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We hypothesize that T1 mapping contributes to the characterization of cardiac masses based on the spectrum of T1 relaxation times in tissue consisting of fat, calcium, melanin, blood and simple fluid. Given the well-established T1 lowering properties of melanin, T1mapping may assist in the evaluation of cardiac masses in patients with melanoma. Differentiating common cardiac tumors, such as myxomas, from thrombi with T1 mapping would also provide clinical utility, particularly in patients with a contraindication to gadolinium.
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The differential diagnosis for cardiac metastases includes thrombi, as exemplified by Case No.4, vegetations, which are the most common causes of cardiac masses  and primary cardiac tumors such as myxoma.
Pathological evaluation remains the most definite method for differentiating neoplastic from non-neoplastic cardiac masses . While preoperative diagnostic cardiac biopsies are rarely performed, postoperative pathological evaluation following resection of these tumors, are always performed regardless of their nature.
The clinical presentation of patients with an underlying malignant disease was more severe with 27.7% reporting syncope as initial disease presentation and 18.2% presenting with cardiac arrest and under mechanical resuscitation. Of note, one patient developed an obstructive left atrial pleomorphic sarcoma 8 years upon heart transplantation in his cardiac allograft. He died within 2 weeks after the onset of initial symptoms including dyspnea due to cardiac arrest. Our non-Hodgkin patient initially presented with palpitations and arrhythmias, however no structural abnormalities could be detected on echocardiography. Within a period of only two weeks she developed progressive dyspnea, facial edema and facial erythema due to almost completely obstructive masses filling the right atrium and right ventricle (superior vena cava syndrome) .
Diagnosis of cardiac masses is still challenging by echocardiography and distinguishing tumors from thrombi has important therapeutical implications. We sought to determine the diagnostic value of real-time perfusion echocardiography (RTPE) for cardiac masses characterization.
Cardiac masses are still a challenging issue during transthoracic echocardiography and can mainly be classified as tumors, thrombi or pseudotumors. Primary cardiac tumors are rarely found (0.001%) . Histologically, 75% of tumors are benign, while 25% are malignant . Secondary cardiac tumors or metastases are at least 100 times more frequent than primary tumors . Intracardiac thrombi are blood clots that may also be erroneously detected as tumors and occur typically in areas of blood stasis, while pseudotumors are normal variations of cardiac structures, which can be confounded with other forms of cardiac masses. The etiology of a cardiac mass is crucial for therapeutic management, however they still pose a significant challenge in the clinical practice; also, an expeditious determination of cardiac masses nature has important practical implications in the clinical management of patients. The analysis of vascularity of these structures may be important for this purpose, and real-time perfusion echocardiography (RTPE) is an emerging approach that can be used to evaluate vascularity.
RTPE has been demonstrated to be a useful technique for the quantification of myocardial perfusion and determination of myocardial blood flow reserve [4-7]. Case reports and a single center study with a small sample of 16 patients have shown the possibility of evaluating vascularization of cardiac masses aiming to distinguish malignant from benign cardiac tumors, and also tumors from thrombi [8-14].
From July 2004 to October 2008, we prospectively studied 107 patients with cardiac masses detected by transthoracic echocardiography who underwent RTPE and subsequent diagnostic investigation of mass etiology. The study protocol was approved by the Ethical Committee of the University of São Paulo Medical School, and all patients provided written informed consent to participate. Exclusion criteria were pregnancy or breast feeding, intracardiac shunt, refusal or inability to sign the informed consent, severe obstructive pulmonary disease, second or third-degree atrioventricular block and history of allergy to components of the echocardiographic contrast agents. Patients in whom the diagnosis of cardiac mass could not be reached based on results of pathology, clinical data and other imaging technique (magnetic resonance imaging or computed tomography), were also excluded.
Each set of digital images was reviewed by a sole experienced and independent observer (EKU), blinded to other study data. Starting from the first frame after the ultrasound destruction of microbubbles, cardiac masses were qualitatively analyzed during optimal cavity contrast enhancement based on a visual assessment of mass contrast enhancement. This assessment included the presence of perfusion, the velocity of perfusion replenishment after flash impulse, and the pattern of perfusion in the mass. A scoring system was established by considering the following parameters:
Diagnostic determination of cardiac masses was performed by anatomical pathology in patients who underwent surgery or, in those who died, by autopsy . The diagnosis of rhabdomyomas was confirmed by other cardiovascular imaging modality (magnetic resonance imaging or computed tomography), clinical association with tuberous sclerosis and serial echocardiographic demonstration of mass regression. The diagnosis of lipoma was performed by biopsy or magnetic resonance imaging with fat saturation approach. The diagnosis of cardiac thrombi was performed based on history and clinical presentation, including atrial flutter, atrial fibrillation, atrial dilatation, valvar stenoses and areas of left ventricular akinesia or diskinesia, associated with serial echocardiography findings of thrombus resolution after anticoagulation. Pseudotumor was defined as an anatomical variation or other cardiac abnormality (megaesophagus, endomyocardialfibrosis, abscess) not characterized as a cardiac tumor .
The diagnosis of cardiac masses is challenging, given the specific characteristics of the disease and the peculiar images that they nearly always generate. Thanks to the advances in cardiovascular imaging modalities in the last 50 years, there has been a noticeable improvement in the knowledge about the prevalence and natural history of cardiac masses. Among these methods, echocardiography has been demonstrated extremely useful for evaluating patients with suspected cardiac masses. Nevertheless, the great limitation of this method resides in its inability to distinguish between thrombi and malignant or benign tumors. The fundamental histologic difference between thrombi and tumors is the intense vascularity of the latter, the thrombi being avascularized or with rare canaliculi inside them. Benign tumors have scarce vascularity, while malignant tumors have abundant neovascularization.
Of note, although there are previous studies demonstrating the value of contrast echocardiography in patients with cardiac masses [8-12,28], this is the first time in the literature that dipyridamole stress RTPE was used in a high number of patients for evaluating cardiac masses and we demonstrated it to be a safe method. Dipyridamole stress significantly contributed for differentiating malignant from benign cardiac tumors. There was an increase in the value of microvascular blood volume (A) in the group with malignant tumors as compared with that of benign tumors. Cardiac tumors presenting a value A > 3.28 dB in dipyridamole stress RTPE had 5.8-times higher chance of being a malignant rather than a benign tumor. It is well known that malignant tumors have intense neovascularization, vessels with thin, tortuous walls with greater variability in diameter. However, until now there was no study in the literature using dipyridamole in patients with cardiac tumors with the purpose of evaluating tumoral perfusion vascular reactivity. Hence, we believe that these data may serve as the initial trigger for future investigation with new quantification techniques as parametric imaging in order to better define tumoral characteristics.
Although one potential limitation of the present study is the great variability in etiology of tumors, the distribution among groups was a proportionate one (28% benign cardiac masses, 38% thrombi, and 27% malignant tumors). Not all patients underwent dipyridamole infusion because of refusal to undergo stress or clinical contraindication to exam. Therefore, one could argue that this analysis was incomplete. We would like to note that the total number of patients evaluated by dipyridamole stress RTPE was still reasonable (32) considering the specific patient population studied and the criteria for inclusion in the study. One possible limitation is heterogeneity in quantification data because of the use of different contrast agents (PESDA and Definity). However, we have recently published studies of myocardial perfusion quantification showing the diagnostic and prognostic value of RTPE using both contrast agents in different patient population [17,25]. Another limitation is the high intraobserver variability found in our study. This probably expresses the difficulty of analyzing perfusion in cardiac tumors due to their amorphous, heterogeneous structure and calls for the development of a more observer independent tool for its analysis. Finally, in some cases thrombi or tumors could have been diagnosed with very high degree of probability based solely on their features in standard echocardiography. In these cases perfusion contrast echocardiography did not add value over clinical and two-dimensional echocardiography. 041b061a72