Cardiovascular toxicities of selective ret-specific tyrosine kinase inhibitors: a pharmacovigilance study based on the United States Food and Drug Administration Adverse Event Reporting System database.

BACKGROUND: Selective RET-specific tyrosine kinase inhibitors (RET-TKIs) treat RET fusion-positive non-small cell lung cancer (NSCLC), but studies on their cardiovascular toxicities are limited. This study aimed to characterize the cardiovascular toxicities associated with selective RET-TKI in real-world settings. RESEARCH DESIGN AND METHODS: Data from the United States Food and Drug Administration Adverse Event Reporting System database from 1 January 2020 to 30 June 2023, were analyzed. Two disproportionality methods, information component and reporting odds ratio (ROR) were used. RESULTS: Both pralsetinib and selpercatinib showed positive signals for hypertension (pralsetinib: ROR: 5.25, 95% CI: 4.40-6.26; selpercatinib: ROR: 2.68, 95% CI: 1.87-3.82). Additionally, pralsetinib showed a positive signal for ischemic heart disease (ROR: 3.92, 95% CI: 2.94-5.23), and selpercatinib for torsade de pointes/QT prolongation (ROR: 2.65, 95% CI: 1.74-4.04). The median time to onset(TTO) of cardiovascular toxicities was 33 days (IQR: 9-73 days) for pralsetinib and 15 days (IQR: 10-50 days) for selpercatinib. The proportion of deaths, life-threatening events, and hospitalizations due to cardiovascular toxicities were 8.57%, 1.19%, and 31.43%, respectively, for total selective RET-TKI. CONCLUSIONS: Selective RET-TKIs are related to multiple cardiovascular toxicities. Pralsetinib was linked to ischemic heart disease, and selpercatinib to torsade de pointes/QT prolongation and thrombotic events.

Relationship Between Hypertension and Hearing Loss: Analysis of the Related Factors.

Purpose: The impact of hypertension extends to hearing loss, aging, and mental Health. The purpose of this study was to investigate the characteristics of hearing loss and hearing thresholds at different frequencies in individuals with hypertension. Through a comprehensive analysis, in the present study, it aimed to uncover the contributing factors that underlie hearing loss in this patient cohort, shedding light on the complex relationship between hypertension and auditory impairment. Patients and Methods: This was a single-center population-based observational study, and clinical, biological, and hospital data were collected from the inpatient ward. In the present study, 517 patients (1034 ears) with or without hypertension were included, and the proportion of patients with hearing loss, mean pure-tone average hearing threshold, low-frequency pure-tone average hearing threshold (LFPTA), medium-frequency pure-tone average hearing threshold (MFPTA) and high-frequency pure-tone average hearing threshold (HFPTA) were evaluated. Risk factors related to hearing loss and hearing threshold were also estimated at different frequencies. Results: The proportion of patients with hearing loss was higher in the hypertensive group than in the nonhypertensive group (P<0.05). After including risk factors for cardiovascular disease that can have an impact on the parameters of hearing and ambulatory blood pressure in the regression model, factors related to hearing loss included the albumin-to-creatinine ratio (ACR) and the standard deviation of the 24-hour systolic blood pressure (24h-SSD). ACR, 24h-SSD, and day systolic blood pressure (Day SBP) were associated with the mean pure-tone average hearing threshold, LFPTA, MFPTA, and HFPTA. The area under the receiver operating characteristic curve of ACR + 24h-SSD for hearing loss was 0.873, with a sensitivity of 86.73%, specificity of 90.52%, and a 95% confidence interval of 0.821-0.914. Conclusion: Hypertension is correlated with hearing loss, and the combination of ACR and 24h-SSD demonstrates an improved predictive capacity for hearing loss in hypertensive patients.

The Role of Vascular Endothelial Dysfunction in Hypertension With Hearing Loss.

Hypertension can cause hearing loss, but there is no clear definition of the mechanism(s) involved. The study aimed to explore the role of vascular endothelial dysfunction in hypertension with hearing loss. Patients with hypertension were divided into two groups based on hearing loss. Pure tone audiometry (PTA) and endothelial function testing were performed. A total of 216 (432 ears) hypertensive patients were divided into hypertension with hearing loss group (n = 104) and hypertension without hearing loss group (n = 112). The vascular endothelial biomarkers, ET-1 (endothelin-1) and vWF (von Willebrand factor) were significantly higher (P < .05) in the hypertension with hearing loss group. RHI (reactive hyperemia index), ET-1, and vWF were the factors related to hearing loss. The area under the receiver operating characteristic (ROC) curve (AUC) of RHI in the diagnosis of hypertension with hearing loss was .652 (95% CI .552-.751, P = .005), and the Youden index was 26.2%. The AUC of ET-1 was .706 (95% CI .612-.799, P = .001), and the Youden index was 38.9%. The AUC of vWF was .617 (95% CI .512-.721, P = .003), and the Youden index was 28.1%. Vascular endothelial dysfunction may play a role in the pathogenesis of hypertension with hearing loss.

Analysis of Systolic Blood Pressure Level and Short-Term Variability in Masked Hypertension.

Background: Patients with masked hypertension are at an elevated risk of cardiovascular events and all-cause death. This risk is close to that of sustained hypertension. The mean value and short-term variability of systolic blood pressure are considered to be risk factors for organ damage in hypertension. Objective: To investigate the mean value and short-term variability of systolic blood pressure in patients with masked hypertension. Methods: According to the results of in-clinic and ambulatory blood pressure measurement, participants were divided into four groups: normotension group, controlled hypertension group, masked hypertension group, and sustained hypertension group. The mean value and short-term variability of systolic blood pressure of masked hypertension group were evaluated by comparison with the other three groups. Results: A total of 250 subjects were enrolled, with an average age of 65.46 ± 8.76 years, and 166 (66.4%) were male, including 62 in the normotension group, 78 in the controlled hypertension group, 69 in the masked hypertension group, and 41 in the sustained hypertension group. Compared with the normotension group and controlled hypertension group, the mean value, blood pressure load, standard deviation, and coefficient of variation of systolic blood pressure over 24 hours and during the day and night, were all higher in the masked hypertension group (P < 0.05), while the rate of the nocturnal systolic blood pressure decline was lower (P < 0.05). There were no statistically significant differences in the above indexes between the masked hypertension group and sustained hypertension group (P > 0.05). Conclusion: There are higher mean value of systolic blood pressure and greater short-term variability in masked hypertension patients. Identification of masked hypertension is an important challenge in the clinic.