Atrial functional tricuspid regurgitation: An underappreciated cause of secondary tricuspid regurgitation

Secondary tricuspid regurgitation (TR) caused by right ventricular enlargement in the setting of left heart disease/pulmonary hypertension has been well described. In contrast, that associated with right atrial enlargement—atrial functional TR (AF‐TR)—remains largely underappreciated. AF‐TR most often occurs in the setting of lone atrial fibrillation, although it is also seen in its absence (idiopathic AF‐TR). Several recent studies have found that the prevalence, hemodynamic significance, and prognosis of AF‐TR are not inconsequential, suggesting increased physician awareness of this novel clinical entity is warranted. This article discusses the pathogenesis, echocardiographic findings, and treatment of this underappreciated cause of secondary TR.     

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.