Ibrutinib and Bruton's Tyrosine Kinase Inhibitors in Chronic Lymphocytic Leukemia: Focus on Atrial Fibrillation and Ventricular Tachyarrhythmias/Sudden Cardiac Death.

BACKGROUND: The natural history of chronic lymphocytic leukemia (CLL) was dramatically improved by the introduction of ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. In this review, we aimed to summarize and critically evaluate the association between first- and second-generation BTK inhibitors and the risk of atrial fibrillation (AF) and ventricular arrhythmias (VA). SUMMARY: Since the first clinical experience, the development of AF was observed as the result of off-target effects that likely combined with patient's predisposing risk factors and concomitant cardiac morbidities. More recently, both ibrutinib dose reduction and arrhythmia management allowed long-term treatment, with positive effects on progression-free survival and reduced all-cause mortality as well. Second-generation BTK inhibitors, acalabrutinib, and zanubrutinib have been tested and validated in CLL. A lower occurrence of AF as compared with ibrutinib has been found, although AF has always been a secondary endpoint of all studies that probed these agents. KEY MESSAGES: For this reason, caution should be exercised before concluding that second-generation BTK inhibitors are safer than ibrutinib. Recent data on the effectiveness of ibrutinib over a follow-up of 8 years show a remarkable benefit on all-cause mortality, which is of great value also for interpreting the clinical impact of the few cases of VA and sudden cardiac death (SCD) reported for ibrutinib, independently of QT lengthening. Since a risk of VA and SCD has been recently reported also during treatment with second-generation BTK inhibitors, it appears that this risk, usually reaching its maximum size effect at long-term follow-up, likely denotes a class effect of BTK inhibitors.

[Optimal therapeutic management in the clinical journey of patients with heart failure]. / L'ottimizzazione terapeutica nel percorso del paziente con scompenso cardiaco.

Heart failure (HF) is still characterized by high mortality rates, despite the progress achieved in terms of treatment options. With regard to the treatment of HF with reduced ejection fraction (HFrEF), the 2016 European Society of Cardiology guidelines included in the therapeutic algorithm the angiotensin receptor-neprilysin inhibitor class, whose efficacy in modifying patient prognosis has been extensively proven in many clinical studies. Sacubitril/valsartan, the only representative of this drug class, can effectively affect the natural history of HF, thus reducing cardiovascular mortality (sudden death and death due to worsening cardiac function), total mortality, as well as first and recurrent hospitalization events, by improving renal function, cardiac remodeling, functional capacity and the patient's health-related quality of life.The purpose of this article is to analyze the different phases of the journey of patients with HFrEF (first general practitioner consultation; admission to the emergency department and subsequent hospitalization; referral to a specialist HF clinic) and promotion of a networking approach involving the general practitioner, the hospital and the HF specialist based on common pre-defined diagnostic and therapeutic protocols, that meets patient needs at all stages of the disease (case-specific dosing assessment, drug titration before follow-up and prevention of adverse events).

Single coronary artery with anomalous origin of right coronary artery from left main stem.

We report the case of a 57-year-old man with unstable angina that was taken up for coronary angiography, which showed an anomalous right coronary artery originating from left main stem.

Provokable left ventricular outflow tract obstruction in a patient without hypertrophy.

BACKGROUND: A 61-year-old man presented with shortness of breath and chest pain on exertion. He had been diagnosed as having hiatus hernia 2 years previously and was taking proton-pump inhibitors as necessary. He had a family history of ischemic heart disease and subarachnoid hemorrhage. INVESTIGATIONS: Physical examination, electrocardiography, echocardiography, cardiopulmonary exercise testing, coronary angiography, transoesophageal echocardiography, stress echocardiography. DIAGNOSIS: Provokable left ventricular outflow tract obstruction without electrocardiographic abnormalities or left ventricular hypertrophy on echocardiography. MANAGEMENT: Pharmacological therapy (atenolol 50 mg daily, disopyramide 250 mg twice daily), dual-chamber pacemaker implantation.