Cardiac Resynchronization Therapy: What\u27s Ticking at UMass

Cardiac Resynchronization Therapy (CRT), or Bi-Ventricular pacing, is a novel therapeutic intervention for patients with heart failure. It is thought that disorganized, dyssynchronous, myocardial contraction may contribute to the progression and pathophysiology of heart failure. CRT, by synchronizing the myocardial electrical-contractile apparatus with pacing leads in both the right and left ventricle, can improve left ventricular mechanical function. In a majority of patients, CRT improves ejection efficiency, reduces heart failure symptoms, and improves overall quality of life. LV reverse- remodeling may occur as well, as evidenced by a decreasing LV chamber size and end diastolic volume after pacer implantation. Traditionally, a prolonged QRS duration on surface ECG has been used to diagnose cardiac dyssynchrony and select patients for CRT. However, up to 40% of thus selected patients do not respond to the treatment, indicating the potential need for better methods to evaluate for the presence of dyssynchrony. QRS prolongation does not necessarily correspond with dyssynchrony and significant levels of dyssynchrony can be demonstrated in patients without QRS prolongation. In other words, patients with significant dyssynchrony irrespective of QRS duration may benefit from CRT and Bi-V pacing. Echocardiography has emerged as a potentially powerful screening tool for the rapid and accurate diagnosis of mechanical dyssynchrony. It could soon represent a new standard of care in diagnosing dyssynchrony and selecting patients for CRT. This project represents an overview of CRT, and explores the ongoing studies, some of which are occurring here at UMass, regarding the use of novel echocardiographic technologies to diagnose dyssynchrony and select patients for CRT. Furthermore, it highlights future plans for the creation of a CRT clinic here at UMass. A dedicated clinic can ensure quality and cost-effective care for this patient population, as well as provide a systematic template for the development of a large patient database from which further investigations can be made into the unanswered questions of this new and developing field

Ipilimumab, Pembrolizumab, or Nivolumab in Combination with BBI608 in Patients with Advanced Cancers Treated at MD Anderson Cancer Center

Background: BBI608 is an investigational reactive oxygen species generator that affects several molecular pathways. We investigated BBI608 combined with immune checkpoint inhibitors in patients with advanced cancers. Methods: BBI608 (orally twice daily) was combined with ipilimumab (3 mg/kg IV every 3 weeks); pembrolizumab (2 mg/kg IV every 3 weeks); or nivolumab (3 mg/kg IV every 4 weeks). We assessed the safety, antitumor activity and the pharmacokinetic profile of BBI combined with immunotherapy. Results: From 1/2017 to 3/2017, 12 patients were treated (median age, 54 years; range, 31–78; 6 men). Treatment was overall well tolerated. No dose-limiting toxicity was observed. The most common adverse events were diarrhea (5 patients: grade (G)1–2, n = 3; G3, n = 2) and nausea (4 patients, all G1). Prolonged disease stabilization was noted in five patients treated with BBI608/nivolumab lasting for 12.1, 10.1, 8.0, 7.7 and 7.4 months. The median progression-free survival was 2.73 months. The median overall survival was 7.56 months. Four patients had prolonged overall survival (53.0, 48.7, 51.9 and 48.2 months). Conclusions: Checkpoint inhibitors combined with BBI608 were well tolerated. Several patients had prolonged disease stabilization and overall survival. Prospective studies to elucidate the mechanisms of response and resistance to BBI608 are warranted