Long QT syndrome associated with inflammatory degeneration of the stel ganglia

Pfeiffer, Dietrich; Fiehring, H; Henkel, Hans; Rostock, K. J.; Rathgen, Karin

doi:10.1002/clc.4960120408

Cited by 9 publications

(4 citation statements)

References 4 publications

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“…On the basis of these findings, the authors speculated that a T-cell-mediated cytotoxicity toward ganglion cells may boost adrenergic activity through release of inflammatory mediators in ganglia and in this manner contribute to the electric instability in LQTS/CPVT patients, particularly in those who are heavily symptomatic. In accordance with this view, intracardiac ganglionitis and its pro-arrythmic potential have been previously described in LQTS patients who died suddenly, the first time over 35 years ago ( 163 – 165 ). Moreover, although the origin of inflammatory infiltrates remains unknown, Rizzo et al ( 162 ) put forward the hypothesis of a viral (however not herpes-virus DNA was found in specimens) or autoimmune pathogenesis.…”

Section: Do Inflammation and Immunity Play A Role In Congenital Lqts?supporting

confidence: 64%

Long QT Syndrome: An Emerging Role for Inflammation and Immunity

Lazzerini

Capecchi

Laghi‐Pasini

2015

Front. Cardiovasc. Med.

137

123

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The long QT syndrome (LQTS), classified as congenital or acquired, is a multi-factorial disorder of myocardial repolarization predisposing to life-threatening ventricular arrhythmias, particularly torsades de pointes. In the latest years, inflammation and immunity have been increasingly recognized as novel factors crucially involved in modulating ventricular repolarization. In the present paper, we critically review the available information on this topic, also analyzing putative mechanisms and potential interplays with the other etiologic factors, either acquired or inherited. Accumulating data indicate inflammatory activation as a potential cause of acquired LQTS. The putative underlying mechanisms are complex but essentially cytokine-mediated, including both direct actions on cardiomyocyte ion channels expression and function, and indirect effects resulting from an increased central nervous system sympathetic drive on the heart. Autoimmunity represents another recently arising cause of acquired LQTS. Indeed, increasing evidence demonstrates that autoantibodies may affect myocardial electric properties by directly cross-reacting with the cardiomyocyte and interfering with specific ion currents as a result of molecular mimicry mechanisms. Intriguingly, recent data suggest that inflammation and immunity may be also involved in modulating the clinical expression of congenital forms of LQTS, possibly triggering or enhancing electrical instability in patients who already are genetically predisposed to arrhythmias. In this view, targeting immuno-inflammatory pathways may in the future represent an attractive therapeutic approach in a number of LQTS patients, thus opening new exciting avenues in antiarrhythmic therapy.

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Section: Do Inflammation and Immunity Play A Role In Congenital Lqts?supporting

confidence: 64%

Long QT Syndrome: An Emerging Role for Inflammation and Immunity

Lazzerini

Capecchi

Laghi‐Pasini

2015

Front. Cardiovasc. Med.

137

123

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“…Normal ganglia also Intracardiac ganglionitis and its potential effect on arrhythmic risk have been previously described in LQTS subjects who died suddendly. [25][26][27] Ganglionitis and neuritis in the sinus node area were found also in liquid-protein-modified fast diet dieters who developed prolongation of the QT interval and ventricular arrhythmias after dieting. 28 In these studies, diffuse infiltration of mononuclear cells associated with neural degeneration was found at histological examination, lacking however of an immune characterization of the cellular composition and activity of the inflammatory population.…”

Section: Discussionmentioning

confidence: 97%

T-Cell–Mediated Inflammatory Activity in the Stellate Ganglia of Patients With Ion-Channel Disease and Severe Ventricular Arrhythmias

Rizzo

Basso

Troost

et al. 2014

Circ: Arrhythmia and Electrophysiology

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Background-Long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are electric diseases characterized by catecholamine-induced ventricular arrhythmias. Unbalanced autonomic innervation of the heart may trigger arrhythmic events and stellectomy is a treatment option for patients who are resistant to pharmacological drugs. We analyzed left stellectomy specimens of LQTS and CPVT patients for signs of inflammatory activity. Methods and Results-Stellate ganglia were retrieved from 12 consecutive patients (8F; 4 mol/L; mean age, 23.4±17 years) with either LQTS (n=8) or CPVT (n=4) and serious arrhythmias. Control stellate ganglia were obtained from 10 accidently deceased patients (6F; 4 mol/L; mean age, 35±17.6 years). Sections were immunostained with antibodies against T cells (CD3, CD4, CD8, CD20, Granzyme B), CD68 (macrophages), and HLA-DR (human leukocyte antigen-DR) antigens (activation marker). Immunopositive cells were quantified as cells/mm 2 . Polymerase chain reaction (PCR) and reverse transcription PCR were performed to screen for herpes virus DNA. Stellate ganglia of all 12 LQTS/CPVT patients revealed mild but distinct inflammatory infiltrates composed of T lymphocytes and macrophages, which were diffusely spread, but also clustered in small foci opposed to ganglion cells, interpreted as T-cell-mediated ganglionitis. Morphometric analysis showed that CD3+ and CD8+ T cells/mm 2 were significantly higher in the ganglia of LQTS/CPVT cases than in healthy controls (P=0.0018 and P=0.0009, respectively). Molecular analyses were negative for neurotropic viruses. Conclusions-T-cell-mediated cytotoxicity toward ganglion cells may boost adrenergic activity as to trigger or enhance electric instability in LQTS/CPVT patients who are already genetically predisposed to arrhythmias. (Circ Arrhythm Electrophysiol. 2014;7:224-229.)

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“…The term 'ganglionitis' was used to describe this phenomenon, and its associated malignant cardiac rhythm. A decade later, Pfeiffer et al (1989) described the first case of a young patient with a structurally normal heart, but with severe inflammation of the SG, linking viral-mediated neuronal dysfunction in SGs to malignant arrhythmogenesis in this patient. Recently, in patients with congenital long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT), Rizzo et al (2014) observed evidence of T cell-mediated inflammation.…”

Section: Extra-cardiac Neuronalmentioning

confidence: 99%

Clinical neurocardiology defining the value of neuroscience‐based cardiovascular therapeutics

Shivkumar¹,

Ajijola²,

Anand

et al. 2016

The Journal of Physiology

262

212

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The autonomic nervous system regulates all aspects of normal cardiac function, and is recognized to play a critical role in the pathophysiology of many cardiovascular diseases. As such, the value of neuroscience-based cardiovascular therapeutics is increasingly evident. This White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology, pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases.

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Long QT syndrome associated with inflammatory degeneration of the stel ganglia

Cited by 9 publications

References 4 publications

Long QT Syndrome: An Emerging Role for Inflammation and Immunity

Long QT Syndrome: An Emerging Role for Inflammation and Immunity

T-Cell–Mediated Inflammatory Activity in the Stellate Ganglia of Patients With Ion-Channel Disease and Severe Ventricular Arrhythmias

Clinical neurocardiology defining the value of neuroscience‐based cardiovascular therapeutics

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