Rationale: Doxorubicin is an effective chemotherapeutic agent for cancer, but its use is often limited by cardiotoxicity. Doxorubicin causes endoplasmic reticulum (ER) dilation in cardiomyocytes, and we have demonstrated that ER stress plays important roles in the pathophysiology of heart failure. Objective: We evaluated the role of ER stress in doxorubicin-induced cardiotoxicity and examined whether the chemical ER chaperone could prevent doxorubicin-induced cardiac dysfunction. Methods and Results: We confirmed that doxorubicin caused ER dilation in mouse hearts, indicating that doxorubicin may affect ER function. Doxorubicin activated an ER transmembrane stress sensor, activating transcription factor 6, in cultured cardiomyocytes and mouse hearts. However, doxorubicin suppressed the expression of genes downstream of activating transcription factor 6, including X-box binding protein 1. The decreased levels of X-box binding protein 1 resulted in a failure to induce the expression of the ER chaperone glucose-regulated protein 78 which plays a major role in adaptive responses to ER stress. In addition, doxorubicin activated caspase-12, an ER membrane–resident apoptotic molecule, which can lead to cardiomyocyte apoptosis and cardiac dysfunction. Cardiac-specific overexpression of glucose-regulated protein 78 by adeno-associated virus 9 or the administration of the chemical ER chaperone 4-phenylbutyrate attenuated caspase-12 cleavage, and alleviated cardiac apoptosis and dysfunction induced by doxorubicin. Conclusions: Doxorubicin activated the ER stress–initiated apoptotic response without inducing the ER chaperone glucose-regulated protein 78, further augmenting ER stress in mouse hearts. Cardiac-specific overexpression of glucose-regulated protein 78 or the administration of the chemical ER chaperone alleviated the cardiac dysfunction induced by doxorubicin and may facilitate the safe use of doxorubicin for cancer treatment.

Fifty-nine patients (57 females, two males) with Takayasu arteritis were retrospectively evaluated. Chest radiographs were abnormal in 68% of patients in whom they were obtained (n = 49). Aortic contour changes and calcification were frequent findings. Sixty-eight percent of patients who underwent total aortography (n = 50) had panaortitis, and 28% had involvement confined to the thoracic aorta and/or its branches. Stenosis was the most common angiographic finding in the aorta and its branches, but occlusion (n = 4), aneurysm (n = 3), and dilatation (n = 15) were not infrequent. Adventitial vascular structures (the vasa vasorum) were seen in three cases. Eighty-six percent (n = 21) of pulmonary arteriograms showed abnormalities. Occlusion was by far the most common finding. There was no predilection for any lobe nor correlation with systemic arteritis. It was concluded that Takayasu arteritis characteristically involves the systemic and the pulmonary arteries independently. Total aortography and pulmonary arteriography are necessary to diagnose and evaluate the extent of the disease.

The effect of torasemide and furosemide therapy was compared in 50 patients who had chronic heart failure and symptoms [NYHA class II-III] despite long-term therapy with both low-dose furosemide and angiotensin-converting enzyme inhibitors. In this randomized 6-month, open-label trial, baseline and follow-up echocardiograms and neurohumoral assays were obtained in 25 group F patients (continued same dose of oral furosemide at 20-40 mg/day) and in 25 group T patients (received torasemide at 4-8 mg/day in place of furosemide). At 6 months, parameters were unchanged in group F whereas the group T patients had a lower left ventricular end-diastolic diameter (p<0.005) and left ventricular mass index (p<0.005) with improved Doppler filling parameters, decreased plasma B-type natriuretic concentration (p<0.001) and increased plasma concentrations of active renin (p<0.005) and aldosterone (p<0.001). The magnitude of these changes appeared dose dependent and it is suggested these favorable effects of switching from furosemide to torasemide may be related to aldosterone receptor blockade.

Backgrounds: Several studies have shown the serum high sensitive cardiac troponin I (hs-TnI) a biomarker of myocardium injury, and C-reactive protein (CRP), a biomarker of inflammation, are associated with worse cardiovascular outcomes. We evaluated the relationship between the hs-TnI level in patients with paroxysmal atrial fibrillation (PAF) after pulmonary vein isolation (PVI) and atrial fibrillation (AF) recurrence. Methods and Results:We enrolled 263 consecutive PAF patients who underwent PVI from May 2017 to April 2018. We investigated the difference in the relationship between the myocardial injury marker (serum hs-TnI), inflammatory marker (CRP, white blood cell) at 36 to 48 hours after the PVI, and early or late recurrence of AF (ERAF; <3 months and LRAF; from 3 months to 1 year) between the radiofrequency ablation group (R group) and cryoballoon ablation group (C group). The R group consisted of 147 patients and the C groups consisted of 116 patients. The serum hs-TnI level in R group was significantly lower than in the C group (2.33 vs 5.08 ng/mL; P < .001), while the CRP was significantly higher in the R group than C group (2.02 vs 1.10 mg/dL; P < .001). The incidences of an ERAF/LRAF were similar between the two groups.Conclusion: Cryoballoon ablation may cause more myocardial injury than radiofrequency catheter ablation, on the contrary, radiofrequency catheter ablation, may cause more inflammation than cryoballoon ablation. However, these phenomena may not affect the recurrence of AF after the PVI in patient with PAF. K E Y W O R D Shigh-sensitive cardiac troponin-T, inflammation, myocardial injury, paroxysmal atrial fibrillation, pulmonary vein isolation, recurrence of AF

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