Safety and Efficacy of PCSK9 Inhibitors in Patients with Acute Coronary Syndrome Who Underwent Coronary Artery Bypass Grafts: A Comparative Retrospective Analysis.

Background. The in-hospital reduction in low-density lipoprotein cholesterol (LDL-C) levels following acute coronary syndrome (ACS) is recommended in the current clinical guidelines. However, the efficacy of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors in those patients undergoing coronary artery bypass graft (CABG) has never been demonstrated. Methods. From January 2022 to July 2023, we retrospectively analyzed 74 ACS patients characterized by higher LDL-C levels than guideline targets and who underwent coronary bypass surgery. In the first period (January 2022-January 2023), the patients increased their statin dosage and/or added Ezetimibe (Group STEZE, 43 patients). At a later time (February 2023-July 2023), the patients received not only statins and Ezetimibe but also Evolocumab 140 mg every 2 weeks starting as early as possible (Group STEVO, 31 patients). After one and three months post-discharge, the patients underwent clinical and laboratory controls with an evaluation of the efficacy lipid measurements and every adverse event. Results. The two groups did not differ in terms of preoperative risk factors and Euroscore II (STEVO: 2.14 ± 0.75 vs. STEZE: 2.05 ± 0.6, p = 0.29). Also, there was no difference between the groups in terms of ACS (ST-, Instable angina, or NSTE) and time of symptoms onset regarding total cholesterol, LDL-C, and HDL-C trends from the preprocedural period to 3-month follow-up, but there was a more significant reduction in LDL-C and total cholesterol in the STEVO group (p = 0.01 and p = 0.04, respectively) and no difference in HDL-C rise (p = 0.12). No deaths were reported. In three STEZE group patients, angina recurrence posed the need for percutaneous re-revascularization. No STEVO patients developed significant adverse events. The statistical difference in these serious events, 7% in STEZE vs. 0% in STEVO, was not significant (p = 0.26). Conclusions. Evolocumab initiated "as soon as possible" in ACS patients submitted to CABG with high-intensity statin therapy and Ezetimibe was well tolerated and resulted in a substantial and significant reduction in LDL-C levels at discharge, 1 month, and 3 months. This result is associated with a reduction but without a statistical difference between groups.

Emergent Conversion to Open Heart Surgery during Transcatheter Aortic Valve Implantation: The Presence of a Rescue Team Improves Outcomes.

OBJECTIVE: Transcatheter aortic valve implant (TAVI) is the gold standard for the high-surgical-risk group of patients with aortic valve disease and it is an alternative to surgery in patients at intermediate risk. Lethal complications can occur, and many of these are manageable only with emergent conversion to open heart surgery. We retrospectively evaluate the outcome of all patients undergoing TAVI in our departments and the impact of a complete cardiac rescue team to reduce 30-day mortality. METHODS: Data from all patients undergoing TAVI between January 2020 and August 2023 in our center were analyzed. An expert complete rescue was present in catheter laboratory. Primary outcomes were in-hospital and at 30-day mortality and evaluation of all cases needed for emergent conversion to open heart surgery. RESULTS: 825 patients were enrolled. The total mortality was 19/825 (2.3%). Eleven of the total patients (1.3%) required emergent conversion to open heart surgery. Among them, eight were alive (73%), with a theoretical decrease of 0.98% in overall mortality. CONCLUSIONS: surgical treatment is rare during TAVI. The presence of an expert complete rescue team as support means an increase in survival. Surgery must be used only to restore circulatory and to treat complication while percutaneous approaches should complete the procedure.

Rapid and portable, lab-on-chip, point-of-care genotyping for evaluating clopidogrel metabolism.

BACKGROUND: Dual antiplatelet therapy with aspirin and a platelet P2Y12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor) is a cornerstone of antithrombotic treatment in patients with acute coronary syndromes (ACS). Clopidogrel has been the standard of care for nearly a decade; however, its clinical efficacy is influenced by a considerable inter-patient variability in response, clearly associated to cytochrome P (CYP) enzyme genetic variations. We used a novel point-of-care lab-on-chip instrument to genotype ACS patients in order to identify carriers of the ATB-binding cassette ABCB1 3435, CYP2C19*2 and CYPC2C19*17 alleles and adjust the pharmacological approach accordingly. METHODS AND RESULTS: Between October 2012 and January 2013, 160 ACS patients were enrolled at the Cardiology Unit of the Ospedale Niguarda Cà Granda and genotyped at the patients' point-of-care using the newly developed Q3 portable real-time PCR instrument, which remarkably scored the CYP2C19*2, CYP2C19*17, and ABCB1 3435 alleles in a time of 70 min from DNA extraction to final genotype calls; concordance with the other gold-standard genotyping techniques was 100%. CONCLUSIONS: The Q3 instrument proved to be as reliable as the current conventional techniques. As genotyping in the ACS setting cannot be delegated to centralised clinical laboratories for reasons of time, genotyping at the patients' bedside provides an opportunity to conduct large-scale randomised trials in order to assess whether adding genotype data to clinical variables improves clinical outcomes.

[A case of electrical storm in a patient with short-coupled variant of torsade de pointes]. / Un caso di tempesta aritmica in una paziente con variante di torsione di punta ad intervallo di accoppiamento breve.

Short-coupled variant of torsade de pointes (TdP) is an uncommon variant of polymorphic ventricular tachycardia with unknown etiology. It is initiated by a closely coupled premature ventricular complex (<300 ms) in the absence of QT prolongation and structural heart disease. Verapamil seems to be the only drug able to suppress the arrhythmia but, as it does not reduce the risk of sudden death, implantation of a cardioverter-defibrillator (ICD) is recommended. We describe the case of a 46-year-old woman referred to our Emergency Department because of palpitations. The initial ECG showed a non-sustained polymorphic ventricular tachycardia with a borderline QTc interval (450 ms). After admission, the patient experienced an episode of TdP that started after short-coupling interval (280 ms) between the last sinus beat and the ventricular premature beat (VPB). DC-shock restored sinus rhythm. Physical examination, exercise testing, echocardiography and cardiac magnetic resonance were all normal, and she had no family history of sudden cardiac death. Baseline ECG showed sinus rhythm and unifocal VPBs with the same morphology of the VPB of TdP. The patient received an ICD and was treated medically with verapamil. She was discharged from the hospital on oral therapy with verapamil (240 mg/day), and she was free of recurrence 12 months later when an electrical storm occurred. The verapamil dose was therefore increased to 480 mg/day. Unifocal VPBs disappeared from her body surface ECG, and the subsequent 3-year follow-up was uneventful.

[Cardiac resynchronization therapy in a patient with congenitally corrected transposition of the great arteries and 2:1 atrioventricular block]. / Terapia di resincronizzazione cardiaca in un paziente con trasposizione corretta dei grossi vasi e blocco atrioventricolare 2:1.

Congenitally corrected transposition of the great arteries (CCTGA) is a rare congenital heart disease with an atrioventricular and ventriculo-arterial discordance in which the morphological right ventricle supports the systemic circulation and the morphological tricuspid valve is the systemic atrioventricular valve. Heart rhythm disturbances and ventricular dysfunction related to electromechanical dyssynchrony are common in adult congenital heart disease patients with a systemic right ventricle. Thus, these patients may require conventional pacemaker implantation, which in the presence of ventricular dysfunction and conduction disease may further compromise cardiac performance. Indeed, cardiac resynchronization therapy may be an effective treatment option for these patients. We report the case of a patient with CCTGA and moderate depression of systemic ventricular systolic function who developed a 2:1 atrioventricular block and was treated with cardiac resynchronization therapy.

[Stent thrombosis and clopidogrel response variability: is the genetic test useful in clinical practice?]. / Trombosi di stent e variabilità di risposta al clopidogrel: il test genetico può essere utile oggi nella pratica clinica?

The antiplatelet agent clopidogrel is an effective drug for the prevention of thrombotic events in patients with acute coronary syndrome and in those undergoing percutaneous coronary intervention with the deployment of a coronary stent. However, it has been reported that, despite adequate treatment, about 30% of patients continue to show the high degree of platelet reactivity that is central to the development of atherothrombotic complications and poorer clinical outcomes. Up to 13% of those taking clopidogrel experience a recurrent ischemic event during the first year after acute coronary syndrome, 1-3% experience subacute stent thrombosis after percutaneous coronary intervention probably due to a poor drug response, and about 1.5% experience major bleeding mainly due to an enhanced response. Recent research findings have highlighted the role of genetic variations in determining antiplatelet response variability, and this has aroused interest in genotyping all thienopyridine-eligible patients in order to identify those who would be at increased risk of harm if treated with clopidogrel. However, it remains to be determined whether this information is necessary or sufficient for risk stratification. Only when there are clinical data to support the hypothesis that genotype-guided therapy reduces the rate of ischemic and bleeding events will it be possible to justify the use of genetic testing in all potential patients. When that happens, genotype-guided antiplatelet therapy will also be available in the field of cardiovascular medicine.

[From vulnerable plaque to vulnerable patient]. / Dalla placca vulnerabile al paziente vulnerabile.

Atherosclerotic plaque instability is directly involved in triggering acute coronary syndromes, including unstable angina, acute myocardial infarction, and sudden coronary death. Different and not completely unknown mechanisms are involved in the pathogenesis of the destabilisation of the vulnerable plaque; currently three mechanisms are considered to play a causal role in this process: embolization, vasoconstriction and plaque rupture that only in a few cases lead to thrombosis; in most cases it is repaired spontaneously. Therefore only some plaques lead to clinical manifestations whereas many others remain asymptomatic. It is possible formulate two hypothesis: in the first case there are different types of plaques, some with strong thrombogenic stimulus; in the second case all the plaques are considered to be equal and instead is the patient who in particular situations has an hypercoagulable state that leads to an high risk of acute coronary syndromes. The aim of this review is to analyze the complex mechanisms leading to plaque and patient vulnerability.