Several quinones have been found to be effective in the treatment of some forms of cancer; however, their cumulative heart toxicity limits their use. The cannabinoid quinone HU-331 [3S,4R-pbenzoquinone-3-hydroxy-2-p-mentha-(1,8)-dien-3-yl-5-pentyl] is highly effective against tumor xenografts in nude mice. We report now a comparison of the anticancer activity of HU-331 and its cardiotoxicity with those of doxorubicin in vivo. General toxicity was assayed in Sabra, nude and SCID-NOD mice. The anticancer activity in vivo was assessed by measurement of the tumors with an external caliper in HT-29 and Raji tumor-bearing mice and by weighing the excised tumors. Left ventricular function was evaluated with transthoracic echocardiography. Myelotoxicity was evaluated by blood cell count. Cardiac troponin T (cTnT) plasma levels were determined by immunoassay. HU-331 was found to be much less cardiotoxic than doxorubicin. The control and the HU-331-treated groups gained weight, whereas the doxorubicintreated group lost weight during the study. In HT-29 colon carcinoma, the tumor weight in the HU-331-treated group was 54% smaller than in the control group and 30% smaller than in the doxorubicin-treated group. In Raji lymphoma, the tumor weight in the HU-331-treated group was 65% smaller than in the control group and 33% smaller than in the doxorubicin-treated group. In contrast to doxorubicin, HU-331 did not generate reactive oxygen species in mice hearts (measured by protein carbonylation levels and malondialdehyde levels). In vivo, HU-331 was more active and less toxic than doxorubicin and thus it has a high potential for development as a new anticancer drug.

Abnormal septal motion, assessed by the presence of SF, is a mechanism amenable to CRT correction. Its correction is associated with a higher likelihood of CRT response in HF patients with long-standing AF. This could improve the selection of candidates to CRT in a subgroup with particularly poor response and long-term prognosis.

Background Strain imaging during left atrial (LA) reservoir phase (LASr) is used as a surrogate for LA structural remodeling and fibrosis. Atrial fibrillation (AF) patients with >5% low‐voltage zones (LVZs) obtained by 3D‐electro‐anatomical‐mapping have higher recurrence rate post‐ablation. We investigated the relationship between LA remodeling using two‐dimensional‐speckle‐tracking echocardiography (2D‐STE) and high‐density voltage mapping in AF patients. Methods A prospective study of 42 consecutive patients undergoing AF ablation. 2D‐echo, 2D‐STE, and high‐density contact LA bipolar voltage maps were constructed before ablation. LVZs were determined with different bipolar amplitudes and their ratio per patient's LA area were investigated for correlation with LASr. We compared 2D‐LASr results in patients with LVZs ≥ 5% (LVZs group) versus those with LVZ < 5% (non‐LVZs group). Results Compared with non‐LVZs group (n = 15), LVZs group (n = 27) included significantly older patients, more women, more persistent AF, higher CHA2DS2‐VASc score, higher E/A ratio and higher LA volume index (p < .05). LVZs group had lower %LASr values (12.4 ± 5.9% vs. 21.1 ± 6.3, respectively; p<.001). LVZs% in different amplitudes (<0.1 mV, <0.2 mV, and <0.5 mV) were negatively correlated with %LASr (r = −.63, r = −.68, and r = −.72, respectively; p< .001). Atrial strain thresholds for LVZs ≥ 5% in amplitudes <0.1 mV, <0.2 mV, and <0.5 mV were associated with %LASr 12.98, 16.16 and 19.55, respectively; p< .05). In a multivariate analysis, %LASr was the only independent indicator of LVZs (OR, 0.8; 95% CI, 0.6–0.9; p= .04). Conclusions LVZs ≥ 5% has a negative association with atrial %LASr. Thus, a simple 2D‐STE measurement of %LASr can be used as a noninvasive method to evaluate significant LA remodeling and fibrosis in AF patients.