Missense and Non-Missense Lamin A/C Gene Mutations Are Similarly Associated with Major Arrhythmic Cardiac Events: A 20-Year Single-Centre Experience.

Arrhythmic risk stratification in patients with Lamin A/C gene (LMNA)-related cardiomyopathy influences clinical decisions. An implantable cardioverter defibrillator (ICD) should be considered in patients with an estimated 5-year risk of malignant ventricular arrhythmia (MVA) of ≥10%. The risk prediction score for MVA includes non-missense LMNA mutations, despite their role as an established risk factor for sudden cardiac death (SCD) has been questioned in several studies. The purpose of this study is to investigate cardiac features and find gene-phenotype correlations that would contribute to the evidence on the prognostic implications of non-missense vs. missense mutations in a cohort of LMNA mutant patients. An observational, prospective study was conducted in which 54 patients positive for a Lamin A/C mutation were enrolled, and 20 probands (37%) were included. The median age at first clinical manifestation was 41 (IQR 19) years. The median follow-up was 8 years (IQR 8). The type of LMNA gene mutation was distributed as follows: missense in 26 patients (48%), non-frameshift insertions in 16 (30%), frameshift deletions in 5 (9%), and nonsense in 7 (13%). Among the missense mutation carriers, two (8%) died and four (15%) were admitted onto the heart transplant list or underwent transplantation, with a major adverse cardiovascular event (MACE) rate of 35%. No statistically significant differences in MACE prevalence were identified according to the missense and non-missense mutation groups (p value = 0.847). Our data shift the spotlight on this considerable topic and could suggest that some missense mutations may deserve attention regarding SCD risk stratification in real-world clinical settings.

The Postoperative Paradoxical Septum (POPS): A Comprehensive Review on Physio-Pathological Mechanisms.

The interventricular septum (IVS) is a core myocardial structure involved in biventricular coupling and performance. Physiologically, during systole, it moves symmetrically toward the center of the left ventricle (LV) and opposite during diastole. Several pathological conditions produce a reversal or paradoxical septal motion, such as after uncomplicated cardiac surgery (CS). The postoperative paradoxical septum (POPS) was observed in a high rate of cases, representing a unicum in the panorama of paradoxical septa as it does not induce significant ventricular morpho-functional alterations nor negative clinical impact. Although it was previously considered a postoperative event, evidence suggests that it might also appear during surgery and gradually resolve over time. The mechanism behind this phenomenon is still debated. In this article, we will provide a comprehensive review of the various theories generated over the past fifty years to explain its pathological basis. Finally, we will attempt to give a heuristic interpretation of the biventricular postoperative motion pattern based on the switch of the ventricular anchor points.