Reassessment of the NF1 variants of unknown significance found during the 20-year activity of a genetics diagnostic laboratory.

The finding of variants of uncertain significance (VUS) in the activity of a diagnostic genetic laboratory is a common issue, which is however provisional and needs to be periodically re-evaluated, due to the continuous advancements in our knowledge of the genetic diseases. Neurofibromatosis type 1, caused by the occurrence of heterozygous pathogenic NF1 variants, is a good model for studying the evolution of VUS, due to the widespread use of genetic testing for the disease, the constant enrichment of the international databases with NF1 variants and the full adult penetrance of the disease, which makes genotyping the parents a crucial step in the diagnostic workflow. The present study retrospectively reviewed and reinterpreted the genetic test results of NF1 in a diagnostic genetic laboratory in the period from January 1, 2000 to December 31, 2020. All the VUS were reinterpreted using the 2015 consensus standards and guidelines for the interpretation. Out of 589 NF1 genetic tests which were performed in the period, a total of 85 VUS were found and reinterpreted in 72 cases (84.7%): 21 (29.2%) were reclassified as benign/likely benign, whereas 51 (70.8%) were recoded as pathogenic/likely pathogenic with a significant trend distribution (Chi square test for trend p = 0.005). Synonymous VUS have mainly been reclassified as class 1 and 2 (7/8, 87.5%), whereas missense variants have been attributed to class 4 and 5 in 38 out of the 58 cases (65.5%). These findings underline an improvement in the classification of variants over time, suggesting that a reinterpretation of the genetic tests should be routinely performed to support the physicians in the clinical diagnosis of genetic diseases.

Surgical repair of postinfarction ventricular septal rupture: current state of the art.

The incidence of postacute myocardial infarction ventricular septal rupture (post-AMI VSR) has decreased over the past two decades. Nevertheless, individuals who suffer from post-AMI VSR continue to represent a subgroup of patients with high morbidity and mortality. The care for these patients is complex and requires a multidisciplinary approach. However, because of the small number of reports that exist to guide clinical practice, there is a significant variability in care among centers. This review summarizes information on post-AMI VSR diagnosis and outline contemporary best management and practice consideration.

Surgical repair of left ventricular free-wall rupture complicating acute myocardial infarction: a single-center 30 years of experience.

Background: Left ventricular free-wall rupture (LVFWR) is a catastrophic complication of acute myocardial infarction (AMI). Historically, cardiac surgery is considered the treatment of choice. However, because of the rarity of this entity, little is known regarding the efficacy and safety of surgical treatment for post-infarction LVFWR. The aim of this study was to report a single-center experience in this field over a period of 30 years. Methods: Patients who developed LVFWR following AMI and underwent surgical repair at our Institution from January 1990 to December 2019 were considered. The primary end-point was in-hospital morality rate; secondary outcomes were long-term survival and postoperative complications. Multivariate analysis was carried out by constructing a logistic regression model to identify risk factors for early mortality. Results: A total of 35 patients were enrolled in this study. The mean age was 68.9 years; 65.7% were male. The oozing type of LVFWR was encountered in 29 individuals, and the blowout type in 6 subjects. Sutured repair was used in 77.1% of patients, and sutureless repair in the remaining cases. The in-hospital mortality rate was 28.6%. Low cardiac output syndrome was the main cause of postoperative death. Multivariable analysis identified age >75 years at operation, preoperative cardiac arrest, concurrent ventricular septal rupture (VSR) as independent predictors of in-hospital death. Follow-up was complete in 100% of patients who survived surgery (mean follow-up: 9.3 ± 7.8 years); among the survivors, 16 patients died during the follow-up with a 3-year and 12-year overall survival rate of 82.5% and 55.2%, respectively. Conclusions: Surgical treatment of LVFWR following AMI is possible with acceptable in-hospital mortality and excellent long-term results. Advanced age, concurrent VSR and cardiac arrest at presentation are independent risk factors of poor early outcome.

Intraoperative left atrial dissection following mitral valve surgery: Report of a case treated surgically.

Left atrial dissection (LatD) is an exceedingly rare but serious complication of cardiac surgery. Its clinical presentation is very different in individual cases. Surgical treatment for LatD is often selected when the patient is hemodynamically unstable; conservative treatments are commonly employed under stable conditions. We report a case of LatD after mitral valve replacement that was treated surgically with creation of an atrial fenestration.