Ventricular Endomyocardial Biopsy Research Articles

Are Endomyocardial Ventricular Biopsies Useful for Assessing Myocardial Fibrosis?

Myocardial fibrosis is an important factor in the progression of cardiovascular diseases. However, there is still no universal lifetime method of myocardial fibrosis assessment that has a high prognostic significance. The aim of the study was to determine the significance of ventricular endomyocardial biopsies for the assessment of myocardial fibrosis and to identify the severity of myocardial fibrosis in different cardiovascular diseases. Material and Methods: Endomyocardial biopsies (EMBs) of 20 patients with chronic lymphocytic myocarditis (CM), endomyocardial fragments obtained during septal reduction of 21 patients with hypertrophic cardiomyopathy (HCM), and 36 patients with a long history of hypertensive and ischemic heart disease (HHD + IHD) were included in the study. The control group was formed from EMBs taken on 12-14 days after heart transplantation (n = 28). Also, for one patient without clinical and morphological data for cardiovascular pathology, postmortem myocardial fragments were taken from typical EMB and septal reduction sites. The relative area of fibrosis was calculated as the ratio of the total area of collagen fibers to the area of the whole biopsy. Endocardium and subendocardial fibrosis were not included in the total biopsy area. Results: The relative fibrosis area in the EMBs in the CM patient group was 5.6 [3.3; 12.6]%, 11.1 [6.6; 15.9]% in the HHD + IHD patient group, 13.4 [8.8; 16.7]% in the HCM patient group, and 2.7 [1.5; 4.6]% in the control group. When comparing the fibrosis area of the CM patients in repeat EMBs, it was found that the fibrosis area in the first EMBs was 7.6 [4.8; 12.0]%, and in repeat EMBs, it was 5.3 [3.2; 7.6]%. No statistically significant differences were found between the primary and repeat EMBs (p = 0.15). In ROC analysis, the area of fibrosis in the myocardium of 1.1% (or lower than one) was found to be highly specific for the control group of patients compared to the study patients. Conclusions: EMB in the assessment of myocardial fibrosis has a questionable role because of the heterogeneity of fibrotic changes in the myocardium.

Long-Term Clinical-Pathologic Results of Enzyme Replacement Therapy in Prehypertrophic Fabry Disease Cardiomyopathy.

The limited ability of enzyme replacement therapy (ERT) in removing globotriaosylceramide from cardiomyocytes is recognized for advanced Fabry disease cardiomyopathy (FDCM). Prehypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here on the long-term clinical-pathologic impact of ERT on prehypertrophic FDCM. Fifteen patients with Fabry disease with left ventricular maximal wall thickness ≤10.5 mm at cardiac magnetic resonance required endomyocardial biopsy because of angina and ventricular arrhythmias. Endomyocardial biopsy showed coronary small-vessel disease in the angina cohort, and vacuoles in smooth muscle cells and cardiomyocytes ≈20% of the cell surface containing myelin bodies at electron microscopy. Patients received α-agalsidase in 8 cases, and β-agalsidase in 7 cases. Both groups experienced symptom improvement except 1 patients treated with α-agalsidase and 1 treated with β-agalsidase. After ERT administration ranging from 4 to 20 years, all patients had control cardiac magnetic resonance and left ventricular endomyocardial biopsy because of persistence of symptoms or patient inquiry on disease resolution. In 13 asymptomatic patients with FDCM, left ventricular maximal wall thickness and left ventricular mass, cardiomyocyte diameter, vacuole surface/cell surface ratio, and vessels remained unchanged or minimally increased (left ventricular mass increased by <2%) even after 20 years of observation, and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed, with larger and more engulfed by globotriaosylceramide myocytes being associated with myocardial virus-negative lymphocytic inflammation. ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with prehypertrophic FDCM. Globotriaosylceramide is never completely removed even after long-term treatment. Immune-mediated myocardial inflammation can overlap, limiting ERT activity.

Can right ventricular endomyocardial biopsy predict left ventricular fibrosis beforehand in dilated cardiomyopathy?

Myocardial fibrosis of the left ventricle (LV) is a prognostic factor in dilated cardiomyopathy (DCM). This study aims to evaluate whether fibrosis of right ventricular (RV) endomyocardial biopsy (EMB) can predict the degree of LV fibrosis beforehand in DCM. Fibrosis extent in 70 RV-EMB specimens of DCM diagnosis was compared with that in the whole cross-sectional LV of excised hearts in the same patients (52 explanted hearts for transplant and 18 autopsied hearts). The median interval between biopsy and excision was 4.1 (0.13-19.3) years. The fibrosis area ratio of the EMBs and excised hearts were evaluated via image analysis. The distribution of cardiovascular magnetic resonance-late gadolinium enhancement (LGE) in the intraventricular septum was classified into four quartile categories. The fibrosis area ratio in RV-EMB correlated significantly with that in the short-axis cut of the LV of excised hearts (r=0.82, P<0.0001) and with a diffuse pattern of LGE (r=0.71, P=0.003). In a multivariate model, after adjusting for the interval between biopsy performance and heart excision, the fibrosis area ratio in RV-EMB was associated with that in LV-excised heart (regression coefficient, 0.82; 95% confidence interval, 0.68-0.95; P<0.0001). The fibrosis observed in RV-EMB positively correlated with the extent of fibrosis in the LV of excised hearts in patients with DCM. The study findings may help predict LV fibrosis, considered a prognostic factor of DCM through relatively accessible biopsy techniques.

Interleukin 17A-correlated myocarditis in patients with psoriasis: cardiac recovery following secukinumab administration

Abstract Background Psoriasis (PS) is a common immune-mediated disease of the skin with possible extension to joints, aorta and eye. Myocardial inflammation has been rarely suggested. Purpose Report of PS-related myocarditis. Methods One hundred consecutive patients with PS were screened for cardiac involvement. Among them, five male patients (aged 56 ± 9.5 years) with moderate-severe form showed a dilated cardiomyopathy (LVEF &amp;lt;35%) with normal coronary arteries and valves. They underwent a left ventricular endomyocardial biopsy for evaluation of myocardial substrate. Endomyocardial samples were processed for histology and immunohistochemistry, including myocardial expression of Toll-Like Receptor 4 (TLR4) and interleukin-17A (IL-17A), which plays a major role in psoriasis pathogenesis; real-time PCR for cardiotropic viruses and Western blot analysis for myocardial expression of IL-17A. Patients’ sera were tested for anti-heart autoantibodies. Results An active lymphocytic myocarditis was revealed in all 5 patients, characterized by absence of viral genomes at PCR, positive anti-heart autoantibodies, overexpression of TLR-4 and enhancement of IL-17-A at western blot analysis showing a 2,48-fold increase in psoriatic myocarditis compared with no psoriatic myocarditis and a 6-fold increase compared to myocardial controls. Treatment included combination of prednisone (1 mg/Kg daily for 4 weeks, tapered to 0.33 mg/Kg) + azathioprine (2 mg/Kg, daily) in 3 pts or secukinumab (SK, 100 mg/monthly) in 2 pts for 6 months. LVEDD and LVEF improved in the first 3 pts (-14% and + 118%, respectively) while completely recovered (LVEF&amp;gt; 50%) in the last 2 pts on SK. Conclusion IL-17A-related myocarditis can occur in up-to 5% of patients with psoriasis. It manifests as a progressive dilated cardiomyopathy. It may completely recover following SK administration. Figure Legend Endomyocardial biopsy findings from pt 5 with PS-related myocarditis including histology (panel A). Immune-histochemistry for IL 17-A (panel B) and anti-heart abs (panels C, D). It shows an active lymphocytic myocarditis with overexpression of IL 17-A and positive anti-heart abs (panel C), cross-reacting with skeletal muscle (panel D).

Tachycardie ventriculaire récidivante révélant une sarcoïdose cardiaque

Sarcoidosis is an inflammatory disease whose diagnosis is suggested by clinical and paraclinical signs and confirmed by histological evidence showing granulomatosis without caseous necrosis. The clinical presentation is sometimes misleading and the diagnosis difficult to confirm. We report here the case of a young woman with cardiac sarcoidosis of difficult diagnosis, revealed by a myocardial infarction with normal coronary angiography and recurrent ventricular tachycardia. Multimodal imaging, combined with left ventricular endomyocardial biopsies guided by electrophysiological analysis and endocavitary mapping, finally confirmed the diagnosis, and allowed effective medical treatment.

Percutaneous device closure of hemodynamically significant coronary fistula following endomyocardial biopsy in a pediatric heart transplant patient.

Coronary artery fistula is a rare but well-documented complication of right ventricular endomyocardial biopsy, particularly in the adult population. Typically, these fistulae never reach clinical or hemodynamic significance, but some may cause coronary steal and ventricular dysfunction. We report a case of a significant coronary artery fistula requiring device closure in the cardiac catheterization laboratory with subsequent improvement of clinical symptoms and cardiac function.

Application of left ventricular endomyocardial biopsy in the diagnosis of mitochondrial cardiomyopathy: a case report

BackgroundThe clinical features of mitochondrial cardiomyopathy (MCM) are diverse. It can present as hypertrophic cardiomyopathy or dilated cardiomyopathy. The diagnosis of MCM is challenging and usually based on biopsy.Case presentationThe 30-year-old man was admitted to hospital due to dyspnea for 1 month and edema of both lower extremities for 1 week. Echocardiography suggested a whole heart enlargement, a whole heart diminished function. Renal impairment and diabetes were observed. Coronary angiography showed single-vessel disease (90% stenosis in the ostium of a small marginal branch). Left ventricular endomyocardial biopsy was performed.ConclusionMyocardial histopathology demonstrated a large number of abnormal mitochondrial accumulation, so the diagnosis was considered as mitochondrial cardiomyopathy.

Circulating Anti-GB3 Antibody as a Biomarker of Myocardial Inflammation in Patients with Fabry Disease Cardiomyopathy.

Fabry disease cardiomyopathy (FDCM) has manifested some resistance to enzyme replacement therapy (ERT), particularly in its advanced phase. Recently, myocardial inflammation of autoimmune origin has been demonstrated in FDCM. The objective of this study was the assessment of circulating anti-globotriaosylceramide (GB3) antibodies as potential biomarkers of myocardial inflammation in FDCM, defined by the additional presence of ≥CD3+ 7 T lymphocytes/low-power field associated with focal necrosis of adjacent myocytes. Its sensitivity was based on the evidence of overlapping myocarditis at left ventricular endomyocardial biopsy. From January 1996 to December 2021, 85 patients received a histological diagnosis of FDCM in our department and 48 (56.5%) of them had an overlapping myocardial inflammation with negative PCR for common cardiotropic viruses, positive antiheart, and antimyosin abs. The presence of anti-GB3 antibodies was evaluated with an in-house ELISA assay (BioGeM scarl Medical Investigational Research, MIR-Ariano Irpino, Italy), along with antiheart and antimyosin abs, in the FDCM patients and compared with control healthy individuals. The correlation between levels of circulating anti-GB3 autoantibody myocardial inflammation and FDCM severity was assessed. Anti-Gb3 antibodies were above the positivity cut-off in 87.5% of FDCM subjects with myocarditis (42 out of 48), while 81.1% of FDCM patients without myocarditis were identified as negative for Gb3 antibodies. Positive anti-Gb3 abs correlated with positive antiheart and antimyosin abs. The present study suggests a potential positive role of anti-GB3 antibodies as a marker of overlapping cardiac inflammation in patients with FDCM.

P354 REMOVAL OF CARDIAC AL–AMYLOID LEADS TO CARDIOMYOCYTE POSITIVE REMODELING AND RESTRICTIVE PATTERN REVERSAL

Abstract Background Properly treated AL cardiac amyloidosis can have a long survival. However, the mechanism involved in arresting or reversing cardiomyopathy, such as toxic suppression of the light chain or removal of the amyloid substance, is still unclear. We describe the case of a patient with AL amyloidosis treated with chemotherapy in whom serial endomyocardial biopsies were performed at diagnosis and after 17 years. Clinical case A 71–year–old lady onset with a hypertrophic phenotype cardiomyopathy (maximum thickness LV 18.2 mm, diastolic dysfunction with E/A ratio 2.45. preserved contractility (EF 55%) and NYHA class 3) received a diagnosis in 2004 of AL amyloidosis and underwent several cycles of chemotherapy. At clinical onset, cardiac amyloidosis was documented by endomyocardial biopsy. After 17 years, in 2021, the patient was hospitalized for palpitations and chest pain and documented intermittent phases of atrial fibrillation. The patient was reevaluated with immunoelectrophoresis, echocardiogram, cardiac magnetic resonance, coronary angiography, and left ventricular endomyocardial biopsy. Serum monoclonal chain AL–K was reduced from initial 233 mg/L to 18.2 mg/L, vn&amp;lt;19.4 mg/L. The echocardiogram showed reduction of the heart walls with reduction of the thickness to 14 mm, with regression of the restrictive pattern (E/A ratio from 2.45 to 0.5). Serum NT–proBNP decreased from 3188 pg/mL to 480 pg/mL (n.v.&amp;lt;334 pg/mL). Cardiac MRI revealed normal myocardial wall thickness, with preserved systolic function, in the absence of the typical late gadolinium enhancement pattern. Histology and electron microscopy showed no more hypo/atrophic cardiomyocytes and the interstitium was almost completely devoid of amyloid fibrils, which were distant from the cardiac cell allowing an improvement in oxygenation and trophism. Conclusions Remission of monoclonal gammopathy is associated with a removal of cardiac amyloid deposits and with a regression of cardiac hypertrophy and restrictive pattern. Histologically, the degradation of amyloid fibrils determines a better trophism of cardiomyocytes.

Aortic valve calcification and myocardial fibrosis determine outcome following transcatheter aortic valve replacement.

There is evidence to suggest that the subtype of aortic stenosis (AS), the degree of myocardial fibrosis (MF), and level of aortic valve calcification (AVC) are associated with adverse cardiac outcome in AS. Because little is known about their respective contribution, we sought to investigate their relative importance and interplay as well as their association with adverse cardiac events following transcatheter aortic valve replacement (TAVR). One hundred consecutive patients with severe AS and indication for TAVR were prospectively enrolled between January 2017 and October 2018. Patients underwent transthoracic echocardiography, multidetector computed tomography, and left ventricular endomyocardial biopsies at the time of TAVR. The final study cohort consisted of 92 patients with a completed study protocol, 39 (42.4%) of whom showed a normal ejection fraction (EF) high-gradient (NEFHG) AS, 13 (14.1%) a low EF high-gradient (LEFHG) AS, 25 (27.2%) a low EF low-gradient (LEFLG) AS, and 15 (16.3%) a paradoxical low-flow, low-gradient (PLFLG) AS. The high-gradient phenotypes (NEFHG and LEFHG) showed the largest amount of AVC (807±421 and 813±281mm3 , respectively) as compared with the low-gradient phenotypes (LEFLG and PLFLG; 503±326 and 555±594mm3 , respectively, P<0.05). Conversely, MF was most prevalent in low-output phenotypes (LEFLG>LEFHG>PLFLG>NEFHG, P<0.05). This was paralleled by a greater cardiovascular (CV) mortality within 600days after TAVR (LEFLG 28%>PLFLG 26.7%>LEFHG 15.4%>NEFHG 2.5%; P=0.023). In patients with a high MF burden, a higher AVC was associated with a lower mortality following TAVR (P=0.045, hazard ratio 0.261, 95% confidence interval 0.07-0.97). MF is associated with adverse CV outcome following TAVR, which is most prevalent in low EF situations. In the presence of large MF burden, patients with large AVC have better outcome following TAVR. Conversely, worse outcome in large MF and relatively little AVC may be explained by a relative prominence of an underlying cardiomyopathy. The better survival rates in large AVC patients following TAVR indicate TAVR induced relief of severe AS-associated pressure overload with subsequently improved outcome.

18F-FDG/13N-ammonia cardiac PET findings in ATTR cardiac amyloidosis

18F-flurodeoxyglycose (FDG)/13N-ammonia positron emission tomography/computed tomography (PET/CT) is frequently utilized to evaluate cardiac sarcoidosis (CS) but findings can reflect other forms of myocardial inflammation or altered myocardial metabolic activity. Herein, we present five cases where cardiac PET findings suggested CS, but right ventricular endomyocardial biopsy samples revealed ATTR-type cardiac amyloidosis.

Infiltration of Conduction Tissue Is a Major Cause of Electrical Instability in Cardiac Amyloidosis

The pathology of conduction tissue (CT) and relative arrhythmias in living subjects with cardiac amyloid have never been reported. To report CT pathology and its arrhythmic correlations in human cardiac amyloidosis. In 17 out of 45 cardiac amyloid patients, a left ventricular endomyocardial biopsy included conduction tissue sections. It was identified by Aschoff-Monckeberg histologic criteria and positive immunostaining for HCN4. The degree of conduction tissue infiltration was defined as mild when ≤30%, moderate when 30-70% and severe when >70% cell area was replaced. Conduction tissue infiltration was correlated with ventricular arrhythmias, maximal wall thickness and type of amyloid protein. Mild involvement was observed in five cases, moderate in three and severe in nine. Involvement was associated with a parallel infiltration of conduction tissue artery. Conduction infiltration correlated with the severity of arrhythmias (Spearman rho = 0.8, p < 0.001). In particular, major ventricular tachyarrhythmias requiring pharmacologic treatment or ICD implantation occurred in seven patients with severe, one patient with moderate and none with mild conduction tissue infiltration. Pacemaker implantation was required in three patients, with complete conduction section replacement. No significant correlation was observed between the degree of conduction infiltration and age, cardiac wall thickness or type of amyloid protein. Amyloid-associated cardiac arrhythmias correlate with the extent of conduction tissue infiltration. Its involvement is independent from type and severity of amyloidosis, suggesting a variable affinity of amyloid protein to conduction tissue.

Proteomic signatures predict depressed cooperativity and increased calcium sensitivity in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) affects over half of all heart failure patients. We recently reported several deficits in the tension-calcium relationship from isolated skinned cardiomyocytes from HFpEF patients, including depressed cooperativity, increased calcium sensitivity, and depressed maximum tension. Here, we sought to identify whether proteomic signatures associate with these deficits. We obtained total proteomic profiles, consisting of 2250 proteins, from right ventricular endomyocardial biopsies in 43 patients. Machine learning based cluster analysis revealed two clusters of proteomic profiles, Group 1 (n=31) and Group 2 (n=12). Compared to Group 1, patients in Group 2 had depressed E/A ratio (p=0.048) and smaller left ventricles (p=0.02) on echocardiography, right ventricular dysfunction (p=0.08) on right heart catheterization, and worsened HF symptoms based on New York Heart Association functional class (p=0.054). Analysis of tension-calcium relationships revealed that myocytes from Group 2 had a higher Hill coefficient (p=0.0001), indicative of better cooperativity, and increased calcium sensitivity (p=0.001), but no differences in maximum tension. We next identified which proteins correlated with Hill coefficient and calcium sensitivity using univariate regression. We found that 330 proteins negatively correlated with Hill coefficient, while 298 proteins positivity correlated with calcium sensitivity, corresponding more to Group 2. Gene ontology pathway analysis revealed these proteins (either set) were enriched for metabolic processes, including fatty acid metabolism, mitochondrial respiration, and cellular biosynthetic processes. This poses an intriguing linkage between downregulation of mitochondrial metabolic processes and enhanced cooperativity and calcium sensitivity. The latter is reported in HF with reduced EF, but the former seems unique to HFpEF. Metabolite perturbations may affect sarcomere post-translational modification, driving shifts in cooperativity and calcium sensitivity. Further studies are ongoing to identify the cause of these myofilament calcium-tension changes and implications.

Abstract 10450: Interleukin-17A-Correlated Myocarditis in Patients With Psoriasis

Background. Psoriasis is a common immune-mediated disease of the skin with possible extension to joints, aorta and eye. Myocardial inflammation has been rarely suggested. However, its incidence and pathologic mechanism have not been elucidated so far. Methods. One hundred consecutive patients (62M/38F, mean age 55 ± 13.7 years) with psoriasis were screened for cardiac involvement. Among them, five male patients (mean age 56 ± 9.5 years) showed a dilated cardiomyopathy (LVEF &lt; 40%) with normal coronary arteries and valves, and underwent a left ventricular endomyocardial biopsy for evaluation of myocardial substrate. Endomyocardial samples were processed for histology and immunohistochemistry, including myocardial expression of Toll-Like Receptor 4 (TLR4) and interleukin-17A (IL-17A), which plays a major role in psoriasis pathogenesis. Real-time PCR for cardiotropic viruses and Western blot analysis for myocardial expression of IL-17A were also performed. As controls for IL-17A expression, myocardial samples from 10 male patients with inflammatory cardiomyopathy and no psoriasis were included. Patients’ sera were tested for anti-heart autoantibodies. Results. An active lymphocytic myocarditis was revealed in all 5 patients, characterized by absence of viral genomes at PCR, positive anti-heart autoantibodies, overexpression of TLR-4 and of IL-17A at both immunohistochemistry (Figure 1A vs 1B) and Western blot analysis (mean value 44 ± 6.7 vs 12 ± 61.9 in patients with no-psoriatic myocarditis and 4± 1.5 in normal controls; Figure 1C). Conclusion. Interleukin-17A-related myocarditis can occur in up-to 5% of patients with psoriasis. It manifests as a progressive dilated cardiomyopathy that can potentially benefit from immunosuppression or monoclonal antibodies as the skin disease.

Downregulation of Mannose-6-Phosphate Receptors in Fabry Disease Cardiomyopathy: A Potential Target for Enzyme Therapy Enhancement.

Background: The efficacy of enzyme replacement therapy (ERT) in mobilizing globotryaosylceramide (GB-3) from Fabry cardiomyocytes is limited. The mechanism involved is still obscure. Methods: Assessment of M6Pr, M6Pr-mRNA, and Ubiquitin has been obtained by Western blot analysis and real-time PCR of frozen endomyocardial biopsy samples, from 17 pts with FD, various degree of left ventricular hypertrophy, and maximal wall thickening (MWT) from 11.5 and 20 mm. The diagnosis and severity of FDCM followed definitions of GLA mutation, α-galactosidase A enzyme activity, cardiac magnetic resonance, and left ventricular endomyocardial biopsy with the quantification of myocyte hypertrophy and the extent of Gb-3 accumulation. All patients have received alpha or beta agalsidase for ≥3 years without a reduction in LV mass nor an increase in T1 mapping at CMR. Controls were surgical biopsies from 15 patients undergoing mitral valve replacement. Results: Protein analysis showed mean M6Pr in FDCM to be 5.4-fold lower than in a normal heart (4289 ± 6595 vs. 23,581 ± 4074, p = 0.0996) (p < 0.001): specifically, 9-fold lower in males, p = 0.009, (p < 0.001) and 3-fold lower in females, p = 0.5799, (p < 0.001) showing, at histology, a mosaic of normal and diseased cells. M6Pr-mRNA expression was normal, while ubiquitin showed an increase of 4.6 fold vs. controls (13,284 ± 1723 vs. 2870 ± 690, p = 0.001) suggesting that ubiquitin-dependent post-translational degradation is likely responsible for the reduction of M6Pr in FDCM. Conclusion: M6Pr expression is remarkably reduced in FDCM as a likely result of post-translational degradation. This may explain the reduced efficacy of ERT and be a therapeutic target for the enhancement of ERT activity.

Findings and Outcome of Transcatheter Right Ventricular Endomyocardial Biopsy and Hemodynamic Assessment in Children with Suspected Myocarditis or Cardiomyopathy.

Objective: The study objective is assessing findings and outcome in children with suspected cardiomyopathy (CMP) or myocarditis undergoing cardiac catheterization with transcatheter right ventricular endomyocardial biopsy (RV-EMB). Methods: All consecutive children undergoing cardiac catheterization with RV-EMB for suspected CMP/myocarditis between 2002–2021 were analysed regarding clinical presentation, cardiac biomarkers, periprocedural management, hemodynamic, histological/immunohistological findings, and outcome. Results: Eighty-five RV-EMBs were performed in 81 patients at a median age of 6.8 (IQR 9.9) years and a bodyweight of 20 (32.2) kg. Histological/immunohistological findings of RV-EMB revealed dilated CMP in 10 (12%), chronic myocarditis in 28 (33%), healing myocarditis in 5 (6%), acute myocarditis in 9 (11%), other heart muscle diseases in 23 (27%) (7 restrictive CMP, 5 hypertrophic CMP, 4 toxic/anthracycline-induced CMP, 4 endocardfibroelastosis, 1 arrhythmogenic right ventricular CMP, 1 laminin CMP, 1 haemangioma), no conclusive histology in 7 (8%), and normal histology in 3 (4%) patients. Median LVEDP was 17 mmHg (IQR 9), LAP 15 mmHg (10), and PVR 1.83 (1.87) Wood Units/m2. There were 3 major complications (3%), all patients recovered without any sequelae. At follow-up (median 1153, IQR 1799 days) 47 (59%) patients were alive, 11 (13%) dead, 15 (18%) underwent cardiac transplantation, and 8 (9%) were lost to follow-up. Death/cardiac transplantation occurred within 3 years from RV-EMB. All patients with an acute myocarditis survived. NT-pro-BNP, echo parameters, and invasive hemodynamics correlate independently with death/cardiac transplant. Conclusion: Hemodynamic invasive data and morphological findings in RV-EMB complete clinical diagnosis in children with suspected CMP/myocarditis and provide important information for further clinical management.

Safety and usefulness of left ventricular endomyocardial biopsy in new- onset acute heart failure requiring mechanical support by an Impella® device

BackgroundIn patients with de novo acute heart failure (AHF) requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO), endomyocardial biopsy (EMB) has been recently shown to be feasible and a helpful method to clarify differential diagnoses, including acute myocarditis. This study aimed to evaluate the feasibility and safety of EMB in patients with a left ventricular (LV) implanted Impella® device. Methods and resultsThis retrospective, single-center study involves 22 cardiogenic shock patients [SCAI shock stage: C (91%)] requiring mechanical circulatory support (MCS) either by Impella® axial pumps [20 patients (91%)] alone or in combination with VA-ECMO [2 patients (9%)] between December 2017 and January 2022. Coronary artery disease (CAD) or severe valvular heart disease were excluded. The study's primary endpoint was to verify the safety of EMB during MCS. Furthermore, histopathological analysis of the EMB samples was described. 30 LV-EMB procedures were performed. No major complications were reported (death, sustained ventricular tachycardia, need for cardiopulmonary resuscitation, cardiac tamponade, stroke, major bleeding). In 14 patients (64%), EMB-derived histology/immunohistology led to the definitive diagnosis of acute myocarditis. ConclusionsEMB can be safely performed in patients suffering from cardiogenic shock requiring an Impella®-based MCS without the risk of major complications. In about 50% of the patients, relevant inflammatory heart disease could be detected, which required a change in treatment decisions.

Utility of Intracardiac Echocardiography to Biopsy Cardiac Tumors

<h3>Introduction</h3> Primary cardiac tumors are extremely rare and associated with poor prognosis, mainly due to its nonspecific symptoms and delayed diagnosis. Tissue diagnosis is the gold standard which often requires open-chest procedures, which itself has a high rate of complications. Alternatives include emerging utilization of intracardiac echocardiography (ICE) - guided biopsy which commonly used for atrial septal closure and advanced electrophysiology procedures, but can be ideally suited for imaging right heart structures. <h3>Case Report</h3> A 62-year-old female with history of left forearm peripheral sheath sarcoma with transhumeral amputation, initially presented for post-MVA care where the CT chest revealed two lung nodules of 1 cm. She was discharged in stable condition and presented a month later for palpitations and diffuse abdominal pain. A repeat chest CT revealed a 5 × 4 c.m. right atrial mass with large pericardial effusion. Pericardiocentesis of 500 cc fluid had negative cytology and TTE showed right atrial free wall mass extending into the tricuspid annulus and into the right atrial cavity. Patient was referred to us for further diagnostic management given the complexity of the cardiac mass. She underwent intracardiac echocardiography with right femoral vein access under local anesthesia. The ICE catheter was advanced through the 8 French sheaths and key images were obtained of the right atrial mass to guide bioptome targeting. A 1.85mm/2.46 mm3 Procure bioptome was advanced under direct fluoroscopic guidance into the right atrium and 3 right ventricular endomyocardial biopsy samples were obtained. Patient tolerated the procedure well without any immediate postoperative complications. The biopsy results showed tissue composed of spindle cells with hyperchromatic pleomorphic nuclei and high mitotic ratio (score 3), changes that are consistent with unclassified high-grade sarcoma. However, patient passed away due to disease progression over the course of the next few months. <h3>Summary</h3> In our study, we demonstrated the feasibility of utilizing ICE for intracardiac mass biopsy on the right side of the heart. It is an innovative and well-described procedure for intracardiac mass that avoids usage of general anesthesia, avoids radiation exposure to the patients and the physicians, and decreases the complications rate as compared to alternate options such as open-chest procedures.

Hypersensitivity Myocarditis after COVID-19 mRNA Vaccination.

Background: Myocarditis, even in a severe and lethal form, may occur after COVID-19 mRNA (BNT162b2) vaccination. However, its pathway, morphomolecular characterization and treatment are still unknown. Methods: Routine hematochemical screening, ECG, Holter monitoring, 2D echocardiogram cardiac magnetic resonance (CMR) and invasive cardiac studies (cardiac catheterization, selective coronary angiography, left ventriculography and left ventricular endomyocardial biopsy) are reported from three patients (39F-pt1, 78M-pt2, 52M-pt3) with severe compromise of conduction tissue (junctional rhythm and syncope, pt1) or cardiac function compromise (LVEF ≤ 35%, pt2 and pt3) after COVID-19 mRNA (BNT162b2). Results: Hematochemical data and coronary angiography were normal in the patients studied. Histology showed in all three patients extensive myocardial infiltration of degranulated eosinophils and elevation of serum cationic protein directly responsible for cardiomyocyte damage. These findings demonstrate myocarditis hypersensitivity to some component of the vaccine (spike protein?) acting as a hapten to some macromolecules of cardiomyocytes. Steroid administration (prednisone, 1 mg/kg die for 3 days, followed by 0.33 mg/kg for 4 weeks) was followed by complete recovery of cardiac contractility in pt2 and pt3. Conclusions: Eosinophilic myocarditis is a possible adverse reaction to the mRNA COVID-19 vaccine. Its pathway is mediated by release of cationic protein and responds to short courses of steroid administration.

The presence of E-selectin in the myocardium indicates a sustained inflammatory reaction in patients with dilated cardiomyopathy

BackgroundIt is still uncertain whether de-novo expression of E-selectin in endothelial cells may be considered an additional marker of chronic inflammation in heart failure (HF). MethodsWe studied 393 consecutive patients (313 M, 80 F) with HF secondary to dilated cardiomyopathy in whom the right ventricular endomyocardial biopsy was performed. For immunohistochemistry, HLA class I and II, E-selectin (ELAM-1), CD3 + lymphocytes and CD68 + macrophages were studied. Patients were divided into two groups: Group A, with ELAM-1 (+), and Group B with ELAM-1 (-) in the biopsy sections. ResultsOf all patients, 140 (35.6%) subjects were presented with ELAM-1 expression in endomyocardial biopsies. Patients in the Group A had a significantly lower LV ejection fraction compared to those from the Group B (31.3 ± 12.9 vs. 34.2 ± 12.7; 95% CI, 0.3–5.6, P = 0.029) and they showed a higher mean number of CD3 (+) lymphocytes in the biopsy sections, P = 0.006. In addition, ELAM-1 reasonably correlated with CD3 lymphocytes (r = 0.3, P < 0.001). ConclusionsOur findings suggest that de-novo ELAM-1 expression in endothelial cells may be a useful marker of chronic inflammation in the biopsies of patients with HF secondary to dilated cardiomyopathy.