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Mesalazine represents a key treatment for intestinal bowel diseases and only in rare cases produces cardiac toxicity, with a not completely known mechanism. We report a case of a 25-year-old man with a first episode of myocarditis after 2 weeks from the first mesalazine intake, documented also by a characteristic cardiac magnetic resonance pattern. Then, after less than 1 month, he suffered myocarditis recurrence and so, guided by a multidisciplinary team evaluation, in the suspicion of mesalazine-induced myocarditis, the drug was promptly stopped, with consequent recovery of cardiac damage. In our patient, the recurrence of myocarditis because of the non-interruption of the drug is very peculiar (only three cases described in literature) and definitively confirms the diagnosis. This paper reports an exemplary case of cardiac toxicity induced by mesalazine, a key treatment for inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. In rare cases, this drug can lead to cardiac impairment, with a mechanism not yet clarified. The young patient described experiencing a first episode of myocarditis (inflammation of the heart muscle cells) after 2 weeks of starting mesalazine. The diagnosis was possible thanks to cardiac magnetic resonance, a noninvasive exam providing high-definition images associated with tissue characterization. Mesalazine was not discontinued because drug-induced etiology was not suspected, due to its rarity. Consequently, the patient suffered a second episode of myocarditis, diagnosed by endomyocardial biopsy, an invasive technique that can accurately assess the etiology of myocardial damage, leading to prompt cessation of treatment. Since myocarditis can have various causes, diagnosis was also facilitated through a multidisciplinary team, which ruled out other possible causes for this condition. This case report is highly educational and underscores the importance of clinicians being vigilant about this side effect and considering it in patients taking mesalazine who present with myocarditis, to promptly discontinue the treatment. Mesalazine interruption is otherwise the only effective therapy for this condition, in addition to anti-inflammatory and analgesic drugs. Furthermore, this paper highlights the increasing importance of multidisciplinary teams, comprising various specialists, for accurate diagnosis and therapeutic decisions. The authors also propose an algorithm for diagnosing mesalazine-induced myocarditis, with certainty derived from recurrence after drug rechallenge, either voluntarily or accidentally, as demonstrated in this case. Article highlights 5-aminosalicylic acid (5-ASA) is an important treatment for inflammatory bowel diseases, and its cardiac toxicity is reported in 0.3% of cases. The mechanism of mesalazine-induced myocarditis is not completely understood. The clinical, instrumental, and laboratory presentation is similar to common forms of myocarditis (e.g., chest pain, troponin increase, electrocardiogram abnormalities). The use of imaging techniques is useful, particularly cardiac magnetic resonance, which has acquired increasing importance because of its potential for tissue characterization. The gold standard for confirming the diagnosis of myocarditis is endomyocardial biopsy, although a certain etiological definition is not always possible. The diagnosis of 5-ASA-induced myocarditis must be made first by ruling out other causes of myocarditis. Two main findings support the suspicion: clinical manifestation within 2–4 weeks after the first drug intake and improvement of the patient's condition immediately after discontinuation of therapy, which represents the only effective treatment for this condition. We report the case of a 25-year-old patient who experienced a first episode of myocarditis 2 weeks after the first mesalazine intake, with a characteristic cardiac magnetic resonance pattern. Then, after less than one month, he experienced myocarditis recurrence due to the non-interruption of 5-ASA. Endomyocardial biopsy, associated with laboratory tests, excluded other possible causes (e.g., infectious, autoimmune). Through multidisciplinary team evaluation, in suspicion of mesalazine-induced myocarditis, the drug was promptly stopped, leading to the recovery of cardiac damage. This case raises awareness about myocardial inflammation as a side effect of 5-ASA, and clinicians should always suspect this condition in patients taking this drug who present with cardiac impairment. In our patient, the recurrence of myocarditis due to the non-interruption of the drug is very peculiar (only 3 cases described in the literature) and definitively confirms the diagnosis, associated with the ex juvantibus criterion. In the end, we propose a diagnostic algorithm for 5-ASA-induced myocarditis; it starts from myocarditis diagnosis and exclusion of other possible causes, reaching progressive levels of likelihood by considering symptoms onset within 2–4 weeks of first drug intake (diagnosis possible), recovery after 5-ASA interruption (diagnosis likely) and myocarditis recurrence after rechallenging/non-stopping 5-ASA (diagnosis certain). [ABSTRACT FROM AUTHOR]

The Epstein-Barr virus (EBV) is frequently found in endomyocardial biopsies (EMBs) from patients with heart failure, but the detection of EBV-specific DNA has not been associated with progressive hemodynamic deterioration. In this paper, we investigate the use of targeted next-generation sequencing (NGS) to detect EBV transcripts and their correlation with myocardial inflammation in EBV-positive patients with heart failure with reduced ejection fraction (HFrEF). Forty-four HFrEF patients with positive EBV DNA detection and varying degrees of myocardial inflammation were selected. EBV-specific transcripts from EMBs were enriched using a custom hybridization capture-based workflow and, subsequently, sequenced by NGS. The short-read sequencing revealed the presence of EBV-specific transcripts in 17 patients, of which 11 had only latent EBV genes and 6 presented with lytic transcription. The immunohistochemical staining for CD3+ T lymphocytes showed a significant increase in the degree of myocardial inflammation in the presence of EBV lytic transcripts, suggesting a possible influence on the clinical course. These results imply the important role of EBV lytic transcripts in the pathogenesis of inflammatory heart disease and emphasize the applicability of targeted NGS in EMB diagnostics as a basis for specific treatment. [ABSTRACT FROM AUTHOR]

Aims: This paper aimed to study the efficacy and safety of mycophenolate mofetil (MM) in combination with corticosteroids in the treatment of lymphocytic myocarditis (LM) when compared to the standard combination of corticosteroids and azathioprine. Methods. The study included 50 adult patients (47.8 ± 10.8 y.o.) in a NYHA III functional class due to LM who were verified using endomyocardial biopsy. The main group included 29 patients who received MM at 2 g/day. The comparison group comprised 21 patients who received azathioprine at 150 [50; 150] mg/day. Both groups were administered with methylprednisolone. The average follow-up period was 30 [22; 35] months, but no less than 6 months. Results. The groups were comparable in the baseline parameters and standard drug therapy. In both groups, there was a comparable significant increase in the ejection fraction (from 30.6 ± 7.7% to 44.0 ± 9.4% vs. 29.2 ± 7.7% to 46.2 ± 11.8%, p < 0.001), and a decrease in systolic pressure in the pulmonary artery and the dimensions of the left ventricle and atrium. The frequency of death was two (6.9%) and two (9.5%), transplantation was one (3.4%) and one (4.8%) patient and the "death + transplantation" endpoint was three (10.3%) and three (14.3%) without differences between the groups. The presence of the parvovirus B19 in the myocardium in 6/5 patients did not affect the results. The incidence of infectious complications was comparable. The most severe infectious complications were pneumonia and fatal purulent encephalitis (both cases in the azathioprine group), leptospirosis meningitis (in the mycophenolate mofetil group). Conclusions. In the patients with LM, the combination of corticosteroids with MM at a dose of 2 g/day was at least no less effective than with azathioprine. There was a tendency toward a better tolerance using MM. [ABSTRACT FROM AUTHOR]

Introduction: Monitoring for graft rejection is a fundamental tenet of post‐transplant follow‐up. In heart transplantation (HT) in particular, rejection has been traditionally assessed with endomyocardial biopsy (EMB). EMB has potential complications and noted limitations, including interobserver variability in interpretation. Additional tests, such as basic cardiac biomarkers, cardiac imaging, gene expression profiling (GEP) scores, donor‐derived cell‐free DNA (dd‐cfDNA) and the novel molecular microscope diagnostic system (MMDx) have become critical tools in rejection surveillance beyond standard EMB. Methods: This paper describes an illustrative case followed by a review of MMDx within the context of other noninvasive screening modalities for rejection. Conclusions: We suggest MMDx be used to assist with early detection of rejection in cases of discordance between EMB and other noninvasive studies. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the clinical course and outcomes of post-COVID myocarditis in patients with cardiomyopathies (CMP). This case series includes 10 patients with different CMPs who had COVID-19 (seven men; 48.4 ± 11.4 yr.): left ventricular non-compaction (n = 2), arrhythmogenic right ventricular CMP in combination with a heterozygous form of hemochromatosis (n = 1, HFE), restrictive CMP (n = 1, MyBPC3), laminopathy (n = 1, LMNA), dilated cardiomyopathy (n = 1, MYH7 + MyBPC3), Danon's disease (n = 1, LAMP2) and AL cardiac amyloidosis (n = 3). Myocardial morphological examination with immunohistochemical staining and PCR for SARS-CoV-2 and cardiotropic viruses was performed in six patients, while cardiac MRI and anti-cardiac antibody titres were evaluated in all patients. Post-COVID lymphocytic myocarditis was confirmed morphologically in six patients (with LVNC, RCM, ARCV, Danon's disease, and AL amyloidosis). Spike and nucleocapsid coronavirus proteins were detected in cell infiltrates, endothelium and cardiomyocytes in all biopsies; SARS-CoV-2 RNA was found in five out of six. In four patients, the diagnosis of myocarditis was based on MRI, high titres of anti-cardiac antibodies and clinical data. The mean time from COVID-19 to the diagnosis of myocarditis was 7 (5; 10.5) months. Myocarditis manifested with the onset/increase of arrhythmias and heart failure. Immunosuppressive therapy with corticosteroids was administered to six patients and led to an increase in ejection fraction and improvement of heart failure symptoms in five of them. CMPs are a favourable background for the development of post-COVID myocarditis. The onset or deterioration of heart failure and/or arrhythmias in patients with CMPs after COVID-19 requires the exclusion of myocarditis and, if present, the administration of immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Aims: Transthyretin 'wild‐type' amyloid cardiomyopathy (ATTRwt‐CM) is a differential diagnosis of heart failure with preserved ejection fraction (HFpEF). The clinical work‐up for ATTRwt‐CM is challenging. Considering a combination of clinical variables specific for ATTRwt‐CM might aid in identifying patients at risk. Methods and results: Sixty patients (78 ± 6 years, 8% female) were diagnosed with ATTRwt‐CM by endomyocardial biopsy. Preserved ejection fraction (LVEF >45%) was present in 41 of the patients. Those were 1:1 propensity score age‐ and sex‐matched to a cohort of patients with HFpEF. ATTRwt‐CM patients had less obesity (P = 0.01) and higher septal thickness (IVSd, P < 0.01) as well as more diastolic dysfunction (E/e′, P < 0.01). On multivariable regression IVSd > 14 mm, E/e′ > 14 and absence of obesity (P > 0.01 for all) were identified as predictors for ATTRwt‐CM. A weighted point‐based score was derived with IVSd > 14 mm = 1 point; absence of obesity = 2 points; and E/e′ > 14 = 3 points. Area under the curve (AUC) for the summation score was 0.91 (0.84–0.97, P < 0.01) and a score of more than 3 points predicted ATTRwt‐CM with good sensitivity (78%) and specificity (90%). The score was validated in an external cohort of 142 patients with ATTRwt‐CM and 419 HFpEF patients showing sufficient accuracy (AUC 0.91, 0.88–0.94, P < 0.01). A value greater than 3 points demonstrated a high sensitivity (93%) and a negative predictive value of 97%. Conclusions: A score based on basic clinical and echocardiographic features helps to distinguish ATTRwt‐CM from typical HFpEF. This could facilitate the diagnostic work‐up for these patients and enable earlier disease screening on a large scale. [ABSTRACT FROM AUTHOR]

Myocarditis is an inflammatory disease of the myocardium caused by infectious and noninfectious agents. Clinical manifestations range from mildly symptomatic forms to acute heart failure, cardiogenic shock, life-threatening arrhythmias and sudden death. Myocarditis is still a challenging diagnosis because of its wide variability in clinical presentation and unpredictable course. Moreover, a standardized, specific treatment in not yet available. Immunosuppressive treatment for virus-negative lymphocytic myocarditis is still controversial. Conversely, immunosuppression is well established in sarcoidosis, eosinophilic, giant-cell, drug hypersensitivity, and trauma-related myocarditis as well as lymphocytic myocarditis associated with connective tissue diseases or with the rejection of a transplanted heart. Recently, immunosuppressive therapy has been also recognized as an effective treatment in virus-negative inflammatory cardiomyopathy. The aim of this review is to underline the role of immunomodulating and immunosuppressive therapies in patients with immune-mediated myocarditis and illustrate the different treatment strategies depending on the etiology. An endomyocardial biopsy remains the gold standard for the diagnosis of myocarditis as well as for a tailored treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In 1900, Fiedler first reported autopsy cases with peculiar inflammation of the myocardium, which he named interstitial myocarditis. He postulated an isolated cardiac inflammation of the myocardium in the absence of multiorgan involvement and with a poor prognosis due to invisible microorganisms, which years later would have been identified as viruses. The revision of original histologic sections by Schmorl showed cases with lymphocytes and others with giant-cell inflammatory histotypes. The in vivo diagnosis of myocarditis became possible thanks to right cardiac catheterization with endomyocardial biopsy (EMB). The gold standard for diagnosis was achieved with the employment of immunohistochemistry and molecular investigation by Polymerase Chain Reaction (PCR), which allows for the detection of viruses as causal agents. Both RNA and DNA were revealed to be cardiotropic, with a common receptor (CAR). A protease, coded by coxsackie virus, disrupts the cytoskeleton and accounts for cell death. Unfortunately, vaccination, despite having been revealed to be effective in animal experiments, has not yet entered the clinical field for prevention. Cardiac Magnetic Resonance turned out to be a revolutionary tool for in vivo diagnosis through the detection of edema (inflammatory exudate). Myocarditis may be fulminant in terms of clinical presentation but not necessarily fatal. The application of ExtraCorporeal Membrane Oxygenation (ECMO) allows for relieving the overloaded native heart. [ABSTRACT FROM AUTHOR]

Aims: In patients with recently diagnosed non‐ischaemic LV systolic dysfunction, left ventricular reverse remodelling (LVRR) and favourable prognosis has been documented in studies with short‐term follow‐up. The aim of our study was to assess the long‐term clinical course and stability of LVRR in these patients. Methods and results: We prospectively studied 133 patients (37 women; 55 [interquartile range 46, 61] years) with recently diagnosed unexplained LV systolic dysfunction, with heart failure symptoms lasting <6 months and LV ejection fraction <40% persisting after at least 1 week of therapy. All patients underwent endomyocardial biopsy (EMB) at the time of diagnosis and serial echocardiographic and clinical follow‐up over 5 years. LVRR was defined as the combined presence of (1) LVEF ≥ 50% or increase in LVEF ≥ 10% points and (2) decrease in LV end‐diastolic diameter index (LVEDDi) ≥ 10% or (3) LVEDDi ≤ 33 mm/m2. LVRR was observed in 46% patients at 1 year, in 60% at 2 years and 50% at 5 years. Additionally, 2% of patients underwent heart transplantation and 12% experienced heart failure hospitalization. During 5‐year follow‐up, 23 (17%) of the study cohort died. In multivariate analysis, independent predictors of mortality were baseline right atrial size (OR 1.097, CI 1.007–1.196), logBNP level (OR 2.02, CI 1.14–3.56), and PR interval (OR 1.02, CI 1.006–1.035) (P < 0.05 for all). The number of macrophages on EMB was associated with overall survival in univariate analysis only. LVRR at 1 year of follow‐up was associated with a lower rate of mortality and heart failure hospitalization (P = 0.025). In multivariate analysis, independent predictors of LVRR were left ventricular end‐diastolic volume index (OR 0.97, CI 0.946–0.988), LVEF (OR 0.89, CI 0.83–0.96), and diastolic blood pressure (OR 1.04, CI 1.01–1.08) (P < 0.05 for all). Conclusions: LVRR occurs in over half of patients with recent onset unexplained LV systolic dysfunction during first 2 years of optimally guided heart failure therapy and then remains relatively stable during 5‐year follow‐up. Normalization of adverse LV remodelling corresponds to a low rate of mortality and heart failure hospitalizations during long‐term follow‐up. [ABSTRACT FROM AUTHOR]

Background Atrioventricular conduction abnormalities due to acute myocarditis are typically transient and do not require ventricular pacing beyond the acute phase of myocardial inflammation. Notwithstanding, selective injury and necrosis of the heart's conduction system may lead to persistent complete heart block (CHB) requiring device implantation. Case summary We report the case of a 23-year-old man with acute lymphocytic myocarditis complicated by cardiogenic shock, cardiac arrest due to ventricular fibrillation, and persistent CHB. Endomyocardial biopsy (EMB) showed signs of subacute myocarditis, with no evidence of granulomas or giant cells, nor criteria for eosinophilic myocarditis. Aetiological work-up found serological evidence of previous Epstein–Barr virus (EBV) infection; Borrelia burgdorferi serology for Lyme disease was negative. The real time–polymerase chain reaction (RT–PCR) of the EMB was positive for the presence of EBV DNA, but in situ hybridization for viral ribosomal RNA (rRNA) was negative. The patient progressed favourably, and left ventricle ejection fraction recovered 2 weeks after initial presentation. However, CHB persisted for more than 3 weeks, and the patient underwent definitive pacemaker implantation with left bundle branch pacing. Discussion Persistent CHB after acute myocarditis is generally considered unlikely, but in rare circumstances the damage portended by inflammation may be irreversible. Besides the play of chance, possible mechanisms behind the apparent predilection for the conduction system of the myocardium warrant further research. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular magnetic resonance (CMR) has emerged as the most accurate, non-invasive method to support the diagnosis of clinically suspected myocarditis and as a risk-stratification tool in patients with cardiomyopathies. We aim to assess the diagnostic and prognostic role of CMR at diagnosis in patients with myocarditis. Methods: We enrolled consecutive single-center patients with 2013 ESC consensus-based endomyocardial biopsy (EMB)-proven or clinically suspected myocarditis undergoing CMR at diagnosis. The pre-specified outcome was defined as NYHA class > I and echocardiographic left ventricular ejection fraction (LVEF) < 50% at follow-up. Results: We included 207 patients (74% male, median age 36 years; 25% EMB-proven). CMR showed the highest sensitivity in myocarditis with infarct-like presentation. Patients with EMB-proven myocarditis were more likely to have diffuse LGE and right ventricular LGE (p < 0.001), which was also more common among patients with arrhythmic presentation (p = 0.001). The outcome was met in 17 patients at any follow-up time point, more commonly in those with larger biventricular volumes (p < 0.001), CMR-based diagnosis of dilated cardiomyopathy (p < 0.001), and ischemic LGE (p = 0.005). Higher biventricular systolic function (p < 0.001) and greater LGE extent (p = 0.033) at diagnosis had a protective effect. Conclusions: In our single-center cohort of rigorously defined myocarditis patients, higher biventricular systolic function and greater LGE extent on CMR at diagnosis identified patients with better functional class and higher left ventricular ejection fraction at follow-up. Conversely, larger biventricular volumes, CMR-based DCM features, and the presence of an ischemic LGE pattern at diagnosis were predictors of worse functional class and LV systolic dysfunction at follow-up. Larger prospective studies are warranted to extend our findings to multi-center cohorts. [ABSTRACT FROM AUTHOR]

Background: Endomyocardial biopsy (EMB) is a safe procedure performed in diagnostic work‐up of cardiac disease. Hypothesis: Data regarding temporal trends of total numbers, characteristics, in‐hospital outcomes, and complications of patients undergoing EMB are sparse. Methods: The nationwide German inpatient sample (2005–2019) was used for this analysis. Patient cases of EBM during the 5‐year cycles from 2005 to 2009, 2010 to 2014, and 2015 to 2019 were compared, and temporal trends regarding total numbers and presumable major and minor EMB‐associated complications were investigated. Results: Overall, 67 745 EMB were performed in Germany 2005–2019. Total number of EMB increased from 3083 in 2005 to 5646 in 2019 (β 0.40 [95% confidence interval [CI] 0.37–0.43], p <.001). Among these EMB, 19 083 (28.2%) were performed during the period 2005–2009, 22 867 (33.7%) 2010–2014, and 25 795 (38.1%) between 2015 and 2019. The proportion of patients aged ≥70 years was highest 2015–2019 (2005–2009: 9.3%; 2010–2014: 13.8%; 2015–2019: 16.1%, p <.001) and the most aggravated comorbidity profile (Charlson Comorbidity Index 2.25 ± 1.93; 2.67 ± 2.14; 3.01 ± 2.29, p <.001) was also detected 2015–2019. Major complications occurred less often in the period 2015–2019 compared to 2005–2009 (odds ratio [OR] 0.921 [95% CI 0.893–0.950], p <.001), whereas minor complications were more frequently observed between 2015 and 2019 (OR 1.067 [95% CI 1.042–1.093], p <.001). While a decrease in major complications was detected irrespective of age, an increase in minor complications was identified only in patients between 30–59 years. Conclusions: Annual numbers of EMB increased significantly in Germany 2005–2019. Patients who underwent EMB in recent years were older and showed an aggravated comorbidity profile accompanied by fewer major complications, underscoring safety of the procedure. [ABSTRACT FROM AUTHOR]

Acute myocarditis covers a wide spectrum of clinical presentations, from uncomplicated myocarditis to severe forms complicated by hemodynamic instability and ventricular arrhythmias; however, all these forms are characterized by acute myocardial inflammation. The term "chronic inflammatory cardiomyopathy" describes a persistent/chronic inflammatory condition with a clinical phenotype of dilated and/or hypokinetic cardiomyopathy associated with symptoms of heart failure and increased risk for arrhythmias. A continuum can be identified between these two conditions. The importance of early diagnosis has grown markedly in the contemporary era with various diagnostic tools available. While cardiac magnetic resonance (CMR) is valid for diagnosis and follow-up, endomyocardial biopsy (EMB) should be considered as a first-line diagnostic modality in all unexplained acute cardiomyopathies complicated by hemodynamic instability and ventricular arrhythmias, considering the local expertise. Genetic counseling should be recommended in those cases where a genotype–phenotype association is suspected, as this has significant implications for patients' and their family members' prognoses. Recognition of the pathophysiological pathway and clinical "red flags" and an early diagnosis may help us understand mechanisms of progression, tailor long-term preventive and therapeutic strategies for this complex disease, and ultimately improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic methods. The multitude of different etiological factors, the diversity of the clinical picture, and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated with diseases that in their natural course can lead to myocardial involvement, as well as the iatrogenic cause of myocarditis, which is due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, such as changes in ECG and echocardiography readings, has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive and is the gold standard for diagnosis and clinical follow-up of these patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening cases with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support, and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high. [ABSTRACT FROM AUTHOR]

The Epstein-Barr virus (EBV) is frequently found in endomyocardial biopsies (EMBs) from patients with heart failure, but the detection of EBV-specific DNA has not been associated with progressive hemodynamic deterioration. In this paper, we investigate the use of targeted next-generation sequencing (NGS) to detect EBV transcripts and their correlation with myocardial inflammation in EBV-positive patients with heart failure with reduced ejection fraction (HFrEF). Forty-four HFrEF patients with positive EBV DNA detection and varying degrees of myocardial inflammation were selected. EBV-specific transcripts from EMBs were enriched using a custom hybridization capture-based workflow and, subsequently, sequenced by NGS. The short-read sequencing revealed the presence of EBV-specific transcripts in 17 patients, of which 11 had only latent EBV genes and 6 presented with lytic transcription. The immunohistochemical staining for CD3+ T lymphocytes showed a significant increase in the degree of myocardial inflammation in the presence of EBV lytic transcripts, suggesting a possible influence on the clinical course. These results imply the important role of EBV lytic transcripts in the pathogenesis of inflammatory heart disease and emphasize the applicability of targeted NGS in EMB diagnostics as a basis for specific treatment.

Background: Fulminant myocarditis is a rare and severe disease whose definite and etiological diagnoses rely on pathological examination. Albeit, myocardial biopsy can be associated with significant morbidity and mortality, its therapeutic consequences are unclear. We conducted a study to determine the diagnostic yield, the safety and the therapeutic consequences of myocardial biopsy in patients with fulminant clinically suspected myocarditis unweanable from mechanical circulatory support (MCS). Methods: Monocenter, retrospective, observational cohort study in a 26-bed French tertiary ICU between January 2002 and February 2019. Inclusion of all fulminant clinically suspected myocarditis patients undergoing in-ICU myocardial biopsy while being on MCS. The primary endpoint was the proportion of patients classified as definite myocarditis using Bonaca criteria before and after including myocardial biopsy results. Results: Forty-seven patients (median age 41 [30–47], female 53%) were included: 55% died before hospital discharge, 34% could be bridged-to-recovery and 15% bridged-to-transplant. Myocardial biopsy was endomyocardial or surgical in 36% and 64% cases respectively. Tamponade requiring emergency pericardiocentesis occurred in 29% patients after endomyocardial biopsy. After adding the biopsy results in the Bonaca classification algorithm the percentage of definite myocarditis raised from 13 to 55% (p < 0.0001). The rate of biopsy-related treatments modifications was 13%, leading to patients' recovery in only 4% patients. Conclusions: In clinically suspected myocarditis unweanable from MCS, myocardial biopsy increased the rate of definite myocarditis but was associated with a low rate of treatment modification and a significant proportion of adverse events. We believe the benefit/risk ratio of myocardial biopsy should be more carefully weighted in these frail and selected patients than suggested by actual guidelines. Further prospective studies are now needed to determine its value in patients under MCS. [ABSTRACT FROM AUTHOR]

The diagnosis and specific and causal treatment of myocarditis and inflammatory cardiomyopathy remain a major clinical challenge. Despite the rapid development of new imaging techniques, endomyocardial biopsies remain the gold standard for accurate diagnosis of inflammatory myocardial disease. With the introduction and continued development of immunohistochemical inflammation diagnostics in combination with viral nucleic acid testing, myocarditis diagnostics have improved significantly since their introduction. Together with new technologies such as miRNA and gene expression profiling, quantification of specific immune cell markers, and determination of viral activity, diagnostic accuracy and patient prognosis will continue to improve in the future. In this review, we summarize the current knowledge on the pathogenesis and diagnosis of myocarditis and inflammatory cardiomyopathies and highlight future perspectives for more in-depth and specialized biopsy diagnostics and precision, personalized medicine approaches. [ABSTRACT FROM AUTHOR]

In this review, we investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly cause myocarditis with severe myocardial damage induced by viral particles. A review of the major data published from 2020 to 2022 was performed by consulting the major databases alongside first-hand experiences that emerged from the cardiac biopsies and autopsy examinations of patients who died of SARS-CoV-2 infections. From this study, a significantly large amount of data suggests that the Dallas criteria were met in a residual percentage of patients, demonstrating that SARS-CoV-2 myocarditis was a rare clinical and pathological entity that occurred in a small percentage of subjects. All cases described here were highly selected and subjected to autopsies or endomyocardial biopsies (EMBs). The most important discovery, through the detection of the SARS-CoV-2 genome using the polymerase chain reaction, consisted in the presence of the viral genome in the lung tissue of most of the patients who died from COVID-19. However, the discovery of the SARS-CoV-2 viral genome was a rare event in cardiac tissue from autopsy findings of patients who died of myocarditis It is important to emphasize that myocardial inflammation alone, as promoted by macrophages and T cell infiltrations, can be observed in noninfectious deaths and COVID-19 cases, but the extent of each cause is varied, and in neither case have such findings been reported to support clinically relevant myocarditis. Therefore, in the different infected vs. non-infected samples examined, none of our findings provide a definitive histochemical assessment for the diagnosis of myocarditis in the majority of cases evaluated. We report evidence suggesting an extremely low frequency of viral myocarditis that has also been associated with unclear therapeutic implications. These two key factors strongly point towards the use of an endomyocardial biopsy to irrefutably reach a diagnosis of viral myocarditis in the context of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest low diagnostic sensitivity of cardiac magnetic resonance (CMR) imaging based on Lake Louise criteria (LLC) to identify patients with complicated presentations of acute myocarditis (AM). We evaluated classic and updated LLC in patients with AM proven by right ventricular septal endomyocardial biopsy (RVS-EMB). Methods: From an initial population of 499 patients with clinically suspected AM from a multicenter retrospective cohort, we included 74 patients with histologically proven myocarditis on RVS-EMB and available CMR within 30 days since admission. The prevalence of total and septal CMR abnormalities [namely, T2-weighted images (T2W), late gadolinium enhancement (LGE), T2 and T1 mapping, and extracellular volume (ECV)] were assessed in patients with complicated vs. uncomplicated AM. Results: Among 74 patients [mean age 38 ± 15 years, 65% males, left ventricular ejection fraction (LVEF) 40 ± 18%] with RVS-EMB-proven AM, 53 (72%) had a complicated presentation. The classic LLC were positive in 56/74 patients (76%), whereas the updated ones were positive in 41/41 of cases (100%). Septal involvement, documented in 48/74 patients (65%) by conventional T2W/LGE and in 39/41 cases (95%) by mapping techniques (p < 0.001), was more common in patients with complicated AM. In the 41 patients undergoing both evaluations, CMR sensitivity for myocarditis was 85% for the classic LLC vs. 100% for the updated LLC (p = 0.006). Conclusion: In patients with myocarditis on RVS-EMB, CMR using updated LLC has high sensitivity in the detection of AM when performed within 30 days. Septal abnormalities are more common in patients with complicated AM. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the inflammatory changes in the myocardium, based on endomyocardial biopsy (EMB) data in patients undergoing radiofrequency ablation (RFA) for idiopathic atrial fibrillation (AF). A total of 67 patients with idiopathic AF were enrolled in the study. Patients underwent the intracardiac examination, RFA of AF, and EMB with histological and immunohistochemical studies. The catheter-treatment effectiveness, and occurrence of early and late recurrences of atrial tachyarrhythmias, were assessed depending on the identified histological changes. Nine patients (13.4%) did not have any histological changes in the myocardium according to EMB. Fibrotic changes were detected in 26 cases (38.8%). Inflammatory changes according to the Dallas criteria were observed in 32 patients (47.8%). The follow-up period for patients averaged 19.3 ± 3.7 months. The effectiveness rates of primary RFA were 88.9% in patients with the intact myocardium, 46.2% in patients with fibrotic changes of varying severity, and 34.4% in patients with the presence of criteria for myocarditis. No early recurrence of arrhythmias was observed in patients with unchanged myocardia. The presence of inflammatory and fibrotic changes in the myocardium increased the rates of early and late arrhythmia recurrences and accordingly halved the effectiveness RFA of AF. [ABSTRACT FROM AUTHOR]

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare multisystem disorder; cardiac involvement may include eosinophilic myocarditis. A 67‐year‐old woman presented with 1‐week history of dyspnoea and orthopnoea. She had a history of adult‐onset asthma and peripheral eosinophilia. The investigations showed T‐wave inversion on lateral leads, peripheral eosinophilia, elevated troponin and BNP values, and severe biventricular systolic dysfunction with diffuse hypokinesia and apical akinesia. Computed tomography excluded coronary disease and showed bilateral basal ground‐glass opacities, air‐space consolidation, and bilateral reticular‐nodular pattern. Cardiac magnetic resonance findings were compatible with active myocardial inflammation. An endomyocardial biopsy (EMB) confirmed the diagnosis of eosinophilic myocarditis, and a therapy with oral corticosteroids and heart failure medications was started. [ABSTRACT FROM AUTHOR]

Endomyocardial biopsy (EMB) is an invasive procedure originally developed for the monitoring of heart transplant rejection. Over the year, this procedure has gained a fundamental complementary role in the diagnostic work-up of several cardiac disorders, including cardiomyopathies, myocarditis, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Major advances in EMB equipment and techniques for histological analysis have significantly improved diagnostic accuracy of EMB. In recent years, advanced imaging modalities such as echocardiography with three-dimensional and myocardial strain analysis, cardiac magnetic resonance and bone scintigraphy have transformed the non-invasive approach to diagnosis and prognostic stratification of several cardiac diseases. Therefore, it emerges the need to re-define the current role of EMB for diagnostic work-up and management of cardiovascular diseases. The aim of this review is to summarize current knowledge on EMB in light of the most recent evidences and to discuss current indications, including challenging scenarios encountered in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: The role of inflammation markers in myocarditis is unclear. We assessed the diagnostic and prognostic correlates of C-reactive protein (CRP) at diagnosis in patients with myocarditis. Methods and results: We retrospectively enrolled patients with clinically suspected (CS) or biopsy-proven (BP) myocarditis, with available CRP at diagnosis. Clinical, laboratory and imaging data were collected at diagnosis and at follow-up visits. To evaluate predictors of death/heart transplant (Htx), a machine-learning approach based on random forest for survival data was employed. We included 409 patients (74% males, aged 37 ± 15, median follow-up 2.9 years). Abnormal CRP was reported in 288 patients, mainly with CS myocarditis (p < 0.001), recent viral infection, shorter symptoms duration (p = 0.001), chest pain (p < 0.001), better functional class at diagnosis (p = 0.018) and higher troponin I values (p < 0.001). Death/Htx was reported in 13 patients, of whom 10 had BP myocarditis (overall 10-year survival 94%). Survival rates did not differ according to CRP levels (p = 0.23). The strongest survival predictor was LVEF, followed by anti-nuclear auto-antibodies (ANA) and BP status. Conclusions: Raised CRP at diagnosis identifies patients with CS myocarditis and less severe clinical features, but does not contribute to predicting survival. Main death/Htx predictors are reduced LVEF, BP diagnosis and positive ANA. [ABSTRACT FROM AUTHOR]

Purpose: Routine endomyocardial (EM) biopsies pose a challenge in the management of heart transplant recipients requiring anticoagulation. Apixaban is a direct‐acting oral anticoagulant (DOAC) with a short half‐life allowing for brief interruptions of anticoagulation for procedures. The study objective was to determine the safety and efficacy of apixaban in heart transplant patients undergoing EM biopsies. Methods: This retrospective case series evaluated patients with a heart transplant from April 1, 2017 to July 30, 2020 who were treated with apixaban within 90 days post‐transplant. The primary outcome was the occurrence of a bleeding or thrombotic event. Results: A total of 12 patients with >100 biopsies were included. The median age was 54 years (IQR 37–59) with a mean weight of 91 ± 20 kg. There were no bleeding or thrombotic events. During therapy, patients underwent an average of eight biopsies. The median time from transplant to initiation of apixaban was 39.5 days (range 9–77). Therapy was maintained without any need for reversal for a median of 276 days (IQR 45–245). Conclusions: Apixaban is safe to use for anticoagulation of heart transplant recipients undergoing routine biopsies. Using apixaban allows for a short interruption of therapeutic anticoagulation to accommodate a biopsy without increased risk of bleeding. [ABSTRACT FROM AUTHOR]

Background. Exercise stress test (EST) has been scarcely investigated in patients with arrhythmic myocarditis. Objectives. To report the results of EST late after myocarditis with arrhythmic vs. nonarrhythmic presentation. Methods. We enrolled consecutive adult patients with EST performed at least six months after acute myocarditis was diagnosed using gold-standard techniques. Patients with ventricular arrhythmia (VA) at presentation were compared with the nonarrhythmic group. Adverse events occurring during follow-up after EST included cardiac death, disease-related rehospitalization, malignant VA, and proven active myocarditis. Results. The study cohort was composed of 128 patients (age 41 ± 9 y, 70% males) undergoing EST after myocarditis. Of them, 64 (50%) had arrhythmic presentation. EST was performed after 15 ± 4 months from initial diagnosis, and was conducted on betablockers in 75 cases (59%). During EST, VA were more common in the arrhythmic group (43 vs. 4, p < 0.001), whereas signs and symptoms of ischemia were more prevalent in the nonarrhythmic one (6 vs. 1, p = 0.115). By 58-month mean follow-up, 52 patients (41%) experienced adverse events, with a greater prevalence among arrhythmic patients (39 vs. 13, p < 0.001). As documented both in the arrhythmic and nonarrhythmic subgroups, patients had greater prevalence of adverse events following a positive EST (40/54 vs. 12/74 with negative EST, p < 0.001). Electrocardiographic features of VA during EST correlated with the subsequent inflammatory restaging of myocarditis. Nonarrhythmic patients with uneventful EST both on- and off-treatment were free from subsequent adverse events. Conclusions. Late after the arrhythmic presentation of myocarditis, EST was frequently associated with recurrent VA. In both arrhythmic and nonarrhythmic myocarditis, EST abnormalities correlated with subsequent adverse outcomes. [ABSTRACT FROM AUTHOR]

Aims: Cancer therapy‐related cardiac dysfunction (CTRCD) is commonly reported, but its histopathology, mechanisms, and risk factors are not known. We aimed to clarify the histopathology and mechanisms of CTRCD to identify risk factors. Methods and results: We performed myocardial histopathological studies on 13 endomyocardial biopsies from CTRCD patients, 35 autopsied cancer cases with or without cardiac dysfunction, and controls without cancer (10 biopsies and 9 autopsies). Cardiotoxicity risk scores were calculated based on medication; and patient‐related risk factors, fibrosis, and cardiomyocyte changes were scored; and p53 and H3K27ac histone modification were evaluated by histological score (H‐score). In the biopsy cases, all histopathological changes and the p53 evaluation were significantly higher in the CTRCD group than in the controls [p53 H‐score; 63 (9.109) vs. 33 (5.099), P < 0.05]. In patients with a short time between drug and disease onset (<4.2 years), fibrosis and p53 positively correlated (r = 0.76, P < 0.05), and in those with late onset disease (>4.2 years), cellular abnormalities and p53 trended to a positive correlation and cardiotoxicity risk scores and p53 positively correlated (r = 0.95, P < 0.05). A year after biopsy, the short‐term group had significant recovery of ejection fraction compared with the long‐term group (P < 0.05). The CTRCD group had a significantly worse overall survival prognosis than the control group [hazard ratio 7.61 (95% confidence interval 1.30–44.6), P < 0.05]. Autopsy cases with cancer treatment also had a high grade of histopathological changes, with even more severe changes in patients with cardiac dysfunction, and had increased p53 and H3K27ac expression levels, compared with controls. H‐scores of p53 and H3K27ac showed a positive correlation in the CTRCD group in biopsy cases (r = 0.62, P < 0.05) and a positive correlation in autopsy cases. Conclusions: Our results indicate distinct morphological characteristics in myocardial histopathology associated with CTRCD. p53 and H3K27ac histone modification could be sensitive markers of CTRCD and suggest a mechanistic involvement of epigenetic changes. [ABSTRACT FROM AUTHOR]

Background: Myocarditis is a highly heterogeneous disorder with a challenging diagnostic work-up. We aimed to focus on the possible diagnostic workup for this condition in settings where endomyocardial biopsy as a gold standard is not always feasible, detect the etiologic cardiotropic viruses in our locality, and follow the clinical course in patients admitted with clinically suspected myocarditis.Methods: This is a prospective observational study. We recruited patients with clinically suspected myocarditis presenting at a university hospital from October 1st, 2020 until March 31st, 2021. All Patients had a diagnostic coronary angiography and were included only if they had a non-obstructive coronary artery disease. All patients also had cardiac magnetic resonance imaging (CMR) with contrast. Sera were obtained from all suspected patients for detection of antibodies against viruses using enzyme-linked immunosorbent assay, and viral genomes using polymerase chain reaction (PCR), and reverse transcription-PCR. Endomyocardial biopsy was done for patients with a typical CMR picture of myocarditis.Results: Out of 2163 patients presenting to the hospital within the 6 months, only 51 met the inclusion criteria. Males represented 73%, with a mean age of 39 ± 16 years. CMR showed an ischemic pattern in 4 patients and thus they were excluded. We classified patients into two categories based on CMR results: group A (CMR-positive myocarditis), 12 patients (25.5%), and group B (CMR-negative myocarditis), 35 (74.5%) patients. On serological analysis, 66% of patients (n = 31/47) showed antibodies against the common cardiotropic viruses. Parvovirus B19 IgM in 22 patients (47%) and coxsackievirus IgM in 16 (34%) were the most observed etiologies. Regarding the outcome, 42.5% of patients recovered left ventricular ejection fraction and three patients died at 6 months' clinical follow-up.Conclusion: Patients with Clinically suspected myocarditis represented 2.2% of total hospital admissions in 6 months. CMR is only a good positive test for the diagnosis of acute myocarditis. Parvovirus B19 and coxsackievirus were the most common pathogens in our locality.Trial Registration: Clinical trial registration no., NCT04312490; first registration: 18/03/2020. First recruited case 01/10/2020. URL: https://register.Clinicaltrials: gov/prs/app/action/SelectProtocol?sid=S0009O3D&selectaction=Edit&uid=U0002DVP&ts=2&cx=9zdfin . [ABSTRACT FROM AUTHOR]

(1) Objectives: To discriminate biopsy-proven myocarditis (chronic vs. healed myocarditis) and to differentiate from dilated cardiomyopathy (DCM) using cardiac magnetic resonance (CMR). (2) Methods: A total of 259 consecutive patients (age 51 ± 15 years; 28% female) who underwent both endomyocardial biopsy (EMB) and CMR in the years 2008–2021 were evaluated. According to right-ventricular EMB results, patients were divided into either chronic (n = 130, 50%) or healed lymphocytic myocarditis (n = 60, 23%) or DCM (n = 69, 27%). The CMR protocol included functional, strain, and late gadolinium enhancement (LGE) imaging, T2w imaging, and T2 mapping. (3) Results: Left-ventricular ejection fraction (LV-EF) was higher, and the indexed end-diastolic volume (EDV) was lower in myocarditis patients (chronic: 42%, median 96 mL/m²; healed: 49%, 86 mL/m²) compared to the DCM patients (31%, 120 mL/m²), p < 0.0001. Strain analysis demonstrated lower contractility in DCM patients vs. myocarditis patients, p < 0.0001. Myocarditis patients demonstrated a higher LGE prevalence (68% chronic; 59% healed) than the DCM patients (45%), p = 0.01. Chronic myocarditis patients showed a higher myocardial edema prevalence and ratio (59%, median 1.3) than healed myocarditis (23%, 1.3) and DCM patients (13%, 1.0), p < 0.0001. T2 mapping revealed elevated values more frequently in chronic (90%) than in healed (21%) myocarditis and DCM (23%), p < 0.0001. T2 mapping yielded an AUC of 0.89 (sensitivity 90%, specificity 76%) in the discrimination of chronic from healed myocarditis and an AUC of 0.92 (sensitivity 86%, specificity 91%) in the discrimination of chronic myocarditis from DCM, both p < 0.0001. (4) Conclusions: Multiparametric CMR imaging, including functional parameters, LGE and T2 mapping, may allow differentiation of chronic from healed myocarditis and DCM and therefore help to optimize patient management in this clinical setting. [ABSTRACT FROM AUTHOR]

Brugada syndrome (BrS) is classified as an inherited cardiac channelopathy attributed to dysfunctional ion channels and/or associated proteins in cardiomyocytes rather than to structural heart alterations. However, hearts of some BrS patients exhibit slight histologic abnormalities, suggesting that BrS could be a phenotypic variant of arrhythmogenic cardiomyopathy. We performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria. Our comprehensive analysis of structural findings did not reveal enough definitive evidence for reclassification of BrS as a cardiomyopathy. The collection and comprehensive analysis of new cases with a definitive BrS diagnosis are needed to clarify whether some of these structural features may have key roles in the pathophysiological pathways associated with malignant arrhythmogenic episodes. [ABSTRACT FROM AUTHOR]

Parvovirus B19 is one of the most frequent causes of pediatric myocarditis, associating high mortality rates or need for cardiac transplantation. The aim of this study is to describe the clinical course of Parvovirus B19 myocarditis in children with emphasis on the role of endomyocardial biopsy and cardiac magnetic resonance, and the use of an innovative therapeutic strategy. Eleven patients and 12 episodes of polymerase chain reaction (PCR)-confirmed Parvovirus B19 myocarditis were prospectively collected for 14 years. Diagnosis was confirmed either histopathologically or by magnetic resonance. A life-threatening clinical presentation is described, similar to previous series, but with 83.3% overall survival without transplantation. We also present a case of recurrent myocarditis, which is extraordinarily rare. Electrocardiographic patterns presented chiefly peaked p waves, low QRS voltages, and negative T waves on inferior or lateral leads. Endomyocardial biopsy is the gold standard diagnostic test; alternatively magnetic resonance could be a useful diagnostic tool. A good concordance between myocardial and blood PCRs was observed. Seven patients received treatment with corticosteroids and beta interferon and all underwent a significant cardiac function improvement. Conclusion: A severe clinical presentation is reported, similar to previous reports but with better outcomes. Endomyocardial biopsy is the gold standard diagnostic test; alternatively magnetic resonance may be used. Both blood and myocardium PCR can be used in children to establish the microbiological etiology. Steroids with IFNß could be a useful therapeutic option, although further multicenter studies are needed to confirm these results. What is Known: • Parvovirus B19 is one of the most frequent causes of myocarditis in children. It is associated with a fulminant clinical presentation. • Endomyocardial biopsy is the gold standard diagnostic test but it is an invasive procedure. What is New: • Myocarditis may recur in pediatrics, even it is extraordinarily rare. • IFNβ with steroids may be a useful therapeutic option to improve the outcomes. [ABSTRACT FROM AUTHOR]

Context: Since the end of 2019 with the identification of the new coronavirus SARS-CoV-2 and the disease it produces, named COVID-19, various manifestations have been described, initially pulmonary due to acute and severe respiratory syndromes, now systemic manifestations have been described. Case Report: We report 3 cases of patients with cardiovascular manifestations associated with SARS-CoV-2 infection, highlighting the diagnostic approach and variety of presentation, from acute myocardial infarction, myocarditis, heart failure, shock, arrhythmias to sudden death. Conclusions: Every day is more frequent to find reports of patients with cardiovascular compromise during COVID-19 affecting the development and prognosis of this disease. [ABSTRACT FROM AUTHOR]

Background: In heart transplant recipients, donor-derived cell-free DNA (ddcfDNA) is a potential biomarker for acute rejection (AR), in that increased values may indicate rejection. For the assessment of ddcfDNA as new biomarker for rejection, blood plasma sampling around the endomyocardial biopsy (EMB) seems a practical approach. To evaluate the effect of the EMB procedure on ddcfDNA values, ddcfDNA values before the EMB were pairwise compared to ddcfDNA values after the EMB. We aimed at evaluating whether it matters whether the ddcfDNA sampling is done before or after the EMB-procedure. Methods: Plasma samples from heart transplant recipients were obtained pre-EMB and post-EMB. A droplet digital PCR method was used for measuring ddcfDNA, making use of single-nucleotide polymorphisms that allowed both relative quantification, as well as absolute quantification of ddcfDNA. Results: Pairwise comparison of ddcfDNA values pre-EMB with post-EMB samples (n = 113) showed significantly increased ddcfDNA concentrations and ddcfDNA% in post-EMB samples: an average 1.28-fold increase in ddcfDNA concentrations and a 1.31-fold increase in ddcfDNA% was observed (p = 0.007 and p = 0.03, respectively). Conclusion: The EMB procedure causes iatrogenic injury to the allograft that results in an increase in ddcfDNA% and ddcfDNA concentrations. For the assessment of ddcfDNA as marker for AR, collection of plasma samples before the EMB procedure is therefore essential. [ABSTRACT FROM AUTHOR]

Acute myocarditis is an inflammatory disease of the myocardium, and it can present as severe heart failure in children. Differential diagnosis with genetic cardiomyopathy can be difficult. The objective of this study is to identify patterns of clinical presentation and to assess invasive and non-invasive measures to differentiate patients with acute myocarditis from patients with dilated genetic cardiomyopathy. We performed a retrospective descriptive study of all paediatric patients (0–16 years old) that presented with new-onset heart failure with left ventricle ejection fraction < 35% in whom we performed an endomyocardial biopsy (EMB) during the period from April 2007 to December 2020. The patients were classified into two groups: Group 1 included 18 patients with myocarditis. Group 2 included 9 patients with genetic cardiomyopathy. Findings favouring a diagnosis of myocarditis included a fulminant or acute presentation (77.8% vs 33.3%, p = 0.01), higher degree of cardiac enzyme elevation (p = 0.011), lower left ventricular dimension z-score (2.2 vs 5.4, p = 0.03) increase of ventricular wall thickness (88.8% vs 33.3%, p = 0.03) and oedema in the EMB. Seven (77.8%) patients with genetic cardiomyopathy had inflammation in the endomyocardial biopsy fulfilling the diagnostic criteria of inflammatory cardiomyopathy. Conclusion: Differentiating patients with a myocarditis from those with genetic cardiomyopathy can be challenging, even performing an EMB. Some patients with genetic cardiomyopathy fulfil the diagnostic criteria of inflammatory cardiomyopathy. Using invasive and non-invasive measures may be useful to develop a predictive model to differentiate myocarditis from genetic cardiomyopathy. What is Known: • Acute myocarditis could present with cardiogenic shock in paediatric patients. • Parvovirus B19 is the main cause of myocarditis in this population. What is New: • Current diagnostic criteria for myocarditis have limited use in paediatric patients presenting with new-onset heart failure. • Some patients with a genetic cardiomyopathy and a new-onset heart failure fulfill the diagnostic criteria of inflammatory cardiomyopathy. [ABSTRACT FROM AUTHOR]

Fulminant myocarditis is an inflammatory disease of the cardiac muscle that severely deteriorates cardiac function and often causes haemodynamic collapse in a manner similar to acute coronary syndrome. In rare cases, the myocardium of the right ventricle is dominantly damaged. In cases of lymphocytic myocarditis, a common type of fulminant myocarditis, cardiac function is often recovered after peak myocardial inflammation subsides; however, some cases show irreversible myocardial damage. Herein, we report the case of a 43‐year‐old woman with irreversible, right‐side dominant ventricular myocardial damage; she presented with various cardiopulmonary conditions including complete atrioventricular block, ventricular tachycardia, right heart failure, right ventricular thrombosis, and pulmonary embolism. The patient was successfully treated with medications and a cardiac resynchronization therapy‐defibrillator device. [ABSTRACT FROM AUTHOR]

Sarcoidosis is an inflammatory disease of unknown cause which results in the formation of non caseating granulomatous lesion. Lung and lymph nodes are most frequently involved however any organ of the body can be affected. Although, it has been observed that approximately one fourth of cases of sarcoidosis develop cardiac involvement, only 5% show clinical manifestations and most cases are diagnosed in autopsy studies. Here, an uncommon case of cardiac sarcoidosis presented, diagnosed on autopsy. A 68-year-old male was brought dead to the hospital to conduct an autopsy. On dissection, in the coronal cut of the heart specimen, multiple small greyish white nodules were seen in left ventricular wall. Special stains like Ziehl Neelsen (ZN) stain for tubercular bacilli and Perioidic Acid Schiff (PAS) stain and Grocott's Methenamine Silver (GMS) stain for fungal aetiology were non contributory. Histopathological examination revealed multiple non caseating granulomas with numerous giant cells rimmed by few scattered lymphocytes along with areas of fibrosis. A diagnosis of granulomatous carditis-sarcoidosis was given. This case report highlights that in all cases revealing non caseating granulomatous inflammation negative for acid fast bacilli and fungus, sarcoidosis should be suspected. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory cardiomyopathy (ICM) frequently leads to myocardial fibrosis, resulting in permanent deterioration of the left ventricular function and an unfavorable outcome. Soluble suppression of tumorigenicity 2 receptor (sST2) is a novel marker of inflammation and fibrosis in cardiovascular tissues. sST2 was found to be helpful in predicting adverse outcomes in heart failure patients with reduced ejection fraction. The aim of this study was to determine the association of sST2 plasma levels with cardiac magnetic resonance (CMR) and echocardiography imaging features of left ventricular impairment in ICM patients, as well as to evaluate the applicability of sST2 as a prognosticator of the clinical status in patients suffering from ICM. Methods: We used plasma samples of 89 patients presenting to the Heart Center Leipzig with clinically suspected myocardial inflammation. According to immunohistochemical findings in endomyocardial biopsies (EMB) conducted in the context of patients' diagnostic work-up, inflammatory cardiomyopathy was diagnosed in 60 patients (ICM group), and dilated cardiomyopathy in 29 patients (DCM group). All patients underwent cardiac catheterization for exclusion of coronary artery disease and CMR imaging on 1.5 or 3 Tesla. sST2 plasma concentration was determined using ELISA. Results: Mean plasma concentration of sST2 in the whole patient cohort was 45.8 ± 26.4 ng/mL (IQR 27.5 ng/mL). In both study groups, patients within the highest quartile of sST2 plasma concentration had a significantly lower left ventricular ejection fraction (LV-EF) compared to patients within the lowest sST2 plasma concentration quartile (26 ± 11% vs. 40 ± 13%, p = 0.05 for ICM and 24 ± 13% vs. 51 ± 10%, p = 0.004 for DCM). sST2 predicted New York Heart Association (NYHA) class III/IV at 12 months follow-up more efficiently in ICM compared to DCM patients (AUC 0.85 vs. 0.61, p = 0.02) and was in these terms superior to NT-proBNP and cardiac troponin T. ICM patients with sST2 plasma concentration higher than 44 ng/mL at baseline had a significantly higher probability of being assigned to NYHA class III/IV at 12 months follow-up (hazard ratio 2.8, 95% confidence interval 1.01–7.6, log rank p = 0.05). Conclusion: Plasma sST2 levels in ICM patients reflect the degree of LV functional impairment at hospital admission and predict functional NYHA class at mid-term follow-up. Hence, ST2 may be helpful in the evaluation of disease severity and in the prediction of the clinical status in ICM patients. [ABSTRACT FROM AUTHOR]

Myocarditis is an inflammatory heart disease induced by infectious and non-infectious causes frequently triggering immune-mediated pathologic mechanisms leading to myocardial damage and dysfunction. In approximately half of the patients, acute myocarditis resolves spontaneously while in the remaining cases, it may evolve into serious complications including inflammatory cardiomyopathy, arrhythmias, death, or heart transplantation. Due to the large variability in clinical presentation, unpredictable course of the disease, and lack of established causative treatment, myocarditis represents a challenging diagnosis in modern cardiology. Moreover, an increase in the incidence of myocarditis and inflammatory cardiomyopathy has been observed in recent years. However, there is a growing potential of available non-invasive diagnostic methods (biomarkers, serum anti-heart autoantibodies (AHA), microRNAs, speckle tracking echocardiography, cardiac magnetic resonance T1 and T2 tissue mapping, positron emission tomography), which may refine the diagnostic workup and/or noninvasive follow-up. Personalized management should include the use of endomyocardial biopsy and AHA, which may allow the etiopathogenetic subsets of myocarditis (infectious, non-infectious, and/or immune-mediated) to be distinguished and implementation of disease-specific therapies. In this review, we summarize current knowledge on myocarditis and inflammatory cardiomyopathy, and outline some practical diagnostic, therapeutic, and follow-up algorithms to facilitate comprehensive individualized management of these patients. [ABSTRACT FROM AUTHOR]

The diagnosis of acute and chronic myocarditis remains a challenge for clinicians. Characterization of this disease has been hampered by its diverse etiologies and heterogeneous clinical presentations. Most cases of myocarditis are caused by infectious agents. Despite successful research in the last few years, the pathophysiology of viral myocarditis and its sequelae leading to severe heart failure with a poor prognosis is not fully understood and represents a significant public health issue globally. Most likely, at a certain point, besides viral persistence, several etiological types merge into a common pathogenic autoimmune process leading to chronic inflammation and tissue remodeling, ultimately resulting in the clinical phenotype of dilated cardiomyopathy. Understanding the underlying molecular mechanisms is necessary to assess the prognosis of patients and is fundamental to appropriate specific and personalized therapeutic strategies. To reach this clinical prerequisite, there is the need for advanced diagnostic tools, including an endomyocardial biopsy and guidelines to optimize the management of this disease. The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has currently led to the worst pandemic in a century and has awakened a special sensitivity throughout the world to viral infections. This work aims to summarize the pathophysiology of viral myocarditis, advanced diagnostic methods and the current state of treatment options. [ABSTRACT FROM AUTHOR]