Viral genome search in myocardium of patients with fulminant myocarditis

Veronese, Giacomo; Ammirati, Enrico; Brambatti, Michela; Merlo, Marco; Cipriani, Manlio; Potena, Luciano; Scocco, Paola; Aoki, Tatsuo; Sugimura, Koichiro; Sawamura, Akinori; Okumura, Takahiro; Pinney, Sean; Hong, Kimberly N.; Shah, Palak; Braun, Öscar; Heyning, Caroline M. Van De; Montero, Santiago; Petrella, Duccio; Huang, Florent; Schmidt, Matthieu; Raineri, Claudia; Lala, Anuradha; Varrenti, Marisa; Foà, Alberto; Leone, Ornella; Gentile, Piero; Artico, Jessica; Agostini, Valentina; Patel, Ravi; Garascia, Andrea; Craenenbroeck, Emeline M. Van; Hirose, Kaoru; Isotani, Akihiro; Murohara, Toyoaki; Arita, Yoh; Sionís, Alessandro; Fabris, Enrico; Hashem, Sherin I.; García-Hernando, Victor; Oliva, Fabrizio; Greenberg, Barry D.; Shimokawa, Hiroaki; Sinagra, Gianfranco; Adler, Eric; Frigerio, Maria; Camici, Paolo G.

doi:10.1002/ejhf.1738

Cited by 24 publications

(27 citation statements)

References 8 publications

(13 reference statements)

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“…PVB19 has been the only virus found in patients with lymphocytic FM in an international registry. 25 , 38 A preliminary report showing a benefit from immunosuppression in chronic infl-CMP with PVB19 presence in the myocardium seems to support the hypothesis that the immune response plays a role in the development of myocardial inflammation after viral infection. 72 Alternatively, low copy number of PVB19 DNA may reflect latent infection and should be interpreted as a bystander, since they can be found also in normal myocardium.…”

Section: Virus-induced and Immune-mediated Lymphocytic Am And Infl-cmmentioning

confidence: 80%

“…To date, it is not known which viruses other than enteroviruses may cause direct tissue damage in humans or act mainly as triggers for autoimmunity-mediated damage or both. 22 , 23 It must be considered that the experimental evidences on murine models of viral myocarditis are based on infections with Coxsackie B viruses, whereas for the most common agent in virus-positive myocarditis patients, parvovirus-B19 (PVB19), 24 , 25 no animal models are available. A possible association between genetic abnormalities and susceptibility to inflammation has been suggested.…”

Section: Definitions Epidemiology and Pathophysiologymentioning

confidence: 99%

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Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy

Ammirati

Frigerio

Adler

et al. 2020

Circ: Heart Failure

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451

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Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally <1 month). In contrast, chronic inflammatory cardiomyopathy indicates myocardial inflammation with established dilated cardiomyopathy or hypokinetic nondilated phenotype, which in the advanced stages evolves into fibrosis without detectable inflammation. Suggested diagnostic and treatment recommendations for AM and chronic inflammatory cardiomyopathy are mainly based on expert opinion given the lack of well-designed contemporary clinical studies in the field. We will provide a shared and practical approach to patient diagnosis and management, underlying differences between the European and US scientific statements on this topic. We explain the role of histology that defines subtypes of myocarditis and its prognostic and therapeutic implications.

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Section: Virus-induced and Immune-mediated Lymphocytic Am And Infl-cmmentioning

confidence: 80%

Section: Definitions Epidemiology and Pathophysiologymentioning

confidence: 99%

Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy

Ammirati

Frigerio

Adler

et al. 2020

Circ: Heart Failure

Self Cite

451

601

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show abstract

“…We therefore used multi-parametric cardiac magnetic resonance imaging, including adenosine stress-perfusion to measure myocardial blood flow and vascular permeability in patients before and during VSPI treatment. 5 All patients over the age of 18 years at the Beatson West of Scotland Cancer Centre in Glasgow, Scotland, who were planned to commence VSPI therapy were considered for participation. Enrolment took place between December 2018 and March 2019.…”

Section: Cardiotoxicity and Myocardial Hypoperfusion Associated With mentioning

confidence: 99%

“…1,4 The role of viruses in myocarditis aetiology has been historically recognized, with parvovirus (PV) B19, adenoviruses, human herpes virus type 6 (HHV6) and enteroviruses being the most common agents identified in myocardium. [4][5][6] A growing body of literature indicates that viruses, particularly PVB19, may be found in a large proportion of patients who do not have myocarditis, and additional studies are needed to determine their causal role. 7 It has been stated that the presence of specific viruses in the heart may contraindicate the use of immunosuppression, particularly in lymphocytic forms, where its role is mostly controversial.…”

Section: Viral Genome Search In Myocardium Of Patients With Fulminantmentioning

confidence: 99%

Cardiotoxicity and myocardial hypoperfusion associated with anti‐vascular endothelial growth factor therapies: prospective cardiac magnetic resonance imaging in patients with cancer

Dobbin

Mangion

Berry

et al. 2020

European J of Heart Fail

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“…32 Further, conventional treatment of HHV-6 positive myocarditis consists of acyclovir administration, and steroid therapy should be avoided due to a subsequent increase in viral load. 9 Currently, there are cut-off values for the viral quantification of PVB19 (> 500 copies/μg DNA) 31,33,34 and HHV-6 (> 500 copies/μg DNA). 7 These are considered clinically relevant thresholds for the maintenance of myocardial inflammation.…”

Section: Role Of Potential Viral Bystander Findingsmentioning

confidence: 99%

Viral presence‐guided immunomodulation in lymphocytic myocarditis: an update

Sinagra

Porcari

Gentile

et al. 2020

European J of Heart Fail

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Latest statements from European and American societies recommend to rule out viral presence in endomyocardial biopsy (EMB) via polymerase chain reaction (PCR) analysis before starting immunosuppression or immunomodulation in acute lymphocytic myocarditis presenting with life-threatening scenarios. However, recommendations in myocarditis are mostly based on heterogeneous studies enrolling patients with inflammatory cardiomyopathies and established heart failure rather than acute myocarditis. Thus, definitive evidence of a survival benefit from immunomodulation guided by viral presence is currently lacking. Finally, distinguishing innocent bystanders from causative agents among EMB-detected viruses remain challenging and a major goal to achieve in the near future. Therefore, considerable divergence remains between official recommendations and clinical practice, including the possibility of starting immunosuppressive therapy empirically, without knowing viral PCR results. This review systematically discusses the unsolved issues of immunomodulation guided by viral presence in acute lymphocytic myocarditis, namely (i) virus epidemiology and prognosis, (ii) variability of viral presence rates, (iii) the role of potential viral bystander findings, and (iv) the main results of immunosuppression controlled trials in lymphocytic myocarditis. Furthermore, a practical approach for the critical use of viral presence analysis in guiding immunomodulation is provided, highlighting its importance before starting immunosuppression or immunomodulation. Future, multicentre studies are needed to address specific scenarios such as fulminant lymphocytic myocarditis and a virus-tailored management as for parvovirus B19.

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Viral genome search in myocardium of patients with fulminant myocarditis

Cited by 24 publications

References 8 publications

Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy

Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy

Cardiotoxicity and myocardial hypoperfusion associated with anti‐vascular endothelial growth factor therapies: prospective cardiac magnetic resonance imaging in patients with cancer

Viral presence‐guided immunomodulation in lymphocytic myocarditis: an update

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