Journal of the American College of Cardiology最新文献

Background: The microaxial flow pump (mAFP) has been shown to improve outcomes in selected patients with ST-elevation myocardial infarction (STEMI) and cardiogenic shock (STEMI-CS), but this effect appears to be less evident in women compared with men.

Objectives: The objective of this secondary analysis of the Danish-German Cardiogenic Shock Trial (DanGer Shock) was to determine sex differences in baseline characteristics, in-hospital course, and the effectiveness of mAFP in STEMI-CS.

Methods: This was a prespecified sex-specific secondary analysis of the international, multicenter, open-label, randomized DanGer Shock Trial. The primary outcome was 180-day all-cause mortality, analyzed by sex and randomized treatment assignment.

Results: From 2013 to 2023, 355 patients (74 [20.8%] women, 281 [79.2%] men) with STEMI-CS excluding comatose cardiac arrest were enrolled; 179 were randomized to mAFP (37 women) and 176 to standard care (37 women). In an accompanying registry of excluded patients (n = 495), women represented 25.7% (P = 0.10). At baseline, women were significantly older, and time from symptom onset to randomization was 2.2-fold longer in women than in men. Compared with men, women had significantly higher 180-day all-cause mortality (64.9% vs 48.8%; P = 0.015). There was no significant interaction for sex and treatment assignment with respect to 180-day all-cause mortality (P value for interaction = 0.18), yet women (HR: 1.01 [95% CI: 0.58-1.79]) appeared to derive less benefit from mAFP treatment than male patients (HR: 0.66 [95% CI: 0.47-0.93]). This difference was attenuated in patients aged ≤76 years: women (n = 41) HR: 0.66 (95% CI: 0.25-1.76) and men (n = 233) HR: 0.61 (95% CI: 0.40-0.92) (P value for interaction = 0.92). Data from up to 10 years of follow-up support the treatment effect in younger patients, regardless of sex: women HR: 0.45 (95% CI: 0.19-1.09); men HR: 0.57 (95% CI: 0.40-0.82).

Conclusions: In DanGer Shock, women with STEMI-CS were older and presented later after onset of symptoms, resulting in higher mortality rates. This may have led to the apparent reduced treatment effect in women, but interaction between treatment allocation and sex was not significant, and data showing a benefit of mAFP appeared particularly in younger patients, regardless of sex. As this is a secondary, nonpowered analysis that includes few women, its results must be considered hypothesis generating. (Danish Cardiogenic Shock Trial [DanShock]; NCT01633502).

Background: Breast cancer chemotherapy increases cardiovascular (CV) risk, particularly in postmenopausal women. Although vascular damage, endothelial dysfunction, and oxidative stress are implicated, the role of menopausal status in vascular mechanisms of increased CV risk remains unknown. Accordingly, we investigated whether estrogens protect premenopausal women from neoadjuvant chemotherapy (TAC protocol)-induced endothelial dysfunction, focusing on the vascular effects of docetaxel. This is the first study to assess how menopausal status affects vascular responses to chemotherapy.

Objectives: The main objective was to elucidate the pathophysiologic mechanisms by which TAC precipitates vascular dysfunction, with an emphasis on the influence of menopausal status.

Methods: Vascular function, oxidative stress, and molecular pathways were evaluated in arterial segments from cancer-free breast tissue of premenopausal and postmenopausal women undergoing surgery with or without prior TAC. Complementary mechanistic studies were conducted in ovariectomized and control female C57BL/6J mice treated with docetaxel or placebo.

Results: TAC-induced endothelial dysfunction, marked by reduced nitric oxide bioavailability, was observed in vessels from postmenopausal women, whereas premenopausal women were protected. The vessels of premenopausal women also resisted TAC-induced oxidative stress, showing significantly lower superoxide and hydrogen peroxide production as well as NOX4 NADPH-oxidase expression compared with their postmenopausal counterparts. No differences were noted between premenopausal and postmenopausal women in the non-TAC groups. At the molecular level, TAC resulted in lower inhibitory phosphorylation of endothelial nitric oxide synthase (eNOS) at threonine-495 and reduced rho-kinase activity in premenopausal women. In mice, docetaxel caused endothelial dysfunction, molecular changes, and hypertension only in ovariectomized animals, with no such effects in age-matched nonovariectomized controls.

Conclusions: TAC-induced vascular dysfunction seen in breast cancer survivors is absent in premenopausal women, likely owing to estrogen-mediated protection against oxidative stress and eNOS inhibition.

Background: The Evolut Low Risk trial enrolled patients with severe aortic stenosis at low surgical risk. Annual follow-up is planned for 10 years, evaluating the composite of all-cause mortality or disabling stroke and key secondary endpoints.

Objectives: Our prespecified objective was to report the 6-year clinical outcomes of transcatheter aortic valve replacement (TAVR) vs surgery from the Evolut Low Risk trial. Given an increase in reintervention rates at 6 years, we performed additional analyses in available 7-year data.

Methods: Low-risk patients with severe symptomatic aortic stenosis were randomized to TAVR or surgery from 2016-2019. Prespecified analyses at 6 years included annual follow-up of clinical outcomes reported as Kaplan-Meier estimates with log-rank test. Because the trial enrolled patients over several years, at the time of data lock, a majority of patients had completed 7-year follow-up. Given an increased reintervention rate at 6 years in the TAVR arm, we performed additional analysis of 7-year data available at the time of the database lock. Reintervention rates are reported as cumulative incidence.

Results: A total of 1,414 patients underwent an attempted implantation (730 TAVR, 684 surgery). At 6 years, the composite endpoint of all-cause mortality or disabling stroke was 23.3% for TAVR and 20.4% for surgery (difference: 2.8% [95% CI: -1.9% to 7.6%]; P = 0.43). All-cause mortality with vital status sweep at 6 years was 23.3% (95% CI: 20.6%-26.4%) for TAVR and 20.2% (95% CI: 17.4%-23.3%) for surgery (P = 0.24). The reintervention rate at 6 years was 5.5% for TAVR and 3.3% for surgery (sHR: 1.66 [95% CI: 0.96-2.86]; P = 0.07). Using available 7-year follow-up (555 TAVR and 480 surgery), the reintervention rate for TAVR was 9.8% and for surgery was 6.0% (sHR: 1.68 [95% CI: 1.10-2.58]; P = 0.02). In the TAVR and surgery groups, the rate of reintervention for regurgitation was 5.6% vs 1.6% (sHR: 3.39 [95% CI: 1.62-7.07]; P < 0.001) and the rate of reintervention for stenosis was 3.6% vs 3.5% (sHR: 1.14 [95% CI: 0.61-2.15]; P = 0.70).

Conclusions: The 6-year results from the Evolut Low Risk trial show no significant difference in the composite endpoint of all-cause mortality or disabling stroke. At 6 and 7 years, the TAVR arm had a higher reintervention rate compared with surgery, driven by an increased incidence of aortic regurgitation. (Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients; NCT02701283).