Safety and feasibility of angiotensin receptor neprilysin inhibitor in real-world patients with acute decompensated heart failure.

BACKGROUND: The aim of this study was to determine the safety and feasibility of in-hospital sacubitril/valsartan initiation after clinical stabilization in patients with acute decompensated heart failure (ADHF) and reduced ejection fraction (EF). METHODS: This retrospective, multicenter observational study included patients admitted for ADHF in 2 Italian centers between February 2017 and January 2022. Feasibility was evaluated by assessing the proportion of patients discharged on sacubitril/valsartan. Key safety endpoints were the incidences of adverse events during hospitalization and during follow-up planned at 1 month, 3-6 months and 12-18 months after discharge. RESULTS: One hundred and twenty-two patients were included. Median age was 71 (60-78) years, 78% male, 63% New York Heart Association (NYHA) Class III at admission with a median left ventricular ejection fraction (EF) of 25% (20-30). During hospitalization, 94 (77%) patients were treated with intravenous diuretics, 39 (32%) with inotrope/vasopressor, 51 (42%) with continuous positive airway pressure ventilation and 7 (6%) were assisted with an intra-aortic balloon pump. Median time from hospitalization to sacubitril/valsartan initiation was 4 (2-7) days. Sacubitril/valsartan was started at a dosage of 12/13 mg in 52 (43%) patients, 24/26 mg in 61 (50%) patients and 49/51 mg in 8 (7%) patients. Overall, 111 (91%) patients were discharged on sacubitril/valsartan. At 12-18-month follow-up, the vast majority of patients were still on sacubitril/valsartan therapy. CONCLUSIONS: In-hospital initiation of sacubitril/valsartan treatment in real-world ADHF patients may be a safe and feasible treatment option.

[A case of severe left main isolated stenosis in a young woman with previous history of non-Hodgkin lymphoma]. / Un caso di stenosi severa isolata del tronco comune coronarico insorto in una giovane donna con pregressa storia di linfoma non-Hodgkin.

We report the case of a 34-year-old female treated with radiotherapy and chemotherapy for non-Hodgkin lymphoma at the age of 16. The patient came to our attention because of progressive dyspnea on effort and a positive result on a pharmacologic stress echo test. Coronary angiography revealed focal critical ostial stenosis of the left main coronary artery. Considering the high surgical risk due to possible post-radiation thoracic adherence and the young patient age, she underwent successful stenting of the left main stenosis with drug-eluting stent, followed by an intravascular ultrasound-guided post-dilation and final kissing balloon inflation. The procedure was uncomplicated.Heart diseases are among the frequently seen long-term effects of chemo/radiotherapy used for lymphoma treatment. The pathogenesis of radiation-induced coronary artery disease is complex and not yet fully understood, the mechanism is multifactorial and likely involves direct damage from radiation exposure or mediated by inflammatory cytokine secretion. Surgery management is often challenging due to radiation sequences, and a percutaneous approach is therefore used. The risk of long-term radiotherapy damage depends on radiation dose and the field of exposure. Modern techniques with lower radiation exposure and smaller treatment volumes may reduce these risks in future.

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.

[Optimal dose of bivalirudin in dialysis patients at high risk of heparin-induced thrombocytopenia undergoing percutaneous coronary intervention: case report]. / La scelta del dosaggio ottimale della bivalirudina nei pazienti in dialisi ad elevato rischio di trombocitopenia da eparina sottoposti a rivascolarizzazione percutanea: descrizione di un caso clinico.

Bivalirudin is a direct thrombin inhibitor that has been approved for use in patients with or at risk for heparin-induced thrombocytopenia undergoing percutaneous coronary intervention. The efficacy of bivalirudin has been well documented in the setting of percutaneous coronary intervention, but there are only few data on its use in chronic dialysis-dependent patients. Bivalirudin is mainly eliminated enzymatically (80%) and to a lesser extent renally (20%). Nevertheless, in patients with chronic kidney disease a substantial increase in coagulation time and bleeding complications has been reported. Therefore, dosage adjustments may be necessary in patients with renal impairment. Dosing and monitoring recommendations in dialysis patients have not yet been established. We describe the case of a 77-year-old man with non-ST-elevation acute coronary syndrome complicated by heparin-induced thrombocytopenia and acute renal failure requiring dialysis treatment. During percutaneous coronary intervention, anticoagulant therapy with bivalirudin was administered at non-standard doses, though already documented in the literature.

[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.

[Genetic basis of ischemic heart disease. Do women have distinctive characteristics?]. / Le basi genetiche della cardiopatia ischemica. C'è qualcosa di peculiare nelle donne?

More women die every year from cardiovascular disease than men from any other cause. Several fundamental variations have been reported in the mechanisms underlying coronary artery disease, which suggest that its genetic basis varies by gender. Such differences are not limited to gonadal hormones and can be seen in the physiology of atherosclerosis, including plaque components, endothelial function and hemostasis. It is possible to speculate that genetic factors are different in men and women and probably involve biological pathways that have not yet been identified. To date, studies performed by means of the candidate gene approach have identified several genetic variants associated with coronary artery disease in women. However, these scientific data have not been translated into clinical practice. It has recently become possible to search for common gene variants that affect the susceptibility to myocardial infarction on the basis of our knowledge of common single nucleotide polymorphisms and haplotypes across the human genome using genome-wide genotyping technologies. Currently more than 20 gene regions have been associated with ischemic heart disease using this approach. However, so far we do not know several genetic variants differently associated with risk of ischemic heart disease in men and women. A challenge for the near future will therefore be to identify genetic variants that maximally differentiate males from females, and also to identify possible relationships between genes and environment and genes and hormones in both sexes.