Although echocardiographic readings were carefully performed by a blinded expert reader, cardiac output by this technique is calculated by the product of the left ventricular outflow track diameter, mean left ventricular outflow track flow velocity, and the heart rate. Precise estimates of the outflow track velocity and diameter can be challenging. Even though at least five blood flow velocities and three outflow track diameters were analyzed, the interobserver and intraobserver reproducibility of these measurements was not addressed nor were day-to-day variations. A placebo treatment group would have been valuable to determine the consistency Ku-0059436 molecular weight of cardiac output measurements over time, as well as to exclude a placebo
effect. There is also a possibility that improvement in cardiac output could have been in part the result of a decrease in anxiety and the
level of adrenergic stress over the course of the study. The investigators recognized the importance of ensuring the safety of their subjects and they employed a two-stage design, analyzing the results on their first seven patients to assure efficacy and safety, before going on to recruit an additional 18 patients. Cancer patients treated with bevacizumab have an increased risk of hemorrhage, thrombotic events, gastrointestinal perforation, and reversible posterior leukoencephalopathy. Side effects are always a concern IWR-1 clinical trial with new cancer therapies and there were potential issues with the use of bevacizumab in HHT patients. Bevacizumab treatment could be problematic in HHT patients due to their susceptibility to epistaxis and gastrointestinal (GI) bleeding, or potential venous
thrombosis and stroke related to paradoxical embolization through pulmonary AVMs. The investigators took measures to avoid risk of hemorrhage by excluding patients with cerebral AVMs or thrombocytopenia and those on anticoagulant therapy. Importantly, selleck chemicals llc they also excluded patients with atrial fibrillation which, as mentioned previously, is a common precipitant of heart failure in these patients. Fortunately, no serious events were observed during the short-term treatment period. There was one case of grade 3 hypertension (>180/110 mmHg), which is a known complication of antiangiogenic therapy and occurs in up to 16% of cancer patients. This patient was successfully treated with a calcium channel blocker. There were also 89 adverse events, judged as possibly or certainly related to bevacizumab, which included headache in 52 patients, nausea and vomiting in 12 patients, and asthenia, abdominal pain, muscular pain, diarrhea, and rash in a small number of others. Again, a placebo-treated control arm would have been very helpful to clarify the causality of these adverse events. Advanced therapies should be used in patients who are very symptomatic, do not respond to medical therapy, and/or have a poor short-term prognosis.