Immunosuppressive therapy in childhood‐onset arrhythmogenic inflammatory cardiomyopathy

Peretto, Giovanni; Barzaghi, Federica; Cicalese, Maria Pia; Resta, Chiara Di; Slavich, Massimo; Benedetti, Sara; Galimberti, Sara; Rizzo, Stefania; Palmisano, Anna; Esposito, Antonio; Cobelli, Francesco De; Gulletta, Simone; Basso, Cristina; Casari, Giorgio; Aiuti, Alessandro; Bella, Paolo Della; Sala, Simone

doi:10.1111/pace.14153

Cited by 11 publications

(8 citation statements)

References 17 publications

(20 reference statements)

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“…It should be noted that although MVP is not conventionally defined as a cardiomyopathy, myocardial inflammation and associated tissue abnormalities do widely overlap with those reported in many other non-ischemic diseases [29][30][31]. The described clinical case showed consistency with this hypothesis, both in the spatial domain, given the basal inferolateral LV wall involvement shared between myocarditis and MVP, with an overall consistent dominant PVC morphology [20], and in the temporal domain, since replacement fibrosis was documented even at the initial EMB, hinting at a non-acute process [18,25,27] despite the abrupt clinical onset. Confirmatory evidence is undoubtedly needed in this area, and would provide novel mechanistic insights into arrhythmogenic MVP pathophysiology.…”

Section: Discussionsupporting

confidence: 79%

“…Concerning risk stratification, the patient was initially implanted with an ICD. In fact, although the current guidelines suggest refraining from a secondary prevention cardiac device implant until myocarditis healing, the patient had persistent, symptomatic episodes of NSVT, premature PVCs, and anti-intercalated disks autoantibodies as an additional hallmark of arrhythmic risk [17,25]. Retrospectively, the strategy was beneficial, and fully fitting with the recommendation for secondary prevention ICD implant in patients with arrhythmogenic MVP [1,2].…”

Section: Discussionmentioning

confidence: 99%

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Autoimmune Myocarditis and Arrhythmogenic Mitral Valve Prolapse: An Unexpected Overlap Syndrome

Villatore

Sala

Stella

et al. 2021

JCDD

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Background: both myocarditis and mitral valve prolapse (MVP) are known uncommon causes of ventricular arrhythmias in young patients. Aim: to report the first clinical case of endomyocardial biopsy (EMB)-proven autoimmune myocarditis and associated arrhythmogenic MVP in a patient with recurrent ventricular fibrillation (VF) episodes. Methods: myocarditis was diagnosed both by cardiac magnetic resonance (CMR) and EMB. Arrhythmogenic MVP was documented by transthoracic echocardiogram, CMR, and electroanatomical mapping of the trigger premature ventricular contractions (PVCs). Results: a 22-year-old woman underwent immunosuppressive therapy after EMB-proven diagnosis of autoimmune myocarditis with VF onset and early implantable cardioverter defibrillator (ICD) placement. Three years later, she experienced two VF recurrences and persistent PVCs, despite no signs of myocarditis recurrence. An echocardiogram revealed bileaflet MVP with high arrhythmic risk features. Finally, electroanatomical mapping and ablation of the trigger PVC were successfully performed. Conclusion: in patients with recurrent VF episodes despite evidence-based medical treatment for myocarditis, MVP should be considered as an alternative arrhythmogenic substrate, and warrants early ICD implant and PVC-targeted therapy.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Autoimmune Myocarditis and Arrhythmogenic Mitral Valve Prolapse: An Unexpected Overlap Syndrome

Villatore

Sala

Stella

et al. 2021

JCDD

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“…With this knowledge, targeting the inflammation cascade may be beneficial for all patients with AC. A recent case report described success with prednisone and azathioprine in controlling recurrent VA not successfully treated with beta‐blockers or anti‐arrhythmic medications in a pediatric patient with AC 38 . Although long‐term broad immunosuppression may not be attractive, especially in younger patients, more targeted approaches may hold promise.…”

Section: Methodsmentioning

confidence: 99%

The role of inflammation in the pathogenesis and treatment of arrhythmias

et al. 2022

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The pathogenesis of arrhythmias is complex and multifactorial. The role of inflammation in the pathogenesis of both atrial and ventricular arrhythmias (VA) has been explored. However, developing successful pharmacotherapy regimens based on those pathways has proven more of a challenge. This narrative review provides an overview of five common arrhythmias impacted by inflammation, including atrial fibrillation (AF), myocardial infarction, arrhythmogenic cardiomyopathy, cardiac sarcoidosis, and QT prolongation, and the potential role for anti‐inflammatory therapy in their management. We identified arrhythmias and arrhythmogenic disease states with the most evidence linking pathogenesis to inflammation and conducted comprehensive searches of United States National Library of Medicine MEDLINE® and PubMed databases. Although a variety of agents have been studied for the management of AF, primarily in an effort to reduce postoperative AF following cardiac surgery, no standard anti‐inflammatory agents are used in clinical practice at this time. Although inflammation following myocardial infarction may contribute to the development of VA, there is no clear benefit with the use of anti‐inflammatory agents at this time. Similarly, although inflammation is clearly linked to the development of arrhythmias in arrhythmogenic cardiomyopathy, data demonstrating a benefit with anti‐inflammatory agents are limited. Cardiac sarcoidosis, an infiltrative disease eliciting an immune response, is primarily treated by immunosuppressive therapy and steroids, despite a lack of primary literature to support such regimens. In this case, anti‐inflammatory agents are frequently used in clinical practice. The pathophysiology of arrhythmias is complex, and inflammation likely plays a role in both onset and duration, however, for most arrhythmias the role of pharmacotherapy targeting inflammation remains unclear.

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“…But to date, none of these agents has been tested neither in pre-clinical models nor in patients with ACM. Interestingly, off-label use of conventional immunosuppressive therapy with prednisolone and azathioprine was beneficial in a child presenting with a clinical picture of autoimmune myocarditis with [ 148 ].…”

Section: Novel Therapeutic Approachesmentioning

confidence: 99%

Insights Into Genetics and Pathophysiology of Arrhythmogenic Cardiomyopathy

Gerull¹,

Brodehl

2021

Curr Heart Fail Rep

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Purpose of Review Arrhythmogenic cardiomyopathy (ACM) is a genetic disease characterized by life-threatening ventricular arrhythmias and sudden cardiac death (SCD) in apparently healthy young adults. Mutations in genes encoding for cellular junctions can be found in about half of the patients. However, disease onset and severity, risk of arrhythmias, and outcome are highly variable and drug-targeted treatment is currently unavailable. Recent Findings This review focuses on advances in clinical risk stratification, genetic etiology, and pathophysiological concepts. The desmosome is the central part of the disease, but other intercalated disc and associated structural proteins not only broaden the genetic spectrum but also provide novel molecular and cellular insights into the pathogenesis of ACM. Signaling pathways and the role of inflammation will be discussed and targets for novel therapeutic approaches outlined. Summary Genetic discoveries and experimental-driven preclinical research contributed significantly to the understanding of ACM towards mutation- and pathway-specific personalized medicine.

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Immunosuppressive therapy in childhood‐onset arrhythmogenic inflammatory cardiomyopathy

Cited by 11 publications

References 17 publications

Autoimmune Myocarditis and Arrhythmogenic Mitral Valve Prolapse: An Unexpected Overlap Syndrome

Autoimmune Myocarditis and Arrhythmogenic Mitral Valve Prolapse: An Unexpected Overlap Syndrome

The role of inflammation in the pathogenesis and treatment of arrhythmias

Insights Into Genetics and Pathophysiology of Arrhythmogenic Cardiomyopathy

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