Moreover, these factors may represent the substrate for electrical instability, which may be triggered by prolonged ischemic events. As hypothesized in Coumel’s triangle theory, myocardial disarray, fibrosis and hypertrophy serve as arrhythmogenic WZ8040 substrates that necessitate a trigger to induce arrhythmic events ; these events may finally be elicited by either ischemia or inflammation, which are detected by CMR as HyT2. The presence of LGE in patients with HCM may be considered relevant in terms of risk stratification, as recent reports have demonstrated that after a clinical follow-up of 3 years, patients with LGE had a worse prognoses than those without. However, LGE is usually detected in most HCM patients during the first CMR evaluation, with a reported prevalence of 60–90%. Thus, the specificity of LGE as a prognostic marker in HCM should be discussed. Moreover, once cardiac fibrosis develops, its progression is relatively rapid. Indeed, we recently demonstrated that the progression of LGE extent was fast and related to clinical worsening. Thus, features other than LGE extent should be investigated as predictors of sudden cardiac death ; for example, the presence of extensive and diffuse LGE is currently indicated as an emerging new arrhythmic risk factor. However, previous studies showed that an extent of LGE.15% of LV mass was related to depressed systolic function, which may contribute to progression to endstage disease.

Other CMR techniques, such as T1 mapping and measurements of the extracellular volume, are currently under evaluation as prognostic factors for HCM. Some limitations of the current study should be mentioned. First, HyT2 may be detected in conditions other than ischemia and inflammation, and the results of the current study did not allow us to understand the nature and etiology of HyT2 in HCM. Second, we assumed that HyT2 in HCM is a sign of acute, transient myocardial damage, although this assumption was based only on the observation of HyT2 in other cardiac diseases. Thus, further studies with serial CMR examinations should be performed to confirm the reversibility of HyT2 and the prognostic role of HyT2 in larger HCM populations. In conclusion, in patients with HCM, the presence of HyT2 upon CMR examination is associated with more advanced disease, ventricular arrhythmias and signs of electrical instability. HyT2 was detected in 42% of patients with HCM, and it was the best predictor of NSVT during a 24-h Holter ECG recording. HyT2 was associated with decreased heart rate variability and a greater number of arrhythmic risk factors.

Membrane proteins account for 20–25% of all open reading frames in sequenced genomes, and fulfill a wide range of functions in cells. Our knowledge of the assembly of this class of proteins is still poor. The study of membrane proteins in situ is difficult for several reasons: proteins assemble in larger complexes; interact with other proteins, and with other cell components. Therefore model bilayer in vitro systems are often used for studying membrane proteins as they negate many of the problems associated with the use of membrane vesicles. Performing in vitro studies requires solubilization of a membrane protein with a suitable detergent, followed by a functional reconstitution in a well-characterized bilayer system. However such studies are greatly hamp