No abstract

Among our population of sarcoid patients with nonspecific symptoms, the presence of myocardial scar indicated by LGE was the best independent predictor of potentially lethal events, as well as other adverse events, yielding a Cox HR of 31.6 and of 33.9, respectively. These data support the necessity for future large, longitudinal follow-up studies to definitely establish LGE as an independent predictor of cardiac death in sarcoidosis, as well as to evaluate the incremental prognostic value of additional parameters.

Background. Enhanced sympathetic activity at the ventricular myocardium can destabilize repolarization, increasing the risk of death. Sympathetic activity is known to cluster in low-frequency bursts; therefore, we hypothesized that sympathetic activity induces periodic low-frequency changes of repolarization. We developed a technique to assess the sympathetic effect on repolarization and identified periodic components in the low-frequency spectral range (≤0.1 Hz), which we termed periodic repolarization dynamics (PRD). Methods.We investigated the physiological properties of PRD in multiple experimental studies, including a swine model of steady-state ventilation (n = 7) and human studies involving fixed atrial pacing (n = 10), passive head-up tilt testing (n = 11), low-intensity exercise testing (n = 11), and beta blockade (n = 10). We tested the prognostic power of PRD in 908 survivors of acute myocardial infarction (MI). Finally, we tested the predictive values of PRD and T-wave alternans (TWA) in 2,965 patients undergoing clinically indicated exercise testing.Results. PRD was not related to underlying respiratory activity (P < 0.001) or heart-rate variability (P = 0.002). Furthermore, PRD was enhanced by activation of the sympathetic nervous system, and pharmacological blockade of sympathetic nervous system activity suppressed PRD (P ≤ 0.005 for both). Increased PRD was the strongest single risk predictor of 5-year total mortality (hazard ratio 4.75, 95% CI 2.94-7.66; P < 0.001) after acute MI. In patients undergoing exercise testing, the predictive value of PRD was strong and complementary to that of TWA. Conclusion.We have described and identified low-frequency rhythmic modulations of repolarization that are associated with sympathetic activity. Increased PRD can be used as a predictor of mortality in survivors of acute MI and patients undergoing exercise testing.Trial registration. ClinicalTrials.gov NCT00196274.Funding. This study was funded by Angewandte Klinische Forschung, University of Tübingen (252-1-0).

No abstract

Overall, our findings uncover a novel function of the anaphylatoxin C3a for platelet function and thrombus formation, highlighting a detrimental role of imbalanced complement activation in cardiovascular diseases.