Cardiac amyloidosis. Contribution of imaging to its diagnosis.
JUAN I. COTELLA, LEILA R. ZALAZAR, JAVIER J. HASBANI, VICTOR HASBANI, EDUARDO HASBANI, MARIANO ESTOFAN, MARTIN PEREA, ALDO D. PRADO.
Centro Privado de Cardiología (CPC).
Tucumán, Argentina. E-mail
Recibido 11-JUN-17 – ACEPTADO despues de revisión el 08-JULIO-2018.
There are no conflicts of interest to disclose.
Restrictive pathologies are a group of diseases of low prevalence. Cardiac amyloidosis is considered to be the prototype of the infiltrative form of restrictive cardiomyopathies. Myocardial involvement is frequent, even as the first expression of the disease. Pleural involvement is less frequent; its presence determines worse prognosis than isolated cardiac presentations. The main problem that concerns these pathologies is their late recognition and the consequences that this implies in patient evolution. Actually, cardiac imaging tools can facilitate diagnosis, and faster disease detection. We share an unusual case of amyloidosis with pleural involvement, where the results of echocardiogram and cardiac magnetic resonance images allowed an accurate diagnostic.
The set of pathologies associated to alterations of the restrictive type of diastolic function are infrequent in clinical practice . Amyloidosis is one of the most characteristic prototypes of these entities. Ambiguity in clinical presentation leads to a late and erroneous diagnosis, being done properly in less than 20% of patients .
Imaging studies are indispensable for the initial diagnosis, with echocardiogram being one of the main tools in diagnostic algorithm. The reported case exemplifies a usual scenario of presentation of this disease, showing that if the corresponding clinical suspicion is not generated, there is a low probability of reaching a proper diagnosis.
The case was a 65-year-old, obese, dysplipidemic, hypertensive, asthmatic woman, with history of NYHA class III, with 3-month evolution and approximate loss of weight of 10 kg. During that period, she made multiple medical consultations. In one of them, her electrocardiogram showed QS pattern from V1 through V6, which led to performing an echocardiogram that reported as pathological findings the presence of concentric hypertrophy and mild pericardial effusion. Then, myocardial perfusion study was made, reporting severe ischemia in the anterior and lateral segments. Finally, coronary angiography was made, showing absence of coronary lesions.
Subsequently, she was admitted into our Institution, with clinical diagnosis of decompensated heart failure, with Stevenson B clinical profile. Chest teleradiography was made, which showed bilateral pleural effusion degree II. In the analytic test, anemia was detected in a mild degree (Hb, 11.1 g/dl). Transthoracic echo (Figure 1) showed normal left ventricular diameters with LV ejection fraction of 47%, mild concentric hypertrophy, biatrial enlargement, mild to moderate mitral valve insufficiency, pattern of pseudonormal ventricular filling, e’ of 4 cm/sec, E/e´ ratio of more than 18, moderate tricuspid insufficiency with estimated values of systolic pulmonary artery pressure of 55 mmHg, and mild pericardial effusion. Before these findings, we inferred the presumptive diagnosis of infiltrative restrictive cardiomyopathy. Myocardial strain test with the speckle tracking technique in 3 dimensions showed normal longitudinal strain pattern of the apical segments and marked decrease of basal and middle segments (Figure 2).
Figure 1. Parasternal long axis view (A), short-axis mid-ventricle view (B) and four-chamber view (C) are observed, showing mild hypertrophy, biatrial enlargement and mild pericardial effusion (white arrow).
Figure 2. Diastolic mitral flow with pseudonormal pattern (A). Openly decreased e’ wave at the level of the lateral mitral annulus (B). Global longitudinal strain with normal values at apical level, and decreased in the middle and basal levels (C).
The patient improved clinically with the administration of diuretics and vasodilators. However, the third day of hospitalization, sudden cardiac death occurs, and ventricular tachycardia was recorded by telemetry, with an appropriate response to cardiopulmonary resuscitation maneuvers.
NMR was made (Figure 3) reporting in inversion-recovery (IR) sequences of late enhancement, the impossibility of properly attenuating the left ventricle, due to global affection in it and hypointense signal at intracavitary level, in spite of IR sequence being made 5 minutes after contrast injection. In the Look-Locker sequence, involvement of more than 50% of the left ventricular myocardium was observed. Before the diagnostic suspicion of amyloidosis, pleural puncture was made, revealing exudate with 6 g/dl of proteins, with a high content of lymphocytes, polymorphonuclear leukocytes, abundant atypical mesothelial cells and small number of atypical plasma cells. Bacterial and mycobacterial cultures were negative.
Later abdominal fat aspiration biopsy was performed, being positive for the presence of amyloid in the sample. The patient was referred to the hematology-oncology service, dying after 22 days.
Figura 3. Late enhancement sequence in short axis and four chambers. Impossibility to attenuate properly the myocardium due to global compromise, accompanied by intracavitary hypointensity. Diffuse subendocardial and subepicardial compromise at left ventricular level, as well as in the left myocardium and interatrial septum.
Cardiac amyloidosis was considered a rare disease; however, currently it is suspected that its low prevalence is associated to the failure or delay in its diagnosis . The diagnostic difficulties are multifactorial, particularly due to the heterogeneity of the presentation, the low initial suspicion and the lack of proper diagnostic strategies.
Amyloidosis is a group of diseases, from different etiologies, that present as their common feature, the deposit of amorphous material at extracellular level, affecting the heart, liver and other tissues. Although the clinical and imaging characteristics of the different types of amyloidosis share may points in common, therapeutic strategies and prognosis usually differ from each other.
Between those affecting the myocardial tissue more frequently, there are two types: those associated to the production of light chains (AL) and those associated to transthyretin (ATTR). Knowing the differences between them helps in the early diagnosis, and of course, its individual therapeutic approach.
In USA, there are around 3,000 new cases per year . Its clinical presentation is usually variable, with cardiac affection being the main prognostic determinant. Myocardial compromise usually manifests by heart failure symptoms of heart failure and by the presence of atrial and ventricular arrhythmias. The pathophysiological mechanism by which systolic and diastolic dysfunction is generated, is determined by the direct effect of amyloid deposit, as by the “toxic” effect of protein precursors deposited and circulating . The presence of heart failure by no apparent cause, associated to hepatomegaly and proteinuria should generate the first diagnostic suspicion. Before this situation, an electrophoresis test should be made to quantify the presence of protein chains (kappa and lambda). Tissue biopsy, to confirm the amyloid deposit, constitutes an essential element in diagnosis, that could be obtained by abdominal fat aspiration. Bone marrow puncture allows to establish the specific clonal diagnosis. Endomyocardial biopsy is only necessary in less than 15% of patients; however, its specificity is 100% [6,7].
Imaging tests are clearly very useful; however, do not contribute characteristic data to differentiate the diverse types of diseases. Classical data include normal-sized ventricles with mild hypertrophy, biatrial enlargement, changes in ventricular filling pattern (pseudonormal or restrictive pattern), and the presence of pericardial effusion. Myocardial effusion with longitudinal strain expresses a characteristic pattern very significant for diagnosis, characterized by decreased longitudinal strain values at basal level and in the middle segments, with normal values in apical segments. These findings are usually present even in the absence of ventricular motility disorders, so its usefulness is manifest . All these manifestations were present in our patient.
As to the electrocardiographic evidence, we remind you that in our case, pseudo-infarction imaging was described, and these manifestations are usually only present in less than half of patients .
The presence of pleural effusion, described in our patient, usually appears in less than 6% of patients with myeloma; however, the incidence of pleural infiltration is usually <0.8% [10,11] with a mean survival of 1.5-3 months .
The diagnosis of amyloidosis of the AL type could be made in 95% of cases where the combination of the finding of light chains in plasma and urine is present, through electrophoresis tests of immunofixation, and with fat tissue aspiration. Even so, a previous diagnosis is very significant, and it is in this aspect that imaging methods are determinant, and thus the characteristic echocardiographic findings, including longitudinal strain, or changes observed in magnetic resonance tests, added to the detection of monoclonal protein expression, help in a great deal to make a diagnosis, not requiring bone marrow or endomyocardial puncture.
Annual mortality of patients with amyloidosis and cardiac compromise reach figures of 24% per year, and in such cases where death appears in the first six months, in half of them, sudden cardiac death occurs [13,14]. The degree of cardiac involvement is a prognostic determinant, and in this sense, nuclear magnetic resonance, through the determination of the degree of extracellular compromise, is a very significant prognostic variable .
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