Intracardiac echocardiography-guided biopsies for right-sided intracardiac tumors: An optimized diagnostic algorithm and case illustrations.

Intracardiac tumors, though uncommon, necessitate a swift and accurate diagnosis for personalized treatment and prognosis estimation. While multi-modality imaging often determines the etiology of these cardiac masses, histological confirmation remains essential for definitive diagnosis and its specific treatment. Since cardiac tumors are often found in high-risk locations (ventricular free wall or atria), precision biopsy is paramount. The least invasive strategy would be to achieve this by means of endomyocardial biopsy (EMB); however real-time additional imaging is essential to reduce the risk of perforation/tamponade and to minimize sampling error. Intracardiac echocardiography (ICE) emerges as an excellent tool to achieve this goal preventing procedural complications and reducing the likelihood of sampling errors obtaining a definitive histopathological diagnosis in all cases. This paper outlines our diagnostic algorithm for optimal patient selection, details three illustrative cases, and elucidates the steps to acquire histopathology via percutaneous transvenous biopsy with ICE guidance in patients with right-sided cardiac tumors. Given the rarity of intracardiac tumors, we advocate these patients be managed by a dedicated multidisciplinary cardio-oncology team including an interventional cardiologist.

The inflammatory spectrum of cardiomyopathies.

Infiltration of the myocardium with various cell types, cytokines and chemokines plays a crucial role in the pathogenesis of cardiomyopathies including inflammatory cardiomyopathies and myocarditis. A more comprehensive understanding of the precise immune mechanisms involved in acute and chronic myocarditis is essential to develop novel therapeutic approaches. This review offers a comprehensive overview of the current knowledge of the immune landscape in cardiomyopathies based on etiology. It identifies gaps in our knowledge about cardiac inflammation and emphasizes the need for new translational approaches to improve our understanding thus enabling development of novel early detection methods and more effective treatments.

Doppler echocardiography for surveillance of acute cardiac allograft rejection: a 28-year single-center experience.

Background: Endomyocardial biopsies (EMB) are recommended for the detection of acute cardiac rejection (ACR) despite limited sensitivity. We report the long-term post-transplant results of Doppler echocardiography as a noninvasive alternative of routine EMB. Methods: Two cohorts of heart transplantation (HT) recipients were chronologically defined as follows: the Dual Monitoring Cohort (DMC) from January 1990 to December 1997 included patients who underwent routine EMB and Doppler echocardiography within 24 hours for ACR surveillance; and the "Echo-First Cohort" (EFC), including patients transplanted from January 1998 to December 2018 with Doppler echocardiography as first-line approach for ACR surveillance. Echocardiographic measurements of interest were collected: early diastolic (E) wave peak velocity; pressure half time (PHT) and isovolumetric relaxation time (IVRT). Post-transplant outcomes were reviewed and the Kaplan-Meier approach was used for survival estimates. Inter-operator variability for ultrasound measurements was investigated. Data were collected from medical records from January 2019 to December 2020. Results: A total of 228 patients were included, 99 patients in the DMC and 129 in the EFC. Overall, 5-, 10- and 15-year survival rates were 65.4%, 55.5% and 44.1% respectively, without any significant difference between the two cohorts (log rank test, P=0.71). Echocardiography variables and EMB findings were associated with a mean area under the receiver operating characteristic curve (AUC-ROC) of 0.73 [95% confidence interval (CI): 0.54-0.91], 0.74 (95% CI: 0.54-0.94) and 0.75 (95% CI: 0.57-0.94) respectively for E wave, PHT and IVRT. IVRT and PHT were significantly decreased, and E wave significantly increased, in case of histologically proven ACR. Inter-operator variability was not significant for E wave and IVRT measurements (P=0.13 and 0.30 respectively). Conclusions: Doppler echocardiography as a first-line method for surveillance of ACR did not impair long-term results after HT. These findings suggest that this non-invasive approach might be a reasonable alternative to systematic EMB, limiting risk and improving the quality of life.

A gentler approach to monitor for heart transplant rejection.

Despite developments in circulating biomarker and imaging technology in the assessment of cardiovascular disease, the surveillance and diagnosis of heart transplant rejection has continued to rely on histopathologic interpretation of the endomyocardial biopsy. Increasing evidence shows the utility of molecular evaluations, such as donor-specific antibodies and donor-derived cell-free DNA, as well as advanced imaging techniques, such as cardiac magnetic resonance imaging, in the assessment of rejection, resulting in the elimination of many surveillance endomyocardial biopsies. As non-invasive technologies in heart transplant rejection continue to evolve and are incorporated into practice, they may supplant endomyocardial biopsy even when rejection is suspected, allowing for more precise and expeditious rejection therapy. This review describes the current and near-future states for the evaluation of heart transplant rejection, both in the settings of rejection surveillance and rejection diagnosis. As biomarkers of rejection continue to evolve, rejection risk prediction may allow for a more personalized approach to immunosuppression.

Heart Transplant Rejection: From the Endomyocardial Biopsy to Gene Expression Profiling.

Heart transplant prolongs life for patients with end-stage heart failure but rejection remains a complication that reduces long-term survival. The aim is to provide a comprehensive overview of the current status in HT rejection. EMB is an invasive diagnostic tool, consisting in the sampling of a fragment of myocardial tissue from the right ventricular septum using fluoroscopic guidance. This tissue can later be subjected to histopathological, immunohistochemical or molecular analysis, providing valuable information for cardiac allograft rejection, but this procedure is not without complications. To increase the accuracy of the rejection diagnosis, EMB requires a systematic evaluation of endocardium, myocardium, interstitium and intramural vessels. There are three types of rejection: hyperacute, acute or chronic, diagnosed by the histopathological evaluation of EMB as well as by new diagnostic methods such as DSA, ddcfDNA and gene expression profiling, the last having a high negative predictive value. More than 50 years after the introduction of EMB in medical practice, it still remains the "gold standard" in monitoring rejection in HT recipients but other new, less invasive diagnostic methods reduce the number of EMBs required.

Danon Disease Presenting as Eosinophilic Myocarditis: Key Role of Endomyocardial Biopsy.

A 21-year-old woman with a history of atopy, peripheral eosinophilia, Wolf-Parkinson-White syndrome, and 5 episodes of myocarditis was diagnosed with eosinophilic myocarditis. Despite adequate immunosuppressive treatment and resolution of the myocarditis episode, the patient developed dilated cardiomyopathy and presented with worsening of her functional class. Finally, genetic testing unveiled an additional diagnosis: Danon disease. (Level of Difficulty: Advanced.).

Soluble tumor endothelial marker 1 in heart failure with reduced ejection fraction: A pilot study.

Background: Tumor endothelial marker 1 (TEM1/CD248) is a transmembrane protein that expresses in mesenchymal lineage derived cells during embryogenesis and becomes undetectable in normal adults after birth. Re-expression of TEM1 is found in organ fibrosis, wound healing and cardiac remodeling indicating its potential role in heart failure (HF). The purpose of this study is to explore the role of soluble TEM1 (sTEM1) in patients with HF with reduced ejection fraction. Methods: We examined endomyocardial biopsy specimens from three HF patients and blood samples from 48 patients admitted for acute decompensated HF (age 72 years, men 61.7%). The expression of TEM1 in cardiac tissue and concentrations of sTEM1 in plasma were evaluated. Cultured rat cardiomyocytes (H9c2) and human cardiac fibroblasts (HCF) were stimulated with hypoxia or transforming growth factor beta (TGF-ß) to observe the release of sTEM1 into culture media. The conditioned media of hypoxia-stimulated H9c2 cells was harvested and added into cultured cardiac fibroblast to evaluate its biological effect. Results: Immunofluorescence study of biopsy specimens from three HF patients showed TEM1 expression in cardiomyocytes and cardiac fibroblasts. The plasma level of sTEM1 was significantly higher in patients (0.90 ± 0.23 vs. 0.33 ± 0.10 ng/mL, p = 0.032) with LVEF ≤ 35% compared with those with LVEF 36-49%. The sTEM1 levels had correlations with HF biomarkers of cardiac fibrosis, including growth differentiation factor-15 (GDF-15) and galectin-3. There was a significant increase in sTEM1 levels in the cultured media of H9c2 and HCF after being stressed with hypoxia or TGF-ß. The conditioned media derived from hypoxia-stimulated H9c2 cells significantly increased cell proliferation of cardiac fibroblasts. This effect was partially reversed by anti-TEM1 antibody. Conclusion: This pilot study demonstrated that cardiac TEM1 expression was upregulated in HF. The levels of sTEM1 were significantly higher in HF patients with LVEF ≤ 35% and correlated with other biomarkers of cardiac fibrosis. In vitro study proved that functional sTEM1 was released into cultured media after stressing cardiomyocytes and HCF.

Case Report: Myocarditis After COVID-19 Vaccination - Case Series and Literature Review.

BACKGROUND: The ongoing COVID-19 pandemic demands a series of measures and, above all, the vaccination of a substantial proportion of the population. Acute myocarditis is a rare complication of the widely used mRNA-based vaccines. CASE PRESENTATION: We present a case series of four patients (three men and one woman, 16 to 47 years old) with acute pericarditis/myocarditis 3 to 17 days after mRNA vaccination. They presented with chest pain, fever, and flu-like symptoms. Diagnosis was made based on the synopsis of clinical presentation, elevated levels of troponin T and NT-proBNP, impaired systolic function on echocardiography, and findings in non-invasive tissue characterization by cardiovascular magnetic resonance imaging. Two patients also underwent endomyocardial biopsies. As none of the patients showed signs of cardiogenic shock, they were discharged from ward care only a few days after their initial presentations. CONCLUSIONS: Our data are consistent with other case reports of myocarditis early after mRNA vaccination and demonstrate the need for multimodal diagnostics. In view of its rarity and mild course, the risk-benefit ratio of vaccination remains positive compared to potential SARS-CoV-2 infection.

Endomyocardial biopsy in differential diagnosis between arrhythmogenic right ventricular cardiomyopathy and dilated cardiomyopathy: an in vitro simulated study.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) and dilated cardiomyopathy (DCM), despite being two dramatically different entities, have overlapping phenotypes. As it is easy to misdiagnose between ARVC and DCM, there is a need to establish a new differential diagnostic parameter to differentiate the two. We investigated the utility of endomyocardial biopsy (EMB) for the differential diagnosis, and our study had three aims. The first was to verify the EMB high diagnostic efficacy. The second was to investigate the EMB perforation risk at the right ventricle (RV) free wall of end-stage ARVC. The third was to determine the best EMB sampling site in differential diagnosis between ARVC and DCM. Transmural tissues were sampled at six sites on the ventricular free walls and interventricular septum of recipient hearts (35 ARVCs and 35 DCMs). Participants with wall thickness <1.7 mm were included in the subgroup with high perforation risk, and the rest were included in a subgroup with low perforation risk. The best EMB sampling site was determined by the largest area under curve (AUC) among receiver operating characteristic curves. We found significant differences (P<.01) in percentages of tissue components in transmural sections between ARVC and DCM. In the subgroup with high perforation risk, there were 12 ARVCs and no DCMs, and paper-like RV walls and transmural fat replacement were their features in the cardiac enhancement computed tomography images. In the subgroup with low perforation risk, the largest AUC was on the myocardium at the ARV: AUC=0.839, cutoff=74.76%, sensitivity=73.68%, specificity=97.14%. We conclude that EMB high differential diagnostic efficacy is a meaningful fact regardless of limited sampling range, that EMB perforation risk at the RV free wall of end-stage ARVC cannot be neglected, and that the best EMB sampling site is the ARV. Among participants with low perforation risk, ARV is still recommended as an EMB sampling site with good differential diagnostic efficacy.

The Changing Role for Endomyocardial Biopsy in the Diagnosis of Giant-Cell Myocarditis.

Endomyocardial biopsy (EMB) is central to the diagnosis of giant-cell myocarditis (GCM) and planning further management. There is, however, no guideline-directed recommendation on re-biopsy or left ventricular EMB in a suspected case of acute, fulminant myocarditis following an indeterminate first biopsy. This manuscript illustrates, with a case, the changing role for EMB in the current era in the diagnosis of GCM.