Research Spotlight

Zhrebker, L., I. Cherni, L. M. Gross, M. M. Hinshelwood, M. Reese, J. Aldrich, J. M. Guileyardo, W. C. Roberts, D. Craig, D. D. Von Hoff, R. G. Mennel and J. D. Carpten (2017). “Case report: Whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies.” BMC Cancer 17(1): 17-eoa.

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BACKGROUND: Primary cardiac angiosarcomas are rare, but they are the most aggressive type of primary cardiac neoplasms. When patients do present, it is with advanced pulmonary and/or cardiac symptoms. Therefore, many times the correct diagnosis is not made at the time of initial presentation. These patients have metastatic disease and the vast majority of these patients die within a few months after diagnosis. Currently the treatment choices are limited and there are no targeted therapies available. CASE PRESENTATION: A 56-year-old male presented with shortness of breath, night sweats, and productive cough for a month. Workup revealed pericardial effusion and multiple bilateral pulmonary nodules suspicious for metastatic disease. Transthoracic echocardiogram showed a large pericardial effusion and a large mass in the base of the right atrium. Results of biopsy of bilateral lung nodules established a diagnosis of primary cardiac angiosarcoma. Aggressive pulmonary disease caused rapid deterioration; the patient went on hospice and subsequently died. Whole exome sequencing of the patient’s postmortem tumor revealed a novel KDR (G681R) mutation, and focal high-level amplification at chromosome 1q encompassing MDM4, a negative regulator of TP53. CONCLUSION: Mutations in KDR have been reported previously in angiosarcomas. Previous studies also demonstrated that KDR mutants with constitutive KDR activation could be inhibited with specific KDR inhibitors in vitro. Thus, patients harboring activating KDR mutations could be candidates for treatment with KDR-specific inhibitors.

Velasco, C. E. and C. Howard (2017). “Trouble on both sides; pulmonary embolism with pneumothorax.” Am J Med: 2017 Jan [Epub ahead of print].

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Potential causes of syncope range from fairly trifling to life threatening. For a 49-year-old, previously healthy, African American man, the trigger proved dangerous. While unloading cargo from a truck, he fainted and fell about 3 feet to the ground. When emergency medical services arrived, his manager reported that the patient lost consciousness but was unable to quantify the period of time. The patient, upon awakening, complained of shortness of breath with severe right-sided chest and back pain. He attributed his accident to fatigue, stating that he had worked as a security guard the previous night, was tired, and simply fell asleep while emptying the vehicle. He denied seizure-like activity, prodrome, drug use, a family history of syncope, and loss of bowel or bladder function.

Cutlip, D. E., K. N. Garratt, V. Novack, M. Barakat, P. Meraj, L. Maillard, A. Erglis, R. Jauhar, J. J. Popma, R. Stoler and S. Silber (2017). “9-month clinical and angiographic outcomes of the cobra polyzene-f nanocoated coronary stent system.” JACC Cardiovasc Interv 10(2): 160-167.

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OBJECTIVES:The aim of this study was to assess the safety and effectiveness of the COBRA Polyzene-F NanoCoated Coronary Stent System (CeloNova Biosciences, San Antonio, Texas) for the treatment of de novo coronary artery lesions.BACKGROUND: Polyzene-F-coated coronary stents have shown reduced thrombogenicity and inflammation in preclinical studies. METHODS: Patients with de novo coronary artery lesions meeting eligibility criteria were enrolled in a nonrandomized, prospective clinical trial. The primary endpoint was target vessel failure (TVF) (defined as a composite of cardiac death, myocardial infarction, or clinically driven target vessel revascularization) at 9 months. A pre-specified subset was planned for routine repeat angiographic follow-up at 9 months. The powered secondary endpoint was mean late lumen loss (LL). The comparator was a performance goal derived from meta-analysis of historical bare-metal stent trials of 19.62% for TVF and 1.1 mm for LL. Other secondary endpoints were clinically driven target lesion revascularization and definite or probable stent thrombosis. CONCLUSIONS: The COBRA Polyzene-F stent met performance goals for TVF and LL at 9 months. There was an excellent safety profile, with infrequent late myocardial infarction and no stent thrombosis.

Alam, R., J. J. Tosoian, O. Okani, A. E. Ross and M. Vuica-Ross (2017). “Metastatic prostate cancer diagnosed by bone marrow aspiration in an elderly man not undergoing psa screening.” Urol Case Rep 11: 7-8.

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Prostate cancer screening by PSA testing remains controversial, particularly in the elderly. Practice guidelines from most clinical societies suggest discontinuing PSA screening at age 70 while the USPSTF recommends against screening at any age. Recent reports have demonstrated an increased incidence of metastatic prostate cancer, with men aged 75 or older accounting for roughly half of those newly diagnosed at an incurable stage. We herein describe the case of an elderly gentleman with no history of prostate cancer screening who presented with anorexia and back pain of unclear etiology. Evaluation with bone marrow aspiration revealed a diagnosis of metastatic prostate cancer.

Mack, M. and D. R. Holmes (2016). “Randomised trials in left main disease: a NOBLE effort.” Lancet 388(10061): 2715-2716.

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The NOBLE trial enrolled 1201 patients in 36 centres, randomly assigned to either PCI primarily with the Biolimus–eluting stent (Biomatrix Flex) or CABG. The primary endpoint was major adverse cardiac and cerebrovascular events including all-cause mortality, myocardial infarction, stroke, and repeat revascularisation at a median follow-up of 3 years. The trial was designed as a non-inferiority trial with a relatively wide confidence interval of 1·35. The primary endpoint occurred in 29% of patients in the PCI group and 19% of patients in the CABG group (HR 1·48 [95% CI 1·11–1·96]), exceeding the limit for non-inferiority and was in fact statistically significant for superiority of CABG over PCI (p=0·0079). Outcomes were similar in both intention-to-treat and per-protocol analyses. Regarding the individual components of the composite primary endpoint, 5 year Kaplan Meier estimates of all-cause mortality and stroke were the same but there were significantly fewer clinically apparent myocardial infarctions and fewer repeat revascularisation procedures with CABG. The conclusion of the trial is that CABG might be superior to PCI for treatment of left main stem coronary artery disease. There are a few specific findings of this trial that are noteworthy and somewhat surprising but there are also some concerns. The first is that the benefit of CABG was noted in all ranges of the SYNTAX score, which is contrary to the SYNTAX trial in which patients with less complex disease did as well with PCI as with CABG. This finding might partly be explained by the fact that 81% of the patients in NOBLE had bifurcation left main disease, which is more difficult to treat than ostial or trunk left main disease and might be associated with a worse outcome with PCI. The second finding is that there was a trend toward a higher incidence of stroke at 5 years with PCI, which is the opposite to what has been noted in most previous comparative trials. This result is perplexing in that with PCI at 30 days, there were no strokes. The stroke rate only gradually increased over time with PCI to an estimated 4·9% at 5 years. The reasons for the late stroke rate in PCI might be due to chance in the absence of any reasons for this late event. The third point is that the trial primary endpoint was changed from the original design. This trial was event driven, in which a specific number of events was needed; this requirement was based on events in the SYNTAX trial. When that number could not be reached in 5 years of follow-up, the primary endpoint was assessed at a median of 3 years. Might that have affected the results? Fourth, procedural purists on both sides will argue that optimal procedures were not done, with only 75% of the patients with PCI undergoing intravascular ultrasound assessment, only 93% of patients with CABG receiving a left internal mammary artery graft, and 86% of patients receiving at least one saphenous vein graft. However, we suspect that this is probably representative of real world practice. (Excerpt from text of this commentary, p. 2715-2716.)