Updates in Small Interfering RNA for the Treatment of Dyslipidemias.

PURPOSE OF REVIEW: Atherosclerotic cardiovascular disease (ASCVD) is still the leading cause of death worldwide. Despite excellent pharmacological approaches, clinical registries consistently show that many people with dyslipidemia do not achieve optimal management, and many of them are treated with low-intensity lipid-lowering therapies. Beyond the well-known association between low-density lipoprotein cholesterol (LDL-C) and cardiovascular prevention, the atherogenicity of lipoprotein(a) and the impact of triglyceride (TG)-rich lipoproteins cannot be overlooked. Within this landscape, the use of RNA-based therapies can help the treatment of difficult to target lipid disorders. RECENT FINDINGS: The safety and efficacy of LDL-C lowering with the siRNA inclisiran has been documented in the open-label ORION-3 trial, with a follow-up of 4 years. While the outcome trial is pending, a pooled analysis of ORION-9, ORION-10, and ORION-11 has shown the potential of inclisiran to reduce composite major adverse cardiovascular events. Concerning lipoprotein(a), data of OCEAN(a)-DOSE trial with olpasiran show a dose-dependent drop in lipoprotein(a) levels with an optimal pharmacodynamic profile when administered every 12 weeks. Concerning TG lowering, although ARO-APOC3 and ARO-ANG3 are effective to lower apolipoprotein(apo)C-III and angiopoietin-like 3 (ANGPTL3) levels, these drugs are still in their infancy. In the era moving toward a personalized risk management, the use of siRNA represents a blossoming armamentarium to tackle dyslipidaemias for ASCVD risk reduction.

Hybrid aortic arch repair procedure: reinforcement of the aorta for a safe and durable landing zone.

OBJECTIVES: Hybrid aortic arch repair procedure was introduced to reduce invasiveness in high-risk patients with aortic arch pathology. The good results are expanding its application, but endoleak, particularly type I, remains its Achilles' heel. DESIGN: We describe our experience with hybrid treatment of aortic arch diseases focussing on techniques and results to avoid type I endoleak. MATERIALS AND METHODS: A total of 15 high-risk patients with zone 0-2 aortic arch pathology underwent supra-aortic debranching on ascending aorta and proximal aortic arch reinforcement with a Dacron prosthesis. Metachronously, the procedure was completed with endovascular stent grafting (ESG). RESULTS: Median age was 70 years with a mean European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 12.7±6.8. One patient died between aortic debranching and ESG. Mean time between surgical debranching and ESG was 32±27.7 days. No major neurological events occurred. Mean length of the landing zone for ESG was 3.8±0.8 cm. Computed tomography (CT) angiography scan performed soon after operation, and at 3, 6, and 12 months did not show any type I endoleak. CONCLUSIONS: Supra-aortic debranching on ascending aorta with proximal aortic arch reinforcement is a useful step to ensure a safe landing zone for ESG, reducing risk early to midterm of endoleak. Longer term follow-up is required to confirm the viability of this technique.

Should pregnancy be considered a risk factor for aortic dissection? Two cases of acute aortic dissection following cesarean section in non-Marfan nor bicuspid aortic valve patients.

Acute aortic dissection in pregnancy is a rare event and rarer still in healthy young women; however, women with a bicuspid aortic valve or the Marfan syndrome are at a higher risk of dissection. The relationship between pregnancy and aortic dissection is still unclear. We describe the cases of two women with no history of cardiovascular disease who developed an acute aortic type A dissection within a few days after term delivery. Surgical repair was performed with ascending aorta replacement and aortic valve sparing. In both cases, the dissection was diagnosed within a few days following cesarean section done neither because of fetal or maternal distress. To date, only one case of type A and two cases of type B aortic dissection following cesarean section have been reported. Compared with spontaneous delivery, scheduled cesarean section, as in our cases, allows for better control of hemodynamic parameters and should protect against aortic dissection. Postoperative screening for inherent connective tissue disorders detected no mutations within the fibrillin and collagen gene chromosome in either patient. Postoperative recovery was uneventful, and the patients were discharged on postoperative days 7 and 8, respectively.

Myocardial revascularization with multiple arterial grafts: comparison between the radial artery and the right internal thoracic artery.

BACKGROUND: Bilateral internal thoracic artery (ITA) harvesting is significantly underused, whereas the radial artery is being used with increasing frequency. We have retrospectively analyzed perioperative and short-term outcomes of patients receiving a radial artery versus those receiving a right ITA as a second arterial graft. METHODS: Between February 1999 and May 2000, 250 patients underwent coronary artery bypass grafting using the radial artery (156 patients) or the right ITA (94 patients) in combination with the left ITA and, when required, the saphenous vein. RESULTS: There was a higher prevalence of risk factors in the radial artery group. More coronary artery bypass graftings (p < 0.001) were performed with the radial artery. Operative mortality was not different (p = not significant). In the right ITA group there was more bleeding (p < 0.001) and a longer hospital stay (p < 0.001). Mean follow-up was 8.1 +/- 3.9 months. The probability of survival was similar (p = not significant). CONCLUSIONS: The radial artery can extend the benefits of multiple arterial grafting to those patients who are usually excluded from bilateral ITA harvesting because of multiple risk factors. Perioperative and short-term results are good.

[Coronary surgery without extracorporeal circulation: the short-term results in high-risk patients]. / Chirurgia coronarica senza circolazione extracorporea: risultati a breve termine nei pazienti ad alto rischio.

BACKGROUND: This study was conducted to assess the impact of coronary bypass surgery (CABG) without cardiopulmonary bypass (CPB) on high-risk patients. METHODS: From February 1997 to July 1998, 71 patients considered at high-risk underwent a CABG off-pump. Using the "Higgins score", eleven preoperative risk factors were identified and stratified in this group of patients. Among 1271 patients who underwent CABG with CPB in the same period, using a computer-based matched comparison, a second identical group of patients was selected according to the 11 risk variables and the number with coronary disease, so that complete preoperative matching included the year of operation, score index and coronary target. Moreover, among seven other preoperative variables that were not included in the matching comparison, the two groups differed only in mean age (64 +/- 10.9 vs 61.6 +/- 7.3 in groups off and on-pump, respectively, p < 0.05). Postoperative outcome and complications and blood requirement were compared. Myocardial cell injury and left ventricular performance were also assessed in the two groups. RESULTS: The global incidence of neurologic complications in the off-pump group was significantly lower (9.8 vs 0%, in on and off-pump groups, respectively; p = 0.02). Patients undergoing CABG off-pump required blood far less often (% of transfused patients: 26.7% for the patients with CPB and 11.2% for the patients without CPB; p = 0.032). Three patients from the on-pump group (4.2%) had a perioperative myocardial infarction (AMI), versus 0% of the off-pump cases (p = ns). Postoperative atrial fibrillation accounted for 14.1% in off-pump patients and 30.9% in on-pump patients (p = 0.027). One patient in both groups (1.4%) suffered from postoperative heart failure. Mean ventilation time and ICU stay did not differ significantly between the two groups. However, hospital discharge occurred earlier in the off-pump group (9.3 +/- 3 vs 12.6 +/- 8, p = 0.007). In-hospital death occurred in one case from the on-pump group (1.4%) versus 0% of patients operated off-pump. CPK-MB release in patients without perioperative AMI was significantly lower in off-pump patients 6 and 12 hours after the operation (36.6 +/- 17 IU/l vs 69.8 +/- 23 IU/l after 6 hours, p < 0.05; and 36.7 +/- 19 IU/l vs 67.3 +/- 26 IU/l after 12 hours, p < 0.05, in off and on-pump groups, respectively) and LVSWI turned out to be better in off-pump patients 6 hours postoperatively (34.2 +/- 2 g*m/m2 vs 27.2 +/- 3 g*m/m2, p < 0.01). CONCLUSIONS: CABG without CPB seems to be a promising technique for high-risk patients. It offers better neurologic and cardiac protection, shortens postoperative hospital stay and reduces the need for blood transfusion.