Alternatives to transvenous lead placement in a patient undergoing surgical tricuspid valve repair.

Tricuspid regurgitation is a widely recognised phenomenon in patients with transvenous cardiac rhythm management (CRM) devices. If tricuspid valve repair or replacement is to be considered, what to do with the existing CRM system requires scrutiny with multidisciplinary input. We present a case of multifactorial tricuspid regurgitation in a 48-year-old female with giant cell myocarditis and a transvenous implantable cardioverter-defibrillator (ICD). Key considerations in management and alternative CRM options are discussed.

Diagnosis, management, and outcome of cardiac sarcoidosis and giant cell myocarditis: a Swedish single center experience.

BACKGROUND: Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) are rare diseases that share some similarities, but also display different clinical and histopathological features. We aimed to compare the demographics, clinical presentation, and outcome of patients diagnosed with CS or GCM. METHOD: We compared the clinical data and outcome of all adult patients with CS (n = 71) or GCM (n = 21) diagnosed at our center between 1991 and 2020. RESULTS: The median (interquartile range) follow-up time for patients with CS and GCM was 33.5 [6.5-60.9] and 2.98 [0.6-40.9] months, respectively. In the entire cohort, heart failure (HF) was the most common presenting manifestation (31%), followed by ventricular arrhythmias (25%). At presentation, a left ventricular ejection fraction of < 50% was found in 54% of the CS compared to 86% of the GCM patients (P = 0.014), while corresponding proportions for right ventricular dysfunction were 24% and 52% (P = 0.026), respectively. Advanced HF (NYHA ≥ IIIB) was less common in CS (31%) than in GCM (76%). CS patients displayed significantly lower circulating levels of natriuretic peptides (P < 0.001) and troponins (P = 0.014). Eighteen percent of patients with CS included in the survival analysis reached the composite endpoint of death or heart transplantation (HTx) compared to 68% of patients with GCM (P < 0.001). CONCLUSION: GCM has a more fulminant clinical course than CS with severe biventricular failure, higher levels of circulating biomarkers and an increased need for HTx. The histopathologic diagnosis remained key determinant even after adjustment for markers of cardiac dysfunction.

Giant Cell Myocarditis in Children: Elusive Giant Cells Might Not Be the Only Clue.

Giant cell myocarditis (GCM) is a form of fulminant myocarditis that is rapidly progressive and frequently lethal even in children. Over the course of 20 years, a definitive histopathologic diagnosis of GCM has been made at our institution in only two pediatric patients, and in neither instance was the diagnosis of GCM rendered on initial cardiac biopsy. We present the two patients and highlight the similarities in their clinical presentation and their challenging and inconclusive- albeit histologically similar- initial cardiac biopsy findings.

Paediatric giant cell myocarditis: a case report.

A previously healthy 15-year-old teenage boy was admitted for fever and heart failure. Myocarditis was suspected, and endomyocardial biopsy revealed giant cell myocarditis. Immunosuppressive treatment was initiated, with excellent response. A plausible link to previous leptospirosis was identified. At 18-month follow-up, left ventricular function is normal. Only one other reported case of paediatric giant cell myocarditis had such a favourable outcome.

Intramyocardial Inflammation after COVID-19 Vaccination: An Endomyocardial Biopsy-Proven Case Series.

Myocarditis in response to COVID-19 vaccination has been reported since early 2021. In particular, young male individuals have been identified to exhibit an increased risk of myocardial inflammation following the administration of mRNA-based vaccines. Even though the first epidemiological analyses and numerous case reports investigated potential relationships, endomyocardial biopsy (EMB)-proven cases are limited. Here, we present a comprehensive histopathological analysis of EMBs from 15 patients with reduced ejection fraction (LVEF = 30 (14-39)%) and the clinical suspicion of myocarditis following vaccination with Comirnaty® (Pfizer-BioNTech) (n = 11), Vaxzevria® (AstraZenica) (n = 2) and Janssen® (Johnson & Johnson) (n = 2). Immunohistochemical EMB analyses reveal myocardial inflammation in 14 of 15 patients, with the histopathological diagnosis of active myocarditis according the Dallas criteria (n = 2), severe giant cell myocarditis (n = 2) and inflammatory cardiomyopathy (n = 10). Importantly, infectious causes have been excluded in all patients. The SARS-CoV-2 spike protein has been detected sparsely on cardiomyocytes of nine patients, and differential analysis of inflammatory markers such as CD4+ and CD8+ T cells suggests that the inflammatory response triggered by the vaccine may be of autoimmunological origin. Although a definitive causal relationship between COVID-19 vaccination and the occurrence of myocardial inflammation cannot be demonstrated in this study, data suggest a temporal connection. The expression of SARS-CoV-2 spike protein within the heart and the dominance of CD4+ lymphocytic infiltrates indicate an autoimmunological response to the vaccination.

Orbital giant cell myositis is an unusual and potentially lethal cause of bilateral ophthalmoplegia - A case report and literature review.

We present a case of orbital giant cell myositis (OGCM), presenting with bilateral subacute progressive ophthalmoplegia and optic nerve dysfunction. An early extraocular muscle biopsy confirmed the diagnosis and guided appropriate management. Comprehensive investigation excluded any underlying systemic disease, including myocarditis. Twenty two months after presentation, the patient remains well on azathioprine with complete resolution of orbital signs.

Fulminant Giant Cell Myocarditis following Heterologous Vaccination of ChAdOx1 nCoV-19 and Pfizer-BioNTech COVID-19.

A 48-year-old female patient underwent a heart transplantation for acute fulminant myocarditis, following heterologous vaccination with the ChAdOx1 nCoV-19 and Pfizer-BioNTech COVID-19. She had no history of severe acute respiratory syndrome coronavirus-2 infection. She did not exhibit clinical signs or have laboratory findings of concomitant infection before or after vaccination. Heart transplantation was performed because her heart failed to recover with venoarterial extracorporeal oxygenation support. Organ autopsy revealed giant cell myocarditis, possibly related to the vaccines. Clinicians may have to consider the possibility of the development of giant cell myocarditis, especially in patients with rapidly deteriorating cardiac function and myocarditis symptoms after COVID-19 vaccination.

Giant cell myocarditis in young woman diagnosed at the autopsy: a case report.

Giant cell myocarditis (GCM) is a rare inflammatory disease of the heart that often affects younger patients. The clinical course is typically rapid with fulminant congestive heart failure. Prognosis is poor; the proper diagnosis is often rendered at the autopsy. Herein, we present a prototypical case of this rare type of myocarditis, affecting a 44-year-old previously healthy woman who was referred to the intensive care department due to an acute onset cardiac arrest followed by resuscitation. The heart ultrasound and imaging examinations revealed a severe dysfunction and dilatation of both ventricles, without any significant finding in the coronary arteries. Twelve days after the initial presentation, the patient died due to congestive heart failure refractory to intensive therapy. The post-mortem histology of the heart revealed multiple small necrotic foci in the myocardium in both ventricles, with dense inflammatory infiltration with abundant multinucleated giant histiocytes, in line with a diagnosis of GCM. The natural history, pathophysiology, and histological differential diagnosis is discussed, together with review of the relevant literature including uncommon and emerging units.

Inflammatory cardiomyopathies: short- and long-term outcomes after heart transplantation-a protocol for a systematic review and meta-analysis.

Heart transplantation (HTx) for patients with "giant cell myocarditis" (GCM) or "cardiac sarcoidosis" (CS) is still controversial. However, no single center has accumulated enough experience to investigate post-HTx outcome. The primary aim of this systematic review is to identify, appraise, and synthesize existing literature investigating whether patients who have undergone HTx because of GCM or CS have worse outcomes as compared with patients transplanted because of other etiologies. A systematic and comprehensive search will be performed using PubMed, Scopus, Web of Science, EMBASE, and Google Scholar, for studies published up to December 2019. Observational and interventional population-based studies will be eligible for inclusion. The quality of observational studies will be assessed using the Newcastle-Ottawa scale, while the interventional studies will be assessed using the Cochrane Effective Practice Organization of Care tool. The collected evidence will be narratively synthesized; in addition, we will perform a meta-analysis to pool estimates from studies considered to be homogenous. Reporting of the systematic review and meta-analysis will be in accordance with the Meta-analysis of Observational Studies in Epidemiology Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. To our knowledge, this will be the first synthesis of outcomes, including survival, acute cellular rejection, and disease recurrence, in patients with either GCM or CS treated with HTx. Reviewing the suitability of HTx in this population and highlighting areas for further research will benefit both patients and healthcare providers. Trial registration: CRD42019140574.

Mechanical Circulatory Support Combined With Immunosuppression for the Treatment of Giant Cell Myocarditis　- A Single-Center Experience in Japan.

BACKGROUND: The therapeutic strategy for giant cell myocarditis (GCM) remains controversial, so we reviewed the clinical status of Japanese patients with GCM.Methods and Results:We retrospectively reviewed 6 consecutive patients with GCM requiring percutaneous mechanical circulatory support (p-MCS), with 3 further requiring ventricular assist devices. One patient died during p-MCS. Cardiac function improved in the other 5 with immunosuppressive therapy, but only 3 patients treated with dual immunosuppressants, including cyclosporine (CyA), achieved >1-year survival. CONCLUSIONS: The prognosis of patients with fulminant GCM is poor, but a treatment that combines MCS and early administration of CyA-based immunosuppressants will be useful.

Heart Transplantation in Giant Cell Myocarditis: Analysis of the United Network for Organ Sharing Registry.

BACKGROUND: Giant cell myocarditis (GCM) is a lethal, rapidly progressive disease, for which heart transplantation is the treatment of choice. We sought to describe the characteristics and outcomes of patients with GCM who undergo heart transplantation. METHODS AND RESULTS: We used the United Network for Organ Sharing thoracic organ transplantation registry to identify adults with GCM as the primary diagnosis and compared their characteristics and outcomes with patients who underwent transplantation for other types of myocarditis and for idiopathic dilated cardiomyopathy (IDCMP). A total of 32 patients with GCM were compared with 219 patients with myocarditis and 14,221 patients with IDCMP. Median age at listing for GCM was 52 years (interquartile range 40-55 y), and the majority were white (94%), male (63%), and listed as 1A (44%). Biventricular assist devices were used more frequently in GCM compared with IDCMP (31% vs 2%; P < .001). After transplantation, there were no statistically significant differences among GCM, myocarditis, and IDCMP patients regarding pacemaker implantation, dialysis initiation, or stroke rate. GCM patients had increased risk of acute rejection compared with IDCMP patients (16% vs 5.0%; P = .021) but no difference in rehospitalization for rejection among the 3 etiologies (P = .88). The cumulative survivals for GCM patients at 1, 5, and 10 years were 94%, 82%, and 68%, respectively, which was similar to the other etiologies (P = .11). CONCLUSIONS: Compared with patients with IDCMP, those with GCM present more acutely and have significantly higher utilization of biventricular mechanical circulatory support. Despite higher rates of early rejection, post-transplantation survival of patients with GCM was similar to that of other myocarditides and IDCMP.

Improved diagnosis of idiopathic giant cell myocarditis and cardiac sarcoidosis by myocardial gene expression profiling.

AIMS: Improvement of clinical diagnostics of idiopathic giant cell myocarditis (IGCM) and cardiac sarcoidosis (CS), two frequently fatal human myocardial diseases. Currently, IGCM and CS are diagnosed based on differential patterns of inflammatory cell infiltration and non-caseating granulomas in histological sections of endomyocardial biopsies (EMBs), after heart explantation or postmortem. We report on a method for improved differential diagnosis by myocardial gene expression profiling in EMBs. METHODS AND RESULTS: We examined gene expression profiles in EMBs from 10 patients with histopathologically proven IGCM, 10 with CS, 18 with active myocarditis (MCA), and 80 inflammation-free control subjects by quantitative RT-QPCR. We identified distinct differential profiles that allowed a clear discrimination of tissues harbouring giant cells (IGCS, CS) from those with MCA or inflammation-free controls. The expression levels of genes coding for cytokines or chemokines (CCL20, IFNB1, IL6, IL17D; P < 0.05), cellular receptors (ADIPOR2, CCR5, CCR6, TLR4, TLR8; P < 0.05), and proteins involved in the mitochondrial energy metabolism (CPT1, CYB, DHODH; P < 0.05) were deregulated in 2- to 300-fold, respectively. Bioinformatic analyses and correlation of the gene expression data with immunohistochemical findings provided novel information regarding the differential cellular and molecular pathomechanisms in IGCM, CS, and MCA. CONCLUSION: Myocardial gene expression profiling is a reliable method to predict the presence of multinuclear giant cells in the myocardium, even without a direct histological proof, in single small EMB sections, and thus to reduce the risk of sampling errors. This profiling also facilitates the discrimination between IGCM and CS, as two different clinical entities that require immediate and tailored differential therapy.

Rituximab in recurrent idiopathic giant cell myocarditis after heart transplantation: a potential therapeutic approach.

Giant cell myocarditis (GCM) is a very aggressive form of myocardial inflammation. While immunosuppressive therapy is usually able to keep under control the disease and prolong the average transplant-free survival in many patients, effective therapeutic strategies to prevent or treat the recurrence of GCM in transplanted organs are still to be defined. We report the case of a young woman with idiopathic GCM who, despite immediate aggressive immunosuppressive therapy, rapidly progressed to irreversible heart failure and required urgent heart transplantation. Yet, 2 months later, the disease recurred in the transplanted heart, despite an intensive four-drug antirejection regimen. The introduction of rituximab, an anti-CD20 monoclonal antibody, 375 mg/m(2) /week i.v. for four consecutive weeks and then every 4 months as maintenance therapy, determined a complete and steady clinical remission of the disease. After nineteen months since rituximab administration, the patient is doing well and repeated follow-up endo-myocardial biopsies confirmed the complete resolution of myocardial inflammation. Our experience seems to suggest that rituximab can be a reasonably effective and safe therapeutic option in GCM recurring in transplanted organs.

Giant cell myocarditis attributable to myositis: therapeutic management under the guidance of serial endomyocardial biopsy-a case report.

Background: Giant cell myocarditis is a fatal disease that could be rapidly progressive if not properly managed. However, the role of immunosuppressive therapy, especially in refractory cases, remains unclear. Case summary: A 76-year-old man presented with back pain with elevated cardiac enzymes. Skeletal muscle and endomyocardial biopsies revealed giant cell myositis and giant cell myocarditis. Despite the initial immunosuppressive therapy, cardiac enzymes continued to rise. Serial endomyocardial biopsies enabled combination treatment of prednisolone, cyclosporine, and mycophenolate mofetil according to histological inflammatory activity. Discussion: We presented a case of refractory giant cell myocarditis preceded by giant cell myositis. While endomyocardial biopsy is an approach with risk of procedural complications, it can guide giant cell myocarditis management when the initial immunosuppressive therapy is ineffective.

Complete remission of giant cell myocarditis by prednisolone monotherapy: A case with mild inflammation demonstrated by mismatch between T2-high intensity areas and late gadolinium enhancement.

Giant cell myocarditis (GCM) is a potentially lethal subtype of myocarditis. Herein, we report a case of a 22-year-old woman with GCM who was successfully treated with prednisolone monotherapy. The patient had a fever and shortness of breath and was referred to our hospital. Laboratory test results revealed elevated troponin I levels. Cardiac magnetic resonance (CMR) showed high intensity in the inferoseptal segment of the left ventricle on T2-weighted short tau inversion recovery imaging without late gadolinium enhancement (LGE), suggesting predominant edema rather than necrosis. The patient was diagnosed with GCM based on an endomyocardial biopsy, which revealed lymphocyte infiltration and multinucleated giant cells in the absence of granuloma formation. Subsequently, the patient received intravenous methylprednisolone at 1000 mg/day for 3 days followed by oral prednisolone at 30 mg/day, which normalized troponin levels. Follow-up CMR revealed improved cardiac inflammation; therefore, the patient was discharged without prescribing another immunosuppressive agent. Prednisolone was tapered and terminated three years after discharge. The patient went one year without medication and had no recurrence of GCM on follow-up. This case highlights the presence of mild GCM, successfully treated by steroid monotherapy, in which the mismatch between high-intensity T2 areas and LGE suggests mild inflammation. Learning objective: Giant cell myocarditis (GCM) is potentially lethal and usually requires multiple immunosuppressive agents. Here, we report a patient with GCM with preserved left ventricular ejection fraction. Cardiac magnetic resonance revealed focal high T2 signal intensity areas without late gadolinium enhancement, indicating myocardial edema without necrosis. The patient remained in remission with prednisolone monotherapy for 2 years. Our report indicates that "mild" GCM may be treated with prednisolone monotherapy.

The Clinical and Histological Intersection of Cardiac Sarcoidosis and Giant Cell Myocarditis.

The clinical and imaging features of cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) are occasionally indistinguishable. This is a case of heart block and ventricular tachycardia where cardiac MRI, fluorodeoxyglucose positron emission tomography (FDG-PET) and biopsy revealed intermediate clinicohistologic phenotype between CS and GCM. This highlights gaps in the management of overlap conditions.

Temporary mechanical circulatory support as a bridge to durable left ventricular assist device as destination therapy in fulminant giant cell myocarditis：A case report.

Fulminant giant cell myocarditis is a fatal form of acute myocarditis leading to a rapid-onset clinical presentation with lethal arrhythmias, acute heart failure, or cardiogenic shock requiring mechanical circulatory support. We report the case of a 52-year-old female diagnosed with fulminant myocarditis requiring veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and intra-aortic balloon pump(IABP) support. Due to hemodynamic instability, she was transferred to our hospital by helicopter on day 4. On arrival at our hospital, she underwent percutaneous balloon atrial septostomy to decompress the left ventricle. Although the left ventricular distension and pulmonary edema improved after atrial septostomy, no signs of biventricular function recovery were identified on day 14. On day 23, V-A ECMO and IABP were switched to a durable left ventricular assist device(LVAD) system and a right ventricular assist device(RVAD) with ECMO (RVAD-ECMO) under median sternotomy. On day 37, RVAD-ECMO was eventually removed and rehabilitation was started with the remaining LVAD support as destination therapy. On day 78, the patient was finally discharged with LVAD support to follow-up as an outpatient. This case underscores the importance of a multidisciplinary approach and rigorous monitoring to optimize outcomes in the treatment of fulminant giant cell myocarditis.

Two case reports of fulminant giant cell myocarditis treated with rabbit anti-thymocyte globulin.

Background: Giant cell myocarditis (GCM) is an inflammatory form of acute heart failure with high rates of cardiac transplantation or death. Standard acute treatment includes multi-drug immunosuppressive regimens. There is a small but growing number of case reports utilizing rabbit anti-thymocyte globulin in severe cases. Case summary: Two cases are presented with similar presentations and clinical courses. Both are middle-aged patients with no significant past medical history, who presented with new acute decompensated heart failure that quickly progressed to cardiogenic shock requiring inotropic and mechanical circulatory support. Both underwent endomyocardial biopsies that diagnosed GCM. Both were treated with a multi-agent immunosuppressive regimen, notably including rabbit anti-thymocyte globulin, with subsequent resolution of shock and recovery of left ventricular ejection fraction. Both remain transplant-free and without ventricular arrhythmias at 7 months and 26 months, respectively. Discussion: In aggregate, these cases are typical of GCM. They add to growing observational data that upfront rabbit anti-thymocyte globulin may reduce morbidity and mortality in GCM, including potentially preventing the need for complex interventions like orthotopic heart transplantation.

Giant cell myocarditis with prolonged cardiac standstill after drug-induced hypersensitivity syndrome: a case report.

Giant cell myocarditis (GCM) is a rare but fatal disease that can lead to cardiac failure. Survival with a cardiac standstill requires mechanical circulatory support or a biventricular assist device (BiVAD) and prolonged survival is extremely rare. Drug-induced hypersensitivity syndrome (DIHS) is a severe cutaneous adverse reaction. Some cases of DIHS are reportedly associated with the onset of GCM. We present a case of a 28-year-old woman who developed GCM during steroid tapering after DIHS. She went into continuous cardiac standstill but survived for 74 days under BiVAD support. Our case is noteworthy because the histopathologic specimens obtained on three occasions contributed to the diagnosis of this particular condition over time. We also reviewed previous literature on concomitant cases of GCM and DIHS. We found that two are potentially associated and most cases of GCM occur within 3 months of DIHS during steroid tapering.

Atrial giant cell myocarditis with preserved left ventricular function: a case report and literature review.

Giant cell myocarditis (GCM) is a rare and fatal inflammatory disorder induced by T-lymphocytes, typically affecting young adults. Generally, this disease presents with a rapidly progressive course and a very poor prognosis. In recent years, atrial GCM (aGCM) has been recognized as a clinicopathological entity distinct from classical GCM. As described by retrievable case reports, although its histopathological manifestations are highly similar to those of classical GCM, this entity is characterized by preserved left ventricular function and atrial arrhythmias, without ventricular arrhythmias. aGCM tends to show benign disease progression with a better clinical prognosis compared with the rapid course and poor prognosis of vGCM. We report a patient with aGCM with a history of renal abscess whose persistent myocardial injury considered to be associated with a history of renal abscess. Infection could be a potential trigger for the development of aGCM in this patient. An extensive literature review was also performed and the following three aspects were summarized: (1) Epidemiology and histopathological characteristics of aGCM; (2) The role of imaging in the evaluation of aGCM; (3) Diagnostic points and therapeutic decisions in aGCM.