Biventricular Endomyocardial Biopsy Research Articles

Value of cardiac magnetic resonance imaging derived spectral myocardial strain pattern for non-invasive diagnosis of myocarditis

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Society of Radiology European Institute for Biomedical Imaging Research Background Traditionally, cardiac function is quantified by measures of peak excursion, for example ejection fraction. However, myocardial strain estimation from cine- cardiac MRI allows quantification of cardiac motion over the whole heart cycle. We propose a spectral decomposition of the strain curves applying Discrete Fourier transformation (DFT). Purpose To evaluate a potential additive diagnostic value of spectral temporal strain curve quantification for non-invasive diagnosis of myocarditis using cardiac MRI. Methods In the single-center prospective study patients with suspected myocarditis underwent comprehensive cardiac MRI followed by biventricular endomyocardial biopsy (EMB) between 2012 and 2014. DFT was applied to myocardial strain curves extracted from cine-Images. As reference model, a L1- and L2-penalized logistic regression model using global native T1 time, T2 time and presence of late-gadolinium enhancement was trained to predict EMB results and compared to two models which additionally include three orders of DFT coefficients and ejection fraction, respectively. Predictive performance was evaluated in a tournament-leave-pair-out cross-validation approach with a bootstrap correction for testing of multiple hyperparameter configurations. Results Out of 100 patients (28 % female, median age 40 [IQR 32 to 56) years) with acute symptom-onset (<30 days) 65 had pathologically proven myocarditis in EMB. The DFT model showed best discrimination (Area under the receiver-operating-curve [AUC] 0.72 [95% CI 52 to 87]). Addition of ejection fraction (AUC 0.60 [95% CI: 0.43 to 0.74]) did not increase AUC compared to the reference (AUC 0.60 [95% CI: 0.43 to 0.74]). Posterior distribution of the bootstrap-corrected AUC difference between DFT and reference model was gaussian (mean 12%, standard deviation 12%) with a posterior probability of 86%, that DFT has a greater AUC. Conclusions Discrimination of myocarditis from similar clinical presentations remains challenging. The results support incremental discriminatory value of DFT-decomposed myocardial strain for non-invasive diagnosis of myocarditis. Future research should address the value of the spectral decomposition of cardiac motion trajectories in larger samples and different disease entities.

Cardiac MRI Texture Analysis of T1 and T2 Maps in Patients with Infarctlike Acute Myocarditis.

Purpose To assess the diagnostic potential of texture analysis applied to T1 and T2 maps obtained with cardiac MRI for the diagnosis of acute infarctlike myocarditis. Materials and Methods This prospective study from August 2012 to May 2015 included 39 participants (overall mean age ± standard deviation, 34.7 years ± 12.2 [range, 18-63 years]; mean age of women, 46.1 years ± 10.8 [range, 24-63 years]; mean age of men, 29.8 years ± 9.2 [range, 18-56 years]) from the Magnetic Resonance Imaging in Myocarditis (MyoRacer) trial with clinical suspicion of acute myocarditis and infarctlike presentation. Participants underwent biventricular endomyocardial biopsy, cardiac catheterization, and cardiac MRI at 1.5 T, in which native T1 and T2 mapping as well as Lake Louise criteria (LLC) were assessed. Texture analysis was applied on T1 and T2 maps by using a freely available software package. Stepwise dimension reduction and texture feature selection was performed for selecting features enabling the diagnosis of myocarditis by using endomyocardial biopsy as the reference standard. Results Endomyocardial biopsy confirmed the diagnosis of acute myocarditis in 26 patients, whereas 13 participants had no signs of acute inflammation. Mean T1 and T2 values and LLC showed a low diagnostic performance, with area under the curve in receiver operating curve analyses as follows: 0.65 (95% confidence interval [CI]: 0.45, 0.85) for T1, 0.67 (95% CI: 0.49, 0.85) for T2, and 0.62 (95% CI: 0.42, 0.79) for LLC. Combining the texture features T2 run-length nonuniformity and gray-level nonuniformity resulted in higher diagnostic performance with an area under the curve of 0.88 (95% CI: 0.73, 1.00) (P < .001) and a sensitivity and specificity of 89% [95% CI: 81%, 93%] and 92% [95% CI: 77%, 93%], respectively. Conclusion Texture analysis of T2 maps shows high sensitivity and specificity for the diagnosis of acute infarctlike myocarditis. © RSNA, 2018 Online supplemental material is available for this article.

Biventricular endomyocardial biopsy in patients with suspected myocarditis: Feasibility, complication rate and additional diagnostic value

BackgroundPrevious retrospective analyses have suggested that biventricular (BV) endomyocardial biopsy (EMB) is superior compared to selective left ventricular (LV) or right ventricular (RV) EMB. This study prospectively assessed the feasibility, safety and diagnostic performance of implementing a routine BV-EMB approach in patients with suspected myocarditis. MethodsConsecutive patients with clinically suspected myocarditis underwent EMB (n=136). Myocarditis was defined as ≥14 infiltrating leukocytes/mm2 in addition to enhanced human leukocyte antigen class II expression in professional antigen-presenting immune cells. The presence of viral genomes was assessed by nested (reverse transcriptase–) polymerase chain reaction. ResultsBV-EMB was attempted in 132 patients (LV thrombus, n=3; complication during RV-EMB, n=1) and resulted in sufficient samples from both ventricles in 127 patients (96.2%). One major complication (pericardial tamponade requiring surgical revision) was observed during the 136 RV-EMB (0.7%). No severe complications occurred during the 132 LV procedures. Of the 127 patients with BV-EMB, myocarditis was diagnosed in 89 patients (70.1%). While 67 patients (75.3%) fulfilled the diagnostic criteria in both ventricles, the diagnosis of myocarditis was based on the results of LV-EMB only in 16 patients (18%) and of RV-EMB only in 6 patients (6.7%). Viral genomes were found in 45 of the 127 patients (35.4%) with evidence of virus genome only in the left ventricle in 10 patients (22.2%) and only in the right ventricle in 3 patients (6.7%). ConclusionsImplementing a routine BV-EMB approach is feasible and safe. In patients with suspected myocarditis, BV-EMB yields superior diagnostic performance compared to selective RV- or LV-EMB.

Comprehensive Cardiac Magnetic Resonance Imaging in Patients With Suspected Myocarditis: The MyoRacer-Trial

BackgroundData suggest that T1 and T2 mapping have excellent diagnostic accuracy in patients with suspected myocarditis. However, the true diagnostic performance of comprehensive cardiac magnetic resonance (CMR) mapping versus endomyocardial biopsy (EMB) has not been determined. ObjectivesThis study assessed the performance of CMR imaging, including T1 and T2 mapping, compared with EMB in an unselected, consecutive patient cohort with suspected myocarditis. It also examined the potential role of CMR field strength by comparing 1.5-T versus 3.0-T imaging. MethodsPatients underwent biventricular EMB, cardiac catheterization (for exclusion of coronary artery disease), and CMR imaging on 1.5- and 3-T scanners. The CMR protocol included current standard Lake Louise criteria (LLC) for myocarditis as well as native T1, calculation of extracellular volume fraction (ECV), and T2 mapping (only on 1.5-T). Patients were divided into 2 groups according to symptom duration (acute: ≤14 days vs. chronic: >14 days). ResultsA total of 129 patients underwent 1.5-T imaging. In patients with acute symptoms, native T1 yielded the best diagnostic performance as defined by the area under the curve (AUC) of receiver-operating curves (0.82) followed by T2 (0.81), ECV (0.75), and LLC (0.56). In patients with chronic symptoms, only T2 mapping yielded an acceptable AUC (0.77). On 3.0-T, AUCs of native T1, ECV, and LLC were comparable to 1.5-T with no significant differences. ConclusionsIn patients with acute symptoms, mapping techniques provide a useful tool for confirming or rejecting the diagnosis of myocarditis and are superior to the LLC. However, only T2 mapping has acceptable diagnostic performance in patients with chronic symptoms. (Magnetic Resonance Imaging in Myocarditis [MyoRacer]; NCT02177630)

Performance of comprehensive cardiac magnetic resonance imaging including T1 and T2 mapping on 1.5 vs. 3.0 Tesla as compared to biventricular endomyocardial biopsy in patients with suspected myocarditis - the MyoRacer trial

Performance of comprehensive cardiac magnetic resonance imaging including T1 and T2 mapping on 1.5 vs. 3.0 Tesla as compared to biventricular endomyocardial biopsy in patients with suspected myocarditis - the MyoRacer trial

Abstract 19159: Performance of T1 Mapping Cardiac Magnetic Resonance Imaging as Compared to Biventricular Endomyocardial Biopsy in Patients With Suspected Myocarditis

Background: The diagnostic performance of cardiac magnetic resonance (CMR) imaging in suspected myocarditis is still limited. Recently, CMR T1 mapping has been suggested to yield excellent diagnostic accuracies in patients with suspected myocarditis as compared to healthy controls. However, the true diagnostic performance of T1 mapping when compared to endomyocardial biopsy (EMB) in patients with a variety of pathologies is till unknown and was therefore assessed in this study. Methods and Results: Within the final analyses, 129 consecutive patients with suspected acute or chronic myocarditis were included. Patients had to fulfill indications for CMR imaging according to the JACC White consensus paper. All patients underwent biventricular EMB, cardiac catheterization for exclusion of coronary artery disease, and MRI on a 1.5 Tesla tomography (Intera, CV, Philips Medical Systems, Best, the Netherlands). The CMR protocol included standard Lake-Louise (LL) parameters as well as native and post contrast T1 mapping using a modified Look-Locker inversion recovery sequence. Patients were divided into 2 groups according to duration of symptoms: patients with acute symptoms ≤14 days and those with chronic symptoms &gt;14 days. The diagnostic performance of LL criteria, native T1 and extracellular volume fraction (ECV) is summarized in the table. In patients with acute symptoms, native T1 yielded best diagnostic performance (81%) followed by ECV (75%), whereas accuracy of LL was found to be inadequate (60%). In patients with chronic symptoms, neither imaging technique or criteria yielded sufficient diagnostic accuracies. Conclusion: In patients with acute symptoms and suspected myocarditis, T1 mapping provides a useful tool for the confirming or rejecting the diagnosis of myocarditis and is superior to LL criteria. In contrast, native T1 and extracellular volume fraction demonstrated unsatisfying diagnostic accuracies in patients with chronic symptoms.

Abstract 18891: Prospective Evaluation of Diagnostic Performance and Safety of Implementing a Biventricular Approach for Endomyocardial Biopsy in Patients With Suspected Myocarditis

Background: Previous retrospective analyses have suggested that biventricular (BV) endomyocardial biopsy (EMB) is superior to right (RV) or left ventricular (LV) EMB only in diagnosing patients with suspected myocarditis. Aim: To prospectively assess the feasibility, safety and diagnostic yield of BV EMB in consecutive patients with suspected myocarditis. Methods: Five to six EMBs were taken from the RV and LV under fluoroscopic guidance. Biopsies were analyzed in a core lab by highly experienced investigators (KK, RK) Myocarditis/myocardial in[[Unable to Display Character: &amp;#64258;]]ammation was de[[Unable to Display Character: &amp;#64257;]]ned as the detection of ≥14 infiltrating leukocytes/mm2 (CD3 T-lymphocytes and/or CD68 macrophages) in addition to enhanced HLA class II expression in professional antigen-presenting immune cells. Results: 100 consecutive patients (mean age 44 ± 15 years) with clinically suspected myocarditis were included. RV EMB was attempted in 100 patients, in 3 the procedure was abandoned due to unsatisfying positioning on the guiding catheter, in 1/97 RV EMBs were inadequate with no myocardial tissue obtained. LV EMB was attempted in 97 patients, in 3, LV EMB was not performed due to presence of LV thrombi, in 1/97 patient LV EMBs were inadequate with no myocardial tissue obtained. Major complication rate for LV EMB was 0% and for RV EMB, 1% (pericardial tamponade requiring surgical revision). Results of adequate BV EMBs were analyzed in 92 patients. On BV EMB, myocarditis was diagnosed in 61/92 patients. When considering LV EMB only, the diagnosis would have been missed in 3/61, when considering RV EMB only in 7/61 patients. Conclusion: BV EMB is feasible and safe in the majority of patients with suspected myocarditis and yields in a superior diagnostic performance as compared to a single ventricle EMBs.

Myocardial and microvascular inflammation/infection in patients with HIV-associated pulmonary artery hypertension.

Right ventricle compromise affects survival of patients with HIV-associated pulmonary artery hypertension (PAH). Myocardial histology with viral assessment may clarify the mechanism of right ventricular deterioration and provide clues on PAH origin. Fifteen patients with HIV infection, PAH and right ventricular dysfunction underwent cardiac magnetic resonance, catheterization, coronary with ventricular angiography and biventricular endomyocardial biopsy. Endothelial expression of HLA-DR, ICAM-1, E-selectin and VCAM-1 was semi-quantitatively evaluated. PCR for HIV, hepatitis C virus, human herpes virus-6, human herpes virus-8, Epstein-Barr virus, adenovirus, cytomegalovirus, enterovirus, influenza A/B and parvovirus B19 was performed. In PCR-positive hearts, viral protein adenovirus-1 and TORDJI-22 were assessed by immunohistology. New York Heart Association class was 2.4 ± 0.5, mean pulmonary artery pressure 49.93 ± 10.15 mmHg and wedge pressure 9.5 ± 2.19 mmHg. Coronaries were normal with slow flow. Left ventricular and/or right ventricular micro-aneurysms were seen in eight patients. Cardiac magnetic resonance documented increased right ventricular end-diastolic volume with reduced ejection fraction, normal left ventricular end-diastolic volume and left ventricular ejection fraction. Subepicardial/mesocardial oedema and delayed enhancement in the inter-ventricular junction and/or left ventricular inferolateral wall was detected in eight patients. Histology showed active lymphocytic myocarditis in 12 patients, with microvasculitis in three. Endothelial adhesion molecules were over-expressed in all patients. PCR was positive in four patients for hepatitis C virus and in two for adenovirus, and viruses localized both in cardiomyocytes and endothelial cells. Inflammation/infection of myocardium and intramural vessels is detectable in patients with HIV-associated PAH. It may adversely affect right ventricular function and have a role in the compromised pulmonary circulation.

Contribution and Risks of Left Ventricular Endomyocardial Biopsy in Patients With Cardiomyopathies

Background— Use of left ventricular (LV) endomyocardial biopsy (EMB) to investigate cardiomyopathies is currently discouraged because it is considered riskier than and as contributive as right ventricular (RV) biopsy. The aim of our study is to report our experience with this option and to discuss its advantages and disadvantages. Methods and Results— In our center from 1983 to 2010, 4221 patients underwent diagnostic EMB. In particular, 2396 (56.8%) underwent biventricular EMB, 1153 (27.3%) underwent selective LVEMB, and 672 (15.9%) underwent selective RVEMB. The rate of complications and histological findings were retrospectively analyzed. The periprocedural major complication rate (perforation with or without cardiac tamponade, embolization) was 0.33% for LVEMB and 0.45% for RVEMB, with a significant decrease in the rate of major complications with time (from 1.6% and 1.9% in 1983–1988 to 0% and 0.3% in 2007–2013, respectively; P &lt;0.001 for both), denoting a steep learning curve. No patients died. When the structural and functional abnormalities affected exclusively the LV, the diagnostic yield of LVEMB was 97.8% compared with 53% for RVEMB. Conversely, when the echocardiographic presence of increased wall thickness, local or global ventricular dilation, or dysfunction also involved the RV, the diagnosis was reached in 98.1% of LVEMBs and 96.5% of RVEMBs. This discrepancy was particularly evident for myocarditis, whereas in infiltrative and storage diseases, the histological abnormalities were always detectable in both ventricles. Conclusions— LVEMB is a safe procedure with very low transient complications, comparable to RVEMB. It appears diagnostically more contributive than RVEMB in patients with cardiomyopathies and clinically preserved RV.

High prevalence of myocarditis in patients with hypertensive heart disease and cardiac deterioration

Structural abnormalities causing cardiac deterioration in hypertensive heart disease (HHD) are poorly understood. The aim of the study was to evaluate left ventricular (LV) myocardial changes in patients with HHD and cardiac failure. Among 1229 patients undergoing an LV or biventricular endomyocardial biopsy because of unexplained LV dysfunction from 2000 to 2010, 45 had HHD. The HHD population had non-invasive assessment of cardiac wall thickness, diameters, and function; endomyocardial samples were processed for histology, immunohistochemistry, and polymerase chain reaction (PCR) for cardiotropic viruses. Mean LV end-diastolic diameter was 63.3 ± 5.9 mm, LV ejection fraction 29.7 ± 7.6%, and maximal wall thickness 12.8 ± 0.9 mm. At histology, hypertrophy with degeneration of cardiomyocytes, increased external/lumen ratio of intramural arterioles, and myocardial fibrosis were observed in 17 patients (38%). In the remaining 28 patients (62%), these histological changes were associated with myocarditis. Myocarditis was present in 40.4% of the cohort without HHD. PCR was negative in HHD without inflammation while it was positive in 10 subjects with myocarditis (enterovirus in 3 cases, adenovirus 4, influenza virus 3). Addition of immunosuppression to supportive therapy in the 18 virus-negative myocarditis subjects was followed at 6 months by significant recovery of LV function in 15 (83%; ejection fraction from 25.3 ± 9.3% to 49.5 ± 9.8%) while LV function improved to a minor extent ( ejection fraction from 25 ± 5.1% to 36 ± 4.4%) in 12 of 27 patients (44%) on supportive treatment alone. Myocarditis is a major cause of cardiac deterioration in patients with HHD; its recognition may improve patient treatment and outcome.

Long-term follow-up after viral myocarditis established by endomyocardical biopsy: Predictors of mortality

Myocarditis is a frequent cardiac disease occurring in all ages that is difficult to diagnose. However, new procedures such as cardiac magnetic resonance imaging (CMR) and biventricular endomyocardial biopsy with histological, immunohistochemical and microbiological work-up have revolutionized the diagnosis of myocarditis in the last years. Nevertheless, the long-term mortality after viral myocarditis established by endomyocardical biopsy, as well as the predictors of long-term mortality are still not known.

Comparative Evaluation of Left and Right Ventricular Endomyocardial Biopsy

Endomyocardial biopsy (EMB) represents the gold standard for diagnosing myocarditis and nonischemic cardiomyopathies. This study focuses on the risk of complications and the respective diagnostic performance of left ventricular (LV), right ventricular (RV), or biventricular EMB in patients with suspected myocarditis and/or cardiomyopathy of unknown origin. In this 2-center study, 755 patients with clinically suspected myocarditis (n=481) and/or cardiomyopathy of nonischemic origin including those with infiltrative or connective tissue disease (n=274) underwent either selective LV-EMB (n=265; 35.1%), selective RV-EMB (n=133; 17.6%), or biventricular EMB (n=357; 47.3%) after coronary angiography and exclusion of significant coronary artery disease. Cardiovascular magnetic resonance, including late gadolinium enhancement, imaging was performed in 540 patients (71.5%). The major complication rate for LV-EMB was 0.64% and for RV-EMB, 0.82%. Considering postprocedural pericardial effusion that occurred after biventricular EMB, the minor complication rate for LV-EMB varied between 0.64% to 2.89% and for RV-EMB, between 2.24% and 5.10%. Diagnostic EMB results were achieved significantly more often in those patients who underwent biventricular EMBs (79.3%) compared to those who underwent either selective LV-EMB or selective RV-EMB (67.3%; P<0.001). In patients with biventricular EMB, myocarditis was diagnosed in LV-EMB samples in 18.7% and in RV-EMB samples in 7.9% (P=0.002) , and it was diagnosed in both ventricles in 73.4%. There were no differences in the number of positive LV-EMB, RV-EMB, or LV- and RV-EMB findings when related to the site of cardiovascular magnetic resonance-based late gadolinium enhancement. Both LV-EMB and RV-EMB are safe procedures if performed by experienced interventionalists. The diagnostic yield of EMB may be optimized when samples from both ventricles are available. Preferential biopsy in regions showing late gadolinium enhancement on cardiovascular magnetic resonance does not increase the number of positive diagnoses of myocarditis.

Cardiac Histological Substrate in Patients With Clinical Phenotype of Brugada Syndrome

The role of structural heart disease and sodium channel dysfunction in the induction of electrical instability in Brugada syndrome is still debated. We studied 18 consecutive patients (15 males, 3 females; mean age 42.0+/-12.4 years) with clinical phenotype of Brugada syndrome and normal cardiac structure and function on noninvasive examinations. Clinical presentation was ventricular fibrillation in 7 patients, sustained polymorphic ventricular tachycardia in 7, and syncope in 4. All patients underwent cardiac catheterization, coronary and ventricular angiography, biventricular endomyocardial biopsy, and DNA screening of the SCN5A gene. Biopsy samples were processed for histology, electron microscopy, and molecular screening for viral genomes. Microaneurysms were detected in the right ventricle in 7 patients and also in the left ventricle in 4 of them. Histology showed a prevalent or localized right ventricular myocarditis in 14 patients, with detectable viral genomes in 4; right ventricular cardiomyopathy in 1 patient; and cardiomyopathic changes in 3. Genetic studies identified 4 carriers of SCN5A gene mutations that cause in vitro abnormal function of mutant proteins. In these patients, myocyte cytoplasm degeneration was present at histology, whereas terminal dUTP nick end-labeling assay showed a significant increase of apoptotic myocytes in right and left ventricle versus normal controls (P=0.014 and P=0.013, respectively). Despite an apparently normal heart at noninvasive evaluation, endomyocardial biopsy detected structural alterations in all 18 patients with Brugada syndrome. Mutations in the SCN5A gene, identified in 4 of the 18 patients, may have induced concealed structural abnormalities of myocardiocytes that accounted for paroxysmal arrhythmic manifestations.

Prevalence of Fabry disease in female patients with late-onset hypertrophic cardiomyopathy.

Fabry disease (FD) has been recognized as the cause of left ventricular hypertrophy in 6% of men with late-onset hypertrophic cardiomyopathy (HCM). Although FD is considered a recessive X-linked disorder, affected women are increasingly reported. The aim of our study was to determine the prevalence of FD in female patients with HCM. Thirty-four consecutive women (mean age, 50+/-13.6 years) who received an ECG and echocardiographic diagnosis of HCM were submitted to an invasive cardiac study that included a biventricular endomyocardial biopsy. Tissue samples were analyzed for histology and electron microscopy. Peripheral blood activity of alpha-galactosidase (alpha-Gal) A was assessed in all patients. None of them had a family history of FD. Histology and electron microscopy showed in 4 patients (12%; mean age, 51.5+/-3.9 years) the presence of cell vacuoles characterized by the accumulation of glycolipid material organized in concentric lamellar structures, diagnostic for FD. In the remaining patients, histology was consistent with HCM. In all the female carriers, the heart was the only organ clinically involved in the disease, showing concentric hypertrophy in 2 patients, asymmetric hypertrophy in 1, and apical hypertrophy in 1. The alpha-Gal A enzymatic activity was 44+/-14% of control values. Genetic analysis showed the presence of alpha-Gal A gene mutation in all 4 cases. FD may account for up to 12% of females with late-onset HCM. Those heterozygous for FD with left ventricular hypertrophy are potential candidates for enzyme enhancement/replacement therapy.

Arrhythmias in acute pericarditis. An endomyocardial biopsy study.

It is still controversial whether the arrhythmias in acute pericarditis are of myocardial or pericardial origin. The aim of the present study was to investigate the occurrence of arrhythmias and conduction disorders in patients with acute pericarditis with no endomyocardial biopsy evidence of myocarditis (group 1: 40 patients, 65% males, mean age 45.6 +/- 15.7 years, mean heart rate [HR] 98.7 +/- 22.2 beats per minute) in comparison to endomyocardial biopsy proven acute myocarditis/perimyocarditis (group 2: 10 patients, 3/10 with perimyocarditis, 70% males, mean age 46.1 +/- 15.8 years, mean heart rate 76.7 +/- 33.1 beats per minute). At the initial assessment all patients underwent comprehensive clinical work-up including echocardiography, cardiac catheterization, and endomyocardial biopsy. In all patients biventricular endomyocardial biopsy was performed using standard femoral approach and Schikumed 7 F or 8 F bioptomes. Tissue samples were stained by H & E, v. Gieson and independently reviewed by two cardiac pathologists. In addition immunohistochemistry and immunocytochemistry were performed, and only patients fulfilling Dallas and World Heart Federation criteria were selected for group 2. Comparative analysis of electrocardiograms and 24-hour Holter recordings at initial presentation revealed in group 1 vs group 2 significantly less frequent paroxysmal supraventricular tachyarrhythmias (5% vs 40%), and ventricular fibrillation (0 vs 20%), in contrast to atrial fibrillation that occurred more often (20% vs 0) (all p < 0.05). Furthermore, in the group 2 one patient died due to VF and two patients underwent ICD implantation. Low voltage (40% vs 30%) and ST/T wave changes (47.5% vs 30%), as well as the incidence of the II degree AV block (5% vs 0) and complete AV block (2.5% vs 10%) were not significantly different between the groups. In conclusion, patients with pericarditis and no endomyocardial biopsy indications of myocarditis had significantly less often life threatening rhythm disorders in contrast to patients with endomyocardial biopsy proven acute myocarditis/perimyocarditis. On the contrary, incidence of transitory atrial fibrillation was higher in acute pericarditis, than in myocarditis.

Prognostic Significance of Left Ventricular Aneurysms With Normal Global Function Caused by Myocarditis

To evaluate the prognosis of left ventricular (LV) aneurysms with normal global function caused by myocarditis. LV aneurysms may result from idiopathic or viral myocarditis. The prognosis of inflammatory LV aneurysms when associated with a normal cardiac function is unknown. Among 353 patients with a histologic diagnosis of myocarditis, 12 (3.3%) had single or multiple localized LV aneurysms (length, 10.6 +/- 3.1 mm; width, 7.4 +/- 4.2 mm) with normal cardiac function. Presenting symptoms were ventricular tachycardia (VT) in nine patients and unexplained chest pain in three. All patients underwent laboratory tests and noninvasive and invasive cardiac examinations, including biventricular endomyocardial biopsy. In all patients, LV endomyocardial biopsy specimen showed a lymphocytic myocarditis with focal intense myocytolysis or damage of intramural vessels, whereas right ventricular biopsy was diagnostic for myocarditis only in three. Serologic study suggested a viral infection in 3 patients and an immunologic disorder in 2, although it was negative in 7. Treatment included antiarrhythmics in 9 patients with VT, ss-blockers in 1 with chest pain, and immunosuppression (prednisone and azathioprine for 5 months) in 4 with active myocarditis (2 with chest pain and 2 with VT). At intermediate-term follow-up (mean, 53 months; range, 12 to 120 months), LV function was persistently normal in all patients, with an LV aneurysm occlusion being observed in two patients. All patients were asymptomatic, with no VT recurrence or major clinical events. None required implantable electrical devices or a surgical intervention. LV aneurysms with normal global function caused by myocarditis are an uncommon benign entity in which major therapeutic regimens are usually unnecessary.

Global biventricular dysfunction in patients with asymptomatic coronary artery disease may be caused by myocarditis.

The causal role of asymptomatic critical coronary artery obstruction in patients presenting with severe global biventricular dysfunction but no evidence of myocardial infarction is uncertain. Among 291 patients aged >40 years undergoing a noninvasive (2-dimensional echocardiography) and invasive (catheterization, coronary angiography, and biventricular endomyocardial biopsy, 6 to 8 samples/patient) cardiac study because of progressive heart failure (New York Heart Association functional class III or IV) with global biventricular dysfunction and no history of myocardial ischemic events, 7 patients (2.4%; 7 men; mean age, 49+/-6.9 years) had severe coronary artery disease (3 vessels in 4 patients; 2 vessels in 1 patient, proximal occlusion of left anterior descending coronary artery in 2 patients). Left ventricular end-diastolic diameter and ejection fraction by 2-dimensional echocardiography were 73+/-10.5 mm and 23+/-6.5%, respectively, and right ventricular end-diastolic diameter and ejection fraction were 39+/-7 mm and 29+/-7.2%, respectively. Biopsy specimens showed extensive lymphocytic infiltrates with focal myocytolysis meeting the Dallas criteria for myocarditis in all patients (in 5 patients with and 2 patients without fibrosis). Cardiac autoantibodies were detected with indirect immunofluorescence in the serum of 2 patients with active myocarditis. The 2 patients with active inflammation received prednisone (1 mg. kg-1. d-1 for 4 weeks followed by 0.33 mg. kg-1. d-1 for 5 months) and azathioprine (2 mg. kg-1. d-1 for 5 months) in addition to conventional drug therapy for heart failure. At 8-month overall follow-up, cardiac volume and function improved considerably in immunosuppressed patients but remained unchanged in conventionally treated patients, of whom 1 died. Global biventricular dysfunction in patients with severe asymptomatic coronary artery disease and no evidence of previous myocardial infarction may be caused by myocarditis. Histologic findings may influence the treatment.

Right Ventricular Aneurysm Associated With Advanced Hypertrophic Cardiomyopathy

A previously undescribed case of right ventricular aneurysm (RVA) associated with hypertrophic cardiomyopathy in an advanced stage is reported. The diagnosis was established by noninvasive (cardiac two-dimensional echocardiogram and nuclear MRI) and invasive (cardiac catheterization, angiography, and biventricular endomyocardial biopsy) cardiac examinations, which documented hypertrophied, dilated and hypokinetic biventricular chambers associated with typical histologic findings (histologic hypertrophic cardiomyopathy index of 66%). A prominent narrowing of myocardial arterioles, extended to the right ventricular myocardium, has been identified and has been hypothesized as being responsible for RVA formation.

Results of biventricular endomyocardial biopsy in survivors of cardiac arrest with apparently normal hearts: Am. J. Cardiol. 1994; 74/9: 890–895

Seventeen young patients (10 males and 7 females, aged 14 to 38 years, mean 26.4) without overt organic heart disease, who had been resuscitated from sudden cardiac arrest and referred to our institution during the period 1984 to 1993 for diagnostic evaluation and electrophysiologic study-guided antiarrhythmic therapy, were studied. Patients underwent noninvasive (electrocardiography, echocardiography [2-dimensional and Doppler], and magnetic resonance imaging) and invasive (left ventricular [LV], right ventricular [RV], and coronary angiography, ergonovine testing, electrophysiologic study, and biventricular endomyocardial biopsy) cardiac studies. Six to 8 biopsy fragments per patient were processed for histology and electron microscopy and read by a pathologist blinded to clinical data. Antiarrhythmic drug testing included amiodarone, propafenone, and metoprolol. A cardioverter-defibrillator was implanted in patients with persistently inducible sustained ventricular tachycardia or ventricular fibrillation. Sequential cardiac biopsy specimens were obtained in patients with active myocarditis undergoing immunosuppressive treatment. Periodic 3-month follow-ups included echocardiography and Holter monitoring. Two groups of patients were distinguished by invasive and noninvasive examinations: group I consisted of 9 patients with entirely normal parameters; group II consisted of 8 patients with structural, nonspecific cardiac abnormalities. In this latter group, mild to moderate dilatation and hypokinesia of the left ventricle were documented in 4 patients, concentric LV hypertrophy was seen in three patients, and RV dysfunction was noted in 1 patient. Histologic examination was abnormal in in all patients and revealed specific lesions in 65% of them; LV biopsy specimens allowed a diagnosis in 3 of 7 myocarditic patients with normal RV histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of biventricular endomyocardial biopsy in survivors of cardiac arrest with apparently normal hearts

Seventeen young patients (10 males and 7 females, aged 14 to 38 years, mean 26.4) without overt organic heart disease, who had been resuscitated from sudden cardiac arrest and referred to our institution during the period 1984 to 1993 for diagnostic evaluation and electrophysiologic study-guided antiarrhythmic therapy, were studied. Patients underwent noninvasive (electrocardiography, echocardiography [2-dimensional and Doppler], and magnetic resonance imaging) and invasive (left ventricular [LV], right ventricular [RV], and coronary angiography, ergonovine testing, electrophysiologic study, and biventricular endomyocardial biopsy) cardiac studies. Six to 8 biopsy fragments per patient were processed for histology and electron microscopy and read by a pathologist blinded to clinical data. Antiarrhythmic drug testing included antiodarone, propafenone, and metoprolol. A cardioverter-defibrillator was implanted in patients with persistently inducible sustained ventricular tachycardia or ventricular fibrillation. Sequential cardiac biopsy specimens were obtained in patients with active myocarditis undergoing immunosuppressive treatment. Periodic 3-month follow-ups included echocardiography and Holter monitoring. Two groups of patients were distinguished by invasive and noninvasive examinations: group I consisted of 9 patients with entirely normal parameters; group II consisted of 8 patients with structural, nonspecific cardiac abnormalities. In this latter group, mild to moderate dilatation and hypokinesia of the left ventricle were documented in 4 patients, concentric LV hypertrophy was seen in 3 patients, and RV dysfunction was noted in 1 patient. Histologic examination was abnormal in all patients and revealed specific lesions in 65% of them; LV biopsy specimens allowed a diagnosis in 3 of 7 myocarditic patients with normal RV histology. An active lymphocytic myocarditis was observed in 7 patients, hypertrophic cardiomyopathy in 3 patients, RV dysplasia in 1 patient, and nonspecific cardiomyopathic changes in 6 patients. At 38-month follow-up, the mortality rate was 29% (all deaths were sudden). Biventricular endomyocardial biopsy may identify diagnostic lesions in young survivors of cardiac arrest with apparently normal hearts. In some patients LV biopsies revealed myocarditis when RV biopsies were normal.