Cardiovascular Imaging A handbook for clinical practice - Part 9 pptx

Mader MT, Poulton TB, White RD. Malignant tumors of the heart and great vessels: MR imaging appearance. Radiographics 1997;17:145. Meng Q, Lai H, Lima J, et al. Echocardiographic and pathologic characteristics of primary cardiac tumors: a study of 149 cases. Int J Cardiol 2002;84:69. Schvartzman PR, White RD. Imaging of cardiac and paracardiac masses. J Thorac Imaging 2000;15:265. Siripornpitak S, Higgins CB. MRI of primary malignant cardiovascular tumors. J Comput Assist Tomogr 1997;21:462. 234 Chapter 18 BCI18 6/15/05 8:41 PM Page 234 CHAPTER 19 Evaluation of the transplanted heart Oberdan Parodi, Maria Frigerio, and Benedetta De Chiara Introduction Cardiac transplantation is an established treatment for advanced heart failure. Clinical experience and progress in immunosuppression have increased recipi- ent survival to more than 80% at 1 year; 10-year survival is more than 50% at many centers. 1 Common complications after heart transplantation (HTx) include acute rejection, infections, cardiac allograft vasculopathy (CAV), and lymphoproliferative disorders and other malignancies, as well as other condi- tions mainly related to side-effects of immunosuppressive drugs (Fig. 19.1). This chapter summarizes briefly the role of cardiac imaging techniques for the diagnosis of acute rejection, and will provide a more in-depth review of current techniques for invasive and non-invasive evaluation of CAV. 235 Diagnosis of acute cardiac allograft rejection Acute rejection is an important cause of death in HTx recipients, accounting for 20% of the deaths occurring in the first post-transplant year, and up to 15% thereafter. 1 Nevertheless, the majority of acute rejections can be safely man- aged, providing diagnosis precedes the occurrence of graft dysfunction. Minor clinical signs of acute cardiac allograft rejection may be absent and are non- specific (Table 19.1). Thus, surveillance for preclinical diagnosis is of utmost importance. Case Presentation A 55-year-old man with idiopathic dilated cardiomyopathy underwent heart transplantation in 1999, from a donor of the same age and gender. The patient had cytomegalovirus infection and one treated acute rejection episode in the early postoperative months. One year after heart transplantation, the resting ECG showed an incomplete right bundle branch block, and further evaluation was sought for surveillance for rejection and allograft vasculopathy. BCI19 6/17/05 9:49 PM Page 235 Endomyocardial biopsy (EMB) is the most widely used and reliable tool for the diagnosis of acute rejection. Acute cardiac allograft rejection may show a wide spectrum of lesions with standard staining (hematoxylin and eosin), rang- ing from sparse perivascular or interstitial infiltrates of small lymphocytes, to more widespread and aggressive infiltration of large, activated lymphocytes, as- 236 Chapter 19 First month Post-surgical complications Acute graft failure Acute rejection Infections (bacterial, fungal) Side-effects of immunosuppressive drugs 2nd month-1 year Acute rejection Infections (typically CMV and other opportunistic infections) Side-effects of immunosuppressive drugs > 12 months CAV Post-transplant lymphoproliferative disorders Other malignancies Late acute rejection Side-effects of immunosuppressive drugs Diabetes Dyslipidemia Arterial hypertension Renal insufficiency Figure 19.1 Common complications after cardiac transplantation. Side-effects of immunosuppressive drugs occur early after heart transplantation and contribute to endothelial dysfunction and progression of cardiac transplant vasculopathy. CAV, coronary allograft vasculopathy; CMV, cytomegalovirus. Table 19.1 Clinical symptoms and signs of acute cardiac allograft rejection. None Malaise, fatigue Fever Tachycardia Supraventricular arrhythmias, conduction disturbances Reduced QRS amplitude (peripheral leads) Reduced systolic blood pressure Reduced pulse pressure Dyspnea Congestive heart failure Sudden death BCI19 6/17/05 9:49 PM Page 236 sociated or not with granulocytes, with various degrees of myocyte disruption and necrosis, up to severe, extensive necrosis, associated with edema, polymor- phonuclear infiltrates and hemorrhages. A less common but ominous condi- tion is the so-called “humoral” or “vascular” rejection, which can be briefly defined as an immunomediated, acute graft dysfunction despite a normal (“negative”) EMB. The main limitations of EMB are patient discomfort, risk of complications (less than 1% when performed by skilled personnel: right ventri- cle perforation, tricuspid leaflet disruption, bleeding, pneumothorax), costs, and sampling error. Despite the debates about rejection classification, the dis- agreement observed between pathologists in EMB interpretation, and the un- certainties regarding therapeutic implications of the EMB results (except in case of very low- or high-grade rejections), EMB remains the cornerstone for rejec- tion surveillance at most HTx centers. Nevertheless, various non-invasive alter- native techniques have been evaluated, with the aim of reducing the need for repeated EMBs, to optimize their timing, and to add information relevant for clinical management. Echocardiography is the most extensively used diagnostic technique for non- invasive monitoring of HTx recipients. During the first postoperative weeks, the echocardiogram reflects the mutual adaptation of the donor’s heart and of the recipient’s hemodynamic profile to the new condition, and postoperative se- quelae: right ventricular dilatation, tricuspid regurgitation, paradoxic septal motion, and pericardial effusion are common. After 1 month, the echocardio- graphic pattern remains quite stable in the absence of significant rejection in most patients, generally up to 1 year. In the long term, the effects of hyperten- sion and CAV may interfere with echocardiographic findings. The main features of acute rejection are alterations of indexes of left ventricular (LV) diastolic function, commonly detected by pulsed wave Doppler (reduction of pressure half-time and of isovolumic relaxation time), increased wall thickness, in- creased myocardial echogenicity, dilated right ventricle, and increased peri- cardial effusion. LV systolic dysfunction is less frequent, is prognostically unfavorable, and is more often associated with high-grade rejection or with biopsy-negative (humoral/vascular) rejection. The accuracy of echocardio- graphic findings may vary according to the operators’ experience and patient body structure; obesity, not uncommon after HTx, may reduce the quality of echocardiography. Recently, tissue Doppler imaging (TDI) has been proposed for early detection of rejection-related diastolic dysfunction in HTx recipients; high sensitivity (93%) and high negative predictive value (96%) have been re- ported, with a favorable impact on the number of EMBs as well as prognostic implications. 2 Magnetic resonance imaging (MRI) has been more recently explored, both in experimental and human research. Labeling of macrophages with dextran- coated, ultrasmall, superparamagnetic iron oxide (USPIO) particles can be used to detect the accumulation of macrophages in rejecting tissue. 3 Furthermore, USPIO can be used alone (i.e. not in macrophages) because blood pool contrast agents leak into the interstitial space in areas of inflammation associated with Evaluation of the transplanted heart 237 BCI19 6/17/05 9:49 PM Page 237 rejection, where the vessels display increased permeability. Moreover, the myocardial T2 relaxation time, determined using a black-blood MRI sequence, has been demonstrated to predict acute heart transplant rejection in humans. An intriguing radioisotope technique is represented by myocardial scintigra- phy with radiolabeled (indium-111 pentetreotide) somatostatin receptor ana- logue. 4 The pathophysiologic hypothesis is that somatostatin receptors are expressed on activated lymphocytes and up-regulated during cardiac allograft rejection. It is noteworthy that somatostatin receptor imaging seems to predict impending rejection at least 1 week before the EMB becomes positive, because of the interval between lymphocyte activation and relevant myocardial infiltra- tion or damage. The possibility of anticipating the occurrence of EMB-proven rejection by means of analysis of gene expression in the peripheral blood is cur- rently under evaluation. Another interesting approach, which implies the possibility of telemonitor- ing of HTx recipients, is represented by continuous recording of high- resolution, intramyocardial electrocardiogram (ECG) by means of special electrodes implanted at the time of transplantation. However, these innovative approaches have not yet gained widespread clini- cal use. At present, echocardiography is used at most HTx centers as an adjunct to clinical, laboratory, ECG, and EMB data: it is helpful in deciding if and how to change the immunosuppressive regimen and for planning patient follow-up, but it is not a substitute for EMB except in small pediatric patients. 238 Chapter 19 Case Presentation (Continued) Echocardiographic evaluation demonstrated normal regional and global left ventricular function (ejection fraction 0.59) and diastolic parameters. A routine biopsy was normal. However, further evaluation was sought for allograft vasculopathy. Coronary allograft vasculopathy CAV is the main factor limiting long-term survival after transplantation, and ac- counts for more than 20% of later mortality. 1 Pretransplant conditions, donor characteristics, and events occurring during the first post-transplant year and thereafter are implicated in the pathogenesis of CAV (Table 19.2). 5 The initial endothelial dysfunction and injury are followed by intimal hyperplasia and vas- cular smooth muscle cell proliferation. The process has been angiographically documented in 40–50% of patients surviving 5 years after transplantation. 1 The histologic hallmark of CAV (intimal proliferation in graft coronary arteries) can be observed in all surviving recipients as soon as 1 year after HTx; its in vivo equivalent can be appreciated by means of intracoronary ultrasound (ICUS). Unfortunately, warning anginal symptoms are often absent, as a result of car- BCI19 6/17/05 9:49 PM Page 238 diac denervation; clinical manifestations of CAV are frequently severe, and in- clude congestive heart failure, myocardial infarction, life-threatening ventricu- lar arrhythmias, and sudden death. Treatment of CAV remains a difficult challenge. The solution for severe, dif- fuse disease is retransplantation, although this option is limited by donor avail- ability. Focal stenoses can be approached by percutaneous angioplasty and stenting, with satisfactory angiographic short-term results, but little is known regarding long-term success and the prognostic relevance of these procedures. Recently, the use of proliferation inhibitors (sirolimus and everolimus) appears promising for preventing, stopping, and perhaps reversing intimal prolifera- tion. This section describes the advantages and limitations of non-invasive ap- proaches, the place of invasive techniques in the detection of CAV and in prognostic stratification of HTx recipients, and the potential of new imaging modalities. Non-invasive testing The availability of accurate non-invasive tests for diagnosis of the presence (and of the functional and prognostic relevance) of CAV is highly desirable for clini- cal, organizational, and economic reasons. Moreover, non-invasive tests may provide information regarding microvascular circulation, which can be im- paired after HTx. Unfortunately, the sensitivity and specificity of non-invasive tests for diagnosis of CAV is difficult to establish in relation to angiography, be- cause anatomic narrowing does not always induce ischemia and, conversely, is- chemia may occur in patients with small vessel coronary artery vasculopathy undetected by angiography. The diffuse nature of CAV may result in balanced is- chemia that is difficult to recognize by imaging modalities, such as perfusion scintigraphy, which are based on intrapatient comparison of different myocar- dial areas. Moreover, new events (e.g. late acute rejection) may occur at any time after HTx, and may accelerate the progression of CAV, thus limiting the Evaluation of the transplanted heart 239 Table 19.2 Factors involved in the pathogenesis of coronary allograft vasculopathy. Non-immune Immune mechanisms mechanisms Recurrent/persistent acute rejection Older donor age Vascular/humoral rejection Hyperlipidemia HLA mismatch Hypertension Diabetes Ischemia reperfusion injury* CMV infection* * These factors are in an intermediate position, because they may be considered partially “immune” inasmuch as they imply exposure of endothelial antigens and/or activation of immune reaction. CMV, cytomegalovirus. BCI19 6/17/05 9:49 PM Page 239 predictive value of any test, irrespective of its accuracy. However, for the indi- vidual patient, a positive non-invasive test indicating inducible myocardial is- chemia may have powerful prognostic value. Stress electrocardiography Most transplant patients have resting ECG abnormalities (mostly incomplete right bundle branch block and T-wave inversion) that make the interpretation of stress ECG less sensitive and specific than in general population. Further- more, sensitivity is reduced because angina is rarely present, and the target heart rate during exercise usually is not achieved because of heart denervation and, in some patients, inadequate physical conditioning. Reported sensitivity and specificity of exercise ECG for the detection of CAV are in the ranges 0–38% and 77–100%, respectively. Ambulatory ECG monitoring is similarly insensi- tive. Arterial hypotension during exercise is quite specific for significant CAV. Additional information may be provided by ECG data when combined with im- aging techniques. In our experience, the appearance of complete right bundle branch block increases the specificity of myocardial perfusion defects for pre- dicting CAV; a blunted heart rate response during dipyridamole-induced va- sodilatation predicts stress perfusion defects, and higher probability of cardiac events during follow-up. Echocardiography Baseline ejection fraction (EF) and regional wall motion are generally normal in HTx recipients, even in the presence of CAV. Thus, regional wall motion abnor- malities and/or a reduced ejection fraction have a low sensitivity for diagnosis of CAV (50–60%), although their prevalence is higher in HTx patients with CAV. Spes et al. 6 reported that resting wall motion abnormalities in any left ventricu- lar territory had a 90% positive predictive value and an 88% specificity, but only a 57% sensitivity in detecting CAV. Furthermore, normal resting echocardiog- raphy had a 90% negative predictive value for cardiac events. In a previous study, 7 we showed that normal resting wall motion at echocardiography cou- pled to normal stress myocardial perfusion scintigraphy ruled out the presence of significant CAV. Conversely, resting wall motion abnormalities and perfusion defects strongly predicted cardiac events. Resting echocardiography alone de- tected significant CAV only in 50% of cases, but it was an independent prognos- tic determinant of cardiac events. The addition of a pharmacologic stress (e.g. dipyridamole or dobutamine) may improve the limited sensitivity of resting echocardiography for detection of CAV (Table 19.3). Ciliberto et al. 8 first report- ed that high-dose dipyridamole stress echocardiography is useful for identifying patients with significant CAV, and more recently found that dipyridamole- induced wall motion abnormalities were associated with adverse prognosis. 9 Dobutamine stress echocardiography (DSE) provides accurate diagnosis as well as useful prognostic information in cardiac transplant recipients. 6 Dobutamine increases contractility, heart rate, and wall stress in a dose-dependent fashion, an attractive approach to evaluate both microvasculature and epicardial coro- 240 Chapter 19 BCI19 6/17/05 9:49 PM Page 240 nary vessels in HTx patients. DSE is more sensitive than exercise echocardiogra- phy because the transplanted heart is more responsive to catecholamine stimu- lation than a normal heart, while the exercise-induced increase in heart rate is limited. Spes et al. 6 suggested that serial routine coronary angiography could be deferred in HTx recipients with normal DSE, because the prognostic value of this test is comparable to that of ICUS. Therefore, resting echocardiography plus DSE appear a reliable method for routine surveillance of patients after HTx. As usual, echocardiography may be limited by poor image quality in obese pa- tients, and its accuracy relies upon the operator’s experience. Myocardial perfusion scintigraphy Stress myocardial scintigraphy with thallium-201 or technetium-99m labeled perfusion tracers and single photon emission computed tomography (SPECT) has a well-established role in detection of atherosclerotic coronary lesions in pa- tients with known or suspected ischemic heart disease. In HTx recipients, stress myocardial scintigraphy provides a low-to-moderate sensitivity and a good specificity for the detection of CAV, with exercise testing performing better than a dipyridamole test (Table 19.4). However, the limitations of exercise testing in HTx patients have been already described. Moreover, most published studies utilized a qualitative (visual) assessment of perfusion defects, or a semi-quanti- tative evaluation of myocardial tracer distribution, without any reference to maps of normal regional perfusion pattern. The limited sensitivity of the tech- nique reported by these studies might be related to the lack of quantitative as- Evaluation of the transplanted heart 241 Table 19.3 Accuracy of stress echocardiography in the detection of coronary allograft vasculopathy. Patients Sensitivity Specificity Study Journal Year (n) Stress (%) (%) Derumeaux et al. J Am Coll 1995 37 Dobutamine 86 91 Cardiol Herregods et al. J Heart Lung 1994 28 Dobutamine 0 100 Transplant Akosah et al. J Heart Lung 1994 41 Dobutamine 95 55 Transplant Ciliberto et al. Eur Heart J 1993 80 Dipyridamole 32 100 Spes et al. Am J Cardiol 1996 46 Dobutamine 79 83 Collings et al. J Heart Lung 1994 51 Exercise 25 86 Transplant Cohn et al. Am J Cardiol 1996 51 Exercise 15 85 Spes et al. Circulation 1999 109 Dobutamine 94 57 BCI19 6/17/05 9:49 PM Page 241 sessment of the regional tracer uptake. More recently, we evaluated the accura- cy of high-dose dipyridamole sestamibi SPECT in the detection of CAV and in prognostic stratification utilizing a semi-quantitative technique corrected for bull’s eye maps of perfusion normalcy rates in 78 HTx recipients. 7 Our findings indicate that this approach is sensitive in the detection of significant CAV (sensi- tivity 92%), and that its combination with resting echocardiography can be a safe and reasonable non-invasive approach for prediction of long-term progno- sis after HTx. In this study, concordant negative tests occurred in over two- thirds of cases, in whom non-invasive testing had an optimal accuracy in ruling out significant CAV (specificity 82%, negative predicting value 100%). These patients also had a high event-free survival. Conversely, a significant CAV was present in 100% of the five patients with abnormalities in both non-invasive tests. Patients with abnormal resting echocardiography had a 10-fold relative risk of cardiac events at follow-up, while a positive dipyridamole SPECT con- ferred a 4 : 1 relative risk of cardiac events. Thus, the association of these tests may be useful to rule out the need for coronary angiography when both are negative, and to recommend it when at least one is positive. In our hands, the 242 Chapter 19 Table 19.4 Accuracy of stress myocardial scintigraphy in the detection of coronary allograft vasculopathy. Patients Sensitivity Specificity Study Journal Year (n) Stress (%) (%) Smart et al. Am J Cardiol 1991 57 Dipyridamole 21 88 Redonnet et al. Transplant 1995 43 Dipyridamole 58 64 Proc Ciliberto et al. Eur Heart J 1993 50 Exercise 67 100 Rodney et al. J Heart Lung 1994 25 Exercise 77 100 Transplant Smart et al. Transplant 1991 35 Exercise 21 81 Proc Valantine et al. Circulation 1988 20 Exercise 36 78 McKillop et al. Clin Radiol 1981 7 Exercise 100 0 Mairesse et al. J Heart Lung 1995 37 Exercise NA 84–92 Transplant Ambrosi et al. Eur Heart J 1994 34 Exercise NA 97 Carlsen et al. J Heart Lung 2000 67 Dip /Exercise 80 92 Transplant Ciliberto et al. Eur Heart J 2001 78 Dipyridamole 92 86 NA, not assessed. BCI19 6/17/05 9:49 PM Page 242 sensitivity of this imaging approach for significant CAV favorably compares with previous studies that used either dipyridamole or exercise thallium-201 scans 10 or visual interpretation of exercise myocardial perfusion imaging by technetium-99m labeled compounds. 11 High-dose dipyridamole may augment the differences in regional tracer distribution among areas with different coro- nary vasodilating capability, improving the detection of minor coronary lesions. It is not yet clearly established which stressor is preferable in the evaluation of blunted coronary flow reserve in heart transplant recipients. In our experience, the dipyridamole test is safe, reproducible, and feasible (in up to 95% of trans- planted patients), and it provides good sensitivity in CAV detection and relevant prognostic information when associated to quantitative evaluation of myocar- dial tracer uptake. To refine the capability of detecting perfusion defects by quantitative bull’s eye imaging in this specific patient population, an ongoing study is being carried out at our institution, where correction for normal perfusion has been per- formed utilizing a map obtained from a database of transplanted patients with normal cardiac function, no rejection, and normal coronary angiography, who underwent dipyridamole SPECT imaging 1 year after HTx. This approach may optimize the rest and stress regional cut-off values used for definition of nor- malcy versus perfusion defects. Regional perfusion and coronary flow reserve may be accurately measured in HTx recipients by positron emission tomography in conjunction with flow tracers ( 13 N-ammonia, 15 O-water). The diffuse nature of CAV is a challenge for all cardiac imaging techniques. Absolute measurements of myocardial blood flow and coronary flow reserve may circumvent the limitations of other imag- ing techniques, which explore regional myocardial differences by means of relative tracer distribution. However, the accuracy of positron emission tomography in the detection of CAV has not yet been tested, probably also be- cause this technique is expensive and is not always clinically feasible, and not widely available. Invasive techniques Coronary angiography After recognition of the occurrence and clinical relevance of CAV, annual coro- nary angiography has been utilized to monitor its development and progres- sion. The classification of angiographic abnormalities of the transplanted heart was proposed by Gao et al. in 1988. 12 Three types of coronary lesions were defined: 1 Type A, with discrete, tubular or multiple stenoses, which resembles coro- nary artery disease of the native heart 2 Type B, characteristic of HTx recipients, which is subclassified as B 1 (sharp onset of distal diffuse concentric narrowing and obliteration, with apparently normal or nearly normal proximal segments) or B 2 (progressive, concentric tapering from proximal to distal segments, with some residual flow in the periphery) Evaluation of the transplanted heart 243 BCI19 6/17/05 9:49 PM Page 243 [...]... 199 8;134 :98 0–7 11 Mairesse GH, Marwick TH, Melin JA, et al Use of exercise electrocardiography, technetium -9 9 m-MIBI perfusion tomography, and two-dimensional echocardiography for coronary disease surveillance in a low-prevalence population of heart transplant recipients J Heart Transplant 199 5;14:222 9 12 Gao SZ, Alderman EL, Schroeder JS, et al Accelerated coronary vascular disease in heart transplant patients:... 2000;27:1754 9 5 Vassalli G, Gallino A, Weis M, et al Alloimmunity and non-immunologic risk factors in cardiac allograft vasculopathy Eur Heart J 2003;24:1180–8 6 Spes HC, Klauss V, Mudra H, et al Diagnostic and prognostic value of serial dobutamine stress echocardiography for non-invasive assessment of cardiac allograft vasculopathy: comparison with coronary angiography and intravascular ultrasound Circulation... Contribution of magnetic resonance imaging in the differential diagnosis of cardiac amyloidosis and symmetric hypertrophic cardiomyopathy Am Heart J 199 8;136:824–30 2 Maceira AM, Joshi J, Prasad SK, et al Cardiovascular magnetic resonance in cardiac amyloidosis Circulation 2005;111:186 93 3 Moon JC, Sachdev B, Elkington AG, et al Gadolinium enhanced cardiovascular magnetic resonance in Anderson–Fabry disease:... Circulation 199 9;100:5 09 15 7 Ciliberto GR, Ruffini L, Mangiavacchi M, et al Resting echocardiography and quantitative dipyridamole technetium -9 9 m sestamibi tomography in the identification of cardiac allograft vasculopathy and the prediction of long-term prognosis after heart transplantation Eur Heart J 2001;22 :96 4–71 8 Ciliberto GR, Massa D, Mangiavacchi M, et al High-dose dipyridamole echocardiography test... 9: 49 PM 250 Page 250 Chapter 19 3 Kanno S, Wu YJ, Lee PC, et al Macrophage accumulation associated with rat cardiac allograft rejection detected by magnetic resonance imaging with ultrasmall superparamagnetic iron oxide particles Circulation 2001;104 :93 4–8 4 Aparici CM, Narula J, Puig M, et al Somatostatin receptor scintigraphy predicts impending cardiac allograft rejection before endomyocardial biopsy... coronary artery disease after heart transplantation Eur Heart J 199 3; 14:48–52 9 Ciliberto GR, Parodi O, Cataldo G, et al Prognostic value of contractile response during high-dose dipyridamole echocardiography test in heart transplant recipients J Heart Lung Transplant 2003;22:526–32 10 Fang JC, Rocco T, Jarcho J, et al Non-invasive assessment of transplant-associated arteriosclerosis Am Heart J 199 8;134 :98 0–7... accurately, which is a very useful quantitative indication of early disease T1-weighted spin-echo images can show fatty replacement This may be patchy, and care is needed to prevent over-reading because of the normal presence of epicardial fat Furthermore, intramyocardial fat may be a normal finding in elderly subjects, particularly at the apex of the RV Overall, CMR is an accurate and reliable means... patients: coronary arteriographic findings J Am Coll Cardiol 198 8;12:334–40 13 Rickenbacher PR, Pinto FJ, Lewis NP, et al Prognostic importance of intimal thickness as measured by intracoronary ultrasound after cardiac transplantation Circulation 199 5 ;92 :3445–52 14 Kobashigawa JA, Katznelson S, Laks H, et al Effect of pravastatin on outcomes after cardiac transplantation N Engl J Med 199 5;333:621–7 15... and no cardiac event occurred This case illustrates how careful observation of transplanted patients by imaging techniques in the first 1–2 years after transplantation may help select patients for treatments that appear to slow the progression of established CAV New imaging modalities Magnetic resonance imaging Magnetic resonance perfusion imaging (MRPI) using gadolinium-based contrast agents has recently... predominant pathophysiologic features The best characterized and clinically most prevalent cardiomyopathies are hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) However, there are other less common but clinically important diseases that affect the myocardium These are either associated with a particular cardiac disorder or are part of a generalized systemic disorder The latter are termed . Circulation 2001;104:1184 91 . Evaluation of the transplanted heart 2 49 BCI 19 6/17/05 9: 49 PM Page 2 49 3 Kanno S, Wu YJ, Lee PC, et al. Macrophage accumulation associated with rat cardiac allograft. transplanted heart Oberdan Parodi, Maria Frigerio, and Benedetta De Chiara Introduction Cardiac transplantation is an established treatment for advanced heart failure. Clinical experience and progress. CAV, coronary allograft vasculopathy; CMV, cytomegalovirus. Table 19. 1 Clinical symptoms and signs of acute cardiac allograft rejection. None Malaise, fatigue Fever Tachycardia Supraventricular arrhythmias,