Sex-based Differences In Outcomes Research Articles

Sex differences in the presentation and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock: a critical review of contemporary data and a look towards future directions.

Cardiogenic shock (CS) is a devasting complicating of acute myocardial infarction (AMI), associated with significant mortality. Prior studies have reported sex differences in the presentation, management and outcomes of patients with AMI and CS. These differences are likely due to a variety of factors influencing therapeutic decision-making and impacting survival. This review highlights the more contemporary studies exploring differences in women and men with AMI-CS, providing a critical perspective towards understanding the factors that might lead to these differences and outlining potential opportunities to reduce disparities in treatment and improve survival for women with AMI-CS. Recent reports demonstrate that women with AMI-CS are older than men and have more cardiovascular comorbidities. When examining an unselected population of patients with AMI-CS, women receive less aggressive treatment compared to men and have poorer outcomes. However, when examining a selected population of patients with AMI-CS treated with mechanical circulatory support (MCS) and/or admitted to centers that implement CS protocols to manage AMI-CS, these sex-based differences in outcomes are largely mitigated. Standardizing protocols for the diagnosis and treatment of patients with AMI-CS, with an emphasis on early revascularization and appropriate invasive therapies, can improve outcomes in women and narrow the gender gap.

Myocardial Aging among a Population-Based Cohort Is Associated with Adverse Cardiovascular Outcomes and Sex-Specific Differences among Older Adults

Introduction: Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit. Methods: Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included. Results: A total of 956 participants (mean age 63 ± 12.9 years, n = 424 males [44%]) were categorized based on mitral peak early-to-late diastolic filling velocity (E/A) ratios: E/A <0.8 (28%), E/A 0.8–1.2 (39%), E/A (29%), E/A >2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI: 2.24–3.56) and 0.45 per 100 person-years (95% CI: 0.26–0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes was significantly different among E/A categories (log-rank p = 0.0269). E/A <0.8 (HR 1.80, 95% CI: 1.031, 3.14, p = 0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI: 2.62–4.84) and 0.75 per 100 person-years (95% CI: 0.39–1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI: 1.56–3.16) and 0.21 per 100 person-years (95% CI: 0.067–0.64) for all-cause death. For E/A <0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8–1.2 category (HR 2.49, 95% CI: 1.18, 5.23, p = 0.017). Conclusion: Myocardial aging was an independent predictor of cardiovascular outcomes in community-dwelling older adults prior to clinical CVD. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology.

Sex-based Differences In Outcomes Of Patients Admitted With Heart Failure And Undergoing Left Ventricular Assist Device Implantation

Sex-based Differences In Outcomes Of Patients Admitted With Heart Failure And Undergoing Left Ventricular Assist Device Implantation

Adverse cardiovascular outcomes and sex-specific differences among older adults with cardiac ageing

Abstract Background Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit. Methods Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included. Results 956 participants [mean age 63±12.9 years, n=424 males (44%)] were categorized based on mitral peak early to late diastolic filling velocity (E/A) ratios: E/A &amp;lt;0.8 (28%), E/A 0.8-1.2 (39%), E/A (29%), E/A &amp;gt;2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI 2.24-3.56), and 0.45 per 100 person-years (95% CI 0.26-0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes were significantly different among E/A categories (log-rank p=0.0269). E/A&amp;lt;0.8 (HR 1.80, 95%CI 1.031, 3.14, p=0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI 2.62-4.84), and 0.75 per 100 person-years (95% CI 0.39-1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI 1.56-3.16), and 0.21 per 100 person-years (95% CI 0.067-0.64) for all-cause death. For E/A&amp;lt;0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8-1.2 category (HR 2.49, 95%CI 1.18, 5.23, p=0.017). Conclusion Myocardial ageing was an independent predictor of cardiovascular outcomes. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology.Myocardial Ageing in the Community

Sex-Specific Differences in Potent P2Y12 Inhibitor Use in British Cardiovascular Intervention Society Registry STEMI Patients.

Sex-based outcome differences for women with ST-segment-elevation myocardial infarction (STEMI) have not been adequately addressed, and the role played by differences in prescription of potent P2Y12 inhibitors (P-P2Y12) is not well defined. This study explores the hypothesis that disparities in P-P2Y12 (prasugrel or ticagrelor) use may play a role in outcome disparities for women with STEMI. Data from British Cardiovascular Intervention Society national percutaneous coronary intervention database were analyzed, and 168 818 STEMI patients treated with primary percutaneous coronary intervention from 2010 to 2020 were included. Among the included women (43 131; 25.54%) and men (125 687; 74.45%), P-P2Y12 inhibitors were prescribed less often to women (51.71%) than men (55.18%; P<0.001). Women were more likely to die in hospital than men (adjusted odds ratio, 1.213 [95% CI, 1.141-1.290]). Unadjusted mortality was higher among women treated with clopidogrel (7.57%), than P-P2Y12-treated women (5.39%), men treated with clopidogrel (4.60%), and P-P2Y12-treated men (3.61%; P<0.001). The strongest independent predictor of P-P2Y12 prescription was radial access (adjusted odds ratio, 2.368 [95% CI, 2.312-2.425]), used in 67.93% of women and 74.38% of men (P<0.001). Two risk adjustment models were used. Women were less likely to receive a P-P2Y12 (adjusted odds ratio, 0.957 [95% CI, 0.935-0.979]) with risk adjustment for baseline characteristics alone, when procedural factors including radial access were included in the model differences were not significant (adjusted odds ratio, 1.015 [95% CI, 0.991-1.039]). Women were less likely to be prescribed prasugrel or ticagrelor, were less likely to have radial access, and had a higher mortality when being treated for STEMI. Improving rates of P-P2Y12 use and radial access may decrease outcome disparities for women with STEMI.

Abstract P3110: Sex Differences In Ventricular Tachycardia Ablation In-hospital Outcomes: An Analysis From The National Inpatient Sample Database

Background: There are limited data available comparing outcomes of ventricular tachycardia (VT) ablation in men versus women. Objectives: For patients undergoing ablation for VT, we sought to determine if sex-based differences in outcomes and procedural complications exist. Methods: We queried the National Inpatient Sample (NIS) database between 2016 and 2018 to identify patients aged ≥18 years hospitalized with a primary diagnosis of VT who underwent ablation. Patients with other cardiac arrhythmias or who had an implantable defibrillator/pacemaker placement were excluded. Multivariable logistic regression analysis was performed to assess independent predictors of any procedural complication. Results: Out of 7,200 identified admissions for VT involving VT ablation, 1,280 (18%) were women and 5920 (82%) were men. Men were older (mean age 64.8 vs 57.4 years in women, P&lt;0.01). Comorbidities as prior myocardial infarction (MI), prior CABG, Chronic kidney disease (CKD), COPD, prior cardiac pacemaker, chronic heart failure (CHF) and peripheral vascular disease (PVD) were all significantly more prevalent in men.The primary outcome of in-hospital mortality occurred in 3% of both men and women. Interestingly, the length of stay was longer in men (6.53±4.2 vs 5.26±2.5 days, p&lt;0.01). The incidence of acute MI, acute ischemic stroke, bleeding, need of blood transfusion, tamponade, complete heart block, pulmonary complications, vascular complications similar between men and women, however acute kidney injury occurred more in men (21% vs. 10%, p&lt; 0.001). The overall complication rate was significantly higher in men (28.8% vs 20.7 %, P= 0.0084). The presence of CKD, as well as CHF were independent predictors of any procedural complication (OR 1.27, 95% CI 1.19-1.36, P &lt;0.01) and (OR 1.08, 95% CI 1.03-1.14, P=0.001). Conclusion: Men had higher rates of in hospital complications following VT ablation which might be related to higher rates of comorbidities. There was no difference in in-hospital mortality between men and women. Women represented only 17.8% of VT ablation admissions. Further studies are needed to distinguish the sex-based differences in VT ablation referrals and to compare long term outcomes post ablation.

Sex-based differences in safety and efficacy of catheter ablation for atrial fibrillation.

Studies have identified significant sex-based differences and disparities in the clinical presentation and treatment of atrial fibrillation (AF). Studies have shown women are less likely to be referred for catheter ablation, are older at the time of ablation, and are more likely to have recurrence after ablation. However, in most studies investigating AF ablation outcomes, the female cohorts were relatively small. The impact of sex on the outcome and safety of ablation procedures is still unclear. To investigate sex-based differences in outcomes and complications after AF catheter ablation, with a significant female cohort METHOD: In this retrospective study, patients undergoing AF ablation from January 1, 2014, to March 31, 2021, were included. We investigated clinical characteristics, duration and progression of AF, number of EP appointments from diagnosis to ablation, procedural data, and procedure complications. Total of 1346 patients underwent first catheter ablation for AF during this period, including 896 (66.5%) male and 450 (33.4%) female patients. Female patients were older at the time of ablation (66.2 vs. 62.4 years; p < .001). Women had higher CHA2 DS2 -VASc (congestive heart failure, hypertension, age, diabetes, stroke, vascular disease, sex category) scores (3 vs. 2; p < .001) than men, expectedly, as the female sex warrants an additional point. 25.3% female patients had PersAF at the time of diagnosis versus 35.3% male patients (p < .001). At the time of ablation, 31.8% female patients had PersAF as compared to 43.1% male patients (p < .001), indicating progression of PAF to PersAF in both sexes. Women tried more AADs than men before ablation (1.13 vs. 0.98; p = .002). Male and female patients had no statistically significant difference in (a) arrhythmia recurrence at 1-year post ablation (27.7% vs. 30%; p = .38) or (b) procedural complication rate (1.8% vs. 3.1%; p = .56). Female patients were older and had higher CHA2 DS2 -VASc scores compared to males at the time of AF ablation. Women tried more AADs than men before ablation. One-year arrhythmia recurrence rates and procedural complications were similar in both sexes. No sex-based differences were observed in safety and efficacy of ablation.

Sex-based differences in outcomes after lower extremity bypass for chronic limb-threatening ischemia

Background and aimsLower extremity bypass surgery is an effective treatment option for patients with chronic limb-threatening ischemia (CLTI). Recent studies have suggested that sex-based differences may impact patient outcomes following lower extremity revascularization, however, results have been inconsistent. MethodsIn this multicenter analysis, we retrospectively identified all infrainguinal bypass procedures performed for CLTI from 2002 to 2021. Patients were separated into two groups based on sex. Primary outcomes were major limb amputation and reintervention for graft patency. ResultsOf 843 bypasses performed over the study period, 347 (41.2%) patients were female. Racial/ethnic distribution and medical comorbidities were similar across sex groups. Surgical indications and operative details were also similar between groups, including conduit type (49.9% autogenous), bypass target (65.4% infrageniculate), and concurrent endarterectomy (38.9%). Female and male patients had similar hospital length of stay (6 days [4-9] vs 6 days [4-9]), hospital readmission (25.6% vs 25.0%), and postoperative complications (p=NS each). Female patients had higher major amputation rates (10.1% vs 6.3%, p=0.04) after one year, whereas reintervention rates were similar between groups (26.2% vs 24.6%, p=NS). After accounting for patient factors, female sex (odds ratio [OR] 1.02 [1.00–1.04]), infrageniculate target (OR 1.02 [1.00–1.04]), and bypass for tissue loss (OR 1.02 [1.00–1.04]) were associated with major amputation after bypass (p<0.05 each). ConclusionsFemale sex is associated with a small but significant increase major amputation after lower extremity bypass surgery for CLTI, despite similar clinical presentation, medical comorbidities, and operative details. These data support the increasingly recognized sex disparities in peripheral arterial disease.

Sex-dependent outcomes of recanalization-treated acute ischemic stroke patients at Shamir (Assaf Harofeh) medical center, Israel, 2011–2020

Background/objectivesSex-based differences in incidence, etiologies, severity and recanalization treatment outcomes of patients with acute ischemic stroke (AIS) have been studied extensively. We set out to determine if there were sex-based differences in outcomes among AIS patients who received recanalization treatments at Shamir (Assaf Harofeh) Medical Center (SMC), Israel, between 2011 and 2020. MethodsThis was a single-center, retrospective chart review. The primary analysis compared outcomes for men and women, overall and stratifying by disease severity. We compared also demographics, risk factors and workflow data. ResultsEight hundred and eleven patients received recanalization treatment between 2011 and 2020: 472 (58.1%) men and 339 (41.8%) women. Mean age, NIHSS score and proportion with an NIHSS score ≥ 6 were higher for women. Cerebrovascular risk factors were more prevalent in women, particularly atrial fibrillation, except that current smoking was more prevalent in men. Six hundred and twenty patients (78.1%) were treated with TPA alone, 89 (11.2%) with TPA and endovascular treatment (EVT), and 85 (10.7%) with EVT alone. Fifty percent of patients were discharged home, 41% to a rehabilitation hospital or nursing home, and 9% did not survive. Twenty-four patients (3%) sustained symptomatic bleeds. Outcomes were worse in patients with NIHSS score ≥ 6. Outcomes did not differ by sex. ConclusionsWhile treated women presented with more severe AIS and more risk factors, we did not find significant sex-related differences in outcomes. Meticulous adherence to risk factor modification remains the best strategy to reduce stroke incidence, morbidity, and mortality in women and in men.

Sex Differences in Outcome and Prescribing Practice in ST-elevation MI Patients with Multivessel Disease and Incomplete Revascularisation.

Objective: To investigate the extent to which multivessel disease, incomplete revascularisation and prescribing differences contribute to sex-based outcome disparities in patients with ST-elevation MI (STEMI) and establish whether differences in cardiac death and MI (CDMI) rates persist at long-term follow-up. Methods and results: This observational study evaluates sex-based outcome differences (median follow-up 3.6 years; IQR [2.4-5.4]) in a consecutive cohort of patients (n=2,083) presenting with STEMI undergoing percutaneous coronary intervention). Of the studied patients 20.3% (423/2,083) were women and 38.3% (810/2,083) had multivessel disease (MVD). Incomplete revascularisation was common. The median residual SYNTAX score (rSS) was 5.0 (IQR [0-9]) in women and 5.0 (IQR [1-11]) in men (p=0.369), and in patients with MVD it was 9 (IQR [6-17]) in women and 10 (IQR [6-15]) in men (p=0.838). The primary endpoint CDMI occurred in 20.3% of women (86/423) and in 13.2% of men (219/1,660) (p=0.028). Differences persisted following multivariable risk adjustment: female sex was independently associated with CDMI (aHR 1.33; IQR [1.02-1.74]). Women with MVD had CDMI more often than all other groups (p<0.001 for all). Significant sex-based prescribing differences were evident: women were less likely to receive guideline-recommended potent P2Y12 inhibitors than men (31% versus 43%; p=0.012), and differences were particularly evident in patients with MVD (25% in women versus 45% in men, p=0.011). Conclusion: Sex-based differences in STEMI patient outcome persist at long-term follow-up. Poor outcomes were disproportionately found in women with MVD and those with rSS>8. Observed differences in P2Y12 prescribing practices may contribute to poor outcomes for women with MVD and incomplete revascularisation.

Ethnic and sex-based differences in outcomes after out-of-hospital cardiac arrest: a glimpse of the largest municipal healthcare system in the United States.

Ethnic and sex-based disparity in outcomes after out-of-hospital cardiac arrest (OHCA) may exist and could be due to social factors and inequality in care. We aimed to study whether ethnic and sex-based differences in out-of-hospital cardiac arrest outcomes occurred in a safety net hospital within the largest municipal healthcare system in the United States. We conducted a retrospective cohort study of patients successfully resuscitated from an OHCA and brought to New York City Health + Hospitals/Jacobi, from January 2019 to September 2021. Out-of-hospital cardiac arrest characteristics, do not resuscitate and withdrawal of life-sustaining therapy orders, and disposition data were collected and analyzed using regression models. Out of 648 patients screened, 154 were included (48.1% women). On multivariable analysis, sex [odds ratio (OR): 0.84; 95% CI: 0.30-2.4; P=0.74] and ethnic background (OR: 0.80; 95% CI: 0.58-1.12; P=0.196) did not predict discharge survival. No significant sex difference in do not resuscitate (P=0.76) or withdrawal of life-sustaining therapy (P=0.39) orders was found. Younger age (OR: 0.96; P=0.04) and initial shockable rhythm (OR: 7.26; P=0.01) independently predicted survival, both at discharge and at one year. Among patients resuscitated after an out-of-hospital cardiac arrest, neither sex nor ethnic background predicted discharge survival and no sex differences in end-of-life preferences were found. These findings are distinct from those of previously published reports. Given the unique population studied, distinct from those of registry-based studies, socioeconomic factors likely served as bigger drivers of out-of-hospital cardiac arrest outcomes rather than ethnic background or sex.

Abstract 9397: Sex-Based Differences in Outcomes After Mitral Valve Repair for Severe Secondary Mitral Regurgitation

Background: Sex-based differences in outcomes after mitral valve repair for severe secondary ischemic mitral regurgitation (SIMR) is poorly understood. We examined differences in outcomes between men and women after mitral valve repair for severe SIMR. Methods: 96 patients with SIMR were randomized to undergo either papillary muscle approximation (PMA) with restrictive mitral annuloplasty (RMA) or RMA alone to evaluate efficacy and safety. The primary endpoint was death and major adverse cardiac or cerebrovascular events (MACCE) at 5 years. Results: 38 of the 96 enrolled (39.5%) were women. Five-year survival was 68% in women and 78% men (HR 1.48; 95% CI 0.67-3.24). Men and women had similar mortality rates in the PMA (HR 2.64; 95% CI 0.77-9.04) and RMA group (HR 0.93; 95%CI 0.31-2.78). Freedom from MACCE at 5 years was lower among women than men (6% vs 23%; HR 1.89; 95%CI 1.20-2.98). The hazard for MACCE was higher in women in the PMA group alone (HR 3.00; 95% CI 1.50-6.02). Freedom from treatment failure was similar between sexes (55% in women and 69% in men; HR 1.58; 95% CI 0.81-3.06). Similar functional status (26.3% vs 24.1%) and rehospitalization rates (23.7% vs 24.1%) were noted at 5 years. There were no significant differences in the percentage of change over 5 years in LVESD and LVEDD between the sexes. Conclusion: Women with SIMR who underwent mitral valve repair displayed no significant differences in the degree of five-year survival. MACCEs however, recurred more frequently in women.

Abstract 13561: Sex-Based Differences in Outcomes for Transcatheter Based Intervention: Insight From the National Inpatient Sample

Introduction: Transcatheter aortic valve replacement (TAVR) is now firmly established as an alternative to surgical aortic valve replacement in the treatment of aortic stenosis in all risk groups. Sex differences may influence procedural outcomes. Our study aims to contribute further data on the impact of sex differences on patients who underwent TAVR using a nationally representative sample. Methods: Data were obtained from the combined National Inpatient Sample (NIS) 2016 and 2018. The NIS was searched for hospitalization for TAVR procedure using the ICD-10 PCS codes. Patients undergoing the TAVR procedure were then stratified by sex into male and female sex. Outcomes of interest include in-patient mortality, length of stay (LOS), Total hospital charge (THC), Post procedural complication, pacemaker implantation, cardiogenic shock, ischemic stroke, intra-aortic balloon pump insertion, post-procedural infection, and post-procedural kidney disease. Multivariate logistic and linear regression analysis was used accordingly to adjust for possible confounders. Results: There were over 105 million discharges in the combined 2016-2018 NIS database. The database contained hospitalizations for adult patients (aged ≥ 18 years) who were hospitalized for the TAVR procedure. Females had more TAVR procedures compared to men (54.1% vs 45.9%, P&lt;0.0001 and were older than men who underwent TAVR. There was similar in-patient mortality in both group (1.7% vs 1.2%, AOR: 1.21, P=0.072, 95% CI 0.98- 1.51). Women had lower rate of cardiogenic shock (AOR: 0.78, P=0.009, 95% CI 0.65-0.94), pacemaker implantation (AOR: 0.84, P=0.001, 95% CI 0.76-0.93) compared to men. Women had higher odds of post-procedural complications compared to men (AOR: 1.18, P=0.001, 95% CI: 1.07-1.29. There were similar rates of ischemic stroke (AOR: 1.23, P=0.502, 95% CI 0.66-2.31), postprocedural kidney injury (AOR: 1.65, P=0.278, 95% CI 0.66-4.12) in women compared to men. In addition, there was no difference in total charge and length of hospital stay. Conclusions: Women had increased post-procedural complications compared to men in regard to TAVR, however, mortality is similar in both groups. There was no difference in resource utilization and length of stay between both sexes.

Sex-Based Differences in Outcomes After Hip Arthroscopic Surgery for Femoroacetabular Impingement: A Systematic Review.

While sex-based differences in outcomes after hip arthroscopic surgery for femoroacetabular impingement syndrome (FAIS) are often recorded, no studies have been dedicated to analyzing the literature as a whole. To investigate whether sex is a predictor of outcomes in studies evaluating hip arthroscopic surgery for FAIS. Systematic review; Level of evidence, 4. A systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched the PubMed, Embase, Cochrane, Ovid, and PubMed Central databases for English-language studies that evaluated sex-specific outcomes in human populations. The search terms used were as follows: ("Hip Arthroscopy") AND ("Femoroacetabular Impingement" OR "FAI") AND ("Sex" OR "Gender" OR "Male" OR "Female"). Studies with evidence levels 2 through 4 were included. The studies were then screened, followed by data extraction. Modified Harris Hip Score (mHHS) outcomes and return-to-sport (RTS) rates were recorded. These were analyzed using random-effects meta-analysis. Heterogeneity was calculated using the I 2 statistic. Of 256 full-text articles screened, 48 articles were included in this analysis; of these, 14 studies (29%) concluded that female sex was a negative predictor of postoperative outcomes, while 6 studies (13%) found female sex to be positive predictor. The remaining 28 studies (58%) found no sex-based differences in postoperative outcomes. Of 7 studies (416 male and 519 female) included in the mHHS analysis, 2 studies concluded that male patients had significantly higher postoperative mHHS scores. Of 6 studies (502 male and 396 female) included in the RTS analysis, 1 study concluded that male patients had a significantly higher RTS rate. Almost one-third of the included studies determined that female sex was a negative predictor of postoperative outcomes, 13% found female sex to be a positive predictor, and 58% found no sex-based differences. Our study illustrates an insufficiency of high-level evidence supporting sex-specific differences in outcomes after hip arthroscopic surgery, but findings indicated that the postoperative mHHS score and RTS rate may be influenced by sex.

Sex-based differences in patients undergoing thoracic endovascular aortic repair for acute complicated type B dissection

Sex-based differences in outcomes for patients undergoing degenerative aortic aneurysm repair have been well described, with female patients having worse early and long-term outcomes compared with male patients. However, differences between men and women after thoracic endovascular aortic repair (TEVAR) of acute complicated type B aortic dissection (TBAD) have not been well characterized. Therefore, the objective of the present study was to assess the sex-based differences in clinical presentation, time to repair, morbidity, and mortality for patients undergoing TEVAR for TBAD. All TEVAR procedures performed for acute complicated TBAD from a single academic medical center from August 2005 to January 2020 were analyzed. The clinical presentation, time to repair, and outcomes were compared by sex. The primary outcome was 30-day mortality. The secondary outcomes were in-hospital complications, reintervention, aorta-related death, and out of hospital survival. The predictors of mortality, including sex, were determined using multivariable logistic regression. A total of 159 patients (38 women [24%]) were included in the analysis. No sex-based differences were found in clinical presentation or comorbidity prevalence between the female and male patients. The female patients had had a longer overall time from initial symptom onset to TEVAR (female patients: median, 3.5days [interquartile range (IQR), 1-10days]; male patients: median, 1day [IQR, 1-3]; P= .007). However, no differences were found in the time to repair after admission to the academic medical center (female patients: median, 1day [IQR, 0-5days]; male patients: median, 1day [IQR, 0-3]; P= .176). No differences were found in the unadjusted aortic-related, in-hospital, or 30-day death between the female and male patients. Similarly, the risk-adjusted analysis revealed that sex was not associated with adverse outcomes. The 1- and 5-year freedom from aortic-related mortality were 82%± 4% and 87%± 6% and 79%± 4% and 80%± 8% for the men and women, respectively. We found no differences between the female and male patients with acute complicated TBAD who had undergone TEVAR in the clinical presentation or comorbidities. The female patients had undergone TEVAR after a longerduration of symptoms, but this was not associated with sex-based differences in early or late morbidity or mortality.

Effects of Initial Graft Tension and Patient Sex on Knee Osteoarthritis Outcomes After ACL Reconstruction: A Randomized Controlled Clinical Trial With 10- to 12-Year Follow-up

Background: The initial graft tension applied during anterior cruciate ligament (ACL) graft fixation may promote posttraumatic osteoarthritis (PTOA). Purpose/Hypothesis: This study sought to assess the effect of initial graft tension and patient sex on PTOA outcomes at 10 to 12 years after ACL reconstruction (ACLR). The hypothesis was that there would be no group- or sex-based differences in outcomes. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients were randomized to receive ACLR with a low or high initial graft tension. Outcomes were evaluated at 10 to 12 years postoperatively and compared with a matched, uninjured control group. Outcomes included clinical assessments (anteroposterior [AP] knee laxity measurement, International Knee Documentation Committee [IKDC] examination score), a functional assessment (single-leg hop for distance), patient-reported outcomes (Knee injury and Osteoarthritis Outcome Score [KOOS], 36-Item Short Form Health Survey, Tegner activity level, patient satisfaction), and PTOA imaging (Osteoarthritis Research Society International [OARSI] radiographic score and Whole-Organ Magnetic Resonance Imaging Score [WORMS]). Two-way mixed-model analyses of variance were used to evaluate differences in outcomes between tension groups and the control group and between female and male patients. Results: Both tension groups scored worse than the control group for the IKDC examination (P≤ .021), KOOS (Pain, Activities of Daily Living, Sport/Recreation, and Quality of Life subscales) (P≤ .049), and WORMS difference score (P≤ .042). The low-tension group scored worse than the control group for KOOS Symptoms (P = .016) and the OARSI difference score (P = .015). The index limb had worse scores than the contralateral limb within the high-tension group for AP laxity (P = .030) and hop deficit (P = .011). This result was also observed within both tension groups for the WORMS (P≤ .050) and within the low-tension group for the OARSI score (P = .001). Male patients had higher Tegner scores (mean ± SE) relative to female patients (male, 5.49 ± 1.88; female, 4.45 ± 1.65) and worse OARSI difference scores (male, 1.89 ± 5.38; female, 0.244 ± 0.668) (P = .007 and .034, respectively). However, no significant differences were detected between tension groups for any of the outcomes measured. Conclusion: Overall, ACLR failed to prevent PTOA regardless of initial graft tension. However, male patients treated with a low initial graft tension may be at greater risk for PTOA. These results do not support the hypothesis of no sex differences in outcomes at 10 to 12 years after ACLR.

Cardiac magnetic resonance defines mechanisms of sex-based differences in outcomes following cardiac resynchronization therapy.

BackgroundMechanisms of sex-based differences in outcomes following cardiac resynchronization therapy (CRT) are poorly understood.ObjectiveTo use cardiac magnetic resonance (CMR) to define mechanisms of sex-based differences in outcomes after CRT and describe distinct CMR-based phenotypes of CRT candidates based on sex and non-ischemic/ischemic cardiomyopathy type.Materials and methodsIn a prospective study, sex-based differences in three short-term CRT response measures [fractional change in left ventricular end-systolic volume index 6 months after CRT (LVESVI-FC), B-type natriuretic peptide (BNP) 6 months after CRT, change in peak VO2 6 months after CRT], and long-term survival were evaluated with respect to 39 baseline parameters from CMR, exercise testing, laboratory testing, electrocardiograms, comorbid conditions, and other sources. CMR was also used to quantify the degree of left-ventricular mechanical dyssynchrony by deriving the circumferential uniformity ratio estimate (CURE-SVD) parameter from displacement encoding with stimulated echoes (DENSE) strain imaging. Statistical methods included multivariable linear regression with evaluation of interaction effects associated with sex and cardiomyopathy type (ischemic and non-ischemic cardiomyopathy) and survival analysis.ResultsAmong 200 patients, the 54 female patients (27%) pre-CRT had a smaller CMR-based LVEDVI (p = 0.04), more mechanical dyssynchrony based on the validated CMR CURE-SVD parameter (p = 0.04), a lower frequency of both late gadolinium enhancement (LGE) and ischemic cardiomyopathy (p < 0.0001), a greater RVEF (p = 0.02), and a greater frequency of LBBB (p = 0.01). After categorization of patients into four groups based on cardiomyopathy type (ischemic/non-ischemic cardiomyopathy) and sex, female patients with non-ischemic cardiomyopathy had the lowest CURE-SVD (p = 0.003), the lowest pre-CRT BNP levels (p = 0.01), the lowest post-CRT BNP levels (p = 0.05), and the most favorable LVESVI-FC (p = 0.001). Overall, female patients had better 3-year survival before adjustment for cardiomyopathy type (p = 0.007, HR = 0.45) and after adjustment for cardiomyopathy type (p = 0.009, HR = 0.67).ConclusionCMR identifies distinct phenotypes of female CRT patients with non-ischemic and ischemic cardiomyopathy relative to male patients stratified by cardiomyopathy type. The more favorable short-term response and long-term survival outcomes in female heart failure patients with CRT were associated with lower indexed CMR-based LV volumes, decreased presence of scar associated with prior myocardial infarction and ICM, and greater CMR-based dyssynchrony with the CURE-SVD.

Sex-based differences in referral of heart failure patients to outpatient clinics: a scoping review.

Guidelines recommend that hospitalized patients newly diagnosed with HF be referred to an outpatient HF clinic (HFC) within 2weeks of discharge. Our study aims were (i) to assess the current literary landscape on the impact of patient sex on HFC referral and outcomes and (ii) to provide a qualitative overview of possible considerations for the impact of sex on referral patterns and HF characteristics including aetiology, symptom severity, investigations undertaken and pharmacologic therapy. We conducted a scoping review using the Arksey and O'Malley framework and searched Medline, EMBASE, PsychINFO, Cochrane Library, Ageline databases and grey literature. Eligible articles included index HF hospitalizations or presentations to the Emergency Department (ED), a description of the HFC referral of patients not previously followed by an HF specialist and sex-specific analysis. Of the 11372 potential studies, 8 met the inclusion criteria. These studies reported on a total of 11484 participants, with sample sizes ranging between 168 and 3909 (25.6%-50.7% female). The included studies were divided into two groups: (i) those outlining the referral process to an HFC and (ii) studies which include patients newly enrolled in an HFC. Of the studies in Group 1, males (51%-82.4%) were more frequently referred to an HFC compared with females (29%-78.1%). Studies in Group 2 enrolled a higher proportion of males (62%-74% vs. 26%-38%). One study identified independent predictors of HFC referral which included male sex, younger age, and the presence of systolic dysfunction, the latter two more often found in males. Two studies, one from each group reported a higher mortality amongst males compared with females, whereas another study from Group 2 reported a higher hospitalization rate amongst females following HFC assessment. Males were more likely than females to be referred to HFCs after hospitalization and visits to the Emergency Department, however heterogeneity across studies precluded a robust assessment of sex-based differences in outcomes. This highlights the need for more comprehensive longitudinal data on HF patients discharged from the acute care setting to better understand the role of sex on patient outcomes.

Sex-Based Differences in Outcomes of Coronavirus Disease 2019 (COVID-19) in Korea

PurposeThis study examined the factors affecting mortality and clinical severity score (CSS) of male and female patients with Coronavirus Disease 2019 (COVID-19) using clinical epidemiological information provided by the Korea Disease Control and Prevention Agency.MethodsThis is a retrospective, observational cohort study. From January 21 to April 30, 2020, a total of 5624 patients who were released from quarantine or died were analyzed.ResultsThe factors influencing release or death that differed by sex were high heart rate and malignancy in males and chronic kidney disease in females. In addition, the factors influencing progression to severe CSS were high BMI (severe obesity) and rheumatic disease in males and high temperature, sputum production, absence of sore throat and headache, chronic kidney disease, malignancy, and chronic liver disease in females. Older age, low lymphocyte count and platelets, dyspnea, diabetes mellitus, dementia, and intensive care unit (ICU) admission affected mortality in all the patients, and older age, low lymphocyte count and platelets, fever, dyspnea, diabetes mellitus, dementia, and ICU admission affected progression to severe stage of CSS.ConclusionsThis study is expected to contribute to the general results by analyzing nationally representative data. The results of this study present an important basis for development of differentiated nursing and medical management strategies in consideration of factors that influence treatment effects and outcomes according to sex of patients with COVID-19.

INTERACTIONS BETWEEN BIOLOGICAL SEX AND THE X-LINKED VARIANT IRAK1 HAPLOTYPE IN MODULATING CLINICAL OUTCOME AND CELLULAR PHENOTYPES AFTER TRAUMA.

Sex-related outcome differences in trauma remain controversial. The mechanisms causing sex-biased outcomes are likely to have hormonal and genetic components, in which X-linked genetic polymorphisms may play distinct roles because of X-linked inheritance, hemizygosity in males, and X chromosome mosaicism in females. The study aimed to elucidate the contribution of biological sex and the common X-linked IRAK1 haplotype to posttrauma clinical complications, inflammatory cytokine and chemokine production, and polymorphonuclear cell and monocyte activation. Postinjury clinical outcome was tested in 1507 trauma patients (1,110 males, 397 females) after stratification by sex or the variant IRAK1 haplotype. Males showed a three- to fivefold greater frequency of posttrauma sepsis, but similar mortality compared to females. Stratification by the variant IRAK1 haplotype revealed increased pneumonia and urinary tract infection in Wild type (WT) versus variant IRAK1 males, whereas increased respiratory failures in variant versus WT females. Cytokine/chemokine profiles were tested in whole blood from a subset of patients (n = 81) and healthy controls (n = 51), which indicated sex-related differences in ex vivo lipopolysaccharide responsiveness manifesting in a 1.5- to 2-fold increased production rate of tumor necrosis factor α, interleukin-1β (IL-1β), IL-10, Macrophage Inflammatory Protein-1 Alpha, and MIP1β in WT male compared to WT female trauma patients. Variant IRAK1 decreased IL-6, IL-8, and interferon gamma-induced protein 10 production in male trauma subjects compared to WT, whereas cytokine/chemokine responses were similar in variant IRAK1 and WT female trauma subjects. Trauma-induced and lipopolysaccharide-stimulated polymorphonuclear cell and monocyte activation determined by using a set of cluster of differentiation markers and flow cytometry were not influenced by sex or variant IRAK1. These findings suggest that variant IRAK1 is a potential contributor to sex-based outcome differences, but its immunomodulatory impacts are modulated by biological sex.