgenol 2006;186: Kristen AV, Perz JB, Schonland SO, et al. Noninvasive predictors of survival in cardiac amyloidosis. Eur J Heart Fail 2007;9: Maceira AM, Prasad SK, Hawkins PN, Roughton M, Pennell DJ. Cardiovascular magnetic resonance and prognosis in cardiac amyloidosis. J Cardiovasc Magn Reson 2008;10:54-65 Page 24 of 25

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