[Inflammatory cardiomyopathies: Diagnosis, correlations with imaging, interest of myocardial biopsy and place of molecular biology]. / Cardiomyopathies inflammatoires : diagnostic, corrélations avec l'imagerie, intérêt de la biopsie myocardique et place de la biologie moléculaire.

Inflammatory cardiomyopathies, also known as "myocarditis" are inflammatory pathologies affecting the myocardium and characterized by vast etiological and clinical heterogeneity. They can be asymptomatic, particularly in viral forms, or be responsible for sudden death, particularly in subjects under 35 years olds. Due to insufficient sensitivity and specificity of imaging and biology, the gold standard is histopathological and is performed on an endomyocardial biopsy or on explanted heart samples in a transplant context. Their classification has considerably evolved and is now based on the identification of a predominant cell pattern such as lymphocytic, neutrophilic or eosinophilic polynuclear, giant cell or granulomatous myocarditis. These different patterns will guide the etiological diagnosis, prognosis and the therapies to be implemented. Due to the importance of viral etiologies, this morphological analysis must be complemented by a virological analysis based on PCR with viral load quantification. In addition, some authors have been able to demonstrate the occurrence of myocarditis in patients with arrhythmogenic cardiomyopathy of genetic origin. The aim of this chapter is to review the current state of knowledge on inflammatory cardiomyopathies and their management.

Elevated aldolase 1A, retrogene 1 expression induces cardiac apoptosis in rat experimental autoimmune myocarditis model.

Acute myocarditis is an unpredictable heart disease that is caused by inflammation-associated cell death. Although viral infection and drug exposure are known to induce acute myocarditis, the molecular basis for its development remains undefined. Using proteomics and molecular analyses in myosin-induced rat experimental autoimmune myocarditis (EAM), we identified that elevated expression of aldolase 1A, retrogene 1 (Aldoart1) is critical to induce mitochondrial dysfunction and acute myocarditis development. Here, we demonstrate that cardiac cell death is associated with increased expressions of proapoptotic genes in addition to high levels of glucose, lactate, and triglyceride in metabolite profiling. The functional protein association network analysis also suggests that Aldoart1 upregulation correlates with high levels of dihydroxyacetone kinase and triglyceride. In H9c2 cardiac cells, lipopolysaccharides (LPS) or high glucose exposure significantly increases the cytochrome c release and the conversion of pro-caspase 3 into the cleaved form of caspase 3. We also found that LPS- or glucose-induced toxicities are almost completely reversed by siRNA-mediated knockdown of Aldoartl, which consequently increases cell viability. Together, our study strongly suggests that Aldoart1 may be involved in inducing mitochondrial apoptotic processes and can be a novel therapeutic target to prevent the onset of acute myocarditis or cardiac apoptosis.

GBP1 exerts inhibitory effects on acute viral myocarditis by inhibiting the inflammatory response of macrophages in mice.

Viral myocarditis (VMC) is a condition that could potentially progress to dilated cardiomyopathy or congestive heart failure, making it the leading cause of the untimely death in young adults. Interferon-induced GBP1 encodes much of the GTPase induced by interferon gamma in many eukaryotic cells. However, little is known regarding the effect of GBP1 on acute VMC (AVMC). Hence, this aim of this study was to assess the effect of GBP1 on AVMC. Once the AVMC mouse models were established, the functional role of GBP1 was determined in AVMC. Serum levels of IL-6, TNF-α, and TGF-ß, and expression levels of GBP1, MIF, iNOS, and COX-2 were detected, together with the viability and apoptosis of cardiomyocytes. AVMC mice presented with increased levels of TGF-ß, IL-6, TNF-α, MIF, iNOS, and COX-2, as well as cell apoptosis, but lower expression of GBP1 and viability of cardiomyocytes. Restored GBP1 or depleted macrophages resulted in decreased levels of TGF-ß, IL-6, TNF-α, MIF, iNOS, and COX-2, as well as cardiomyocyte apoptosis, while increasing cardiomyocyte viability. In conclusion, our results highlight the potential role of GBP1 in inhibiting AVMC development. The experimental results indicate that GBP1 up-regulation and macrophage depletion can alleviate AVMC-related cardial damage by inhibiting inflammatory responses and cardiomyocyte apoptosis while increasing cardiomyocyte viability.

[A rare case of recurrent myocarditis revealing pheochromocytoma]. / Un rare cas de myocardite récurrente révélant un phéochromocytome.

Pheochromocytoma is a rare neuroendocrine tumor characterized by overproduction of catecholamines. The overproduction of catecholamines leads to cardiac remodeling which manifests in several forms ranging from Takotsubo to dilated cardiomyopathy. Studies suggest that pheochromocytoma-induced cardiomyopathy can take various forms depending on the duration of catecholamine exposure. Myocarditis is a fairly rare presentation of cardiac manifestations of pheochromocytoma which are mainly dominated by Takotsubo and dilated cardiomyopathies. We report a rare case of recurrent myocarditis in a young 37-year-old patient revealing the diagnosis of adrenal pheochromocytoma. Through this case and through a review of the literature we will take stock of the epidemiology of cardiac involvement in pheochromocytoma, mainly cardiomyopathies, and we will take stock of the value of diagnosis and early management in improving the prognosis of patients.

[Tableau d'insuffisance cardiaque congestive révélant une myocardite lupique : cas clinique]. / Lupus myocarditis presenting as acute congestive heart failure : A case report.

Systemic lupus erythematosus (SLE or lupus) is a disease in which the immune system attacks healthy cells and tissues throughout the body. Lupus myocarditis is a life-threatening condition, observed clinically in 3-9 % of patients with SLE. We report the case of a patient followed for multisystem SLE, presenting with de novo heart failure with severe left ventricular dysfunction revealing lupus myocarditis.

[Acute myocarditis in a patient with dengue infection]. / Myocardite aiguë induite par la dengue.

Dengue is a febrile viral illness transmitted by Aedes Aegypti mosquito with growing incidence, it could be associated with cardiovascular complication mediated by inflammation and notably acute myocarditis. We report the case of a 36-year old woman admitted in cardiology department with initial diagnosis of acute coronary syndrome and ultimately diagnosed to have an acute myocarditis induced by dengue infection; we describe diagnostic modalities and clinical evolution.

[Diagnostic and prognostic utility of cardiac magnetic resonance imaging in myocarditis]. / Apports diagnostique et pronostique de l'imagerie par résonance magnétique cardiaque dans la myocardite.

Cardiac magnetic resonance imaging (CMR) became over the last 30 years an essential tool in the management of patients with myocarditis. Noninvasive diagnosis of acute myocarditis relies on a clinical picture compatible with myocarditis and fulfilling of the updated 2018 Lake Louise criteria. These criteria include highlights of myocardial edema by conventional T2-weighted sequences or by T2 mapping in one hand and evidence of myocardial injury using late gadolinium enhancement sequences, T1 mapping or extra-cellular volume measurement in the other hand. It is recommended to perform basal examination in the 2 or 3 weeks following acute episode and to repeat CMR during follow-up. The literature reports excellent diagnostic accuracy, between 80% and 90%, making CMR a robust and reliable noninvasive alternative to endomyocardial biopsy. Besides, beyond its diagnostic performance, CMR can also help to identify patients with unfavourable long-term outcome. For instance, medio-ventricular and septal location of late gadolinium enhancement, degree of late gadolinium enhancement extent or high T2 mapping values are independent predictive factors of major cardio-vascular events.

Association of early electrical changes with cardiovascular outcomes in immune checkpoint inhibitor myocarditis.

BACKGROUND: Immune-checkpoint inhibitor-associated myocarditis (ICI-myocarditis) often presents with arrhythmias, but the prognostic value of early electrocardiogram findings is unclear. Although ICI-myocarditis and acute cellular rejection (ACR) following cardiac transplantation use similar treatment strategies, differences in arrhythmia burden are unknown. OBJECTIVE: To evaluate the association of electrocardiogram findings in ICI-myocarditis with myocarditis-related mortality and life-threatening arrhythmia. METHODS: A total of 125 cases of ICI-myocarditis were identified retrospectively across 49 hospitals worldwide; 50 cases of grade 2R or 3R ACR were included as comparators. Two cardiologists blinded to clinical data interpreted electrocardiograms. Associations between electrocardiogram features, myocarditis-related mortality and the composite of myocarditis-related mortality and life-threatening arrhythmias were examined. Adjusted hazard ratios (aHRs) were calculated. RESULTS: The cohort had 78 (62.4%) men; median (interquartile range) age was 67 (58-76) years. At 30 days, myocarditis-related mortality was 20/124 (16.1%), and 28/124 (22.6%) met the composite endpoint. Patients who developed complete heart block (aHR by subdistribution hazards model [aHR(sh)] 3.29, 95% confidence interval [CI] 1.24-8.68; P=0.02) or life-threatening cardiac arrhythmias (aHR(sh) 6.82, 95% CI: 2.87-16.21; P<0.001) had a higher risk of myocarditis-related mortality. Pathological Q waves (aHR(sh) 3.40, 95% CI: 1.38-8.33; P=0.008), low QRS voltage (aHR(sh) 6.05, 95% CI: 2.10-17.39; P<0.001) and Sokolow-Lyon index (aHR(sh)/mV 0.54, 95% CI: 0.30-0.97; P=0.04) on admission electrocardiogram were also associated with increased risk of myocarditis-related mortality. These associations were mirrored in the composite outcome analysis. Compared with ACR, ICI-myocarditis had a higher incidence of life-threatening cardiac arrhythmias (15/125 [12.0%] vs 1/50 [2%]; P=0.04) and third-degree heart block (19/125 [15.2%] vs 0/50 [0%]; P=0.004). CONCLUSIONS: Electrocardiograms in ICI-myocarditis with ventricular tachycardias, heart block, low-voltage and pathological Q waves were associated with myocarditis-related mortality and life-threating arrhythmia. Arrhythmia burden in ICI-myocarditis exceeds that of ACR after heart transplant.

[Reverse Takotsubo ou myocardite fulminante ? Succès de VA ECMO chez une patiente ayant une atteinte cardiaque liée COVID 19]. / Reverse TakoTsubo or Fulminant myocarditis ? Life saving VA ECMO in a COVID 19 patient.

A 45 years old female patient was admitted to our facility for COVID -19 infection complicated by fulminant cardiac injury and refractory cardiogemic shock. She had echographic findings of reverse takotsubo cardiomyopathy. She was successfully treated by VA-ECMO allowing complete revocery of the left ventricule function and weaning from support.

[Heart involvement in systemic lupus erythematosus and antiphospholipid syndrome]. / Cœur et médecine interne : lupus systémique et syndrome des antiphospholipides.

Cardiac involvement in systemic lupus (SL) and antiphospholipid syndrome (APS) can be due to variables and involve different presentations. Pericarditis is the most common lupus manifestation and occurs in 16% to 25% of patients. While corticosteroids are usually very effective, colchicine may avoid steroids and prevent relapse. Myocarditis during SL is rare and often inaugural. They may manifest as chest pain, acute heart failure, arrhythmias or conduction disturbances, and may progress to dilated cardiomyopathy and/or permanent heart failure. Their prognosis is however generally good, even in the absence of treatment with cyclophosphamide for the less serious forms. Finally, coronary involvement in SL is most often due to atherosclerotic, thrombotic origin (generally in the context of associated APS), and exceptionally explained by coronary vasculitis. During APS, valve disease is frequent and usually asymptomatic. Thrombotic damage can be (1) coronary, typically manifesting as a myocardial infarction in a young subject with healthy coronary arteries, (2) much more rarely intracardiac, or (3) microcirculatory, generally as part of a catastrophic antiphospholipid syndrome (CAPS) leading to a multiorgan failure. Finally, iatrogenic cardiac manifestations can exceptionally be seen during treatment with cyclophosphamide or antimalarials characterized by conduction disorders and/or heart failure.

[COVID-19 myocarditis : "About a monocentric series of 33 cases"]. / Myocardite à COVID-19 : « à propos d'une série monocentrique de 33 cas ¼.

INTRODUCTION: The world is experiencing a pandemic linked to the respiratory spread of SARS-CoV2 which can affect the heart with elevated troponins, ECG abnormalities and kinetic disturbances in echocardiography, of ischemic or non-ischemic origin (most often fulminant myocarditis). OBJECTIVE: To describe the evolutionary modalities of post-COVID-19 myocarditis and to identify factors of poor ejection fraction (EF) recovery under treatment of heart failure. METHOD: Monocentric observational study including patients with post-COVID-19 non-fulminant myocarditis confirmed by cardiac MRI. These patients were divided into 2 groups according to the evolution of their EF at 3 months (EF > 50% vs EF < 50%). RESULTS: 33 patients (19♂/14♀) aged from 30 to 61 were included, all of whom had repolarization disorder; mean EF at baseline was 44.3% (30-52%) with a troponin level 480 times normal (20-2100). Conventional treatment for heart failure was initiated in all patients with clinical, electrical and echocardiographic monitoring at 1 and 3 months. A significant improvement (EF > 50%) was observed in 29 patients. Gender, congestive signs, electrical and angiographic abnormalities do not seem to influence the evolution of EF (P > 0.10). Age > 60 years, troponins > 1200 times normal, pericardial effusion and a combined criterion of the three seem to be associated with poor evolution of EF (P at 0.07, 0.02, 0.035 and 0.01 respectively). DISCUSSION: Non-fulminant post-COVID-19 myocarditis have a good prognosis (EF recovery in 87.88%). Factors of poor recovery are age > 60 years, elevated troponins, appearance of pericardial effusion and the combined criterion of the three. CONCLUSION: Non-fulminant post-COVID-19 myocarditis seems to have a favorable course. Patients presenting factors of poor evolution had to have a longer follow-up.

[Characteristics of cardiac involvement in eosinophilic granulomatosis with polyangiitis]. / Caractéristiques de l'atteinte cardiaque au cours de la granulomatose éosinophilique avec polyangéite.

AIM OF THE STUDY: Our study aimed to identify the characteristics of cardiac involvement in eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: We conducted a retrospective analytic study including EGPA cases diagnosed between 2000 and 2019 in an internal medicine department. Diagnosis was made according to the 1990 American College of Rheumatology criteria and the 2012 Chapel Hill Concensus. RESULTS: Eleven EGPA cases were included, 64% of patients were female. Median age at diagnosis was 52 years [42-58]. Heart damage revealed EGPA in 55% of cases with a significant predominance of women (p=0.015). The main cardiac manifestations were myocarditis, ischemic cardiomyopathy due to small vessel vasculitis, cardiac tamponade and intracardiac thrombus. Cardiac magnetic resonance imaging (MRI) mainly showed subendocardial hyposignal in early infusion and late enhancement in the same areas, nodular by locations, associated with impaired left ventricle function and micro-infarctions by distal vasculitis. Cardiac damage was associated to ANCA negativity in 83.3% of cases. The median Birmingham Vasculitis Activity Score version3 (BVAS v3) was 16 [10-17]. Under conventional treatment, no relapses had occurred. The median vasculitis damage index (VDI) was 2 [1-2.3] and the mortality rate was zero after a mean follow-up of 43 months. CONCLUSION: Cardiomyopathy is a frequent revealing mode of EGPA. A late onset asthma and hypereosinophilia should guide the diagnosis. As ANCA research often turns out to be negative, histological evidence is recommended in this context. The contribution of cardiac MRI in the diagnosis of EGPA remains to be defined.

Pheochromocytoma presenting as an authentic small vessel vasculitis and complicated with pulmonary embolism: An original presentation.

Diagnosis of pheochromocytoma can be simple when classic manifestations are present. It can also be challenging and complicated in some cases because of its wide array of faces and presentations. We present a case of a 30-year-old female patient who came with acute respiratory distress, chest pain, hemoptysis, asthenia, anorexia, weight loss of 20kg, and paresthesia in her lower limbs. Clinical examination found high blood pressure, accelerated heart and respiratory rates, signs of acute right heart failure with jugular venous distention and ankle edema, reticularis livedo in the four limbs, ulcers in both knees and in the 3rd metacarpo-phalangeal articulations and necrotic lesions in both calcaneal tendons and in the right toes. Further investigations concluded on myocarditis associated with alveolar hemorrhage, pericardic and pleuritic effusions and a segmental pulmonary embolism of the right inferior lobe. Neuro-muscular biopsy was suggestive of myositis. Cutaneous biopsy found nonspecific chronic dermatitis. ANCA antibodies were tested twice and were negative. Cryoglobulinemia was also negative. Thoraco-abdomino-pelvic scan was performed showing a large right adrenal mass suggestive of pheochromocytoma. Diagnosis of right adrenal pheochromocytoma was confirmed by MIBG-I123 hyperfixation findings and urinary normetanephrin levels. The patient was treated surgically. Postoperative outcomes were remarkably favorable with a complete regression of the cutaneous lesions and normalization of the blood pressure. Paresthesia significantly decreased. Control echocardiography at 3 months showed an improved heart function with a persistent apical and septal akinesis.

[COVID-19 and arrhythmias]. / COVID-19 et troubles du rythme.

In the pandemic caused by the SARS-CoV2 virus, arrhythmias were not in the foreground. However, the virus seems to affect many organs and the cardiac tropism is now well known. Knowledge in this area is still far from exhaustive, but several series published concerning patients with COVID-19 find a significant proportion of arrhythmias, some of which can potentially lead to a fatal outcome. These rhythm disorders are mainly supraventricular, such as atrial fibrillation (AF) or flutter but also ventricular disorders like ventricular tachycardias (VT) ventricular fibrillation (VF) and more rarely torsades de pointe (TdP). The causes are multiple, due to the multiorgan damage caused by the virus and potential drug interactions. In addition, the question of monitoring rhythm disorders that may emerge in the medium and long term after an infection remains to be explored.

[SARS-COV-2 myocarditis. An update]. / Myocardite et maladie à COVID-19 : où en est-on ?

The outbreak of the SARS-CoV-2 virus responsible for the COVID-19 disease has given rise to a new disease whose boundaries are still to be discovered. While the first data suggested a purely respiratory infection, the most recent publications highlight a large pleomorphism of the disease, responsible for multiple organ damage, of which cardiac injury seems to be the most represented. This cardiac injury can present as acute myocarditis. Our aim was to discuss the pathophysiological rationale underlying the existence of SARS-CoV-2 myocarditis and to analyze the literature data regarding the diagnosis and treatment of this particular entity.

[Acute autoimmune myocarditis secondary to Graves' disease: a case report]. / Myocardite aiguë auto-immune secondaire à une maladie de Basedow : à propos d'un cas.

INTRODUCTION: Interactions between heart and thyroid are strong. Main cardiac complications of Graves' disease are supra-ventricular tachycardia or high output cardiac failure, without real myocardial involvement. OBSERVATION: A 40-year-old man with history of refractory Graves' disease was hospitalized for an acute chest pain with elevated cardiac biomarkers and normal coronarography. Acute myocarditis was confirmed by cardiac MRI. We found no evidence for an infectious etiology. We retained the hypothesis of acute autoimmune myocarditis in the context of active Graves' disease. CONCLUSION: Acute myocarditis is an exceptional complication of Graves' disease, with most likely an autoimmune mechanism. Possible occurrence of fulminant rhythmic or hemodynamic complications justify minimal cardiological check-up before introducing beta blockers.

[IRM et myocardite infectieuse]. / IRM et myocardite infectieuse.

Over the past ten years, cardiac MRI has become an indispensable tool for acute myocarditis diagnosis. Under appropriate conditions, cardiac MRI may allow postponement of initial coronary angiography in many instances. The 2020 ESC guidelines give a class I recommendation to its use in the setting of MINOCA for differential diagnosis between acute myocardial infarction, myocarditis, Tako-Tsubo and other cardiac pathologies, in order to improve therapeutic management and follow-up. This article describes the technical characteristics of MRI in myocarditis (Lake Louise diagnostic criteria and criteria based on myocardial tissue mapping), the main differential diagnoses, the prognostic value and addresses the issue of myocarditis in the setting of COVID-19.

[COVID-19 and mechanical circulatory support]. / COVID-19 et assistance circulatoire.

Extracorporeal membrane oxygenation (ECMO) is mainly used as a rescue therapy in COVID-19 patients with severe acute respiratory distress syndrome (ARDS). More rarely, COVID-19 can be complicated by hemodynamic failure due to fulminant myocarditis or massive pulmonary embolism necessitating the implantation of venous-arterial ECMO. The management of ECMO during the COVID-19 pandemic is challenging due to some specificities related to the disease characteristics, such as the management of anticoagulation in patients with a hypercoagulable state and an increased risk of venous thromboembolism. In large retrospective cohorts, survival of ECMO-rescued COVID-19 patients with ADRS was reported to be similar to that reported in previous studies on ECMO support for severe ARDS. Full consideration of ECMO candidacy is crucial for appropriate allocation of resources.

[Third degree atrio-ventricular blockade during a myocarditis occurring under anti-PD1 : Case report and literature review]. / Bloc atrio-ventriculaire de grade III compliquant une myocardite au décours d'un traitement par anti-PD1 : observation d'un cas et revue de la littérature.

INTRODUCTION: Immune Checkpoint Inhibitor (ICI) therapy is now a standard of care in numerous cancers with very promising results. Nevertheless, adverse events, and especially immune-related adverse events (irAEs) not reported during clinical trials, are emerging and can be life-threatening. OBSERVATION: We report here a teachable case of a 80 year-old man, of third-degree atrioventricular block consecutive to myocarditis associated with the administration of nivolumab (anti-PD1) monotherapy. CONCLUSION: Myocarditis occurring during ICI treatment is a rare but potentially lethal event. Daily serum troponin level seems to predict ICI-related myocarditis but interpretation could be difficult in the context of associated myositis. Echocardiography and cardiac MRI are also useful but can remain negative. Electrocardiogram is a cornerstone of myocarditis diagnosis. In case of cardiac involvement, continuous heart rhythm monitoring should be performed in addition to the administration of high-dose corticosteroids therapy and the cessation of ICI therapy. Add-on treatments should be discussed with a well-trained multidisciplinary team.

[Cocaine-induced acute myocarditis]. / Myocardite aiguë induite par la cocaïne.

Cocaine is a potent sympathomimetic drug usually associated with cardiotoxicity, including ventricular arrhythmia, systemic hypertension and acute myocardial infarction. It constitutes the most frequent cause of drug-related death reported by medical examiners in the US, and these events are most often related to the cardiovascular manifestations of the drug. However; to the best of our knowledge; cocaine induced acute myocarditis has very rarely been reported. We describe the case of a 19 year-old male regular user of marijuana and cocaine who was admitted for a suspicion on an acute lateral-wall myocardial infarction and in whom the final diagnosis of acute cocaine myocarditis has been made. We report diagnosis modalities and evolution.