Systemic inflammation was present in 80% of patients with Torsades de pointes, and therapeutic reduction of CRP was associated with a significant QTc shortening of 22.3 ms.
Cohort (n=86)
Does systemic inflammation contribute to QT prolongation and the occurrence of Torsades de pointes?
Systemic inflammation, particularly via elevated IL-6, is a novel risk factor for QT prolongation and Torsades de pointes, and its resolution significantly shortens the QTc interval.
Mean Difference: -22.3
OBJECTIVE: Increasing evidence indicates systemic inflammation as a new potential cause of acquired long QT syndrome (LQTS), via cytokine-mediated changes in cardiomyocyte ion channels. Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia occurring in patients with LQTS, usually when multiple QT-prolonging factors are simultaneously present. Since classical risk factors cannot fully explain TdP events in a number of patients, we hypothesised that systemic inflammation may represent a currently overlooked risk factor contributing to TdP development in the general population. METHODS: Forty consecutive patients who experienced TdP (TdP cohort) were consecutively enrolled and circulating levels of C-reactive protein (CRP) and proinflammatory cytokines (interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα), interleukin-1 (IL-1)) were compared with patients with active rheumatoid arthritis (RA), comorbidity or healthy controls. An additional 46 patients with different inflammatory conditions (acute infections, n=31; immune-mediated diseases, n=12; others, n=3) and elevated CRP (inflammatory cohort) were prospectively enrolled, and corrected QT (QTc) and cytokine levels were measured during active disease and after a CRP decrease of >75% subsequent to therapy. RESULTS: In the TdP cohort, 80% of patients showed elevated CRP levels (median: ~3 mg/dL), with a definite inflammatory disease identifiable in 18/40 cases (acute infections, n=12; immune-mediated diseases, n=5; others, n=1). In these subjects, IL-6, but not TNFα and IL-1, was ~15-20 times higher than in controls, and comparable to RA patients. In the inflammatory cohort, where QTc prolongation was common (mean values: 456.6±30.9 ms), CRP reduction was associated with IL-6 level decrease and significant QTc shortening (-22.3 ms). CONCLUSION: The data are first to show that systemic inflammation via elevated IL-6 levels may represent a novel QT-prolonging risk factor contributing to TdP occurrence in the presence of other classical risk factors. If confirmed, this could open new avenues in antiarrhythmic therapy.
Lazzerini et al. (Wed,) conducted a cohort in Torsades de pointes and systemic inflammation (n=86). Systemic inflammation vs. Healthy controls or post-therapy state (CRP decrease >75%) was evaluated on QTc shortening after CRP decrease >75% (-22.3 ms). Systemic inflammation was present in 80% of patients with Torsades de pointes, and therapeutic reduction of CRP was associated with a significant QTc shortening of 22.3 ms.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: