Percutaneous Endomyocardial Biopsy Research Articles

Endomyocardial Biopsy: short- and long-term safety in myocarditis patients.

To assess the short-term and long-term outcomes of percutaneous endomyocardial biopsy (EMB) in patients with myocarditis and to identify the risk factors for EMB-related complications in this patient population. A retrospective analysis was conducted on 294 hospitalized patients with clinically suspected myocarditis at Tongji Hospital from October 2019 to October 2023, with a median follow-up duration of 18 months. Patients were divided into an EMB group (n = 151) and a non-EMB group (n = 143) based on whether they underwent EMB procedure. The incidence of endpoints was compared between the two groups, and the Kaplan-Meier survival curve was used to assess the survival rate without endpoints. Endpoints included major adverse cardiovascular events (MACE), ventricular enlargement, and decline in cardiac function. Multivariate logistic regression analysis was employed to evaluate the risk factors for EMB-related complications. The incidence of major short-term complications following EMB was 2.0% (3/151), while the incidence of minor complications was 9.3% (14/151). Multivariate risk regression analysis revealed that operative duration (OR: 1.101, 95% CI: 1.02-1.079, p < 0.05) and BNP levels (OR: 1.083, 95% CI: 0.931-1.26, p < 0.05) were associated with short-term complications following EMB. Compared to the non-EMB group, the EMB group had no significant increase in hospital stay (10 [8, 15] vs. 9 [7, 16], p = 0.27) and no significant decline in cardiac function. Long-term follow-up results showed that 8 patients (5.3%) in the EMB group experienced MACE, 14 patients (9.3%) had left ventricular enlargement, and 18 patients (11.9%) had a decline in left ventricular ejection fraction (LVEF) after discharge; in the non-EMB group, 12 patients (8.4%) experienced MACE, 30 patients (19.9%) had left ventricular enlargement, and 18 patients (11.9%) had a decline in LVEF after discharge. The Kaplan-Meier curve revealed a lower incidence of endpoint events in the EMB group (p < 0.05). In patients with myocarditis, EMB is associated with a risk of short-term complications, with higher levels of BNP and operative duration being independent risk factors for EMB-related complications. However, EMB does not adversely affect cardiac function or hospital stay during the inpatient period and may contribute to the improvement of long-term outcomes in patients with myocarditis.

Histopathological Characteristics of Percutaneous Endomyocardial Biopsy in Heart Transplant Rejection Surveillance: A Single Center Experience.

Heart transplantation (HT) remains the ultimate treatment for end-stage heart failure. An endomyocardial biopsy (EMB) is "the gold standard" diagnostic procedure used in HT rejection surveillance. The aim of this study is to provide a detailed analysis of the histopathological characteristics of the EMB and to investigate if there is a correlation between some histopathological changes, such as fibrosis, vasculitis, Quilty effect (Q.E.), myocytes damage, and the presence of episodes of acute rejection. In this retrospective study, 200 EMBs were included, coming from 65 patients transplanted in the Emergency Institute for Cardiovascular Diseases and Transplantation (ICvDT) Targu Mures between 2012 and 2024. Fibrosis, vasculitis, Q.E., myocyte damage, etc., were microscopically evaluated to see if these parameters correlate with rejection episodes. The mean age was 38.18 years (SD 15.67), 25% of biopsies being recorded in the 41-50 age group. 77.14% of total acute cellular rejection (ACR) was of mild rejection, with most registered in the 11-20 age group; the cases of severe rejection being recorded in the 41-50 age group. Antibody-mediated rejection (AMR) was recorded more frequently in women with a representation of 23.4%, compared to 8.5% of men. 86.7% (39 cases) of the total number of EMBs with fibrosis score 3 and 71.4% (15 cases) of the total EMBs with fibrosis score 2 were recorded in men, compared to the 28.6% (6 cases) of fibrosis score 2 recorded in women (p = 0.013). 50.0% of all the EMB recorded in the 61-70 age group showed fibrosis score 3, compared to 34.8% of those from the 21-30 age group. The Q.E. was identified in 13% of the biopsies and, in some patients, it was observed across 3-4 successive biopsies. Mild vasculitis was associated in 34.9% of cases with ISHLT ≥ 1R and moderate vasculitis was associated in 87.5% of cases with ISHLT ≥ 1R. Fibrosis was detected much more frequently in men and in the 61-70 age group. In addition to the histopathological changes specific to acute rejection, there are other pathological changes, such as the Q.E., and vasculitis and myocytes damage and disarray, that seem to suggest a close connection with rejection, but extensive studies are needed to confirm this.

Anything But a Biopsy: The Quest for Noninvasive Alternatives in Heart Transplantation.

Anything But a Biopsy: The Quest for Noninvasive Alternatives in Heart Transplantation.

73 WHICH IS THE CULPRIT OF THIS MYOCARDIAL INFILTRATION?

Abstract Introduction Myocardial infiltration by primary cardiac neoplasm is a rare condition and the pathological spectrum includes more widespread benign cell types, providing exceptional diagnostic and therapeutic challenges. Refractory heart failure, pericardial effusion and arrhythmias due to infiltrative mass are the most common clinical manifestations. Multimodality imaging, with echocardiography, computed tomography and magnetic resonance imaging, is essential to determine the characteristics of a cardiac tumor. Clinical case: A 35-year-old man without cardiovascular risk factors presented with two months of shortness of breath and weight loss. A previous history of acute myeloid leukemia undergoing allogenic bone marrow transplant was reported. Transthoracic echocardiography revealed an apical thrombus in left ventricle with inferior and septal hypokinesia conditioning mildly reduced ejection fraction, circumferential pericardial effusion without cardiac tamponade and abnormal right ventricular thickening (Figure 1). The cardiac magnetic resonance imaging confirmed diffuse thickening of the right ventricular free wall (maximum diameter 30 mm), suspected for myocardial infiltration, extending to the right atrium and left ventricle with an ischemic pattern of the inferior wall (Figure 2). No coronary artery disease was found by coronary angiography, but the right coronary artery was incorporated by the pathological tissue in chest computed tomography scan. Cardiac positron emission tomography demonstrated the presence of neoplastic tissue with increased metabolic activity, whose similar characteristics were also evident in the ascending aorta and aortic arch. Being the percutaneous endomyocardial biopsy inconclusive, a pericardiectomy was performed through a median sternotomy incision, showing widespread cardiac neoplastic infiltration. Histopathological analysis, done on samples taken by surgical myocardial biopsy, revealed tissue involvement by a rare and aggressive cardiac anaplastic large T-cell non-Hodgkin lymphoma (ALK -, Ki-67 90%). Few days after surgery, the patient developed a refractory cardiogenic shock and unluckily died before establishing an adequate therapy. Conclusion Primary cardiac lymphoma is very infrequent and the non-specificity of the symptoms makes the diagnosis extremely challenging and often limited to autopsy findings. Our case highlights the importance of an appropriate diagnostic algorithm that can allow an early diagnosis and an adequate therapy of this otherwise fatal pathology. In this condition surgical removal of the tumor in not indicated, being chemotherapy the only effective treatment. However, because of rarity, data are lacking to produce definitive regarding guidelines.

Standard Operation Procedure of Percutaneous Endomyocardial Biopsy in Peking Union Medical College Hospital

Abstract Percutaneous endomyocardial biopsy (EMB) is a technique that biopsy samples are obtained using bioptome through peripheral blood vessel. This technique has been used and refined more than 50 years in clinical application. Now EMB has become an important diagnostic tool in the diagnosis of myocarditis and cardiomyopathy. Department of cardiology, Peking Union Medical College Hospital (PUMCH) has performed more than 500 cases of EMB and accumulated abundant practical experience. The clinical practice guideline of percutaneous EMB in PUMCH was also established, including indications, contradictions, operation key points, sample handling and processing, post-procedure monitoring, and treatment strategy for potential complications, etc. Due to the limitation of EMB, cardiologists should collaborate with experts in echocardiography, cardiac magnetic resonance and cardiac pathology to avoid missed diagnosis and misdiagnosis. Cardiologists should pay more attention to the value of EMB and actively perform EMB to improve the diagnosis level for myocarditis and cardiomyopathy in China.

Standard operation procedure of percutaneous endomyocardial biopsy in Peking Union Medical College Hospital

Percutaneous endomyocardial biopsy (EMB) is a technique that biopsy samples are obtained using the bioptome through a peripheral blood vessel. The technique has been used and refined for more than 50 years in clinical application. Now EMB has become an important tool of the diagnosis of myocarditis and cardiomyopathy. The department of cardiology of Peking Union Medical College Hospital (PUMCH) has performed more than 500 cases of EMB and accumulated abundant practical experience. The clinical practice guideline of percutaneous EMB was also established in PUMCH, including indications, contradictions, key points of the operation, sample handling and processing, post-procedure monitoring, and the treatment strategy for potential complications, etc. Due to the limitation of EMB, cardiologists should collaborate with experts on echocardiography, cardiac magnetic resonance and cardiac pathology to decrease the probability of missed diagnosis and misdiagnosis. Cardiologists should pay much attention to the value of EMB and actively perform EMB to improve the diagnosis level of myocarditis and cardiomyopathy in China.

Role of endomyocardial biopsy guided by electroanatomic voltage mapping for the diagnosis of cardiomyopathies in patients with arrhythmic presentation

Abstract Background A myocardial substrate assessment through percutaneous endomyocardial biopsy (EMB) represents an important additional diagnostic test for cardiomyopathies when uncertainties remain after non-invasive evaluation. Yet, extensive application of EMB has been limited by the low sensitivity of biopsies. Electroanatomic voltage mapping (EVM) is a promising modality for guiding Endomyocardial biopsies (EMB). Aim The aim of our study is to evaluate the diagnostic yield of EVM-guided EMB and the role of histological analysis in the diagnosis of patients with suspected cardiomyopathies and arrhythmic presentation. Methods One-hundred and sixty-two consecutive patients undergoing EMB at our Institution from 2010 to 2019 were included. Demographics, clinical data, CMR data and peri-procedural complications were retrospectively retrieved. All procedures were guided by endo-cavitary EVM. According to non-invasive data collected before proceeding with EMB a suspected clinical diagnosis was expressed and compared to histological diagnosis Results One-hundred and sixty-two patients were included in the study. Mean age of the cohort resulted 40.9±14.7 years, with 26.5% of the included patients being females. ECG alterations were present in 51.3% of the population, with the most common abnormality being T wave inversion. Sustained or non-sustained ventricular tachycardia was registered in 51 (31.5%) of the patients, while 44 (27.2%) patients were referred for frequent isolated premature ventricular complex (PVC), and 19 (11.7%) after an episode of an arrhythmogenic syncope or resuscitated cardiac arrest. Suspected ARVC (41.6%) together with acute/chronic myocarditis (28.0%) were the main clinical diagnosis leading to an invasive approach. The sampling site was the right ventricle in 116 (72.5%), the left ventricle in 31 (19.4%), and both ventricles in 13 (8.1%) patients. Biopsy samplings were judged appropriate for histological analysis in 141 (87.0%) patients. Among the analyzed samples, a diagnosis was reached in 120 patients (74.1%). In the remaining 21 cases (25.9%), the analysis yielded nonspecific histologic findings, inconclusive results, or sampling error. The biopsy allowed to confirm the clinical diagnosis in 72 (60.0%) patients, while a different diagnosis was reached in 48 (39.0%) cases (Reclassification are showed Figure 1).In particular of 67 (41.6%) patients suspected for ARVC, only 32 (22.7) reached a confirmation. Conversely, the number of patients with acute/chronic myocarditis augmented from 45 (28.0%) to 47 (33.3%). Conclusion EMB guided by EVM reached a diagnostic yield as high as 74.1%. EMB proved to be a useful tool in the clinical management of patients, as it allowed to correctly reclassify a significant number of patients who would have been misdiagnosed based only on non-invasive assessment. Sankey Diagram Funding Acknowledgement Type of funding source: None

P5560Assessing etiology in a cohort of patients with myocarditis presenting with complex ventricular arrhythmias: can the percutaneous endomyocardial biopsy help?

Abstract Background Myocarditis represents a common but often under-diagnosed disease, with a wide range of clinical presentations; diagnosis is often presumptive and a clear etiology leading to a specific therapeutic approach is usually not identified. Purpose To describe and assess disease etiology in a cohort of myocarditis patients (pts) with arrhythmic presentation undergoing an invasive diagnostic work-up. Methods All pts with myocarditis presenting with ventricular arrhythmias undergoing an electro-anatomical mapping (EAM) guided endo-myocardial biopsy (EMB) at our institution were enrolled. All enrolled pts also underwent cardiac magnetic resonance imaging (MRI) and an electrophysiological study (EPS). Demographics, arrhythmic presentation, MRI data, arrhythmic inducibility at EPS, EAM and EMB biopsy data were retrieved and analyzed. Molecular biology testing for cardio-tropic virus genome as well as leukocyte immunohistochemical typization were routinely performed on all EMB samples. Results Twenty-six pts were enrolled (85% male, 39±6 y.o.). Clinical presentation was an organized ventricular arrhythmia in 16 (62%) pts (n=3 non-sustained ventricular arrhythmia; n=9 sustained ventricular arrhythmia; n=4 ventricular fibrillation) while frequent (&gt;10.000) premature ventricular complexes (PVCs) in the remaining 10 (38%) pts. MRI showed a late gadolinium enhancement (LGE) pattern consistent with myocarditis in all pts (35% left LGE; 65% right LGE). At the EPS, 10 (38%) pts showed inducibility for SVTs and underwent an intra-cardiac defibrillator (ICD) implant, while 4 (16%) more were implanted for secondary arrhythmic prevention. EAM was performed in 18 (70%), 6 (22%) and 2 (8%) pts in the right, left and in both ventricle respectively; in all cases, abnormal myocardial voltages were retrieved in the area showing LGE at MRI. Extensive myocardial scarring was detected in 7 (27%) pts. All EMB were performed without peri-procedural complications; inflammatory infiltrate and substrate alteration consistent with myocarditis were retrieved in 100% of the bioptic samples. Viral genome was identified in 13 (50%) samples (n=5 Human Herpes Virus 6; n=2 Parvovirus B 19; n=3 Adenovirus; n=1 Ebstein Barr Virus; n=1 Cytomegalovirus; n=1 Rhinovirus) and specific human immunoglobulin treatment was undergone by a single pt; eosinophilic infiltration was found in 2 (8%) patients; lymphocite invasion and auto-antibodies consistent with auto-immune myocarditis were detected in 2 (8%) patients and appropriate immunosuppressive therapy was started, while a myocardial band contraction pattern typical of toxic myocarditis was found in a single (4%) patient [Figure 1]. Different Myocarditis Etiology Rates Conclusion In our myocarditis cohort, EMB confirmed viruses to represented the first myocarditis etiological agent. Despite an invasive work-out, 31% of the cohort etiology still remains unclear.

P4652Magnetic resonance and electroanatomical guided endomyocardial biopsy as a diagnostic tool in the clinician's box: a 5 year experience

Abstract Background Percutaneous endo-myocardial biopsy (EMB) is an invasive diagnostic test used to reach or confirm a diagnosis when structural or substrate anomalies are suspected, such as in cardiomyopathies or myocarditis evaluation. In recent years, cardiac magnetic resonance imaging (MRI) and endo-cavitary electro-anatomical mapping (EAM) have been used to localize the most significant myocardial area to sample, therefore increasing EMB overall effectiveness and reliability. Purpose To describe and characterize safety, feasibility and anatomical findings of a large cohort of patients (pts) undergoing diagnostic EMB and to assess its impact on the treatment decision making algorithm. Methods A cohort of all pts undergoing a percutaneous EMB at our Institution from January 2014 to January 2019 was analyzed. All EMB procedures were guided by a pre-procedural cardiac MRI radiological alteration analysis and an endo-cavitary EAM. Intra-cardiac echography (ICE) was used in all procedures, to directly visualize the sample area and to evaluate in real time post-EBM complications. Demographics, clinical data, MRI data, pathological EMB features, and peri-procedural data were systematically retrieved. Results One-hundred and eleven pts were enrolled (78% male, 47±4 y.o., 33% athletes). EMB indication was abnormal MRI findings in 94 (85%), pathological EMB voltages in 10 (9%) and clinical suspect and patient history in 7 (6%) pts. EMB sample area was determined by both MRI and EAM pathological area analysis in 92 (83%) pts, while by EAM alone in 19 (17%) pts (n=6 pathological unipolar EAM; n=13 bipolar and unipolar pathological EAM). The sample site was the right ventricle in 89 (80%), the left ventricle in 20 (18%), and both in 3 (2%) pts. In 103 (93%) pts a concomitant electrophysiological induction study was performed (40% positive for sustained ventricular arrhythmias) and 35 (32%) pts underwent a trans-catheter ablation (TCA) (n=8 epicardial TCA; n=2 endo-epicardial TCA; n=25 endocardial ATC). Only 2 (2%) peri-procedural adverse events were witnessed, specifically femoral pseudo-aneurysms, requiring surgical repair. EMB analysis allowed to confirm 58 (52%) pre-procedural diagnosis and to reach 32 (29%) new diagnosis, while resulting inconclusive or non-specific in the diagnostic process only in 21 (19%) cases [Figure1]. A total of 33 (30%) intra-cardiac devices (ICDs) were implanted contextually in the cohort, of which 9 (8%) solely upon EMB indication; in 4 (4%) other patients, biopsy represented a strong decisional factor in the multi-modality decision process for abstaining from ICD implant. Dashed lines: diagnosis changed upon EMB Conclusion MRI and EAM guided EMBs allowed to finely define a large cohort of patients by representing a disease defining parameter in over 80% of the enrolled pts while and a decision shifting parameter in ICD implant algorithm in a high % of pts.

Cardiosphere-Derived Cells Require Endoglin for Paracrine-Mediated Angiogenesis.

SummaryClinical trials of stem cell therapy to treat ischemic heart disease primarily use heterogeneous stem cell populations. Small benefits occur via paracrine mechanisms that include stimulating angiogenesis, and increased understanding of these mechanisms would help to improve patient outcomes. Cardiosphere-derived-cells (CDCs) are an example of these heterogeneous stem cell populations, cultured from cardiac tissue. CDCs express endoglin, a co-receptor that binds specific transforming growth factor β (TGFβ) family ligands, including bone morphogenetic protein 9 (BMP9). In endothelial cells endoglin regulates angiogenic responses, and we therefore hypothesized that endoglin is required to promote the paracrine pro-angiogenic properties of CDCs. Cre/LoxP technology was used to genetically manipulate endoglin expression in CDCs, and we found that the pro-angiogenic properties of the CDC secretome are endoglin dependent both in vitro and in vivo. Importantly, BMP9 pre-treatment of endoglin-depleted CDCs restores their pro-angiogenic paracrine properties. As BMP9 signaling is normally required to maintain endoglin expression, we propose that media containing BMP9 could be critical for therapeutic CDC preparation.

EComment. Primary cardiac malignancy

An interesting case report is presented by Liu et al [1]. A 41-year old immunocompetent female patient underwent a surgical excision of a primary cardiac B-cell lymphoma (74 mm x 49 mm) from the right atrium. Only 25% of primary cardiac tumours are malignant, and sarcomas represent more than two-thirds of these malignancies. Primary cardiac lymphoma (PCL) is the second most common malignancy affecting the heart. Thus, PCL is a very rare entity and is classified as primary lymphomas inside the heart chamber, primary lymphomas developing in the epicardial space and primary large cell lymphomas involving the pericardium. PCL is defined by the absence of lymphoma outside the pericardium after a complete clinical and radiological examination and by the confinement of the bulk of the tumour to the pericardial sac. Cardiac metastases of extra-cardiac lymphomas are far more common than PCL. This case report has an interesting feature that could be of use to all of us when faced with a symptomatic right a trial tumour in a young patient. Cardiac surgeons should be highly suspicious of primary cardiac malignancy when the signs are suggestive. Right-sided cardiac tumours are usually malignant and appear as infiltrative, bulky and fast- growing masses that develop in an outward fashion. They do not present with congestive heart failure until the later stages of disease progression. The diagnostic algorithm of choice when suspecting a primary cardiac malignancy is to perform after transthoracic echocardiography, cardiac computed tomography and cardiac magnetic resonance imaging [2]. Cardiovascular magnetic resonance can recognize, with high specificity, non-surgical cardiac masses: pseudo-tumours, lipomas, thrombi, and lipomatous hypertrophy. Most other cardiac tumours will necessitate tissue sample diagnosis to help in the establishment of a treatment plan. Should the use of multiple imaging techniques fail to identify the cardiac mass at the outset, a biopsy (percutaneous endomyocardial biopsy or a biopsy by thoracotomy) is best obtained if it can be done safely [3]. This will not only diagnose the tumour but will exclude benign masses and other malignant tumours, such as lymphoma, that are best treated non-surgically. Treatment of PCL is usually bimodal [4] with aggressive systemic chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) as well as radiation therapy. Conflict of Interest: None declared

Mid-ventricular obstruction occurred in hypertrophic left ventricle of heterozygous Fabry's disease—Favorable effects of cibenzoline: A case report

A 54-year-old woman visited our hospital because of palpitation and dizziness. Systolic ejection murmur, Levine IV/VI, was heard at the left sternal border and atrial gallop was auscultated at apex. Echocardiogram demonstrated diffuse hypertrophy of the left ventricular walls extending to the apex. The left ventricular walls increased symmetrically; the septal and the posterior wall measured approximately 26mm and 30mm in thickness, respectively. Apical two-chamber views revealed a narrow outflow of the left ventricular cavity at apex with a distinct convergence zone, where color flow Doppler imaging showed turbulent jet flow from mid to late systole. The leukocyte α-galactosidase A activity was lower than normal. Percutaneous endomyocardial biopsy showed specific change for Fabry's disease by electron microscopy. On cardiac catheterization, mid-ventricular resting pressure gradient of approximately 90mmHg was shown. This pressure gradient dramatically disappeared after intravenous administration of 70mg of cibenzoline. We describe a rare case of Fabry's disease that revealed diffuse hypertrophy having dynamic obstruction at mid-left ventricle, like mid-ventricular obstruction, and the administration of cibenzoline had beneficial effects on pressure gradient of mid-left ventricle.

Primary Cardiac Extranodal B-Cell Lymphoma Mimicking Right Atrial Thrombus

A 60-year-old woman who underwent permanent pacemaker implantation presented with superior vena cava syndrome a few months later. Transthoracic echocardiography (Fig 1, arrow) demonstrated a large mass in the right atrium (3.99 cm × 6.33 cm). The positron emission tomography scan (Fig 2A) showed a hypermetabolic thrombus involving the superior vena cava and the right atrium. We performed a lateral thoracotomy after we failed to complete an endovascular biopsy. Histopathologic examination revealed a proliferation of large lymphoid cells intermingled with small regular lymphocytes of a diffuse large B-cell lymphoma (Fig 2B, hematoxylin and eosin, ×200).

Bioptome injury to the tricuspid valve in a cardiac allograft recipient visualized by three-dimensional echocardiography

Tricuspid regurgitation (TR) is the most commonly seen valvular pathology after orthotopic heart transplantation (OHT). The reported incidence ranges from 47 to 98%, depending on the definition of significant regurgitation and the surgical method. Multiple aetiologies are implicated in the development of TR after OHT; percutaneous transvenous endomyocardial biopsy (EMB), performed to detect rejection, is the most important contributor to significant …

Long-term disease-free survival of patients with primary cardiac lymphoma treated with systemic chemotherapy and radiotherapy

Primary cardiac lymphoma (PCL) is a rare disease entity with only a few reported cases in Korea. In this paper, we report a case of PCL in a 59-year-old man presenting with chest pain. Diffuse large B-cell lymphoma was diagnosed through a cardiac catheterization-assisted percutaneous endomyocardial biopsy, and there was no evidence of extracardiac involvement of the lymphoma.The patient had a complete clinical response after systemic chemotherapy with a rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen and additional post-chemotherapeutic radiation therapy. The patient experienced a long-term disease-free survival of over 4 years. However, he received coronary artery bypass graft surgery due to an acute myocardial infarction that occurred 3 years after the completion of the radiation therapy. Although the addition of radiation therapy to the treatment is thought to decrease the risk of relapse in patients with PCL, a careful and thorough consideration of the potential complications of radiation therapy, particularly with respect to cardiac complications, should be considered.

Human Cardiac Stem Cells

The view of the heart as a static organ implies that myocyte death and formation play a negligible role in cardiac homeostasis. Although stem cells have been unexpectedly identified in several organs, including the brain, kidney, lung, and skeletal muscle, the search for a cardiac stem cell (CSC) has been perceived as a futile effort, given the acknowledged lack of regenerative potential of the myocardium. Nevertheless, in the past several years, the demonstration of myocyte renewal in the normal and diseased heart has revealed a new, dynamic, and lively picture of this organ. Components of the cell cycle machinery and markers of cell replication have been detected in cardiomyocytes. The demonstration that karyokinesis and cytokinesis involve cells expressing contractile proteins has provided evidence that cardiomyocyte division occurs in the adult heart.1 More recently, pulse-chase assays with thymidine analogs,2 lineage tracing protocols,3 and 14C birth dating of cells4 have shown the existence of myocyte turnover, a process that has been found to differ in magnitude according to the methods used for its documentation and quantification. Article see p 2559 Over the years, the heart has provided us with the evidence that solves the critical problem of the origin of cardiomyocytes. At this moment in time, paraphrasing Eugenio Montale, we could say that the human heart is “on the verge of betraying [its] final secret offering the opportunity to uncover…the still point of the world, the link that won't hold, the thread to untangle that will finally lead to the heart of a truth.”5 Newly generated myocytes may derive from division of preexisting parenchymal cells or from activation and differentiation of resident CSCs. Discriminating between these two possibilities is not an easy task. Fate-mapping strategies, which are commonly used to track the origin of cells and …

Extensive Primary Cardiac Lymphoma Diagnosed by Percutaneous Endomyocardial Biopsy

Primary cardiac lymphoma (PCL) is an extranodal non-Hodgkin's lymphoma exclusively located in the heart and/or pericardium. It is rare in immunocompetent patients and represents 1.3% of primary cardiac tumors and 0.5% of extranodal lymphomas. The clinical behavior is aggressive and the early symptoms are cardiac failure, syncope, arrhythmia, or pericardial effusion. Although echocardiography, computed tomography (CT) scan, magnetic resonance image (MRI) are the mainly used imaging techniques to detect cardiac tumors, pathologic examination is always required to confirm the diagnosis. Diagnosis of PCL is difficult due to non-specific clinical manifestations and requires invasive approach to get histopathologic evidence. While surgery with systemic chemotherapy or in combination with irradiation has been attempted, the only effective treatment is chemotherapy. However, the prognosis remains poor. We report on a 42-year-old woman who is diagnosed histopathologically as PCL by cardiac catheterization assisted percutaneous endomyocardial biopsy and treated successfully by anthracycline based chemotherapy.

Imaging of Cardiotoxicity

A driamycin (ADR; doxorubicin HCl), is a potent anthracycline chemotherapeutic agent that is effective against a wide range of human malignancies, such as leukemias, lymphomas, and many solid tumors. For many malignancies (eg, breast cancer, lymphoma), it is the most effective single agent. The use of ADR has been limited, however, by the development of a dose-dependent cardiomyopathy induced by this antineoplastic agent. The overall incidence of clinical cardiotoxicity for patients treated with ADR is approximately 2%, with the incidence of congestive heart failure increasing to 10% at 500 mg/m and to over 40% at 700 mg/m. The cardiac-specific injury of ADR is usually irreversible, although aggressive support for a low cardiac output may reverse the dysfunction in some patients. Nevertheless, once ADR-induced heart failure has been diagnosed, the prognosis is poor; mortality varies from 30 to 60%. It is also noteworthy that various other commonly used antineoplastic agents, cyclophosphamide, 5-fluorouracil, paclitaxel, streptozotocin, bevacizumab (Avastin), etoposide, bleomycin, tamoxifen, and trastuzumab (Herceptin), as well as radiation therapy, which is commonly used as an adjuvant to lumpectomy, are also cardiotoxic, although different mechanisms may be involved. Therefore, the development of sensitive methods for early detection of drugor radiation-induced cardiotoxicity in individual patients could greatly facilitate the management of a wide range of neoplastic diseases. Development of ADR-induced cardiomyopathy is dose dependent and cumulative. To reduce the incidence of cardiotoxicity, limiting treatment with this agent to a total lifetime dose of ADR of 550 mg/m is recommended. However, the individual response to ADR is highly variable, and bolus administration of up to 900 mg/m has been reported without evidence of heart failure; up to 1,500 mg/m has been administered by continuous infusion without evidence of cardiotoxicity. In some patients, drug resistance, rather than toxicity, is dose limiting; in other instances, restriction of ADR therapy to the recommended guidelines may lead to the premature discontinuation of treatment in patients who might otherwise benefit from higher doses. Conversely, some patients may be highly sensitive to ADR, experiencing toxicity at doses that are lower than the recommended limit. Patients with cardiac disorders or with previous radiation therapy to the mediastinum are generally excluded from ADR treatment protocols. It has also been reported that in some pediatric cases, for which treatment with ADR was well within the recommended limit, congestive heart failure developed several years after treatment. Consequently, the availability of a sensitive, noninvasive method for assessing the early onset of ADR cardiomyopathy in the individual patient would have a significant clinical impact. At the present time, there does not appear to be any effective method for predicting which patients will develop ADR-induced heart failure or for sensitively detecting its onset at a very early stage, when administration can effectively be discontinued or useful treatment for cardiomyopathy can be initiated. Current methods of assessing cardiotoxicity are limited to measurement of cardiac function by radionuclide ventriculography (RNV), echocardiography, and detection of tissue damage by percutaneous endomyocardial biopsy. RNV is not particularly sensitive for detecting early damage as assessed by endomyocardial biopsy scores. In combination with exercise, RNV sensitivity improves, but at the expense of specificity. Artifactual errors of 5% or more in ejection fraction measurements are common. Therefore, it has been recommended that a combination of RNV or echocardiography and biopsy examinations be employed in the From the Department of Radiology, University of Pennsylvania, Philadelphia, PA; Department of Radiology, University of Florida, Miami, FL; and Division of Cardiovascular Disease, Department of Medicine, University of Alabama in Birmingham, Birmingham, AL.

Regenerative Potential of Cardiosphere-Derived Cells Expanded From Percutaneous Endomyocardial Biopsy Specimens

Ex vivo expansion of resident cardiac stem cells, followed by delivery to the heart, may favor regeneration and functional improvement. Percutaneous endomyocardial biopsy specimens grown in primary culture developed multicellular clusters known as cardiospheres, which were plated to yield cardiosphere-derived cells (CDCs). CDCs from human biopsy specimens and from comparable porcine samples were examined in vitro for biophysical and cytochemical evidence of cardiogenic differentiation. In addition, human CDCs were injected into the border zone of acute myocardial infarcts in immunodeficient mice. Biopsy specimens from 69 of 70 patients yielded cardiosphere-forming cells. Cardiospheres and CDCs expressed antigenic characteristics of stem cells at each stage of processing, as well as proteins vital for cardiac contractile and electrical function. Human and porcine CDCs cocultured with neonatal rat ventricular myocytes exhibited biophysical signatures characteristic of myocytes, including calcium transients synchronous with those of neighboring myocytes. Human CDCs injected into the border zone of myocardial infarcts engrafted and migrated into the infarct zone. After 20 days, the percentage of viable myocardium within the infarct zone was greater in the CDC-treated group than in the fibroblast-treated control group; likewise, left ventricular ejection fraction was higher in the CDC-treated group. A method is presented for the isolation of adult human stem cells from endomyocardial biopsy specimens. CDCs are cardiogenic in vitro; they promote cardiac regeneration and improve heart function in a mouse infarct model, which provides motivation for further development for therapeutic applications in patients.

A new method for isolation of cardiac myocytes by percutaneous endomyocardial biopsy.

The objective of this study was to demonstrate the feasibility of isolating viable canine cardiac myocytes from percutaneous right ventricular endomyocardial biopsy specimens. Although histologic data can be obtained from percutaneous endomyocardial biopsies, this approach has not been used as a source of viable cells for evaluating pathological conditions. Study of isolated viable myocytes may provide insight into the electrical, biochemical, and physiologic functions of the heart. Using a standard 8F sheath, a 5F bioptome was introduced via the right femoral vein and advanced to the right ventricle, where 85 biopsies were obtained from 8 mongrel dogs. An average of six biopsy specimens were pooled for processing to provide adequate tissue substrate. This resulted in 14 groups of specimens which were then processed to isolate individual myocytes. Viable myocytes were striated, rod-shaped, and excluded trypan blue dye. Nonviable myocytes were rounded, had no cross-striations, and did stain with trypan blue. Partially-injured myocytes contracted spontaneously and had a region of loss of cross-striations. The average number of viable cells recovered per group of pooled specimens was 1.8 x 10(4) (1.8 x 10(3) cells/mg of tissue). The greatest yield of viable myocytes recovered was 8.0 x 10(4), which represented a viability of 90% by trypan blue dye exclusion and morphological criteria. Percutaneous right ventricular endomyocardial biopsy is a novel method for obtaining viable cardiac myocytes. Its feasibility and utility in humans warrant further investigation.