Need For Endomyocardial Biopsy Research Articles

Characterization of the ultrashort-TE (UTE) MR collagen signal.

Although current cardiovascular MR (CMR) techniques for the detection of myocardial fibrosis have shown promise, they nevertheless depend on gadolinium-based contrast agents and are not specific to collagen. In particular, the diagnosis of diffuse myocardial fibrosis, a precursor of heart failure, would benefit from a non-invasive imaging technique that can detect collagen directly. Such a method could potentially replace the need for endomyocardial biopsy, the gold standard for the diagnosis of the disease. The objective of this study was to measure the MR properties of collagen using ultrashort TE (UTE), a technique that can detect short T2* species. Experiments were performed in collagen solutions. Via a model of bi-exponential T2* with oscillation, a linear relationship (slope = 0.40 ± 0.01, R(2) = 0.99696) was determined between the UTE collagen signal fraction associated with these properties and the measured collagen concentration in solution. The UTE signal of protons in the collagen molecule was characterized as having a mean T2* of 0.75 ± 0.05 ms and a mean chemical shift of -3.56 ± 0.01 ppm relative to water at 7 T. The results indicated that collagen can be detected and quantified using UTE. A knowledge of the collagen signal properties could potentially be beneficial for the endogenous detection of myocardial fibrosis.

End of an Era: Reduced Severity of Tricuspid Regurgitation in Cardiac Transplant Recipients Managed with Molecular Diagnostic Testing

Purpose A well-established complication of right ventricular endomyocardial biopsy (EMB) used for the diagnosis of acute cellular rejection is damage to the tricuspid valve and subsequent tricuspid regurgitant flow. Since the advent of Molecular Diagnostic Testing (MDT) as a screening test for determining which patients require EMB, the need for EMB at our center has decreased significantly. We hypothesized that the severity of tricuspid regurgitation (TR) should therefore be reduced with greater reliance on MDT and reduced utilization of EMB. Methods and Materials 58 echocardiograms from cardiac transplant patients who survived at least two years post-transplant were reviewed by observers blinded to post-transplant rejection surveillance strategies. 30 patients were in the pre-MDT group, from 2002-2004, when only EMB was used for post-transplant rejection surveillance. 28 patients were in the MDT group, from 2008-2010, when MDT was used as a screen to determine if EMB was required. TR was graded on a scale of zero to four, with zero representing no regurgitation present on echocardiography, one representing trace, two representing mild, three representing moderate and four representing severe TR. Results Of the 30 patients evaluated from the pre-MDT group, from 2002-2004, the average TR score was 1.87. In the 28 patients evaluated after routine MDT testing was implemented, from 2008-2010, the average score was 1.30, indicating a statistically significant reduction in tricuspid regurgitation severity(p = 0.0297). There was no evidence of severe TR in the MDT patients. Conclusions Our findings demonstrate that with greater use of MDT, the severity of tricuspid regurgitation has been reduced. MDT has become an established method for monitoring immune activation and as a screen for identifying the need for EMB in low risk cardiac transplant recipients. Our findings further support the continued use of MDT as a screening test before resorting to EMB.

A 50-year-old man with eosinophilia and cardiomyopathy: need for endomyocardial biopsy?

A 50-year-old man was admitted with a suspected acute coronary syndrome. The coronary angiogram, however, was normal. He was found to have a cardiomyopathy and eosinophilia. The diagnosis was established as a perimyocarditis secondary to the Churg-Strauss syndrome. An important question is whether an endomyocardial biopsy should have been performed.

Cardiovascular magnetic resonance in the diagnosis of acute heart transplant rejection: a review.

BackgroundScreening for organ rejection is a critical component of care for patients who have undergone heart transplantation. Endomyocardial biopsy is the gold standard screening tool, but non-invasive alternatives are needed. Cardiovascular magnetic resonance (CMR) is well suited to provide an alternative to biopsy because of its ability to quantify ventricular function, morphology, and characterize myocardial tissue. CMR is not widely used to screen for heart transplant rejection, despite many trials supporting its use for this indication. This review summarizes the different CMR sequences that can detect heart transplant rejection as well as the strengths and weaknesses of their application.ResultsT2 quantification by spin echo techniques has been criticized for poor reproducibility, but multiple studies show its utility in screening for rejection. Human and animal data estimate that T2 quantification can diagnose rejection with sensitivities and specificities near 90%. There is also a suggestion that T2 quantification can predict rejection episodes in patients with normal endomyocardial biopsies.T1 quantification has also shown association with biopsy proven rejection in a small number of trials. T1 weighted gadolinium early enhancement appeared promising in animal data, but has had conflicting results in human trials. Late gadolinium enhancement in the diagnosis of rejection has not been evaluated.CMR derived measures of ventricular morphology and systolic function have insufficient sensitivity to diagnose mild to moderate rejection. CMR derived diastolic function can demonstrate abnormalities in allografts compared to native human hearts, but its ability to diagnose rejection has not yet been tested.There is promising animal data on the ability of iron oxide contrast agents to illustrate the changes in vascular permeability and macrophage accumulation seen in rejection. Despite good safety data, these contrast agents have not been tested in the human heart transplant population.ConclusionT2 quantification has demonstrated the best correlation to biopsy proven heart transplant rejection. Further studies evaluating diastolic function, late gadolinium enhancement, and iron oxide contrast agents to diagnose rejection are needed. Future studies should focus on combining multiple CMR measures into a transplant rejection scoring system which would improve sensitivity and possibly reduce, if not eliminate, the need for endomyocardial biopsy.

B-type Natriuretic Peptide Is a Sensitive Screening Test for Acute Rejection in Pediatric Heart Transplant Patients

The utility of B-type natriuretic peptide (BNP) for detecting acute rejection (AR) is unclear. The purpose of our study was to evaluate BNP as a screening test for AR in pediatric heart transplant patients. All endomyocardial biopsies (EMBs) with concurrent BNP levels from February 2004 through March 2007 at the study institution were reviewed and the association between BNP levels and acute rejection was assessed. Eighty-six patients underwent a total of 560 EMBs. The median age at EMB was 10.5 years (interquartile range [IQR] 3.7 to 15.4 years). There were 59 episodes of AR, 32 (54%) occurring at <1 year post-transplant. BNP levels were higher in patients with AR, median 387 pg/ml (IQR 125 to 931 pg/ml), compared with those without AR, median 66 pg/ml (IQR 37 to 148 pg/ml) (p < 0.001). The receiver operating characteristic (ROC) curve for BNP demonstrated an area under the curve (AUC) of 0.82 (95% confidence interval [CI] 0.76 to 0.88) (p < 0.001). A BNP level of 100 pg/ml corresponded to a sensitivity of 0.85 (95% CI 0.73 to 0.92) and a negative predictive value (NPV) of 0.97 (95% CI 0.95 to 0.99) for detecting AR. The ROC curve for patients at >1 year post-transplant demonstrated an AUC of 0.86 (95% CI 0.80 to 0.93) (p < 0.001), and a BNP level of 100 pg/ml corresponded to a sensitivity of 0.96 (95% CI 0.79 to 0.99) and NPV of 0.994 (95% CI 0.962 to 0.999) for detecting AR. BNP levels have a high sensitivity and NPV for evaluating AR in pediatric heart transplant patients. In patients >1 year post-transplant, a BNP level of <100 pg/ml correlates with a <1% chance of AR and may obviate the need for EMB in some cases.

The role of endomyocardial biopsy in the management of cardiovascular disease: A Scientific Statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology

The role of endomyocardial biopsy (EMB) in the diagnosis and treatment of adult and pediatric cardiovascular disease remains controversial, and the practice varies widely even among cardiovascular centers of excellence. A need for EMB exists because specific myocardial disorders that have unique prognoses and treatment are seldom diagnosed by noninvasive testing.1 Informed clinical decision making that weighs the risks of EMB against the incremental diagnostic, prognostic, and therapeutic value of the procedure is especially challenging for nonspecialists because the relevant published literature is usually cited according to specific cardiac diseases, which are only diagnosed after EMB. To define the current role of EMB in the management of cardiovascular disease, a multidisciplinary group of experts in cardiomyopathies and cardiovascular pathology was convened by the American Heart Association (AHA), the American College of Cardiology (ACC), and the European Society of Cardiology (ESC). The present Writing Group was charged with reviewing the published literature on the role of EMB in cardiovascular diseases, summarizing this information, and making useful recommendations for clinical practice with classifications of recommendations and levels of evidence. The Writing Group identified 14 clinical scenarios in which the incremental diagnostic, prognostic, and therapeutic value of EMB could be estimated and compared with the procedural risks. The recommendations contained in the present joint Scientific Statement are derived from a comprehensive review of the published literature on specific cardiomyopathies, arrhythmias, and cardiac tumors and are categorized according to presenting clinical syndrome rather than pathologically confirmed disease. The ultimate intent of this document is to provide an understanding of the range of acceptable approaches for the use of EMB while recognizing that individual patient care decisions depend on factors not well reflected in the published literature, such as local availability of specialized facilities, cardiovascular pathology expertise, and operator experience. The use of EMB …

The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease

The role of endomyocardial biopsy (EMB) in the diagnosis and treatment of adult and pediatric cardiovascular disease remains controversial, and the practice varies widely even among cardiovascular centers of excellence. A need for EMB exists because specific myocardial disorders that have unique prognoses and treatment are seldom diagnosed by noninvasive testing.1 Informed clinical decision making that weighs the risks of EMB against the incremental diagnostic, prognostic, and therapeutic value of the procedure is especially challenging for nonspecialists because the relevant published literature is usually cited according to specific cardiac diseases, which are only diagnosed after EMB. To define the current role of EMB in the management of cardiovascular disease, a multidisciplinary group of experts in cardiomyopathies and cardiovascular pathology was convened by the American Heart Association (AHA), the American College of Cardiology (ACC), and the European Society of Cardiology (ESC). The present Writing Group was charged with reviewing the published literature on the role of EMB in cardiovascular diseases, summarizing this information, and making useful recommendations for clinical practice with classifications of recommendations and levels of evidence. The Writing Group identified 14 clinical scenarios in which the incremental diagnostic, prognostic, and therapeutic value of EMB could be estimated and compared with the procedural risks. The recommendations contained in the present joint Scientific Statement are derived from a comprehensive review of the published literature on specific cardiomyopathies, arrhythmias, and cardiac tumors and are categorized according to presenting clinical syndrome rather than pathologically confirmed disease. The ultimate intent of this document is to provide an understanding of the range of acceptable approaches for the use of EMB while recognizing that individual patient care decisions depend on factors not well reflected in the published literature, such as local availability of specialized facilities, cardiovascular pathology expertise, and operator experience. The use of EMB …

Serial signal‐averaged electrocardiography in children after cardiac transplantation

In patients with myocytolysis detected in endomyocardial biopsy, there is a tendency towards a shift of ventricular electrical axes from normal to strain pattern on surface ECG. Their 12-lead signal-averaged electrocardiogram (SAECG) show a significant increase in filtered QRS duration (QRSD) compared with those with specimens without myocytolysis. Late potentials were generally found more frequently in individual SAECG leads than in the vector magnitude. An increase in filtered QRSD and the presence of late potentials compared with a baseline study emphasizes the need for endomyocardial biopsy. Consequently, no change in these parameters may preclude the indication for endomyocardial biopsy.

Noninvasive monitoring of rejection therapy based on intramyocardial electrograms after orthotopic heart transplantation. Initial experience with 14 cases

Despite the use of increasingly specific immunosuppressive therapy, rejection remains the leading cause of death in cardiac transplant patients. Endomyocardial biopsy (EMB) is the gold standard for early detection and monitoring of cardiac transplant rejection. However, this approach is invasive and not suitable for routine use. A noninvasive alternative for monitoring cardiac transplant patients uses the analysis of the ventricular evoked response (VER) obtained by programmed electrical stimulation. Rejection-sensitive parameters (RSP) and infection-specific parameters (ISP) are extracted from changes in the slope of the T-wave and from the duration of repolarization, respectively. For the analysis of intramyocardial electrograms, separate left and right ventricular pacing at a rate of 100 beats/min and lasting 60 s is required, following the same protocol. From year 2000, telemetric pacemakers were implanted in 14 patients undergoing heart transplantation at this institution. A total of 95 endomyocardial biopsies and 275 ventricular evoked response measurements were carried out. Five out of 6 cases with significant rejection were correctly identified by RSP values below a threshold of 98% (sensitivity=80%, specifity=50%, negative predictive value=97%, positive predictive value=11%; P<0.002). Of the EMBs, 45% could have been saved if the diagnosis model had been used to indicate need for EMB. Noninvasive cardiac graft monitoring can reduce the need for surveillance biopsies and may offer a tool to optimize immunosupressive therapy after heart transplantation. Rejection grade 2 or higher can safely be detected.

Computerized heart allograft-recipient monitoring: a multicenter study.

Computerized heart allograft recipient monitoring (CHARM) is a unique concept of patient surveillance after heart transplantation (HTx), based on the evaluation of intramyocardial electrograms (IEGMs) recorded non-invasively with telemetric pacemakers. Previous open, single-center studies had indicated a high correlation between CHARM results and clinical findings. The present study was initiated to assess the suitability of CHARM for monitoring the absence of rejection in a blind, multicenter context. During the HTx procedure, telemetric pacemakers and two epimyocardial leads were implanted in 44 patients at four European HTx centers. IEGMs during pacing were recorded and transferred via the Internet to the CHARM computer center, for automatic data processing and extraction of diagnostically relevant information, i.e., the maximum slew rate of the descending part of the repolarization phase of the ventricular evoked response (VER T-slew). The study period comprised the first 6 months after HTx, during which the transplant centers were blind to the CHARM results. A single threshold diagnosis model was prospectively defined to assess the ability of the VER T-slew to indicate clinically significant rejection, which was defined as an endomyocardial biopsy (EMB) grade greater than or equal to 2, according to the grading system of the International Society for Heart and Lung Transplantation. All EMB slides from three centers were reviewed blind by the pathologist of the fourth center in order that agreement among the histological diagnoses at the various centers could be assessed. Totals of 839 follow-ups and 366 EMBs were obtained in 44 patients. Thirty-seven patients were alive at the end of the study period. Age at HTx, EMB grade distribution, and rejection prevalence varied significantly between the centers. Review of the EMB results showed considerable differences with respect to classification of significant rejection. Comparison of average VER T-slew values with and without rejection in the 15 patients who exhibited both states revealed significantly lower values under the influence of rejection (97+/-13% vs 79+/-15%, P<0.0001). Twenty out of the 25 cases with significant rejection were correctly identified by VER T-slew values below a threshold of 98% (sensitivity =80%, specificity =50%, negative predictive value =97%, positive predictive value =11%; P<0.0005). Of the EMBs, 48% could have been saved if the diagnosis model had been used to indicate the need for EMB. A high negative predictive value for the detection of cases with significant rejection has been obtained in a prospective, blind, multicenter study. The presented method can, therefore, be used to supplement patient monitoring after HTx non-invasively, in particular to indicate the need for EMBs. In centers with patient management similar to the ones who participated in the study, this may allow a reduction in the number of surveillance EMBs.

Diagnosis of heart graft rejection

Despite refinements in immunosuppressive therapy, acute allograft rejection remains a major cause of mortality in heart transplant recipients. The high reliability, noninvasiveness, possibility of day-to-day monitoring, absence of interobserver variability, and cost effectiveness are essential components of the ideal diagnostic method for the detection of allograft rejection. This paper reviews the experimental and clinically established methods for the diagnosis of acute allograft rejection. The most promising tools seem to be electrophysiologic, because these tools provide the potential for continuous noninvasive distant rejection monitoring, and echocardiographic techniques that enable the safe assessment of changes in cardiac structure and function and further reduce the need for endomyocardial biopsy and, more importantly, provide a better definition of the threshold for antirejection treatment. Additional research and refinements of techniques and evaluation in prospective randomized multicenter studies are needed to further advance the use of noninvasive methods for diagnosis of heart graft rejection.

Will permanent LVADs be better than heart transplantation?

Current interest in permanent mechanical support systems has been renewed as a result of the present shortage of human heart donors, and in view of the satisfactory results obtained with their use as a bridge-to-transplant. As the number of donors is unlikely to increase dramatically in the near future, there is an urgent need to develop mechanical alternatives to transplantation. Preliminary data on the use of the implantable electric LVAD as a bridge-to-transplant indicate that the adverse clinical and mechanical events in outpatients are few and do not preclude use of the device on a permanent basis. Except for infections, transplant issues relating to need for endomyocardial biopsies, rejection, malignancies, and graft arteriosclerosis do not apply to LVAD recipients who face important issues relating to device durability, cost, and potential need for concomitant right heart support. This lack of data on long-term durability contrasts with a yearly mortality rate of about 5% after the first year of transplant. With the initiation of clinical trials on the permanent use of the electric LVAD, several design modifications and upgrading of the currently available devices are expected. Completely sealed systems with steadily improving durability will hopefully appear. Inductive coupling techniques under investigation and development appear to be able to transmit energy without damage across the skin. It is anticipated that with more reliable electronic microprocessors, the future generation of implantable LVADs will be smaller, more reliable and longer lasting.

Imciromab Pentetate (Monoclonal Antimyosin Antibody Fab)

Imciromab (monoclonal antimyosin antibody Fab) pentetate is a murine monoclonal antibody Fab (fragment antigen binding) derivative. It is specific for the human cardiac myosin heavy chain and localises to areas of cardiac myocyte necrosis. Indium In-111 imciromab pentetate imaging is a well tolerated, non-invasive method of assessing the presence and severity of cardiac allograft rejection. It has also been successfully used to confirm the presence and size of acute myocardial infarction (AMI), the presence of myocarditis and for the early detection of anthracycline cardiotoxicity. However, the 24- to 48-hour delay between administration and imaging restricts its use in conditions where the rapid diagnosis of cardiac disorders is essential, and the decay half-life of indium In-111 (67 hours) limits the dose of radiolabel to approximately 2 mCi. Nevertheless, except in patients requiring an immediate diagnosis of AMI, indium In-111 imciromab pentetate imaging provides significant diagnostic and prognostic information, aiding patient management and the selection of appropriate treatment, and, in some patients, abrogating the need for endomyocardial biopsy. Imciromab (monoclonal antimyosin antibody Fab) pentetate is a murine monoclonal antibody Fab (fragment antigen binding) fragment linked to a bifunctional chelating agent. It is specific for human cardiac myosin heavy chains and localises to areas of cardiac myocyte necrosis, where disruption of the cell membrane exposes cardiac myosin. Imciromab pentetate is chelated to indium In-111 prior to administration for radioimaging. Indium In-111 imciromab pentetate imaging facilitated assessment of infarct size and location in animal models of acute myocardial infarction (AMI). It indicated the location and severity of rejection in animal models of cardiac transplantation, and identified acute murine myocarditis. The elimination half-life in blood of indium In-111 imciromab pentetate in patients with AMI is about 5 hours. In mice, uptake of the radiolabel was concentrated in the kidneys (20 to 25% of the dose) and liver (5% of the dose) 24 hours after administration. Uptake in the heart was 6% in animals with acute myocarditis but only 1% in uninfected mice. In studies involving a total of more than 800 patients, indium In-111 imciromab pentetate imaging correctly identified AMI in patients with or without definitive clinical findings, with an overall sensitivity of 93%. It also provided an assessment of infarct size and, in dual isotope imaging with thallium Tl-201, identified patients at risk of developing further cardiac ischaemia. Indium In-111 imciromab pentetate imaging had a sensitivity of 80 to 100% in studies in patients with cardiac allograft rejection, with the ratio of cardiac to pulmonary uptake (HLR) providing an indication of rejection severity. In patients with suspected myocarditis a negative indium In-111 imciromab pentetate scan may abrogate the need for endomyocardial biopsy. A positive scan in patients with suspected myocarditis or acute-onset idiopathic dilated cardiomyopathy identifies those more likely to subsequently show clinical improvement. Preliminary data suggest indium In-111 imciromab pentetate imaging may also be useful in the early detection of anthracycline-associated cardiotoxicity. Indium In-111 imciromab pentetate has been very well tolerated in clinical trials, with few adverse events reported. Wheal and flare reactions to intradermal testing prior to intravenous administration are seen only rarely (2 reported cases in >330 patients). The development of human-antimurine antibodies is seldom noted and has not been associated with clinical sequelae. Eosinophilia, and hypotension and confusion have each been reported in 1 patient receiving indium In-111 imciromab pentetate but causality has not been established. Patients should receive intravenous indium In-111 imciromab pentetate 0.5mg (2 mCi). Imaging is usually performed 24 and/or 48 hours after administration. Planar imaging with a gamma camera is usually performed in 3 views, each over 10 minutes. Single photon emission computed tomography (SPECT) imaging comprises 64 frames over 180° at 30 seconds per frame.

Ventricular tachycardias of right ventricular origin: Markers of subclinical right ventricular disease

The diagnosis of subclinical myocardial disease in patients with ventricular tachycardias of right ventricular (RV) origin and no overt cardiac abnormalities is important, inasmuch as the presence of RV cardiomyopathy or arrhythmogenic dysplasia can be associated with a poor prognosis. To this end the relative value of symptoms, ECG features of ventricular tachycardia, signal-averaged ECGs, and RV echocardiograms as compared with endomyocardial biopsy findings was prospectively evaluated. Twenty-seven patients with chronic ventricular tachycardias with a left bundle branch block-like morphology, presumed to be of RV origin, were studied. Clinical examination findings, 12-lead ECGs in sinus rhythm, radiographs of the chest, coronary angiograms, and left ventricular cineangiograms were normal in all patients. RV biopsies were abnormal in 11 patients (41%) with findings suggestive of RV dysplasia or cardiomyopathy. A multivariate analysis showed a significant correlation between an abnormal biopsy and sustained ventricular tachycardia (p < 0.05), tachycardia with a superior frontal plane axis (p < 0.001), an abnormal signal-averaged ECG (p < 0.05), and an abnormal RV echocardiogram (p < 0.001). An abnormal RV echocardiogram was both a sensitive (73%) and a specific (94%) indicator of an abnormal RV biopsy. Sustained tachycardia although sensitive (90%) had a low specificity (56%). In comparison, a superior frontal plane axis of ventricular tachycardia and an abnormal signal-averaged ECG were indicative of high specificity and low sensitivity for abnormal myocardial histologic findings. We conclude that in a patient with RV tachycardia and no overt cardiac abnormalities, sustained tachycardia, a superior frontal plane axis of ventricular tachycardia, an abnormal signal-averaged ECG, and an abnormal RV echocardiogram suggest the presence of subclinical RV disease. An abnormal RV echocardiogram is both a specific and a sensitive indicator of myocardial abnormalities and precludes the need for endomyocardial biopsy.

Scintigraphic methods in the diagnosis of myopericarditis

A noninvasive tool for the diagnosis of human myopericardial inflammation is desirable so that the need for endomyocardial biopsy may be decreased. Gallium-67 citrate (67Ga), an inflammation-avid radioisotope, was studied in an effort to define its role in the evaluation of patients with inflammatory heart disease. Following a preliminary report in which four patients with pericarditis showed 67Ga avidity, 16 patients with postpericardiotomy syndrome were studied following cardiac surgery. In each of the patients in whom this syndrome was present for more than 2 weeks following the surgical procedure, there was active uptake of 67Ga over the myocardium. Gallium-67 was also studied in the context of myocardial inflammation in patients with dilated cardiomyopathy. In these studies, a subset of patients who showed 67Ga uptake over the myocardium responded to immunosuppressive therapy; the presence of67Ga uptake over the myocardium improved the yield of biopsy in the diagnosis of myocarditis from 8 to 36%. Definitive conclusions on the role of scintigraphic techniques in myopericardial inflammation await the results of a multicentre myocarditis study.