See Appendix for individual names.Background: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. Patients and methods:In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8 mg/kg loading dose, then 6 mg/kg every 3 weeks (q3w)] and pertuzumab (840 mg loading dose, then 420 mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results:Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nabpaclitaxel in 65; 7 discontinued before starting taxane). Median age was 54 years; 29% had received prior trastuzumab. Median treatment duration was 16 months for pertuzumab and trastuzumab and 4 months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1 months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%).Conclusions: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile.ClinicalTrials.gov: NCT01572038.

The mechanism of sudden cardiac death (SCD) in patients with nonischemic dilated cardiomyopathy (NIDCM) is mostly due to sustained ventricular tachycardia and ventricular fibrillation. The clinical guidelines for the therapeutic management of this set of patients are mostly based on left ventricular ejection fraction value which has a low specificity to differentiate the risk of SCD from the risk of mortality associated with heart failure or other comorbidities. Moreover, since SCD can occur in patients with normal or mildly depressed ejection fraction, it is necessary to identify new markers to improve the prognostic stratification of SCD. Several studies that analyzed the ventricular arrhythmia substrate found that myocardial fibrosis plays an important role in the genesis of ventricular arrhythmias in patients with NIDCM. The surrounding zone of the area of fibrosis is a heterogeneous medium, where tissue with different levels of fibrosis coexists, resulting in both viable and nonviable myocardium. This myocardial fibrosis may constitute a substrate for ventricular arrhythmias, where slow and heterogeneous conduction may favor the genesis of reentry mechanism increasing the chance to develop sustained ventricular tachycardia or ventricular fibrillation. Therefore, the evaluation of ventricular fibrosis by late gadolinium enhancement (LGE) cardiac magnetic resonance imaging has been suggested as an indicator for SCD risk stratification. Indeed, LGE in patients with NIDCM is associated with increased risk of all-cause mortality, heart failure hospitalization, and SCD. Detection of myocardial fibrosis as LGE by cardiac magnetic resonance imaging can be considered as a useful pathway of prediction of malignant ventricular arrhythmias since it has excellent prognostic characteristics and may help guide risk stratification and management in patients with NIDCM.

Due to the lack of prospective, randomized, controlled clinical studies on inflammation and cardiovascular involvement, the exact mechanism of cardiac injury among patients with Coronavirus Disease 2019 (COVID-19) still remains uncertain. It was demonstrated that there is a high and significantly positive linear correlation between troponin T and plasma high-sensitivity C-reactive protein levels, biomarkers of cardiac injury and systemic inflammation, respectively. Cardiac injury and inflammation is a relatively common association among patients hospitalized with COVID-19, and it is related to higher risk of in-hospital mortality. In our literature search, we identified several potential mechanisms of myocardial tissue damage, namely, coronavirus-associated acute myocarditis, angiotensin-converting enzyme 2 receptor binding affinity to the virus Spike protein, increased cytokine secretion, and hypoxia-induced cardiac myocyte apoptosis. Elucidation of the disease pathogenesis and prospective histopathological studies are crucial for future proper treatment in case of renewed outbreaks. Of interest is that with hundred of thousands of bodies available for autopsy studies, no prospective investigation has been reported so far. Strong efforts and continued research of the cardiovascular complications and identification of risk factors for poor prognosis in COVID-19 are steadily needed. The high morbidity and mortality of COVID-19, its monumental economic burden and social impact, the despair of a new pandemic outbreak, and the thread of potential utilization of novel severe acute respiratory syndrome coronavirus 2 as biologic weapons make it a preponderant necessity to better comprehend the therapeutic management of this lethal disease. Emerging as an acute infectious disease, COVID-19 may become a chronic epidemic because of genetic recombination. Therefore, we should be ready for the reemergence of COVID-19 or other coronaviruses.

No abstract

Background There is a lack of evidence regarding the benefits of β-blocker treatment after invasively managed acute myocardial infarction (MI) without reduced left ventricular ejection fraction (LVEF). Methods and results TREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fraction (REBOOT) trial is a pragmatic, controlled, prospective, randomized, open-label blinded endpoint (PROBE design) clinical trial testing the benefits of β-blocker maintenance therapy in patients discharged after MI with or without ST-segment elevation. Patients eligible for participation are those managed invasively during index hospitalization (coronary angiography), with LVEF >40%, and no history of heart failure (HF). At discharge, patients will be randomized 1:1 to β-blocker therapy (agent and dose according to treating physician) or no β-blocker therapy. The primary endpoint is a composite of all-cause death, nonfatal reinfarction, or HF hospitalization over a median follow-up period of 2.75 years (minimum 2 years, maximum 3 years). Key secondary endpoints include the incidence of the individual components of the primary composite endpoint, the incidence of cardiac death, and incidence of malignant ventricular arrhythmias or resuscitated cardiac arrest. The primary endpoint will be analyzed according to the intention-to-treat principle. Conclusion The REBOOT trial will provide robust evidence to guide the prescription of β-blockers to patients discharged after MI without reduced LVEF.