Differential effect of regadenoson versus dipyridamole on heart rate in patients with left bundle branch block: How does it affect the results of pharmacological nuclear stress testing?

BACKGROUND: Myocardial perfusion imaging (MPI) stress test is performed either using exercise as a stress modality or through the use of pharmacological vasodilator agents in those who cannot exercise. Regadenoson and dipyridamole are some of the most common vasodilator agents used. We aim to study the effect of these agents on the heart rate and the imaging results. METHODS: This was a retrospective study which included 187 patients with left bundle branch block. Patients received either dipyridamole or regadenoson during the myocardial perfusion imaging stress test. Charts were reviewed, and patient characteristics were recorded, as well as baseline heart rate, peak heart rate during stress, and angiographic data if available. RESULTS: Regadenoson increased peak, absolute and relative heart rates significantly more compared to dipyridamole. The peak heart rate for Regadenoson was 94.1 ± 17.36 and for dipyridamole it was 85.38 ± 16.48 BPM (P < 0.001). The relative and absolute heart rate increase in the regadenoson group were 40.75 ± 23.01% and 26.06 ± 13.44 BPM, respectively. The relative and absolute heart rate increase in the dipyridamole group were 24.61 ± 18.25% and 16.23 ± 10.97 BPM. The frequency of reversible septal defects was similar in both groups (54% for Regadenoson vs. 63% for Dipyridamole; P = 0.24). CONCLUSIONS: There is a statistically significant increase in heart rate with the use of regadenoson for MPI compared to dipyridamole. However, the number of septal perfusion defects was similar between the two groups. The effect of this increase in heart rate, while statistically significant, is likely of no clinical significance.

Imaging Reporters for Proteasome Activity Identify Tumor- and Metastasis-Initiating Cells.

Tumor-initiating cells, also designated as cancer stem cells, are proposed to constitute a subpopulation of malignant cells central to tumorigenesis, metastasis, and treatment resistance. We analyzed the activity of the proteasome, the primary organelle for targeted protein degradation, as a marker of tumor- and metastasis-initiating cells. Using human and mouse breast cancer cells expressing a validated fluorescent reporter, we found a small subpopulation of cells with low proteasome activity that divided asymmetrically to produce daughter cells with low or high proteasome activity. Breast cancer cells with low proteasome activity had greater local tumor formation and metastasis in immunocompromised and immunocompetent mice. To allow flexible labeling of cells, we also developed a new proteasome substrate based on HaloTag technology. Patient-derived glioblastoma cells with low proteasome activity measured by the HaloTag reporter show key phenotypes associated with tumor-initiating cells, including expression of a stem cell transcription factor, reconstitution of the original starting population, and enhanced neurosphere formation. We also show that patient-derived glioblastoma cells with low proteasome activity have higher frequency of tumor formation in mouse xenografts. These studies support proteasome function as a tool to investigate tumor- and metastasis-initiating cancer cells and a potential biomarker for outcomes in patients with several different cancers.

Macroscopic stiffness of breast tumors predicts metastasis.

Mechanical properties of tumors differ substantially from normal cells and tissues. Changes in stiffness or elasticity regulate pro-metastatic behaviors of cancer cells, but effects have been documented predominantly in isolated cells or in vitro cell culture systems. To directly link relative stiffness of tumors to cancer progression, we combined a mouse model of metastatic breast cancer with ex vivo measurements of bulk moduli of freshly excised, intact tumors. We found a high, inverse correlation between bulk modulus of resected tumors and subsequent local recurrence and metastasis. More compliant tumors were associated with more frequent, larger local recurrences and more extensive metastases than mice with relatively stiff tumors. We found that collagen content of resected tumors correlated with bulk modulus values. These data establish that relative differences in tumor stiffness correspond with tumor progression and metastasis, supporting further testing and development of tumor compliance as a prognostic biomarker in breast cancer.